Osteomyelitis Treatment with Nanometer-Sized Hydroxyapatite Particles as a Delivery Vehicle for a Ciprofloxacin- Bisphosphonate Conjugate; New Fluoroquinolone-Bisphosphonate Derivatives Show Similar Binding Affinity to Hydroxyapatite and Improved Antibacterial Activity Against Drug-Resistant Pathogens

DTIC Science & Technology

2008-12-01

1 OSTEOMYELITIS TREATMENT WITH NANOMETER-SIZED HYDROXYAPATITE PARTICLES AS A DELIVERY VEHICLE FOR A CIPROFLOXACIN- BISPHOSPHONATE CONJUGATE; NEW...FLUOROQUINOLONE-BISPHOSPHONATE DERIVATIVES SHOW SIMILAR BINDING AFFINITY TO HYDROXYAPATITE AND IMPROVED ANTIBACTERIAL ACTIVITY AGAINST DRUG-RESISTANT...vivo OM model. Current studies contrast two CP homeostatic bone-substitute particles, nanometer-sized hydroxyapatite NanOss™ (Nan), and µ-sized

Antibiotics as immunomodulant agents in COPD.

PubMed

Blasi, Francesco; Mantero, Marco; Aliberti, Stefano

2012-06-01

It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Designer antibacterial peptides kill fluoroquinolone-resistant clinical isolates.

PubMed

Otvos, Laszlo; Wade, John D; Lin, Feng; Condie, Barry A; Hanrieder, Joerg; Hoffmann, Ralf

2005-08-11

A significant number of Escherichia coli and Klebsiella pneumoniae bacterial strains in urinary tract infections are resistant to fluoroquinolones. Peptide antibiotics are viable alternatives although these are usually either toxic or insufficiently active. By applying multiple alignment and sequence optimization steps, we designed multifunctional proline-rich antibacterial peptides that maintained their DnaK-binding ability in bacteria and low toxicity in eukaryotes, but entered bacterial cells much more avidly than earlier peptide derivatives. The resulting chimeric and statistical analogues exhibited 8-32 microg/mL minimal inhibitory concentration efficacies in Muller-Hinton broth against a series of clinical pathogens. Significantly, the best peptide, compound 5, A3-APO, retained full antibacterial activity in the presence of mouse serum. Across a set of eight fluoroquinolone-resistant clinical isolates, peptide 5 was 4 times more potent than ciprofloxacin. On the basis of the in vitro efficacy, toxicity, and pharmacokinetics data, we estimate that peptide 5 will be suitable for treating infections in the 3-5 mg/kg dose range.

Isobolographic Analysis of Pharmacodynamic Interactions between Antifungal Agents and Ciprofloxacin against Candida albicans and Aspergillus fumigatus▿

PubMed Central

Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Papaioannidou, Paraskevi; Tsiouris, Ioannis; Roilides, Emmanuel; Walsh, Thomas J.

2008-01-01

Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 μg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis. PMID:18299413

DNA topoisomerase I and DNA gyrase as targets for TB therapy.

PubMed

Nagaraja, Valakunja; Godbole, Adwait A; Henderson, Sara R; Maxwell, Anthony

2017-03-01

Tuberculosis (TB) is the deadliest bacterial disease in the world. New therapeutic agents are urgently needed to replace existing drugs for which resistance is a significant problem. DNA topoisomerases are well-validated targets for antimicrobial and anticancer chemotherapies. Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy. Here, we review the exploitation of topoisomerases as antibacterial targets and summarize progress in developing new agents to target DNA topoisomerase I and DNA gyrase from Mycobacterium tuberculosis. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Robust Synthesis of Ciprofloxacin-Capped Metallic Nanoparticles and Their Urease Inhibitory Assay.

PubMed

Nisar, Muhammad; Khan, Shujaat Ali; Qayum, Mughal; Khan, Ajmal; Farooq, Umar; Jaafar, Hawa Z E; Zia-Ul-Haq, Muhammad; Ali, Rashid

2016-03-25

The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap metallic (silver and gold) nanoparticles by a robust one pot synthetic method under optimized conditions, using NaBH₄ as a mild reducing agent. Metallic nanoparticles (MNPs) showed constancy against variations in pH, table salt (NaCl) solution, and heat. Capping with metal ions (Ag/Au-cip) has significant implications for the solubility, pharmacokinetics and bioavailability of fluoroquinolone molecules. The metallic nanoparticles were characterized by several techniques such as ultraviolet visible spectroscopy (UV), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) methods. The nanoparticles synthesized using silver and gold were subjected to energy dispersive X-ray tests in order to show their metallic composition. The NH moiety of the piperazine group capped the Ag/Au surfaces, as revealed by spectroscopic studies. The synthesized nanoparticles were also assessed for urease inhibition potential. Fascinatingly, both Ag-cip and Au-cip NPs exhibited significant urease enzyme inhibitory potential, with IC50 = 1.181 ± 0.02 µg/mL and 52.55 ± 2.3 µg/mL, compared to ciprofloxacin (IC50 = 82.95 ± 1.62 µg/mL). MNPs also exhibited significant antibacterial activity against selected bacterial strains.

Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.

PubMed

Davidson, Ross J; Davis, Ian; Willey, Barbara M; Rizg, Keyro; Bolotin, Shelly; Porter, Vanessa; Polsky, Jane; Daneman, Nick; McGeer, Allison; Yang, Paul; Scolnik, Dennis; Rowsell, Roy; Imas, Olga; Silverman, Michael S

2008-07-16

Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations. In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.

The role of topical moxifloxacin, a new antibacterial in Europe, in the treatment of bacterial conjunctivitis.

PubMed

Benitez-Del-Castillo, Jose; Verboven, Yves; Stroman, David; Kodjikian, Laurent

2011-01-01

This article discusses current practice in the treatment of conjunctivitis and how the use of topical moxifloxacin can increase therapeutic effectiveness, reduce treatment failures and, consequently, be cost effective and reduce the societal burden of the disorder. Current practice and effectiveness data were derived from the literature. Data on healthcare utilization as a result of treatment failure were collected by survey and the cost of treatment was defined using national costings. A decision-analytic model to assess cost effectiveness was developed and the impact on the healthcare budget was calculated to define the health economic impact. Bacterial conjunctivitis represents a significant health problem and accounts for an estimated 1-1.5% of primary-care consultations. The disorder is highly contagious and causes a substantial healthcare and societal burden. Bacterial conjunctivitis is generally self-limiting, resolving within 1-2 weeks. However, the use of antibacterials significantly improves clinical and microbiological remission, shortens symptom duration, and enables more effective use of healthcare resources, compared with placebo. From a health economic perspective this benefits the healthcare system and society, since fewer healthcare resources are needed and the adult affected, or the parent/caregiver of the child affected, can return to full work capacity sooner, reducing loss of productivity. Treatment strategies vary significantly between countries. Most patients are first seen in primary care, where 'wait-and-see', lubrification and antiseptic or antibacterial treatment is provided. In Europe, when antibacterials are prescribed most general practitioners (GPs) prescribe a broad-spectrum topical antibacterial. The most commonly used drugs are chloramphenicol and fusidic acid, with fluoroquinolones rarely reported as first-line treatment by GPs. At the specialist (ophthalmologist) level, or for second-line treatment at the GP level, topical antibacterials are frequently used. However, in most countries, topical fluoroquinolones, particularly those recently approved by the European Medicines Agency, such as topical levofloxacin and topical moxifloxacin, are rarely used and instead are reserved for use as a last resort. In other parts of the world topical lomefloxacin, gatifloxacin and/or besifloxacin are also available. The strategy of using novel topical fluoroquinolones as a last resort reflects a belief that the use of topical fluoroquinolones may enhance the development of resistance, jeopardizing future availability of antibacterial treatment for ocular infections. In fact, most cases of bacterial resistance arise as a result of systemic treatment. Thus, this concern should not be extrapolated to topical use of fluoroquinolones, which results in antibacterial concentrations at the ocular surface that can significantly exceed mutant prevention concentrations. In addition, with products such as topical moxifloxacin, a dual-step mutation is required for resistance to emerge. Moxifloxacin restricts the selection of resistant mutants, meaning that emergence of resistance is unlikely. The strategy of not using the most effective fluoroquinolones such as topical moxifloxacin may lead to more patients with no improvement or worsening of symptoms, requiring re-intervention, additional examination and new treatment; these outcomes are defined as 'treatment failures'. Treatment failures cause an extra societal burden and increased costs due to the extra healthcare resources required (additional GP/specialist visits, laboratory tests, additional treatment, etc.). Compared with non-fluoroquinolones, topical moxifloxacin has a higher potency and faster in vitro 'speed-to-kill'. It has also been shown that, within the fluoroquinolone class, topical moxifloxacin and besifloxacin achieve the highest mean concentrations in conjunctival tissue, have the longest residence times and display favourable area under the concentration-time curve from time zero to 24 hours (AUC(24))/minimum inhibitory concentration ratio required to inhibit the growth of 90% of organisms (MIC(90)) and thus favourable pharmacokinetic/pharmacodynamic characteristics. This can result in reduced time-to-cure and a lower number of treatment failures, leading to better disease management and a healthcare-economic benefit arising from the associated reduction in utilization of healthcare resources. The high potency and mean concentration in conjunctival tissue combined with the long residence time of topical moxifloxacin enables a dosing strategy of three times daily for 5 days. Topical moxifloxacin is also the first ophthalmic antibacterial in Europe provided as a multidose, self-preserved, topical solution, thus avoiding the risk of benzalkonium chloride preservative-related allergic reactions and swelling. In addition, topical moxifloxacin has a near neutral pH (6.8) and is well tolerated by patients. Given the characteristics of the novel topical fluoroquinolones, a change in the healthcare treatment strategy for acute infectious conjunctivitis is to be recommended. Topical application of fluoroquinolones, such as moxifloxacin multidose self-preserved solution, should be considered earlier in the treatment path for conjunctivitis. Notwithstanding the premium price attached to this novel topical antibacterial, use of topical moxifloxacin for bacterial conjunctivitis can be cost effective and even generate total healthcare budget savings by reducing both the costs of managing treatment failures and the use of clinicians' time to manage such failures.

Surveillance of Wisconsin Antibacterial Susceptibility Patterns.

PubMed

Munson, Erik; Block, Timothy K; Bowles, Erin J; Costello, Michael; Dern, Richard; Fritsche, Thomas R; Helgesen, Michael A; Kropp, Joshua L; Podzorski, Raymond P; Siebers, Karen; Simmons, Brian; Smith, Mary A; Spray, Frances; Van, Tam T; Warshauer, David M

2016-02-01

Antimicrobial resistance presents a threat to quality patient care. Knowledge of localantibacterial susceptibility patterns can guide clinicians in empiric antibacterial administration andassist pharmacists and infectious disease physicians in development of appropriate therapeutic pathways. To characterize Wisconsin antibacterial susceptibility patterns and elucidate geographicor temporal variation in antibacterial resistance, a retrospective, observational analysis of antibiogram data was performed. Seventy-two members of the Wisconsin Clinical Laboratory Network(WCLN) submitted antibiograms describing clinically significant isolates tested in calendar year 2013 to the WCLN Laboratory Technical Advisory Group. In the context of commonly reported antibacterial agents, data were compiled for approximately 75,800 isolates of Escherichia coi; 13,300 Klebsiella pneumoniae; 6300 Proteus mirobilis;2800 Enterobacter cloacae; 8400 Pseudomonas aeruginosa; 30,000 S aureus; 11,200 coagulase-negative Staphylococcus spp; and 13,800 Enterococcus spp. P mirobilis isolates from northern Wisconsin were more likely to demonstrate resistance than those in the southern region. In contrast, P aeruginosa isolates from southern Wisconsin had decreased susceptibility to a number ofagents when compared to other regions. Temporal trending in decreased E coli and P mirabilis susceptibility to fluoroquinolones and trimethoprimsulfamethoxazole was observed. Increased methicillin-resistant Staphylococcus oureus (MRSA) rates were observed in northwest and southeastWisconsin. In general, northeast Wisconsin exhibited less frequency of antibacterial resistance. Geographic variation exists with respect to antibacterial resistance, particularly inareas of Wisconsin adjacent to large population centers of neighboring states. Antibacterial surveillance in Wisconsin is indicated on a regular basis to assess emerging trends in antibacterial resistance. Existing WCLN infrastructure allows for such investigations.

Using In Vitro Dynamic Models To Evaluate Fluoroquinolone Activity against Emergence of Resistant Salmonella enterica Serovar Typhimurium

PubMed Central

Lee, Seung-Jin; Awji, Elias Gebru; Park, Na-hye

2016-01-01

ABSTRACT The objectives of this study were to determine pharmacokinetic/pharmacodynamic (PK/PD) indices of fluoroquinolones that minimize the emergence of resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) using in vitro dynamic models and to establish mechanisms of resistance. Three fluoroquinolones, difloxacin (DIF), enrofloxacin (ENR), and marbofloxacin (MAR), at five dose levels and 3 days of treatment were simulated. Bacterial killing-regrowth kinetics and emergence of resistant bacteria after antibacterial drug exposure were quantified. PK/PD indices associated with different levels of antibacterial activity were computed. Mechanisms of fluoroquinolone resistance were determined by analyzing target mutations in the quinolone resistance-determining regions (QRDRs) and by analyzing overexpression of efflux pumps. Maximum losses in susceptibility of fluoroquinolone-exposed S. Typhimurium occurred at a simulated AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 47 to 71. Target mutations in gyrA (S83F) and overexpression of acrAB-tolC contributed to decreased susceptibility in fluoroquinolone-exposed S. Typhimurium. The current data suggest AUC/MIC (AUC/mutant prevention concentration [MPC])-dependent selection of resistant mutants of S. Typhimurium, with AUC/MPC ratios of 69 (DIF), 62 (ENR), and 39 (MAR) being protective against selection of resistant mutants. These values could not be achieved in veterinary clinical areas under the current recommended therapeutic doses of the fluoroquinolones, suggesting the need to reassess the current dosing regimen to include both clinical efficacy and minimization of emergence of resistant bacteria. PMID:27895011

Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases.

PubMed

Basarab, Gregory S; Kern, Gunther H; McNulty, John; Mueller, John P; Lawrence, Kenneth; Vishwanathan, Karthick; Alm, Richard A; Barvian, Kevin; Doig, Peter; Galullo, Vincent; Gardner, Humphrey; Gowravaram, Madhusudhan; Huband, Michael; Kimzey, Amy; Morningstar, Marshall; Kutschke, Amy; Lahiri, Sushmita D; Perros, Manos; Singh, Renu; Schuck, Virna J A; Tommasi, Ruben; Walkup, Grant; Newman, Joseph V

2015-07-14

With the diminishing effectiveness of current antibacterial therapies, it is critically important to discover agents that operate by a mechanism that circumvents existing resistance. ETX0914, the first of a new class of antibacterial agent targeted for the treatment of gonorrhea, operates by a novel mode-of-inhibition against bacterial type II topoisomerases. Incorporating an oxazolidinone on the scaffold mitigated toxicological issues often seen with topoisomerase inhibitors. Organisms resistant to other topoisomerase inhibitors were not cross-resistant with ETX0914 nor were spontaneous resistant mutants to ETX0914 cross-resistant with other topoisomerase inhibitor classes, including the widely used fluoroquinolone class. Preclinical evaluation of ETX0914 pharmacokinetics and pharmacodynamics showed distribution into vascular tissues and efficacy in a murine Staphylococcus aureus infection model that served as a surrogate for predicting efficacious exposures for the treatment of Neisseria gonorrhoeae infections. A wide safety margin to the efficacious exposure in toxicological evaluations supported progression to Phase 1. Dosing ETX0914 in human volunteers showed sufficient exposure and minimal adverse effects to expect a highly efficacious anti-gonorrhea therapy.

Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases

PubMed Central

Basarab, Gregory S.; Kern, Gunther H.; McNulty, John; Mueller, John P.; Lawrence, Kenneth; Vishwanathan, Karthick; Alm, Richard A.; Barvian, Kevin; Doig, Peter; Galullo, Vincent; Gardner, Humphrey; Gowravaram, Madhusudhan; Huband, Michael; Kimzey, Amy; Morningstar, Marshall; Kutschke, Amy; Lahiri, Sushmita D.; Perros, Manos; Singh, Renu; Schuck, Virna J. A.; Tommasi, Ruben; Walkup, Grant; Newman, Joseph V.

2015-01-01

With the diminishing effectiveness of current antibacterial therapies, it is critically important to discover agents that operate by a mechanism that circumvents existing resistance. ETX0914, the first of a new class of antibacterial agent targeted for the treatment of gonorrhea, operates by a novel mode-of-inhibition against bacterial type II topoisomerases. Incorporating an oxazolidinone on the scaffold mitigated toxicological issues often seen with topoisomerase inhibitors. Organisms resistant to other topoisomerase inhibitors were not cross-resistant with ETX0914 nor were spontaneous resistant mutants to ETX0914 cross-resistant with other topoisomerase inhibitor classes, including the widely used fluoroquinolone class. Preclinical evaluation of ETX0914 pharmacokinetics and pharmacodynamics showed distribution into vascular tissues and efficacy in a murine Staphylococcus aureus infection model that served as a surrogate for predicting efficacious exposures for the treatment of Neisseria gonorrhoeae infections. A wide safety margin to the efficacious exposure in toxicological evaluations supported progression to Phase 1. Dosing ETX0914 in human volunteers showed sufficient exposure and minimal adverse effects to expect a highly efficacious anti-gonorrhea therapy. PMID:26168713

In vitro characterization of the antibacterial spectrum of novel bacterial type II topoisomerase inhibitors of the aminobenzimidazole class.

PubMed

Mani, Nagraj; Gross, Christian H; Parsons, Jonathan D; Hanzelka, Brian; Müh, Ute; Mullin, Steve; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Charifson, Paul S; Grossman, Trudy H

2006-04-01

Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities.

In Vitro Characterization of the Antibacterial Spectrum of Novel Bacterial Type II Topoisomerase Inhibitors of the Aminobenzimidazole Class

PubMed Central

Mani, Nagraj; Gross, Christian H.; Parsons, Jonathan D.; Hanzelka, Brian; Müh, Ute; Mullin, Steve; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Charifson, Paul S.; Grossman, Trudy H.

2006-01-01

Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities. PMID:16569833

[Determination of in vitro susceptibilities of Brucella spp. strains against 11 different antibacterial gents isolated from blood cultures].

PubMed

Keşli, Recep; Bilgin, Hüseyin; Yılmaz, Halim

2017-07-01

Brucellosis is a worldwide zoonotic disease and still continuous to be a major public health problem. In this study, it was aimed to identify the Brucella strains to the species level isolated from blood cultures, and to determine the rate of antimicrobial susceptibility against eleven antibacterial agents. A total of 106 Brucella spp. strains were included in the study, which were isolated from blood cultures in University of Health Sciences, Konya Training and Research Hospital, Medical Microbiology Laboratory between January 2011 and June 2013. Identification of the isolated strains were mainly based on conventional methods. In vitro antibacterial susceptibilities of azithromycin, ciprofloxacin, doxycycline, gentamicin, levofloxacin, moxifloxacin, rifampicin, streptomycin, tetracycline, tigecycline, and trimethoprim/sulfamethoxazole, were evaluated by using the gradient (E-test, bioMerieux, France) strip method. The bacterial suspensions adjusted to 0.5 McFarland turbidity was inoculated to Mueller Hinton agar plates, supplemented with 5% sheep blood, and E-test strips of selected antibacterial were applied. The plates were incubated in ambient air 48 hours at 37ºC and Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 were used as quality control strains for antimicrobial susceptibility testing. Minimum inhibitors concentration (MIC) values were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines for slow-growing bacteria such as Haemophilus spp. Of the 106 Brucella spp. strains included in to the study, 90 were identified as Brucella melitensis, and 16 were Brucella abortus. MIC90 values of azithromycin, ciprofloxacin, doxycycline, gentamicin, levofloxacin, moxifloxacin, rifampicin, streptomycin, tetracycline, tigecycline, and trimethoprim/sulfamethoxazole were determined as 1 µg/ml, 0.25 µg/ml, 0.19 µg/ml, 0.25 µg/ml, 0.19 µg/ml, 0.75 µg/ml, 0.25 µg/ml, 0.75 µg/ml, 0.38 µg/ml, 0.64 µg/ml, and 0.19 µg/ml respectively. According to MIC90 values, gentamicin, moxifloxacin, and trimethoprim/sulfamethoxazole, were the most effective antibacterial agents. All the Brucella strains were sensitive to all the tested antibacterial agents except rifampicin. Only six isolates showed intermediate susceptibility to rifampicin. With regard to fluoroquinolones, the most active antibacterial agent was moxifloxacin, followed by ciprofloxacin and levofloxacin. In our study, no resistance was found for the classically recommended antibacterial agents used in the treatment of Brucella species in our hospital but antibiotic susceptibility patterns of Brucella spp. may vary geographically. As a result it was concluded that, the antimicrobial susceptibilities of Brucella species should be determined and controlled periodically to avoid the possible development of resistance problems in the future.

Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria.

PubMed

Charrier, Cédric; Salisbury, Anne-Marie; Savage, Victoria J; Duffy, Thomas; Moyo, Emmanuel; Chaffer-Malam, Nathan; Ooi, Nicola; Newman, Rebecca; Cheung, Jonathan; Metzger, Richard; McGarry, David; Pichowicz, Mark; Sigerson, Ralph; Cooper, Ian R; Nelson, Gary; Butler, Hayley S; Craighead, Mark; Ratcliffe, Andrew J; Best, Stuart A; Stokes, Neil R

2017-05-01

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC 90 values were 4 and 8 μg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli , respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10 -8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary in vitro safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC 50 ], >100 μM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents. Copyright © 2017 American Society for Microbiology.

Covalent modification of a ten-residue cationic antimicrobial peptide with levofloxacin

NASA Astrophysics Data System (ADS)

Rodriguez, Carlos; Papanastasiou, Emilios; Juba, Melanie; Bishop, Barney

2014-09-01

The rampant spread of antibiotic resistant bacteria has spurred interest in alternative strategies for developing next-generation antibacterial therapies. As such, there has been growing interest in cationic antimicrobial peptides (CAMPs) and their therapeutic applications. Modification of CAMPs via conjugation to auxiliary compounds, including small molecule drugs, is a new approach to developing effective, broad-spectrum antibacterial agents with novel physicochemical properties and versatile antibacterial mechanisms. Here, we’ve explored design parameters for engineering CAMPs conjugated to small molecules with favorable physicochemical and antibacterial properties by covalently affixing a fluoroquinolone antibiotic, levofloxacin, to the ten-residue CAMP Pep-4. Relative to the unmodified Pep-4, the conjugate was found to demonstrate substantially increased antibacterial potency under high salt concentrations. Historically, it has been observed that most CAMPs lose antibacterial effectiveness in such high ionic strength environments, a fact that has presented a challenge to their development as therapeutics. Physicochemical studies revealed that P4LC was more hydrophobic than Pep-4, while mechanistic findings indicated that the conjugate was more effective at disrupting bacterial membrane integrity. Although the inherent antibacterial effect of the incorporated levofloxacin molecules did not appear to be substantially realized in this conjugate, these findings nevertheless suggest that covalent attachment of small molecule antibiotics with favorable physicochemical properties to CAMPs could be a promising strategy for enhancing peptide performance and overall therapeutic potential. These results have broader applicability to the development of future CAMP-antibiotic conjugates for potential therapeutic applications.

Comparative activity of pradofloxacin against anaerobic bacteria isolated from dogs and cats.

PubMed

Silley, Peter; Stephan, Bernd; Greife, Heinrich A; Pridmore, Andrew

2007-11-01

To compare the intrinsic activity of pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats. One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology. Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC(50), MIC(90) and mode MIC values, pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones. Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.

Triprotic site-specific acid-base equilibria and related properties of fluoroquinolone antibacterials.

PubMed

Rusu, Aura; Tóth, Gergő; Szőcs, Levente; Kökösi, József; Kraszni, Márta; Gyéresi, Árpád; Noszál, Béla

2012-07-01

The complete macro- and microequilibrium analyses of six fluoroquinolone drugs - ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, ofloxacin and moxifloxacin - are presented. Previous controversial literature data are straightened up, the protonation centers are unambiguously identified, and the protonation macro- and microconstant values are reported. The macroconstants were determined by (1)H NMR-pH titrations while the microconstants were determined by a multi-modal spectroscopic-deductive methodology, in which methyl ester derivatives were synthesized and their NMR-pH titration data contributed to the evaluation of all the microconstants. The full (1)H, (13)C and (15)N NMR assignments, NMR-pH profiles, macro- and microprotonation schemes and species-specific diagrams are included. Our studies show that the fluoroquinolones have three protonation centers: the carboxylate group, the N-1' and N-4' piperazine nitrogens and concentration of the uncharged microspecies is way below the values published earlier. The results could be well interpreted in terms of structural properties. The protonation macro- and microconstant values allow the pre-planned method development in techniques such as capillary zone electrophoresis and also, the interpretation of fluoroquinolone mechanism of biological action, including the pharmacokinetic properties, and antibacterial activities that are all heavily influenced by the states of protonation. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparative antibacterial effects of moxifloxacin and levofloxacin on Streptococcus pneumoniae strains with defined mechanisms of resistance: impact of bacterial inoculum.

PubMed

Bowker, K E; Garvey, M I; Noel, A R; Tomaselli, S G; Macgowan, A P

2013-05-01

We aim to further define the impact of the mechanism of fluoroquinolone resistance and inoculum load on the pharmacodynamic effects of levofloxacin and moxifloxacin on Streptococcus pneumoniae. The antibacterial effects of and emergence of resistance (EoR) to moxifloxacin (400 mg once daily) or levofloxacin (750 mg once daily or 500 mg twice daily) were compared using five S. pneumoniae strains containing no known resistance mechanisms, efflux resistance mechanisms, a parC mutation or parC and gyrA mutations, at high (10(8) cfu/mL) and low (10(6) cfu/mL) inocula. An in vitro pharmacokinetic model was used and simulations were performed over 96 h. After drug exposure, isolates were tested for the presence of efflux pumps and mutations in the quinolone resistance-determining regions. A high inoculum diminished the antibacterial effect of moxifloxacin and levofloxacin. Levofloxacin at both dosages produced EoR with all strains. Levofloxacin regimens with AUC/MIC ratios <100 produced EoR. Moxifloxacin produced EoR with the parC strain only. Levofloxacin dosing regimens with low AUC/MIC ratios select for efflux pump overexpression, leading to fluoroquinolone resistance. Levofloxacin dosing may select for gyrA mutations, inducing moxifloxacin resistance. These data confirm that a fluoroquinolone AUC/MIC ratio of >100 is required for prevention of EoR.

Allicin-inspired thiolated fluoroquinolones as antibacterials against ESKAPE pathogens.

PubMed

Sheppard, Jordan G; Long, Timothy E

2016-11-15

Thiolated fluoroquinolones were synthesized from ciprofloxacin and evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA) exhibited the highest level of increased sensitivity toward ciprofloxacin bound with a N-propylthio substituent. Evidence was found that the antibiotics form disulfides with low molecular weight thiols in bacteria and potentiate generation of cytosolic reactive oxygen species (ROS). In final analysis, the enhanced anti-MRSA activity of thiolated fluoroquinolones was attributed to increased cell permeability and reaction with cytosolic thiols that yields an inactive disulfide metabolite and the parent drug ciprofloxacin as an inhibitor of DNA synthesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exposure to antibacterial agents with QT liability in 14 European countries: trends over an 8-year period

PubMed Central

Raschi, Emanuel; Poluzzi, Elisabetta; Zuliani, Chiara; Muller, Arno; Goossens, Herman; De Ponti, Fabrizio

2009-01-01

AIMS (i) To classify antibacterial agents with QT liability on the basis of the available evidence, and (ii) to assess trends in their consumption over an 8-year period (1998–2005) in 14 European countries. METHODS Current published evidence on QT liability of antibiotics was retrieved through MEDLINE search and joined to official warnings from regulatory agencies. Each drug was classified according to an already proposed algorithm based on the strength of evidence: from group A (any evidence) to group E (clinical reports of torsades de pointes and warnings on QT liability). Consumption data were provided by the European Surveillance of Antibacterial Consumption (ESAC) project and were expressed as defined daily doses per 1000 inhabitants per day (DID). RESULTS Among 21 detected compounds, nine [six fluoroquinolones (FQs) and three macrolides (MACs)] belonged to group E. Use of group E drugs ranged from 1.3 (Sweden) to 4.1 DID (Italy) in 1998 and from 1.2 (Sweden) to 6.5 DID (Italy) in 2005. Significant exposure was observed in Italy and Spain (6.5 and 3.8 DID, respectively, in 2005). Only Denmark, Sweden and UK showed a slight decrease in use. Exposure to clarithromycin increased in 10 out of 14 countries, with a marked increment in Italy (3 DID in 2005). CONCLUSIONS Notwithstanding regulatory measures, in 2005 there was still significant exposure to antibacterials with strong evidence of QT liability and, in most countries, it was even increased. This warrants further investigation of appropriateness of use and suggests closer monitoring of group E drugs. Physicians should be aware when prescribing them to susceptible patients. PMID:19076158

Different mechanisms for the photoinduced production of oxidative DNA damage by fluoroquinolones differing in photostability.

PubMed

Spratt, T E; Schultz, S S; Levy, D E; Chen, D; Schlüter, G; Williams, G M

1999-09-01

Several fluoroquinolone antibacterial agents exhibit an adverse phototoxic effect in humans and are photo-cocarcinogenic in mice. The UV-induced production of reactive oxygen species plays a role in the toxicity and may be involved in carcinogenicity. Four fluoroquinolones were examined for the ability to photochemically produce oxidative damage in naked DNA. The major structural difference in the fluoroquinolones that would have an effect on their photostability is the functionality at the 8-position. At this position, 1-cyclopropyl-7-(2,8-diazbicyclo[4.3.0]non-8-yl)-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (BAY y3118) contains a chlorine atom, lomefloxacin a fluorine atom, ciprofloxacin a proton, and moxifloxacin a methoxy group. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in calf thymus DNA was assessed by HPLC with electrochemical detection, and strand breaks were measured in pBR322 with agarose gel electrophoresis. The relative photolability of the fluoroquinolones correlated to the extent of production of 8-oxodGuo and strand breaks, with both UVA and UVB irradiation, in the following order: BAY y3118 approximately lomefloxacin > ciprofloxacin > moxifloxacin. Experiments were performed to determine whether the mechanism of damage was due to a type I (radical) or type II (singlet oxygen) pathway. Nitrogen depletion of oxygen resulted in a decrease in the extent of formation of 8-oxodGuo, suggesting that oxygen was involved. The use of selective radical or singlet oxygen inhibitors was inconclusive with respect to which pathway was involved. The use of D(2)O as a solvent, which would extend the lifetime of singlet oxygen, suggested that this species is involved in the formation of 8-oxodGuo by moxifloxacin and ciprofloxacin, but not by lomefloxacin and BAY y3118. Similarly, it was found that singlet oxygen was not involved in strand break formation. Thus, the evidence suggests that fluoroquinolones can photochemically produce DNA damage by both type I and type II mechanisms.

Degradation of fluoroquinolone antibiotics during ionizing radiation treatment and assessment of antibacterial activity, toxicity and biodegradability of the products

NASA Astrophysics Data System (ADS)

Tegze, Anna; Sági, Gyuri; Kovács, Krisztina; Homlok, Renáta; Tóth, Tünde; Mohácsi-Farkas, Csilla; Wojnárovits, László; Takács, Erzsébet

2018-06-01

This work aimed at investigating the ionizing radiation induced degradation of two fluoroquinolone antibiotics: norfloxacin and ciprofloxacin. At 0.1 mmol dm-3 concentration a low dose, 2 kGy was sufficient to degrade the initial molecules. However, despite of the high removal efficiency the degrees of both the mineralization and the oxidation were low, ∼10% and ∼25%, respectively. (The difference between the results obtained in norfloxacin and ciprofloxacin solutions was not statistically significant.) Broth microdilution tests carried out on Staphylococcus aureus evidenced removal of antibacterial activity in samples irradiated with 2 kGy. Acute toxicity determined on Vibrio fischeri bacteria showed increased toxicity at low doses indicating that the early degradation products were more toxic than the initial molecules. The results of biodegradation experiments performed in activated sludge have shown that the degradation products have become available to the metabolic processes of the microorganisms.

The expanding role of fluoroquinolones.

PubMed

Schaeffer, Anthony J

2003-02-01

There has been a growing rate of resistance among common urinary tract pathogens, such as Escherichia coli, to traditional antimicrobial therapies including the "gold standard" trimethoprim-sulfamethoxazole (TMP-SMX). Consequently, fluoroquinolone antimicrobial agents have taken on an expanding management role for UTIs. In fact, the recent Infectious Diseases Society of America clinical management guidelines for UTI recommend fluoroquinolones as first-line therapy for uncomplicated UTI in areas where resistance is likely to be of concern. Fluoroquinolones have demonstrated high bacteriologic and clinical cure rates, as well as low rates of resistance, among most common uropathogens. There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin. Many of the fluoroquinolone agents have once-daily dosing regimens, enhancing patient adherence. In addition, levofloxacin and gatifloxacin have same-dose bioequivalency between their intravenous and oral formulations, allowing for "switch" or step-down therapy from parenteral to oral formulations of the same agent at the same dose. Fluoroquinolones are indicated for the management of acute uncomplicated UTIs, as well as complicated and severe UTI and pyelonephritis, in adults. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance >10% to 20% to TMP-SMX, or who have risk factors for such resistance. Fluoroquinolone properties include a broad spectrum of coverage, low rates of resistance, and good safety profiles.

Maintaining Fluoroquinolone Class Efficacy: Review of Influencing Factors

PubMed Central

2003-01-01

Previous experience with antimicrobial resistance has emphasized the importance of appropriate stewardship of these pharmacotherapeutic agents. The introduction of fluoroquinolones provided potent new drugs directed primarily against gram-negative pathogens, while the newer members of this class demonstrate more activity against gram-positive species, including Streptococcus pneumoniae. Although these agents are clinically effective against a broad range of infectious agents, emergence of resistance and associated clinical failures have prompted reexamination of their use. Appropriate use revolves around two key objectives: 1) only prescribing antimicrobial therapy when it is beneficial and 2) using the agents(s) with optimal activity against the expected pathogens(s). Pharmacodynamic principles and properties can be applied to achieve the latter objective when prescribing agents belonging to the fluoroquinolone class. A focused approach emphasizing “correct-spectrum” coverage may reduce development of antimicrobial resistance and maintain class efficacy. PMID:12533274

Design of dual action antibiotics as an approach to search for new promising drugs

NASA Astrophysics Data System (ADS)

Tevyashova, A. N.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

2015-01-01

The review is devoted to the latest achievements in the design of dual action antibiotics — heterodimeric (chimeric) structures based on antibacterial agents of different classes (fluoroquinolones, anthracyclines, oxazolidines, macrolides and so on). Covalent binding can make the pharmacokinetic characteristics of these molecules more predictable and improve the penetration of each component into the cell. Consequently, not only does the drug efficacy increase owing to inhibition of two targets but also the resistance to one or both antibiotics can be overcome. The theoretical grounds of elaboration, design principles and methods for the synthesis of dual action antibiotics are considered. The structures are classified according to the type of covalent spacer (cleavable or not) connecting the moieties of two agents. Dual action antibiotics with a spacer that can be cleaved in a living cell are considered as dual action prodrugs. Data on the biological action of heterodimeric compounds are presented and structure-activity relationships are analyzed. The bibliography includes 225 references.

Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties.

PubMed

Jorgensen, Sarah C J; Mercuro, Nicholas J; Davis, Susan L; Rybak, Michael J

2018-03-31

Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.

New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes.

PubMed

Ge, Linke; Na, Guangshui; Zhang, Siyu; Li, Kai; Zhang, Peng; Ren, Honglei; Yao, Ziwei

2015-09-15

The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (td,E) and hydroxyl-radical oxidation half-lives (tOH,E) in sunlit surface waters. The td,E values range from 0.56 min to 28.8 min at 45° N latitude, whereas tOH,E ranges from 3.24h to 33.6h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. Copyright © 2015. Published by Elsevier B.V.

Delafloxacin: an improved fluoroquinolone developed through advanced molecular engineering.

PubMed

Bassetti, Matteo; Righi, Elda; Pecori, Davide; Tillotson, Glenn

2018-05-16

The emergence of antimicrobial resistance threatens current clinical practice across a range of infection types. Delafloxacin, a non-zwitterionic fluoroquinolone recently approved by the US FDA for the treatment of acute bacterial skin and skin structure infections, has been developed to address some of these challenges. Uniquely delafloxacin has increased intracellular penetration and enhanced antibacterial activity under acidic conditions, an environment seen in many infection sites including abscesses. Delafloxacin is active against a wide range of Gram-positive and -negative species including methicillin-resistant Staphylococcus aureus and many fluoroquinolone-resistant strains. Additionally, according to preclinical and clinical trial data, well-known adverse events related to fluoroquinolone class do not appear to occur with this new molecule. Delafloxacin has been studied in acute bacterial skin and skin structure infections with >1400 patients exposed to both intravenous and oral formulation for up to 14 days and has shown noninteriority to vancomycin with or without aztreonam. For its interesting microbiological and pharmacokinetic/pharmacodynamics characteristics and for its safety profile, delafloxacin represents a very promising option for the treatment of infections caused by multidrug-resistant pathogens.

An active structure preservation method for developing functional graphitic carbon dots as an effective antibacterial agent and a sensitive pH and Al(iii) nanosensor.

PubMed

Hou, Peng; Yang, Tong; Liu, Hui; Li, Yuan Fang; Huang, Cheng Zhi

2017-11-16

Functional engineering is a crucial prerequisite for specific and wide applications of optical probes. In this study, we proposed a facile active structure preservation (ASP) method to directly develop new self-functional graphitic carbon dots (g-CDs) through a hydrothermal synthesis route by taking ciprofloxacin hydrochloride, an antibiotic belonging to a group of fluoroquinolone drugs, as an example. To retain the functional structures of the starting materials, the reaction temperature is intentionally controlled below the decomposition temperature of the reactants that hold the functional groups. As a proof of concept, we successfully prepared g-CDs with ciprofloxacin-like structures on its surface, as identified by mass spectrometric (MS) analysis. The as-prepared g-CDs not only exhibit effective antibacterial activity towards the bacteria Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative), but can also optically sense pH in the range from 5.02 to 9.91. Furthermore, the g-CDs can coordinate with aluminum ions to show a chelation-enhanced photoluminescence (CHEP) effect. These results indicate that the ASP method can be promising for engineering CDs with various properties.

Evaluation of in vitro inhibitory effect of enoxacin on Babesia and Theileria parasites.

PubMed

Omar, Mosaab A; Salama, Akram; Elsify, Ahmed; Rizk, Mohamed Abdo; Al-Aboody, Mohammad Saleh; AbouLaila, Mahmoud; El-Sayed, Shimaa Abd El-Salam; Igarashi, Ikuo

2016-02-01

Enoxacin is a broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid used mainly in the treatment of urinary tract infections and gonorrhea. Also it has been shown recently that it may have cancer inhibiting effect. The primary antibabesial effect of Enoxacin is due to inhibition of DNA gyrase subunit A, and DNA topoisomerase. In the present study, enoxacin was tested as a potent inhibitor against the in vitro growth of bovine and equine Piroplasms. The in vitro growth of five Babesia species that were tested was significantly inhibited (P < 0.05) by micro molar concentrations of enoxacin (IC50 values = 33.5, 15.2, 7.5 and 23.2 μM for Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi, respectively). Enoxacin IC50 values for Babesia and Theileria parasites were satisfactory as the drug is potent antibacterial drug with minimum side effects. Therefore, enoxacin might be used for treatment of Babesiosis and Theileriosis especially in case of mixed infections with bacterial diseases or incase of animal sensitivity against diminazin toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of the corneal epithelium on the intraocular penetration of fluoroquinolone ophthalmic solution.

PubMed

Fukuda, Masamichi; Inoue, Amane; Sasaki, Kazuyuki; Takahashi, Nobuo

2004-01-01

Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed. We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography. The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea. Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.

Integrating fluoroquinolones into the hospital formulary.

PubMed

Bertino, J S

2001-10-01

With the increasing availability of new agents, selection of fluoroquinolones for formulary inclusion can be difficult. Appropriate evaluation of the important characteristics (pharmacokinetic and pharmacodynamic properties, antimicrobial activity, efficacy, tolerability, cost) of these agents should allow selection of the most cost-effective ones. Evidence from in vitro studies and clinical trials indicates differences exist among fluoroquinolones, especially in terms of activity against gram-positive, aerobic organisms. For selected clinical situations, it may be important to choose an agent that is available in both intravenous and oral formulations. Comparative drug costs, as well as costs associated with potential clinical failure and adverse events, should be evaluated carefully. Dosage regimens should be considered, as shorter durations of therapy and less frequent dose administration may lead to reduced labor costs and increased patient compliance, thereby improving effectiveness and economic efficiency.

Evolution from a natural flavones nucleus to obtain 2-(4-Propoxyphenyl)quinoline derivatives as potent inhibitors of the S. aureus NorA efflux pump.

PubMed

Sabatini, Stefano; Gosetto, Francesca; Manfroni, Giuseppe; Tabarrini, Oriana; Kaatz, Glenn W; Patel, Diixa; Cecchetti, Violetta

2011-08-25

Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, norA-overexpressing strains. © 2011 American Chemical Society

Re-evolution of the 2-phenylquinolines: ligand-based design, synthesis, and biological evaluation of a potent new class of Staphylococcus aureus NorA efflux pump inhibitors to combat antimicrobial resistance.

PubMed

Sabatini, Stefano; Gosetto, Francesca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Sancineto, Luca; Manfroni, Giuseppe; Tabarrini, Oriana; Dimovska, Mirjana; Kaatz, Glenn W; Cecchetti, Violetta

2013-06-27

Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump.

Levofloxacin for the treatment of pyelonephritis.

PubMed

Rafat, Cédric; Debrix, Isabelle; Hertig, Alexandre

2013-06-01

Levofloxacin , the l-isomer of ofloxacin has become one of the cornerstones of antibiotic therapy of pyelonephritis since its introduction in the 1990s, thanks to its exceptional pharmacokinetic (PK) and pharmacodynamic (PD) profile, broad-spectrum antibacterial action and satisfactory tolerance. However, the emergence of widespread fluoroquinolone resistance over the past decade, has prompted to re-examine its place in the treatment of urinary tract infection. This review covers the medical literature in any language through December 2012, on 'levofloxacin'. To identify relevant articles, the search terms 'pyelonephritis', 'urinary tract infections', 'levofloxacin', 'levaquin' and 'ofloxacin' were obtained through PubMed, MEDLINE and Clinicaltrials.gov queries. The authors focus on clinical trials, articles related to the PK and PD properties of levofloxacin as well as recent development in the mechanisms and prevalence of levofloxacin resistance. Major points stemming from international guidelines are also reviewed. Levofloxacin has achieved satisfactory bacterial eradication rates and clinical success across all available trials, similar to the antibiotic comparator. High-dose (750 mg) orally administrated levofloxacin over a short 5-day course is a reasonable option for patients eligible for outpatient management. Levofloxacin is no longer a suitable option for first-line empirical treatment of pyelonephritis in areas where resistance rates are high (> 10%) when pyelonephritis is hospital-acquired. Efforts to promote fluoroquinolone-sparing agents should be encouraged and its prescription should be performed in compliance with antimicrobial guidelines.

Energy-Dependent Accumulation of Fluoroquinolones in Quinolone-Resistant Klebsiella pneumoniae Strains

PubMed Central

Martínez-Martínez, Luis; García, Isabel; Ballesta, Sofía; Benedí, Vicente Javier; Hernández-Allés, Santiago; Pascual, Alvaro

1998-01-01

The intracellular accumulation of norfloxacin and pefloxacin in Klebsiella pneumoniae was evaluated. The roles of lipopolysaccharide, capsule, and outer membrane proteins were not important for the intrabacterial accumulation of fluoroquinolones in isogenic strains with known outer membrane alterations. In fluoroquinolone-resistant clinical isolates also expressing GyrA alterations, an active efflux leading to decreased accumulation of the drugs enhanced their resistance to these agents. PMID:9661034

Effect of magnesium complexation by fluoroquinolones on their antibacterial properties.

PubMed Central

Lecomte, S; Baron, M H; Chenon, M T; Coupry, C; Moreau, N J

1994-01-01

By using infrared and 19F nuclear magnetic resonance spectroscopies, we localized the binding site and measured the affinity of magnesium for six fluoroquinolones. It was proven that magnesium is situated between the ketone and the carboxylate groups. We determined the binding constants for the 1:1 Mg(2+)-drug complex in solution. Sparfloxacin and pefloxacin, with affinity constants (Ka) of (10.1 +/- 0.6) x 10(2) M-1 and (21 +/- 1) x 10(2) M-1, respectively, were the least and the most bound, respectively. The trend of the affinities of the assayed fluoroquinolones for magnesium was correlated with their antimicrobial activities against four bacteria and with their accumulation by these bacteria. The reference strain, Escherichia coli KL16, and two resistant mutants, NalA (gyrase mutation) and NalB (uptake defect), plus Staphylococcus aureus 209P were used. It appeared that, in every case, an impairment of accumulation is responsible for the increase in the MICs observed upon the addition of magnesium. Images PMID:7695267

HPLC of fluoroquinolone antibacterials using chiral stationary phase based on enantiomeric (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6.

PubMed

Choi, Hee Jung; Cho, Hwan Sun; Han, Sang Cheol; Hyun, Myung Ho

2009-02-01

A residual silanol group-protecting chiral stationary phase (CSP) based on optically active (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 was successfully applied to the resolution of fluoroquinolone compounds including gemifloxacin mesylate. The chiral recognition ability of the residual silanol group-protecting CSP was generally greater than that of the residual silanol group-containing CSP. From these results, it was concluded that the simple protection of the residual silanol groups of the latter CSP with lipophilic n-octyl groups can improve its chiral recognition ability for the resolution of racemic fluoroquinolone compounds. The chromatographic resolution behaviors were investigated as a function of the content and type of organic and acidic modifiers and the ammonium acetate concentration in aqueous mobile phase and the column temperature. Especially, the addition of ammonium acetate to the mobile phase was found to be a quite effective means of reducing the enantiomer retentions without sacrificing the chiral recognition efficiency of the CSP.

Intensity and Mechanisms of Fluoroquinolone Resistance within the H30 and H30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli.

PubMed

Johnson, James R; Johnston, Brian; Kuskowski, Michael A; Sokurenko, Evgeni V; Tchesnokova, Veronika

2015-08-01

The recent expansion of the H30 subclone of Escherichia coli sequence type 131 (ST131) and its CTX-M-15-associated H30Rx subset remains unexplained. Although ST131 H30 typically exhibits fluoroquinolone resistance, so do multiple other E. coli lineages that have not expanded similarly. To determine whether H30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistant E. coli isolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistant E. coli isolates (48 non-H30 and 41 H30 [23 H30Rx and 18 H30 non-Rx]). We compared the MICs with the H30 and H30Rx status, the presence/number of nonsynonymous mutations in gyrA, parC, and parE, the presence of aac(6')-1b-cr (an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recent E. coli clinical isolates, ST131 H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates, H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations in gyrA, parC, and parE (specifically gyrA D87N, parC E84V, and parE I529L), and a numerically higher prevalence of (H30Rx-associated) aac(6')-1b-cr but lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [for aac(6')-1b-cr: ciprofloxacin and norfloxacin only]. parC D87N corresponded with ST131 H30 and parE I529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131 H30, especially H30Rx [if aac(6')-1b-cr positive], with subtle fitness advantages over other fluoroquinolone-resistant E. coli strains. This urges both parsimonious fluoroquinolone use and a search for other fitness-enhancing traits within ST131 H30. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Biscatecholate-Monohydroxamate Mixed Ligand Siderophore-Carbacephalosporin Conjugates are Selective Sideromycin Antibiotics that Target Acinetobacter baumannii

PubMed Central

Wencewicz, Timothy A.; Miller, Marvin J.

2013-01-01

Chemical syntheses and biological evaluation of biscatecholate-monohydroxamate mixed ligand sideromycins utilizing the carbacephalosporin β-lactam antibiotic loracarbef and the fluo-roquinolone antibiotic ciprofloxacin are described. The mixed ligand β-lactam sideromycin (1b) had remarkably selective and extremely potent antibacterial activity against the Gram negative pathogen Acinetobacter baumannii ATCC 17961 (MIC = 0.0078 μM). The antibacterial activity of the β-lactam sideromycin was inversely related to the iron(III) concentration in the testing media and was antagonized by the presence of the competing parent siderophore. These data suggested that active transport of the mixed ligand β-lactam sideromycin across the outer cell membrane of A. baumannii via siderophore uptake pathways was responsible for the selective and potent antibacterial activity. PMID:23614627

Clonal group distribution of fluoroquinolone-resistant Escherichia coli among humans and companion animals in Australia.

PubMed

Platell, Joanne L; Cobbold, Rowland N; Johnson, James R; Trott, Darren J

2010-09-01

To determine the phylogenetic group distribution and prevalence of three major globally disseminated clonal groups [clonal group A (CGA) and O15:K52:H1, associated with phylogenetic group D, and sequence type ST131, associated with phylogenetic group B2] among fluoroquinolone-resistant extra-intestinal Escherichia coli isolates from humans and companion animals in Australia. Clinical extra-intestinal fluoroquinolone-resistant E. coli isolates were obtained from humans (n = 582) and companion animals (n = 125), on Australia's east coast (October 2007-October 2009). Isolates were tested for susceptibility to seven antimicrobial agents, and for phylogenetic group, O type and clonal-group-specific single nucleotide polymorphisms by PCR. The fluoroquinolone-resistant isolates were typically resistant to multiple agents (median of four). Analysis revealed that clonal group ST131 accounted for a large subset of the human isolates (202/585, 35%), but for a much smaller proportion of the companion animal isolates (9/125, 7.2%; P

Sales of veterinary antibacterial agents in nine European countries during 2005-09: trends and patterns.

PubMed

Grave, Kari; Greko, Christina; Kvaale, Mari K; Torren-Edo, Jordi; Mackay, David; Muller, Arno; Moulin, Gerard

2012-12-01

To identify trends and patterns of sales of veterinary antimicrobial agents in nine European countries during 2005-09 in order to document the situation. Existing sales data, in tonnes of active ingredients, of veterinary antimicrobial agents by class were collected from nine European countries in a standardized manner for the years 2005-09 (one country for 2006-09). A population correction unit (PCU) is introduced as a proxy for the animal population potentially treated with antimicrobial agents. The sales data are expressed as mg of active substance/PCU. Data coverage was reported to be 98%-100% for the nine countries. Overall, sales of veterinary antimicrobials agents, in mg/PCU, declined during the reporting period in the nine countries. Substantial differences in the sales patterns and in the magnitude of sales of veterinary antimicrobial agents, expressed as mg/PCU, between the nine countries are observed. The major classes sold were penicillins, sulphonamides and tetracyclines. The sales accounted for by the various veterinary antimicrobial agents have changed substantially for most countries. An increase in the sales of third- and fourth-generation cephalosporins and fluoroquinolones were observed for the majority of the countries. Through re-analysis of existing data by application of a harmonized approach, an overall picture of the trends in the sales of veterinary antimicrobial agents in the nine countries was obtained. Notable differences in trends in sales between the countries were observed. Further studies, preferably including data by animal species, are needed to understand the factors that explain these observations.

Use of fluoroquinolones for prophylaxis of murine Pneumocystis carinii pneumonia.

PubMed Central

Brun-Pascaud, M; Fay, M; Zhong, M; Bauchet, J; Dux-Guyot, A; Pocidalo, J J

1992-01-01

We compared the prophylactic activities of six fluoroquinolones against Pneumocystis carinii pneumonia in immunosuppressed rats. Pefloxacin was the only agent which was as effective as the reference drug trimethoprim-sulfamethoxazole. Clinical trials with pefloxacin in patients at risk for P. carinii pneumonia appear to be justified. Images PMID:1605613

In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone.

PubMed

Nilius, Angela M; Shen, Linus L; Hensey-Rudloff, Dena; Almer, Laurel S; Beyer, Jill M; Balli, Darlene J; Cai, Yingna; Flamm, Robert K

2003-10-01

ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family Enterobacteriaceae, although it was less active than the comparators against Citrobacter freundii and Serratia marcescens. The activity of ABT-492 was greater than those of the comparators against fastidious gram-negative species, including Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. and against Pseudomonas aeruginosa and Helicobacter pylori. ABT-492 was as active as trovafloxacin against Chlamydia trachomatis, indicating good intracellular penetration and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant Streptococcus pneumoniae, including strains resistant to penicillin and macrolides, and H. influenzae, including beta-lactam-resistant strains. It retained greater in vitro activity than the comparators against S. pneumoniae and H. influenzae strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target topoisomerases. ABT-492 was a potent inhibitor of bacterial topoisomerases, and unlike the comparators, DNA gyrase and topoisomerase IV from either Staphylococcus aureus or Escherichia coli were almost equally sensitive to ABT-492. The profile of ABT-492 suggested that it may be a useful agent for the treatment of community-acquired respiratory tract infections, as well as infections of the urinary tract, bloodstream, and skin and skin structure and nosocomial lung infections.

In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone

PubMed Central

Nilius, Angela M.; Shen, Linus L.; Hensey-Rudloff, Dena; Almer, Laurel S.; Beyer, Jill M.; Balli, Darlene J.; Cai, Yingna; Flamm, Robert K.

2003-01-01

ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family Enterobacteriaceae, although it was less active than the comparators against Citrobacter freundii and Serratia marcescens. The activity of ABT-492 was greater than those of the comparators against fastidious gram-negative species, including Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. and against Pseudomonas aeruginosa and Helicobacter pylori. ABT-492 was as active as trovafloxacin against Chlamydia trachomatis, indicating good intracellular penetration and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant Streptococcus pneumoniae, including strains resistant to penicillin and macrolides, and H. influenzae, including β-lactam-resistant strains. It retained greater in vitro activity than the comparators against S. pneumoniae and H. influenzae strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target topoisomerases. ABT-492 was a potent inhibitor of bacterial topoisomerases, and unlike the comparators, DNA gyrase and topoisomerase IV from either Staphylococcus aureus or Escherichia coli were almost equally sensitive to ABT-492. The profile of ABT-492 suggested that it may be a useful agent for the treatment of community-acquired respiratory tract infections, as well as infections of the urinary tract, bloodstream, and skin and skin structure and nosocomial lung infections. PMID:14506039

Besifloxacin ophthalmic suspension, 0.6%: a novel topical fluoroquinolone for bacterial conjunctivitis.

PubMed

O'Brien, Terrence P

2012-06-01

Acute bacterial conjunctivitis, the most common cause of conjunctivitis, is responsible for approximately 1% of all primary-care consultations. Of the topical ophthalmic antibiotics used to treat acute bacterial conjunctivitis, fluoroquinolones are especially useful because they possess a broad antibacterial spectrum, are bactericidal in action, are generally well tolerated, and have been less prone to development of bacterial resistance. Besifloxacin, the latest advanced fluoroquinolone approved for treating bacterial conjunctivitis, is the first fluoroquinolone developed specifically for topical ophthalmic use. It has a C-8 chlorine substituent and is known as a chloro-fluoroquinolone. Besifloxacin possesses relatively balanced dual-targeting activity against bacterial topoisomerase IV and DNA gyrase (topoisomerse II), two essential enzymes involved in bacterial DNA replication, leading to increased potency and decreased likelihood of bacterial resistance developing to besifloxacin. Microbiological data suggest a relatively high potency and rapid bactericidal activity for besifloxacin against common ocular pathogens, including bacteria resistant to other fluoroquinolones, especially resistant staphylococcal species. Randomized, double-masked, controlled clinical studies demonstrated the clinical efficacy of besifloxacin ophthalmic suspension 0.6% administered three-times daily for 5 days to be superior to the vehicle alone and similar to moxifloxacin ophthalmic solution 0.5% for bacterial conjunctivitis. In addition, besifloxacin ophthalmic suspension 0.6% administered two-times daily for 3 days was clinically more effective than the vehicle alone for bacterial conjunctivitis. Besifloxacin has also been shown in preclinical animal studies to be potentially effective for the "off-label" treatment of infections following ocular surgery, prophylaxis of endophthalmitis, and the treatment of bacterial keratitis. Taken together, clinical and preclinical animal studies indicate that besifloxacin is an important new option for the treatment of ocular infections.

In vitro synergistic antibacterial activity of the essential oil from Zingiber cassumunar Roxb against extensively drug-resistant Acinetobacter baumannii strains.

PubMed

Boonyanugomol, Wongwarut; Kraisriwattana, Kairin; Rukseree, Kamolchanok; Boonsam, Kraisorn; Narachai, Panchaporn

In this study, we determined the antibacterial and synergistic activities of the essential oil from Zingiber cassumunar against the extensively drug-resistant (XDR) Acinetobacter baumannii strains. The antibacterial and synergistic properties of the essential oil from Z. cassumunar were examined by agar disc diffusion tests. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated by broth microdilution using the resazurin assay. The in vitro time-kill antibacterial kinetics was analyzed using the plate count technique. We found that the essential oil from Z. cassumunar had antibacterial activity against A. baumannii, with MIC and MBC ranging from 7.00 to 9.24mg/ml. The essential oil could completely inhibit A. baumannii at 1h, and coccoid-shaped bacteria were found after treatment. In addition, the essential oil had a synergistic effect when combined with antibiotics, e.g., aminoglycosides, fluoroquinolones, tetracyclines, and folate pathway inhibitors. Thus, the essential oil from Z. cassumunar has strong antibacterial and synergistic activities against XDR A. baumannii, which may provide the basis for the development of a new therapy against drug-resistant bacteria. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5.

PubMed

Arakawa, Hiroshi; Shirasaka, Yoshiyuki; Haga, Makoto; Nakanishi, Takeo; Tamai, Ikumi

2012-09-01

Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K(m) value of 140 µm, and naringin inhibited the uptake with an IC(50) value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC(50) value of 7.5 µm by the Ussing-type chamber method. The estimated IC(50) values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp. Copyright © 2012 John Wiley & Sons, Ltd.

Accumulation of 10 Fluoroquinolones by Wild-Type or Efflux Mutant Streptococcus pneumoniae

PubMed Central

Piddock, Laura J. V.; Johnson, M. M.

2002-01-01

A method for measuring fluoroquinolone accumulation by Streptococcus pneumoniae was rigorously examined. The accumulation of ciprofloxacin, clinafloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, sitafloxacin, and trovafloxacin in the presence and absence of either carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) or reserpine was determined for two wild-type fluoroquinolone-susceptible capsulated S. pneumoniae strains (M3 and M4) and the noncapsulated strain R6. Two efflux mutants, R6N (which overexpresses PmrA) and a mutant of M4, M22 (no expression of PmrA), were also examined. Essentially, the fluoroquinolones fell into two groups. (i) One group consisting of ciprofloxacin, grepafloxacin, and norfloxacin accumulated to 72 to 92 ng/mg (dry weight) of cells in all strains. (ii) The remainder of the agents accumulated to 3 to 30 ng/mg (dry weight) of cells. With a decrease in hydrophobicity, there was a decrease in the concentration accumulated. With an increase in the molecular weight of the free form of each agent, there was also a decrease in the concentration accumulated. The strains differed in their responses to reserpine and CCCP. For the three fluoroquinolone-susceptible strains, only reserpine had a significant effect upon accumulation of moxifloxacin and clinafloxacin by M3 and showed no effect for the other agents and strains. For M3 and M4, CCCP enhanced the concentration of ciprofloxacin and norfloxacin accumulated, whereas for R6, the effect was only statistically significant for ofloxacin. Efflux mutant M22 accumulated less ciprofloxacin, gatifloxacin, and ofloxacin than M4 did. M22 accumulated more norfloxacin than M4 did. Reserpine and CCCP had variable effects as for the other strains. Differences in the accumulation of fluoroquinolones by R6 and R6N were highly dependent upon growth phase, and only for norfloxacin was there a significant difference between two strains. PMID:11850266

SatR Is a Repressor of Fluoroquinolone Efflux Pump SatAB

PubMed Central

Escudero, Jose Antonio; San Millan, Alvaro; Montero, Natalia; Gutierrez, Belen; Ovejero, Cristina Martinez; Carrilero, Laura

2013-01-01

Streptococcus suis is an emerging zoonotic agent responsible for high-mortality outbreaks among the human population in China. In this species, the ABC transporter SatAB mediates fluoroquinolone resistance when overexpressed. Here, we describe and characterize satR, an open reading frame (ORF) encoding a MarR superfamily regulator that acts as a repressor of satAB. satR is cotranscribed with satAB, and its interruption entails the overexpression of the pump, leading to a clinically relevant increase in resistance to fluoroquinolones. PMID:23650171

[Microorganism test systems and antibiograms useful for the proper use of antibacterial agents].

PubMed

Takahashi, Shunji

2010-07-01

Antimicrobial agents are used for the accurate diagnosis of infectious diseases and effective implementation of antibacterial chemotherapy. The role of microbiological technologists is to provide data from microorganism tests useful for rapid infection treatment. Gram strain can be used to observe microorganisms and neutrophils from specimens of a patient. It is also possible to estimate the kinds of microorganism. If bacterial infectious disease is negative, there is no need for antibacterial chemotherapy. The applied dose of antibacterial agents is different in every hospital. Also, there is a difference in the percentage antibacterial agent susceptibility of isolates. Antibiograms must be created to investigate local factors. For empiric therapy, antibiograms are useful when choosing antibacterial agents showing marked efficacy against the clinical isolate. Microorganism test systems which are useful for the proper use of antibacterial agents are necessary to facilitate safe antibacterial chemotherapy and prevent the development of resistant bacteria. We report a microorganism test system employed at the Sapporo City General Hospital.

Antibacterial activity of antibacterial cutting boards in household kitchens.

PubMed

Kounosu, Masayuki; Kaneko, Seiichi

2007-12-01

We examined antibacterial cutting boards with antibacterial activity values of either "2" or "4" in compliance with the JIS Z 2801 standard, and compared their findings with those of cutting boards with no antibacterial activity. These cutting boards were used in ten different households, and we measured changes in the viable cell counts of several types of bacteria with the drop plate method. We also identified the detected bacterial flora and measured the minimum antimicrobial concentrations of several commonly used antibacterial agents against the kinds of bacteria identified to determine the expected antibacterial activity of the respective agents. Cutting boards with activity values of both "2" and "4" proved to be antibacterial in actual use, although no correlation between the viable cell counts and the antibacterial activity values was observed. In the kitchen environment, large quantities of Pseudomonas, Flavobacterium, Micrococcus, and Bacillus were detected, and it was confirmed that common antibacterial agents used in many antibacterial products are effective against these bacterial species. In addition, we measured the minimum antimicrobial concentrations of the agents against lactobacillus, a typical good bacterium, and discovered that this bacterium is less sensitive to these antibacterial agents compared to more common bacteria.

National and regional assessment of the antibacterial soap market: a step toward determining the impact of prevalent antibacterial soaps.

PubMed

Perencevich, E N; Wong, M T; Harris, A D

2001-10-01

Consumer antibacterial soaps contain triclosan or triclocarban. No scientific data have been published to suggest that the use of antibacterial agents in household products prevents infection, and triclosan resistance mechanisms have recently been identified. Little data are available regarding the prevalence of antibacterial agents contained in consumer soaps. In a physician-performed survey of 23 stores in 10 states from December 1999 to April 2000, investigators determined the number of national brand liquid and bar soaps and percent of each containing antibacterial agents sold at national chain, regional grocery, and Internet stores. Antibacterial agents were present in 76% of liquid soaps and 29% of bar soaps available nationally. There were no differences found between national, regional, and Internet stores. Overall, 45% of surveyed soaps contain antibacterial agents. With limited documented benefits and experimental laboratory evidence suggesting possible adverse effects on the emergence of antimicrobial resistance, consumer antibacterial use of this magnitude should be questioned.

Modification of Norfloxacin by a Microbacterium sp. Strain Isolated from a Wastewater Treatment Plant▿

PubMed Central

Kim, Dae-Wi; Heinze, Thomas M.; Kim, Bong-Soo; Schnackenberg, Laura K.; Woodling, Kellie A.; Sutherland, John B.

2011-01-01

Antimicrobial residues found in municipal wastewater may increase selective pressure on microorganisms for development of resistance, but studies with mixed microbial cultures derived from wastewater have suggested that some bacteria are able to inactivate fluoroquinolones. Medium containing N-phenylpiperazine and inoculated with wastewater was used to enrich fluoroquinolone-modifying bacteria. One bacterial strain isolated from an enrichment culture was identified by 16S rRNA gene sequence analysis as a Microbacterium sp. similar to a plant growth-promoting bacterium, Microbacterium azadirachtae (99.70%), and a nematode pathogen, “M. nematophilum” (99.02%). During growth in medium with norfloxacin, this strain produced four metabolites, which were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) analyses as 8-hydroxynorfloxacin, 6-defluoro-6-hydroxynorfloxacin, desethylene norfloxacin, and N-acetylnorfloxacin. The production of the first three metabolites was enhanced by ascorbic acid and nitrate, but it was inhibited by phosphate, amino acids, mannitol, formate, and thiourea. In contrast, N-acetylnorfloxacin was most abundant in cultures supplemented with amino acids. This is the first report of defluorination and hydroxylation of a fluoroquinolone by an isolated bacterial strain. The results suggest that some bacteria may degrade fluoroquinolones in wastewater to metabolites with less antibacterial activity that could be subject to further degradation by other microorganisms. PMID:21724893

Safety Concerns Surrounding Quinolone Use in Children

PubMed Central

Patel, Karisma; Goldman, Jennifer L.

2016-01-01

Fluoroquinolones are highly effective antibiotics with many desirable pharmacokinetic and pharmacodynamic properties including high bioavailability, large volume of distribution, and a broad spectrum of antimicrobial activity. Despite their attractive profile as anti-infective agents, their use in children is limited, primarily due to safety concerns. In this review we highlight the pharmacological properties of fluoroquinolones and describe their current use in pediatrics. In addition, we provide a comprehensive assessment of the safety data associated with fluoroquinolone use in children. Although permanent or destructive arthropathy remains a significant concern, currently available data demonstrate that arthralgia and arthropathy are relatively uncommon in children and resolve following cessation of fluoroquinolone exposure without resulting in long-term sequelae. The concern for safety and risk of adverse events associated with pediatric fluoroquinolone use is likely driving the limited prescribing of this drug class in pediatrics. However, in adults, fluoroquinolones are the most commonly prescribed broad-spectrum antibiotics, resulting in the development of drug-resistant bacteria that can be challenging to treat effectively. The consequence of misuse and overuse of fluoroquinolones leading to drug resistance is a greater, but frequently overlooked, safety concern that applies to both children and adults and one that should be considered at the point of prescribing. PMID:26865283

In Vitro and In Vivo Antibacterial Activities of DC-159a, a New Fluoroquinolone▿

PubMed Central

Hoshino, Kazuki; Inoue, Kazue; Murakami, Yoichi; Kurosaka, Yuichi; Namba, Kenji; Kashimoto, Yoshinori; Uoyama, Saori; Okumura, Ryo; Higuchi, Saito; Otani, Tsuyoshi

2008-01-01

DC-159a is a new 8-methoxy fluoroquinolone that possesses a broad spectrum of antibacterial activity, with extended activity against gram-positive pathogens, especially streptococci and staphylococci from patients with community-acquired infections. DC-159a showed activity against Streptococcus spp. (MIC90, 0.12 μg/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 μg/ml. The MIC90s of DC-159a against Staphylococcus spp. were 0.5 μg/ml or less. Against quinolone- and methicillin-resistant Staphylococcus aureus strains, however, the MIC90 of DC-159a was 8 μg/ml. DC-159a was the most active against Enterococcus spp. (MIC90, 4 to 8 μg/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC90s of DC-159a against Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae were 0.015, 0.06, and 0.25 μg/ml, respectively. The activity of DC-159a against Mycoplasma pneumoniae was eightfold more potent than that of levofloxacin. The MICs of DC-159a against Chlamydophila pneumoniae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC90s of DC-159a against Peptostreptococcus spp., Clostridium difficile, and Bacteroides fragilis were 0.5, 4, and 2 μg/ml, respectively; and among the quinolones tested it showed the highest level of activity against anaerobic organisms. DC-159a demonstrated rapid bactericidal activity against quinolone-resistant Streptococcus pneumoniae strains both in vitro and in vivo. In vitro, DC-159a showed faster killing than moxifloxacin and garenoxacin. The bactericidal activity of DC-159a in a murine muscle infection model was revealed to be superior to that of moxifloxacin. These activities carried over to the in vivo efficacy in the murine pneumonia model, in which treatment with DC-159a led to bactericidal activity superior to those of the other agents tested. PMID:17938194

White Paper: Recommendations on the Conduct of Superiority and Organism-Specific Clinical Trials of Antibacterial Agents for the Treatment of Infections Caused by Drug-Resistant Bacterial Pathogens

PubMed Central

2012-01-01

There is a critical need for new pathways to develop antibacterial agents to treat life-threatening infections caused by highly resistant bacteria. Traditionally, antibacterial agents have been studied in noninferiority clinical trials that focus on one site of infection (eg, pneumonia, intra-abdominal infection). Conduct of superiority trials for infections caused by highly antibiotic-resistant bacteria represents a new, and as yet, untested paradigm for antibacterial drug development. We sought to define feasible trial designs of antibacterial agents that could enable conduct of superiority and organism-specific clinical trials. These recommendations are the results of several years of active dialogue among the white paper's drafters as well as external collaborators and regulatory officials. Our goal is to facilitate conduct of new types of antibacterial clinical trials to enable development and ultimately approval of critically needed new antibacterial agents. PMID:22891041

Development of a novel genetically modified bioluminescent-bacteria-based assay for detection of fluoroquinolones in animal-derived foods.

PubMed

Cheng, Guyue; Dong, Xiaobing; Wang, Yulian; Peng, Dapeng; Wang, Xu; Hao, Haihong; Xie, Shuyu; Qu, Wei; Liu, Zhenli; Yuan, Zonghui

2014-12-01

Fluoroquinolones (FQNs) are broad-spectrum antibacterial agents widely used in animal husbandry and aquaculture. The residues and antimicrobial resistance of such antibiotics are a major public health concern. To realize multianalyte detection of FQN residues, a genetically modified bacterium, Escherichia coli pK12 harboring plasmid pRecAlux3, was constructed in this study to develop a bioluminescent-bacteria-based assay for the detection of FQNs in animal-derived foods. This assay was based on the principle of induction of an SOS response by FQNs via inducing the recA-promoter-fused luciferase reporter gene existing on the plasmid pRecAlux3. E. coli pK12 was able to recognize 11 FQNs: difloxacin, enrofloxacin, ciprofloxacin, sarafloxacin, norfloxacin, danofloxacin, ofloxacin, pefloxacin, lomefloxacin, marbofloxacin, and orbifloxacin. This method could be applied to 11 edible tissues, including milk, fish muscle, and the muscles, livers, and kidneys of cattle, chickens, and pigs, with a very simple and rapid sample extraction procedure using only phosphate-buffered saline. The limits of detection of the FQNs were between 12.5 and 100 μg kg(-1), all of which were lower than the maximum residue limits. Most of the recoveries of the FQNs were in the range from 60 to 120 %, and the interassay coefficients of variation were less than 30 %. This method, confirmed by high-performance liquid chromatography, is reliable and can be used as both a screening test and a semiquantitative assay, when the identity of a single type of FQN is known.

Fluoroquinolone-Gyrase-DNA Complexes

PubMed Central

Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M.; Hiasa, Hiroshi; Marks, Kevin R.; Kerns, Robert J.; Berger, James M.; Drlica, Karl

2014-01-01

DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys466 gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly81 and GyrB-Glu466 residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases. PMID:24497635

[Association between use of antibacterial agents in the first year of life and childhood asthma: a Meta analysis].

PubMed

Xie, Meng-Yao; Yuan, Yong-Hua; Liu, Li-Mei; Gu, Rong; Zhao, Xiao-Dong

2016-10-01

To evaluate the association between the use of antibacterial agents in the first years of life and childhood asthma. The Chinese and English databases CNKI, Wanfang Data, VIP, PubMed, and EBSCO were searched for prospective cohort studies on the association between the use of antibacterial agents in the first years of life and childhood asthma. Stata12.0 software was used to analyze the association through a Meta analysis. The articles with a high quality score and adjusted effective values for factors for lower respiratory tract infection were pooled, and a total of 8 studies were included. The results of the Meta analysis showed that the use of antibacterial agents in the first years of life increased the risk of childhood asthma (OR=1.14, 95%CI: 1.10-1.17, P<0.05). Compared with the children who used antibacterial agents 0-1 times in the first years of life, those who used more than 4 times had an increased risk of asthma (OR=1.28, 95%CI: 1.19-1.38, P<0.05). High-risk children (at least one immediate family member had asthma) who used antibacterial agents had an increased risk of asthma (OR=1.47, 95%CI: 1.20-1.81, P<0.05). The use of antibacterial agents in the first years of life increases the risk of childhood asthma. High-risk children who use antibacterial agents have an increased risk of asthma. The increased frequency of use of antibacterial agents in the first years of life is associated with an increased risk of childhood asthma, but the detailed dose relationship needs further investigation.

Fluoroquinolone antimicrobial agents.

PubMed Central

Wolfson, J S; Hooper, D C

1989-01-01

The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous system toxicities occurring most commonly, but only rarely necessitating discontinuance of therapy. In 17 of 18 prospective, randomized, double-blind comparisons with another agent or placebo, fluoroquinolones were tolerated as well as or better than the comparison regimen. Bacterial resistance has been uncommonly documented but occurs, most notably with P. aeruginosa and Staphylococcus aureus and occasionally other species for which the therapeutic ratio is less favorable. Fluoroquinolones offer an efficacious, well-tolerated, and cost-effective alternative to parenteral therapies of selected infections. PMID:2680058

Delafloxacin: First Global Approval.

PubMed

Markham, Anthony

2017-09-01

Delafloxacin (Baxdela™) is a fluoroquinolone antibacterial with activity against both gram-positive and gram-negative pathogens being developed by Melinta Therapeutics. The drug is being investigated or considered as a treatment for various bacterial infections and in June 2017 received approval in the USA for the treatment of acute bacterial skin and skin structure infections. This article summarizes the milestones in the development of delafloxacin leading to this first global approval for the treatment of acute bacterial skin and skin structure infections.

Study of zwitterionic sulfopropylbetaine containing reactive siloxanes for application in antibacterial materials.

PubMed

Chen, Shiguo; Chen, Shaojun; Jiang, Song; Mo, Yangmiao; Luo, Junxuan; Tang, Jiaoning; Ge, Zaochuan

2011-07-01

Antibacterial agents receive a great deal of attention around the world due to the interesting academic problems of how to combat bacteria and of the beneficial health, social and economic effects of successful agents. Scientists are actively developing new antibacterial agents for biomaterial applications. This paper reports the novel antibacterial agent siloxane sulfopropylbetaine (SSPB), which contains reactive alkoxysilane groups. The structure and properties of SSPB were systematically investigated, with the results showing that SSPB contains both quaternary ammonium compounds and reactive siloxane groups. SSPB has good antibacterial activity against both Escherichia coli (E. coli, 8099) and Staphylococcus aureus (S. aureus, ATCC 6538). The minimal inhibition concentration is 70 μmol/ml SSPB against both E. coli and S. aureus. In addition, the SSPB antibacterial agent can be used in both weak acid and weak alkaline environments, functioning within the wide pH range of 4.0-9.0. The SSPB-modified glass surface killed 99.96% of both S. aureus and E. coli organisms within 24 h. No significant decrease was observed in this antibacterial activity after 20 washes. Moreover, SSPB does not induce a skin reaction and is nontoxic to animals. Thus, SSPB is an ideal candidate for future applications as a safe, environmentally friendly antibacterial agent. Copyright © 2011 Elsevier B.V. All rights reserved.

Antibacterial activities of gemifloxacin, levofloxacin, gatifloxacin, moxifloxacin and erythromycin against intracellular Legionella pneumophila and Legionella micdadei in human monocytes.

PubMed

Baltch, Aldona L; Bopp, Lawrence H; Smith, Raymond P; Michelsen, Phyllis B; Ritz, William J

2005-07-01

The antibacterial activity of a new fluoroquinolone, gemifloxacin, was tested against intracellular Legionella pneumophila and Legionella micdadei and was compared with the activities of levofloxacin, gatifloxacin, moxifloxacin and erythromycin. For intracellular assays, bacteria were used to infect human monocyte-derived macrophages prepared from heparinized blood of healthy volunteers. Antibiotics were added following phagocytosis. Numbers of viable bacteria were determined at 0, 24, 48, 72 and 96 h. The intracellular antibacterial activity of gemifloxacin was concentration- and time-dependent. All of the quinolones had similar activities against L. pneumophila and L. micdadei at 10 x MIC, but there were minor differences: at 24 h moxifloxacin was significantly more active than the other quinolones against L. pneumophila, while gemifloxacin was more active against L. micdadei (P < 0.01). All of the quinolones were markedly more active than erythromycin (P < 0.01). The antibacterial effect of gemifloxacin against L. pneumophila following drug removal at 24 h persisted for 72 h at 20 x MIC but not at 10 x MIC, while for L. micdadei the antibacterial effect persisted for 24 h at 10 x MIC. All of the quinolones had similar activities against intracellular L. pneumophila and L. micdadei and were markedly more effective than erythromycin.

Preparation of active antibacterial LDPE surface through multistep physicochemical approach: I. Allylamine grafting, attachment of antibacterial agent and antibacterial activity assessment.

PubMed

Bílek, František; Křížová, Táňa; Lehocký, Marián

2011-11-01

Low-density polyethylene (LDPE) samples were treated in air plasma discharge, coated by polyallyamine brush thought copolymeric grafting surface-from reaction and deposited four common antibacterial agents (benzalkonium chloride, bronopol, chlorhexidine and triclosan) to gain material with active antibacterial properties. Surface characteristics were evaluated by static contact angle measurement with surface energy evaluation ATR-FTIR, X-ray Photoelectron Spectroscopy (XPS) and SEM analysis. Inhibition zone on agar was used as in vitro test of antibacterial properties on two representative gram positive Staphylococcus aureus (S. aureus) and gram negative Escherichia coli (E. coli) strains. It was confirmed, that after grafting of polyallyamine, more antibacterial agent is immobilized on the surface. The highest increase of antibacterial activity was observed by the sample containing triclosan. Samples covered by bronopol did not show significant antibacterial activity. Copyright © 2011 Elsevier B.V. All rights reserved.

Fragments of the Bacterial Toxin Microcin B17 as Gyrase Poisons

PubMed Central

Collin, Frédéric; Thompson, Robert E.; Jolliffe, Katrina A.; Payne, Richard J.; Maxwell, Anthony

2013-01-01

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex. PMID:23593482

Fragments of the bacterial toxin microcin B17 as gyrase poisons.

PubMed

Collin, Frédéric; Thompson, Robert E; Jolliffe, Katrina A; Payne, Richard J; Maxwell, Anthony

2013-01-01

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex.

Antibiotics and Resistance: Glossary

MedlinePlus

... R S T U V W X Y Z Antibacterials (see Antibacterial agents ) Antibiotics (see About bacteria and antibiotics ) Antibiotic ... antibiotic resistance? When and how to take antibiotics Antibacterial agents Bioterrorism & stockpiling antibiotics The Cost of Resistance ...

Antibacterial Resistance, Wayampis Amerindians, French Guyana

PubMed Central

Grenet, Karine; Guillemot, Didier; Jarlier, Vincent; Moreau, Brigitte; Dubourdieu, Stéphane; Ruimy, Raymond; Armand-Lefevre, Laurence; Bau, Pierre

2004-01-01

Drug resistance in fecal bacteria was high in Wayampis Amerindians who did not take antibacterial agents and were not hospitalized for 1 year. In the Wayampis Amerindians, an isolated traditional community in French Guyana, antibacterial use was 0.64 treatments per person per year. Hospitalization rate was 6.1% per year. Antibacterial drug–resistant bacteria can spread in persons who are not taking antibacterial agents. PMID:15207074

Comparative study of the in vitro activity of a new fluoroquinolone, ABT-492.

PubMed

Harnett, S J; Fraise, A P; Andrews, J M; Jevons, G; Brenwald, N P; Wise, R

2004-05-01

The in vitro activity of a new fluoroquinolone, ABT-492, was determined. MICs were compared with those of two beta-lactams, telithromycin, ciprofloxacin and four later generation fluoroquinolones. The effects of human serum and of inoculum concentration were also investigated. MIC data indicate that ABT-492 has potent activity against Gram-positive organisms with enhanced anti-staphylococcal activity compared with earlier fluoroquinolones, in addition to activity against beta-haemolytic streptococci, pneumococci including penicillin- and fluoroquinolone-resistant strains and vancomycin-susceptible and -resistant Enterococcus faecalis but not Enterococcus faecium. ABT-492 was the most active agent tested against Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, fluoroquinolone-susceptible Neisseria gonorrhoeae and anaerobes. Good activity was observed for ABT-492 amongst the Enterobacteriaceae and anaerobes tested, but ciprofloxacin showed superior activity for species of Proteus, Morganella and Providencia, as well as for Pseudomonas spp. In common with the other fluoroquinolones tested, organisms with reduced susceptibility to ciprofloxacin had raised MIC(90)s to ABT-492. The one isolate of H. influenzae tested with reduced fluoroquinolone susceptibility had an ABT-492 MIC close to that of the population lacking a mechanism of quinolone resistance. ABT-492 was more active than ciprofloxacin against Chlamydia spp. An inoculum effect was observed with a number of isolates of Staphylococcus aureus, Streptococcus pneumoniae, E. faecium, Klebsiella spp. and Escherichia coli, in addition to moderately raised MICs in the presence of 70% serum protein. The clinical significance of these findings is yet to be determined. ABT-492 is a new fluoroquinolone with excellent activity against both Gram-positive and Gram-negative organisms, with many potential clinical uses.

Antibacterial property of fabrics coated by magnesium-based brucites

NASA Astrophysics Data System (ADS)

Wang, Ying; Sha, Lin; Zhao, Jiao; Li, Qian; Zhu, Yimin; Wang, Ninghui

2017-04-01

A kind of environmental-friendly magnesium-based antibacterial agent was reported for the first time, which was composited by brucites with different particle sizes. The antibacterial fabrics were produced by coating the magnesium-based antibacterial agents on the 260T polyester pongee fabrics with waterborne polyurethane. The coating process was simple, low-cost, and harmless to human health and environment. Characteristics of the antibacterial agents and fabrics were studied by particulate size distribution analyzer (PSDA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results demonstrated that the coating layer was covered tightly on the fabrics and compositing of different particles by a certain proportion made full filling of the coating layer. Meanwhile, compositing did not change the structure of brucites. The antibacterial fabrics presented strong antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with the reduction percentage of 96.6% and 100%, respectively, and the antibacterial fabrics attained excellent washing durability.

Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

PubMed Central

2011-01-01

Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role played by efflux systems in the development of resistance to fluoroquinolones in clinical isolates of S. aureus. PMID:22032541

[Susceptibility surveillance of clinical isolates to fluoroquinolone antimicrobial agents from 2003 to 2008: post-marketing study of prulifloxacin].

PubMed

Kawai, Shin; Yoshida, Atsushi; Okazaki, Mitsuhiro; Tsujihara, Yoshito; Inuzuka, Kazuhisa; Takeuchi, Kazuhide; Yamashita, Naoko; Onodera, Makoto; Hiraishi, Toru; Ida, Takashi; Maebashi, Kazunori

2010-06-01

Yearly changes in the susceptibility of clinical isolates to ulifloxacin (UFX) and other fluoroquinolones were examined through surveys over 3 periods. In the first survey, 534 strains derived from 19 species were collected from clinical specimens during 6 months from December 2003 to May 2004. In the same way, 805 strains were collected from December 2005 to May 2006 in the second survey, and 863 strains were from December 2007 to May 2008 in the third survey. Over these 3 study periods, the susceptibilities of fluoroquinolones against methicillin-susceptible Staphylococcus aureus and Escherichia coli were decreased. The isolation frequency of levofloxacin-nonsusceptible strain was increased from 0% to 11.8% and from 14.6% to 20.8%, respectively. MIC90s of UFX against these pathogens were also increased, but its MIC90 for E. coli was 2 to 4 times lower than that of levofloxacin. On the other hand, the susceptibility of strains of Klebsiella pneumoniae to UFX was increased. Among the fluoroquinolones tested, UFX showed the most potent activity against Pseudomonas aeruginosa, and no changes in the MIC90s occurred during the surveillance. Although one strain of Streptococcus pneumoniae isolated in the third study period showed levofloxacin-resistance (MIC, 8 microg/mL), there were nearly no changes in the MIC90s of any agents tested including UFX against S. pneumoniae during the surveillance. As for other bacterial species, a tendency to increase in resistance to UFX was not observed. The activity of UFX against Salmonella spp. and Shigella spp. was superior/equal to those of fluoroquinolones tested.

Epidemiology of infections caused by multiresistant gram-negatives: ESBLs, MBLs, panresistant strains.

PubMed

Rossolini, Gian Maria; Mantengoli, Elisabetta; Docquier, Jean-Denis; Musmanno, Rosa Anna; Coratza, Grazietta

2007-07-01

Microbial drug resistance is a growing problem of global magnitude. In gram-negative pathogens, the most important resistance problems are encountered in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter, with increasing trends observed for all major anti-gram-negative agents (beta-lactams, fluoroquinolones and aminoglycosides). A matter of major concern is the emergence of new beta-lactamases capable of degrading the expanded-spectrum cephalosporins and/or carbapenems, such as the extended-spectrum beta-lactamases (ESBLs) and the carbapenemases. These beta-lactamase genes are often associated with resistance determinants to non-beta-lactam agents (e.g. aminoglycosides and fluoroquinolones), and strains producing ESBLs or carbapenemases often exhibit complex multidrug resistant phenotypes and sometimes are panresistant. The problem is worsened by the dearth of new agents active on multidrug-resistant Gram-negatives in the pipeline. The importance to develop better strategies to control resistance is underscored.

Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

PubMed

Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

2014-05-02

DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases.

One-step synthesis and characterization of polyaniline nanofiber/silver nanoparticle composite networks as antibacterial agents.

PubMed

Poyraz, Selcuk; Cerkez, Idris; Huang, Tung Shi; Liu, Zhen; Kang, Litao; Luo, Jujie; Zhang, Xinyu

2014-11-26

Through a facile and effective seeding polymerization reaction via a one-step redox/complexation process, which took place in aqueous medium at ambient temperature, silver nanoparticles (Ag NPs) embedded polyaniline nanofiber (PANI NF) networks were synthesized as antibacterial agents. During the reaction, not only NF morphology formation of the resulting conducting polymers (CPs) but also amplification of the aqueous silver nitrate (AgNO3) solutions' oxidative potentials were managed by vanadium pentoxide (V2O5) sol-gel nanofibers, which acted as well-known nanofibrous seeding agents and the auxiliary oxidative agent at the same time. The PANI/Ag nanocomposites were proven to exhibit excellent antibacterial property against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Antibacterial property performance and average life span of the nanocomposite network were optimized through the homogeneous distribution/embedment of Ag NPs within one-dimensional (1-D) PANI NF matrix. The antibacterial efficacy tests and nanocomposite material characterization results further indicated that the sole components of PANI/Ag have a synergistic effect to each other in terms of antibacterial property. Thus, this well-known catalytic seeding approach via a one-step oxidative polymerization reaction can be considered as a general methodology and a substantial fabrication tool to synthesize Ag NP decorated nanofibrillar PANI networks as advanced antibacterial agents.

Concentrations of gatifloxacin in plasma and urine and penetration into prostatic and seminal fluid, ejaculate, and sperm cells after single oral administrations of 400 milligrams to volunteers.

PubMed

Naber, C K; Steghafner, M; Kinzig-Schippers, M; Sauber, C; Sörgel, F; Stahlberg, H J; Naber, K G

2001-01-01

Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid. GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined by a high-performance liquid chromatography method after oral intake of a single 400-mg dose in 10 male Caucasian volunteers in the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine. GTX was well tolerated. The means (standard deviations) for the following parameters were as indicated: time to maximum concentration of drug in serum, 1.66 (0. 91) h; maximum concentration of drug in serum, 2.90 (0.39) microg/ml; area under the concentration-time curve from 0 to 24 h, 25.65 microg. h/ml; and half life, 7.2 (0.90) h. Within 12 h about 50% of the drug was excreted unchanged into the urine. The mean renal clearance was 169 ml/min. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations which were 1.92 (0.27) microg/ml at approximately the same time point (4 h after drug intake). The concentrations in sperm cells (0.195, 0.076, and 0.011 microg/ml) could be determined in three subjects. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad antibacterial spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption.

Concentrations of Gatifloxacin in Plasma and Urine and Penetration into Prostatic and Seminal Fluid, Ejaculate, and Sperm Cells after Single Oral Administrations of 400 Milligrams to Volunteers

PubMed Central

Naber, Christoph K.; Steghafner, Michaela; Kinzig-Schippers, Martina; Sauber, Christian; Sörgel, Fritz; Stahlberg, Hans-Jürgen; Naber, Kurt G.

2001-01-01

Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid. GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined by a high-performance liquid chromatography method after oral intake of a single 400-mg dose in 10 male Caucasian volunteers in the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine. GTX was well tolerated. The means (standard deviations) for the following parameters were as indicated: time to maximum concentration of drug in serum, 1.66 (0.91) h; maximum concentration of drug in serum, 2.90 (0.39) μg/ml; area under the concentration-time curve from 0 to 24 h, 25.65 μg · h/ml; and half life, 7.2 (0.90) h. Within 12 h about 50% of the drug was excreted unchanged into the urine. The mean renal clearance was 169 ml/min. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations which were 1.92 (0.27) μg/ml at approximately the same time point (4 h after drug intake). The concentrations in sperm cells (0.195, 0.076, and 0.011 μg/ml) could be determined in three subjects. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad antibacterial spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption. PMID:11120980

[E. coli: resistance to quinolones and beta-lactams of clinical strains isolated in the Franche-Comté region of France].

PubMed

Talon, D; Lallemand-De-Conto, S; Thouverez, M; Bertrand, X

2004-03-01

Numerous European studies have reported an increase of resistance to quinolones among E. coli. We conducted a regional study to update our knowledge on this evolution. We evaluated the resistance phenotype and genotype of 115 clinical strains of E. coli. We collected data on individual treatment with fluoroquinolones, and the evolution of the use of these antimicrobial agents. Resistance to nalidixic acid and ciprofloxacin was 13.0 and 6.9, respectively. The frequency of resistance increased from 1999 to 2001, from 7.5% to 13.0% for nalidixic acid and from 5.4% to 6.9% for fluoroquinolones. Resistance to quinolones was significantly associated to beta-lactams resistance and was slightly higher for nosocomial isolates compared to community-acquired isolates. Previous treatment with fluoroquinolones was the major risk factor associated to E. coli resistance. From 1997 to 2001, fluoroquinolones use has increased in our hospital and particularly in the community. Analysis of molecular epidemiology shows a large clonal diversity among E. coli isolates. This study confirms the evolution through resistance to quinolones of E. coli isolates. This observation is not due to dissemination of resistant clonal strains and the selective pressure exerted by fluoroquinolones influences this evolution. Therapeutic alternatives, surveillance, and restriction of fluoroquinolones use are needed to control this spread of resistance.

Preparation, characterization and cytotoxicity studies of some transition metal complexes with ofloxacin and 1,10-phenanthroline mixed ligand

NASA Astrophysics Data System (ADS)

Sadeek, S. A.; El-Hamid, S. M. Abd

2016-10-01

[Zn(Ofl)(Phen)(H2O)2](CH3COO)·2H2O (1), [ZrO(Ofl)(Phen)(H2O)]NO3·2H2O (2) and [UO2(Ofl)(Phen)(H2O)](CH3COO)·H2O (3) complexes of fluoroquinolone antibacterial agent ofloxacin (HOfl), containing a nitrogen donor heterocyclic ligand, 1,10-phenathroline monohydrate (Phen), were prepared and their structures were established with the help of elemental analysis, molar conductance, magnetic properties, thermal studies and different spectroscopic studies like IR, UV-Vis., 1H NMR and Mass. The IR data of HOfl and Phen ligands suggested the existing of a bidentate binding involving carboxylate O and pyridone O for HOfl ligand and two pyridine N atoms for Phen ligand. The coordination geometries and electronic structures are determined from electronic absorption spectra and magnetic moment measurements. From molar conductance studies reveals that metal complexes are electrolytes and of 1:1 type. The calculated bond length and force constant, F(Udbnd O), in the uranyl complex are 1.751 Å and 641.04 Nm-1. The thermal properties of the complexes were investigated by thermogravimetry (TGA) technique. The activation thermodynamic parameters are calculated using Coats-Redfern and Horowitz-Metzger methods. Antimicrobial activity of the compounds was evaluated against some bacteria and fungi species. The activity data show that most metal complexes have antibacterial activity than that of the parent HOfl drug. The in vitro cytotoxicities of ligands and their complexes were also evaluated against human breast and colon carcinoma cells.

Investigation of Mg(OH)2 nanoparticles as an antibacterial agent

NASA Astrophysics Data System (ADS)

Dong, Chunxu; Cairney, John; Sun, Qunhui; Maddan, Orville Lee; He, Gaohong; Deng, Yulin

2010-08-01

Our experimental results of using Mg(OH)2 nanoparticles as an antibacterial agent are reported in this study. The antibacterial behavior of Mg(OH)2 nanoparticles in liquid culture and in paper sheets was investigated. The colony forming units (CFU) counting and the headspace gas chromatography (HS-GC) measurement were used to determine the cell viability. Results indicate that Mg(OH)2 nanoparticles are effective antibacterial agent against Escherichia coli ( E. coli) and Burkholderia phytofirmans, and the OH- and Mg2+ ions in Mg(OH)2 water suspension were found not to be the reason for killing the bacteria. Mg(OH)2 nanoparticles could be added directly to wood pulp to make paper sheets, whose antibacterial efficiency increased with the increase of the nanoparticle amount. The possible mechanism of antibacterial effect of Mg(OH)2 nanoparticles is discussed.

Investigation of functional selenium nanoparticles as potent antimicrobial agents against superbugs.

PubMed

Huang, Xiaoquan; Chen, Xu; Chen, Qingchang; Yu, Qianqian; Sun, Dongdong; Liu, Jie

2016-01-01

Developing highly effective antibacterial agents is important for a wide range of applications. However, the emergence of multiple antibiotic-resistant bacteria poses a public health threat. Many developed agents have limited practical application due to chemical instability, low biocompatibility, and poor long-term antibacterial efficiency. In the following study, we synthesize a synergistic nanocomposite by conjugating quercetin (Qu) and acetylcholine (Ach) to the surface of Se nanoparticles (Qu-Ach@SeNPs). Quercetin has been reported to exhibit a wide range of biological activities related to their antibacterial activity and acetylcholine as a neurotransmitter, which can combine with the receptor on the bacterial cell. Arrows indicate NPs and arrowheads indicate compromised cell walls. The study demonstrated how Qu-Ach@SeNPs exhibit a synergistically enhanced antibacterial performance against the multidrug-resistant superbugs (MDRs) compared to Qu@SeNPs and Ach@SeNPs alone. Qu-Ach@SeNPs are effective against MDRs, such as Methicillin-resistant Staphylococcus aureus (MRSA), at a low dose. The mechanistic studies showed that Qu-Ach@SeNPs attach to the bacterial cell wall, causing irreversible damage to the membrane, and thereby achieving a remarkable synergistic antibacterial effect to inhibit MRSA. The findings suggested that the synergistic properties of quercetin and acetylcholine enhance the antibacterial activity of SeNPs. In this way, Qu-Ach@SeNPs comprise a new class of inorganic nano-antibacterial agents that can be used as useful applications in biomedical devices. The Qu-Ach@SeNPs have low cytotoxicity when tested on normal human cells in vitro. Qu-Ach@SeNPs are effective against MDRs, such as Methicillin-resistant S. aureus (MRSA), at a low dose. Importantly, Qu-Ach@SeNPs showed no emergence of resistance. These results suggest that Qu-Ach@SeNPs have excellent antibacterial activities. These agents can serve as good antibacterial agents against superbugs. Our data suggest that these antibacterial agents may have widespread application in the field of medicine for combating infectious diseases caused by MDRs, as well as other infectious diseases. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Evaluation of the antibacterial activity of selected Pakistani honeys against multi-drug resistant Salmonella typhi.

PubMed

Hussain, Muhammad Barkaat; Hannan, Abdul; Akhtar, Naeem; Fayyaz, Ghulam Qadir; Imran, Muhammad; Saleem, Sidrah; Qureshi, Imtiaz Ahmed

2015-02-26

The development of resistance to conventional anti-typhoid drugs and the recent emergence of fluoroquinolone resistance have made it very difficult and expensive to treat typhoid fever. As the therapeutic strategies become even more limited, it is imperative to investigate non-conventional modalities. In this context, honey is a potential candidate for combating antimicrobial resistance because it contains a broad repertoire of antibacterial compounds which act synergistically at multiple sites, thus making it less likely that the bacteria will become resistant. The in vitro antibacterial activity of 100 unifloral honey samples against a blood culture isolate of multi-drug resistant (MDR) Salmonella typhi were investigated. All honey samples were evaluated for both total (acidity, osmolarity, hydrogen peroxide and non-peroxide activity) and plant derived non-peroxide antibacterial activity by agar well diffusion assay at 50% and 25% dilution in sterile distilled water and 25% in catalase solution. Manuka (Unique Manuka Factor-21) honey was used for comparison. The phenol equivalence of each honey sample from 2% to 7% (w/v) phenol was obtained from regression analysis. The antibacterial potential of each honey sample was expressed as its equivalent phenol concentration. The honey samples which showed antibacterial activity equivalent to or greater than manuka honey were considered therapeutically active honeys. Nineteen honey samples (19%) displayed higher hydrogen peroxide related antibacterial activity (16-20% phenol), which is more than that of manuka honey (21-UMF). A total of 30% of the honey samples demonstrated antibacterial activity between 11 and 15% phenol similar to that of manuka honey while 51% of the honey samples did not exhibit any zone of inhibition against MDR-S. typhi at 50% (w/v) dilution. None of the indigenous honey samples displayed non-peroxide antibacterial activity. Only manuka honey showed non-peroxide antibacterial activity at 25% dilution (w/v) in catalase solution. The honey samples which displayed antibacterial activity equal to or greater than manuka honey may be useful in the clinical conditions where higher hydrogen peroxide related antibacterial activity is required. Manuka honey, which is known to possess non-peroxide antibacterial activity, warrants further evaluation in a suitable typhoid animal model.

Preparation of active antibacterial LDPE surface through multistep physicochemical approach II: graft type effect on antibacterial properties.

PubMed

Bílek, František; Sulovská, Kateřina; Lehocký, Marián; Sáha, Petr; Humpolíček, Petr; Mozetič, Miran; Junkar, Ita

2013-02-01

Three monomers (allylamine, N-allylmethylamine and N,N-dimethylallylamine) were used for grafting onto air plasma activated LDPE surface. Antibacterial agent triclosan was anchored on such substrates. Influence of graft type on the antibacterial properties was determined. Increase of antibacterial activity and amount of deposited antibacterial agent for N-allylmethylamine and N,N-dimethylallylamine monomers were examined. Surface characteristics were measured by means of static contact angle measurement with surface energy evaluation, ATR-FTIR spectroscopy, XPS and SEM characterization analysis. Antibacterial properties were tested in vitro by inhibition zone method on agar plates for Staphylococcus aureus and Escherichia coli strains. Copyright © 2012 Elsevier B.V. All rights reserved.

Polyethyleneimine Capped Silver Nanoclusters as Efficient Antibacterial Agents.

PubMed

Xu, Dong; Wang, Qingyun; Yang, Tao; Cao, Jianzhong; Lin, Qinlu; Yuan, Zhiqin; Li, Le

2016-03-18

Development of efficient antibacterial agents is critical for human health. In the present study, we investigated the antibacterial activity of polyethyleneimine (PEI)-capped silver nanoclusters (PEI-AgNCs), based on the fact that nanoclusters normally have higher surface-to-volume ratios than traditional nanomaterials and PEI itself has a strong antimicrobial capacity. We synthesized stable silver nanoclusters by altering PEI molecular weight from 0.6 kDa to 25 kDa and characterized them by UV-Vis absorption and fluorescence spectroscopy and high resolution transmission electron microscopy. The sizes of AgNCs were around 2 nm in diameter and were little influenced by the molecular weight of PEIs. The antibacterial abilities of the four PEI-AgNCs were explored on agar plate and in liquid systems. Our results revealed that the antibacterial activity of PEI-AgNCs is excellent and the reduction of PEI molecular weight could result in the increased antibacterial capacity of PEI-AgNCs. Such proposed new materials might be useful as efficient antibacterial agents in practical clinical applications.

Antibiotics in Serbian Households: a Source of Potential Health and Environmental Threats?

PubMed

Kusturica, Milica Paut; Tomić, Zdenko; Bukumirić, Zoran; Horvat, Olga; Pavlović, Nebojša; Mikov, Momir; Sabo, Ana

2015-06-01

Worldwide data indicate that antibiotics are frequently used inappropriately. The objective of this study was to investigate the extent of storage and wastage of antibacterial agents in households in Novi Sad, Serbia. The study was performed in 8 months period (December 2011-July 2012) in households in Novi Sad, Serbia. The households were randomly selected from the telephone directory. The interviewer performed the survey visiting each household. The total number of antibacterial agents in the 383 surveyed households was 318, constituting 7.3% of the total stored medications. From 383 families included in the study antibiotics were found in 178 (46.5%). In 13 (7.3%) families were found more than one pack of the same antibiotics. The median number of antibacterial agents per household was 1 (range 1-5). The most common antibacterial agents that were not in current use were cephalexin (22.1%) and amoxicillin (16.6%), followed by doxycycline (11.4%), sulfamethoxazole/trimethoprim (11.4%) and amoxicillin/clavulanic acid (9.2%). The percentage of expired antibacterial agents was 20.8%, while 85.2% were not currently in use. Antibacterial agents were commonly encountered in Serbian households, and a relatively large percentage was wasted. Informational and educational activities aimed at improving the public knowledge about antimicrobials play the leading role in reducing imprudent use of antibiotics. Copyright© by the National Institute of Public Health, Prague 2015.

Developing of a novel antibacterial agent by functionalization of graphene oxide with guanidine polymer with enhanced antibacterial activity

NASA Astrophysics Data System (ADS)

Li, Ping; Sun, Shiyu; Dong, Alideertu; Hao, Yanping; Shi, Shuangqiang; Sun, Zijia; Gao, Ge; Chen, Yuxin

2015-11-01

New materials with excellent antibacterial activity attract numerous research interests. Herein, a facile synthetic method of polyethylene glycol (PEG) and polyhexamethylene guanidine hydrochloride (PHGC) dual-polymer-functionalized graphene oxide (GO) (GO-PEG-PHGC), a novel antibacterial material, was reported. The as-prepared products were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), X-ray pattern (XRD) and elemental analysis. The antibacterial effect on the bacterial strain was investigated by incubating both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). The results show that GO-PEG-PHGC has enhanced antibacterial activity when compared to GO, GO-PEG or GO-PHGC alone. The improved antibacterial activity was described to be related to a better dispersion of GO-PEG-PHGC in the presence of PEG. This better dispersion leads to a greater contact between the bacteria membrane and nanomaterials, therefore leading to greater cell damage. Not only Gram-negative bacteria but also Gram-positive bacteria are greatly inhibited by this antibacterial agent. With the powerful antibacterial activity as well as its low cost and facile preparation, the GO-PEG-PHGC as a novel antibacterial agent can find potential application in the areas of healthcare and environmental engineering.

Cellulosic/wool pigment prints with remarkable antibacterial functionalities.

PubMed

Ibrahim, N A; Eid, B M; Khalil, H M

2015-01-22

Several bio-active agents namely choline chloride, triclosan derivative, PEG-600 and 4-hydroxybenzophenone were successfully included into solvent-free pigment formulations, in a single-stage process, followed by screen printing and microwave-fixation to obtain antibacterial functionalized cellulosic/wool pigment prints. Results obtained signify that both the improvement in functionalization and coloration properties are governed by type of antibacterial agent, kind of substrate as well as pigment colorant. The imparted antibacterial activity of the loaded bio-active agents follows the decreasing order: G+ve (Staphylococcus aureus)>G-ve (Escherichia coli), keeping other parameters constant. The imparted functional and coloration properties showed no significant decrease even after 15 washings. Mode of interactions among the nominated substrates, the pigment paste constituents and the bioactive agents were also proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and in vitro antibacterial activity of oxazolidine LBM-415 analogs as peptide deformylase inhibitors.

PubMed

Yu, Linliang; Zhou, Weicheng; Wang, Zhenyu

2011-03-01

The drug resistant bacteria pose a severe threat to human health. The increasing resistance of those pathogens to traditional antibacterial therapy renders the identification of new antibacterial agents with novel antibacterial mechanisms an urgent need. In this study, a series of (2S)-N-substituted-1-[(formyhydroxyamino)methyl]-1-oxohexyl]-2-oxazolidinecarboxamides were designed, synthesized and evaluated for in vitro antibacterial activity. Most of these compounds displayed good activities against Gram-positive organisms comparable to reference agent LBM-415. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity.

PubMed

Kersten, B; Zhang, J; Brendler-Schwaab, S Y; Kasper, P; Müller, L

1999-09-15

Recent reports on the photochemical carcinogenicity and photochemical genotoxicity of fluoroquinolone antibacterials led to an increasing awareness for the need of a standard approach to test for photochemical genotoxicity. In this study the micronucleus test using V79 cells was adapted to photogenotoxicity testing. Results of using different UVA/UVB relationships enabled us to identify a suitable irradiation regimen for the activation of different kinds of photosensitizers. Using this regimen, 8-methoxypsoralen and the fluoroquinolones lomefloxacin, grepafloxacin and Bay Y 3118 were identified to cause micronuclei and toxicity upon photochemical activation. Among the phenothiazines tested, chlorpromazine and 2-chlorophenothiazine, were positive for both endpoints, whereas triflupromazine was only slightly photoclastogenic in the presence of strong phototoxicity. Among the other potential human photosensitizers tested (oxytetracycline, doxycycline, metronidazole, emodin, hypericin, griseofulvin), only hypericin was slightly photogenotoxic. Photochemical toxicity in the absence of photochemical genotoxicity was noted for doxycycline and emodin. With the assay system described, it is possible to determine photochemical toxicity and photochemical genotoxicity concomitantly with sufficient reliability.

Simultaneous determination of quinolones for veterinary use by high-performance liquid chromatography with electrochemical detection.

PubMed

Rodríguez Cáceres, M I; Guiberteau Cabanillas, A; Galeano Díaz, T; Martínez Cañas, M A

2010-02-01

A selective method based on high-performance liquid chromatography with electrochemical detection (HPLC-ECD) has been developed to enable simultaneous determination of three fluoroquinolones (FQs), namely danofloxacin (DANO), difloxacin (DIFLO) and sarafloxacin (SARA). The fluoroquinolones are separated on a Novapack C-18 column and detected in a high sensitivity amperometric cell at a potential of +0.8 V. Solid-phase extraction was used for the extraction of the analytes in real samples. The range of concentration examined varied from 10 to 150 ng g(-1) for danofloxacin, from 25 to 100 ng g(-1) for sarafloxacin and from 50 to 315 ng g(-1) for difloxacin, respectively. The method presents detection limits under 10 ng g(-1) and recoveries around 90% for the three analytes have been obtained in the experiments with fortified samples. This HPLC-ECD approach can be useful in the routine analysis of antibacterial residues being less expensive and less complicated than other more powerful tools as hyphenated techniques. 2009 Elsevier B.V. All rights reserved.

Intracellular and membrane-damaging activities of methyl gallate isolated from Terminalia chebula against multidrug-resistant Shigella spp.

PubMed

Acharyya, Saurabh; Sarkar, Prodipta; Saha, Dhira R; Patra, Amarendra; Ramamurthy, T; Bag, Prasanta K

2015-08-01

Shigella spp. (Shigella dysenteriae, Shigella flexneri, Shigella boydii and Shigella sonnei) cause bacillary dysentery (shigellosis), which is characterized by bloody mucous diarrhoea. Although a variety of antibiotics have been effective for treatment of shigellosis, options are becoming limited due to globally emerging drug resistance. In the present study, in vitro antibacterial activity of methyl gallate (MG) isolated from Terminalia chebula was determined by performing MIC, minimal bactericidal concentration (MBC) and time-kill kinetic studies. Bacterial membrane-damaging activity of MG was determined by membrane perturbation and transmission electron microscopy (TEM). Cellular drug accumulation, cell infection and assessment of intracellular activities of MG and reference antibiotics were performed using HeLa cell cultures. The bactericidal activity of MG against multidrug-resistant (MDR) Shigella spp. in comparison with other commonly used drugs including fluoroquinolone was demonstrated here. TEM findings in the present study revealed that MG caused the total disintegration of inner and outer membranes, and leakage of the cytoplasmic contents of S. dysenteriae. The level of accumulation of MG and tetracycline in HeLa cells incubated for 24  h was relatively higher than that of ciprofloxacin and nalidixic acid (ratio of intracellular concentration/extracellular concentration of antibiotic for MG and tetracycline>ciprofloxacin and nalidixic acid). The viable number of intracellular S. dysenteriae was decreased in a time-dependent manner in the presence of MG (4 × MBC) and reduced to zero within 20  h. The significant intracellular activities of MG suggested that it could potentially be used as an effective antibacterial agent for the treatment of severe infections caused by MDR Shigella spp.

Mesoporous TiO2 implants for loading high dosage of antibacterial agent

NASA Astrophysics Data System (ADS)

Park, Se Woong; Lee, Donghyun; Choi, Yong Suk; Jeon, Hoon Bong; Lee, Chang-Hoon; Moon, Ji-Hoi; Kwon, Il Keun

2014-06-01

We have fabricated mesoporous thin films composed of TiO2 nanoparticles on anodized titanium implant surfaces for loading drugs at high doses. Surface anodization followed by treatment with TiO2 paste leads to the formation of mechanically stable mesoporous thin films with controllable thickness. A series of antibacterial agents (silver nanoparticles, cephalothin, minocycline, and amoxicillin) were loaded into the mesoporous thin films and their antibacterial activities were evaluated against five bacterial species including three oral pathogens. Additionally, two agents (silver nanoparticles and minocycline) were loaded together on the thin film and tested for antibacterial effectiveness. The combination of silver nanoparticles and minocycline was found to display a wide range of effectiveness against all tested bacteria.

Conclusions: the future of antimicrobial therapy - Augmentin and beyond.

PubMed

Ball, Peter

2007-12-01

Since most infectious microorganisms inevitably develop resistance to any agents used to combat them, there has been a constant need to produce improved, more potent, antimicrobials. At least in part, the emergence and spread of resistant organisms has been provoked by inappropriate over-use of antibacterials. In the last decade, many fewer new antibacterials have been developed but overall prescribing has continued to increase. Consensus prescribing principles have now been defined with the aim of optimising therapy and preventing further increases in, or even to prompt a reduction in, the prevalence of resistance to antibacterial agents. Whilst it is important to encourage continued development of new classes of antibacterials, it is also vital to make the best use of available agents. The development of new dosages and formulations of amoxicillin/clavulanate allows this agent to continue to fill the important role in therapy which it has occupied, and continues to occupy, 25 years after it was launched.

Dual antibacterial agents of nano-silver and 12-methacryloyloxydodecylpyridinium bromide in dental adhesive to inhibit caries

PubMed Central

Zhang, Ke; Li, Fang; Imazato, Satoshi; Cheng, Lei; Liu, Huaibing; Arola, Dwayne D.; Bai, Yuxing; Xu, Hockin H. K.

2013-01-01

Dental resins containing 12-methacryloyloxydodecylpyridinium bromide (MDPB) showed potent antibacterial functions. Recent studies developed antibacterial resins containing nanoparticles of silver (NAg). The objectives of this study were to develop an adhesive containing dual agents of MDPB and NAg for the first time, and to investigate the combined effects of antibacterial adhesive and primer on biofilm viability, metabolic activity, lactic acid, dentin bond strength, and fibroblast cytotoxicity. MDPB and NAg were incorporated into Scotchbond Multi-Purpose (SBMP) adhesive “A” and primer “P”. Five systems were tested: SBMP adhesive A; A+MDPB; A+NAg; A+MDPB+NAg; P+MDPB+NAg together with A+MDPB+NAg. Dental plaque microcosm biofilms were cultured using mixed saliva from ten donors. Metabolic activity, colony-forming units, and lactic acid production of biofilms were investigated. Human fibroblast cytotoxicity of bonding agents was determined. MDPB+NAg in adhesive/primer did not compromise dentin bond strength (p>0.1). MDPB or NAg alone in adhesive substantially reduced the biofilm activities. Dual agents MDPB+NAg in adhesive greatly reduced the biofilm viability compared to each agent alone (p<0.05). The greatest inhibition of biofilms was achieved when both adhesive and primer contained MDPB+NAg. Fibroblast viability of groups with dual antibacterial agents was similar to control using culture medium without resin eluents (p>0.1). In conclusion, this study showed for the first time that the antibacterial potency of MDPB adhesive could be substantially enhanced via NAg. Adding MDPB+NAg into both primer and adhesive achieved the strongest anti-biofilm efficacy. The dual agent (MDPB+NAg) method could have wide applicability to other adhesives, sealants, cements and composites to inhibit biofilms and caries. PMID:23529901

Antibacterial and remineralization effects of orthodontic bonding agents containing bioactive glass

PubMed Central

Kim, Dong-Hyun; Song, Chang Weon; Yoon, Seog-Young; Kim, Se-Yeon; Na, Hee Sam; Chung, Jin

2018-01-01

Objective The aim of this study was to evaluate the mechanical and biological properties of orthodontic bonding agents containing silver- or zinc-doped bioactive glass (BAG) and determine the antibacterial and remineralization effects of these agents. Methods BAG was synthesized using the alkali-mediated solgel method. Orthodontic bonding agents containing BAG were prepared by mixing BAG with flowable resin. Transbond™ XT (TXT) and Charmfil™ Flow (CF) were used as controls. Ion release, cytotoxicity, antibacterial properties, the shear bond strength, and the adhesive remnant index were evaluated. To assess the remineralization properties of BAG, micro-computed tomography was performed after pH cycling. Results The BAG-containing bonding agents showed no noticeable cytotoxicity and suppressed bacterial growth. When these bonding agents were used, demineralization after pH cycling began approximately 200 to 300 µm away from the bracket. On the other hand, when CF and TXT were used, all surfaces that were not covered by the adhesive were demineralized after pH cycling. Conclusions Our findings suggest that orthodontic bonding agents containing silver- or zinc-doped BAG have stronger antibacterial and remineralization effects compared with conventional orthodontic adhesives; thus, they are suitable for use in orthodontic practice. PMID:29732302

Enhancing the Prevention and Treatment of Orthopaedic Infections Associated with Traumatic Injury

DTIC Science & Technology

2017-10-01

minipeg-2 derivative have antimicrobial activity in and of themselves (see previous progress report). This absence of antibacterial activity is not...necessarily desirable, as antibacterial activity of the targeting agent itself could prove useful. However, it does suggest that these agents are less...of the minipeg linker (BS-4-134 and BS-4-142). However, unlike our daptomycin conjugates, antibacterial activity was essentially abolished with all of

Quality evaluation and in vitro interaction studies between levofloxacin 250mg and diclofenac sodium 50mg tablets.

PubMed

Fayyaz, Muhammad; Yousuf, Rabia Ismail; Shoaib, Muhammad Harris; Ali, Tariq; Nasiri, Iqbal; Ashraf, Nida

2015-01-01

Fluoroquinolones are broad-spectrum antibiotics, work against Gram-positive and Gram-negative bacteria and are a clinically proven option for many resistant infections. Among fluoroquinolones Levofloxacin works best against acute sinusitis, inflammation of the lower airways, acute exacerbation of chronic bronchitis, community acquired pneumonia, complicated urinary tract infection including Pyelonephritis, chronic bacterial prostatitis and skin and soft tissue infection. Levofloxacin is a frequently prescribed antibacterial agent with Diclofenac Sodium for pain management in infectious conditions. The objective of the present work is to evaluate the level of interaction between Levofloxacin and Diclofenac Sodium. In this work market available brands of both drugs were also evaluated for quality.The physiochemical parameters like weight variation, thickness variation, and mechanical strength were determined. Similarly the percentage drug release and content uniformity test were also analyzed; the tested quality attributes were found within the recommended pharmacopeia ranges except brand L(6) that had high drug content 124.629±3.614 while brand L(4) and L(5) were not found similar in pH 1.2. When subjected to model dependent analysis Levofloxacin showed compliance with (first order, Higuchi, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8). However Diclofenac Sodium showed adherence with (first order, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8) but following Higuchi at pH 1.2 and 4.5 only. The interaction studies were also performed spectrophotometrically and simultaneous equation was used to estimate the percentage availability of both the drugs at pH 4.5, 6.8, FaSSGF and FaSSIF. The studies showed that the percent availability of Levofloxacin was increased significantly in FaSSIF i.e. 129.173±0.323 at 45 minutes in the presence of Diclofenac Sodium.

A clinical trial of pefloxacin and ofloxacin in lepromatous leprosy.

PubMed

Fajardo, Tranquilino T; Villahermosa, Laarni G; Cruz, Eduardo C Dela; Cellona, Roland V; Balagon, Ma Victoria F; Abalos, Rodolfo M; Gelber, Robert H

2004-12-01

A 2-month clinical trial of pefloxacin and ofloxacin in previously untreated multibacillary patients was conducted at the Leonard Wood Memorial Leprosy Research Center, Cebu, the Philippines. Treatment with either pefloxacin or ofloxacin resulted in rapid clinical improvement, in this regard pefloxacin appearing somewhat superior. Reactions and side effects were minimal. Single doses of either agent did not result in significant killing of Mycobacterium leprae, but significant bactericidal activity was observed for all fluoroquinolone-treated patients by one week of daily therapy (n = 21), and either agent independently by 3 weeks of daily therapy. At the completion of therapy only two of 10 pefloxacin-treated patients and 0 of 11 ofloxacin-treated patients harboured any detectable viable M. leprae from active lesions, confirming previous work that these fluoroquinolones exhibit bactericidal activity in leprosy patients and more than that found previously for dapsone and clofazimine.

What is an "ideal" antibiotic? Discovery challenges and path forward.

PubMed

Singh, Sheo B; Young, Katherine; Silver, Lynn L

2017-06-01

An ideal antibiotic is an antibacterial agent that kills or inhibits the growth of all harmful bacteria in a host, regardless of site of infection without affecting beneficial gut microbes (gut flora) or causing undue toxicity to the host. Sadly, no such antibiotics exist. What exist are many effective Gram-positive antibacterial agents as well as broad-spectrum agents that provide treatment of certain Gram-negative bacteria but not holistic treatment of all bacteria. However effectiveness of all antibacterial agents is being rapidly eroded due to resistance. This viewpoint provides an overview of today's antibiotics, challenges and potential path forward of discovery and development of new (ideal) antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

Extraction of chitosan from shrimp shells waste and application in antibacterial finishing of bamboo rayon.

PubMed

Teli, M D; Sheikh, Javed

2012-06-01

Chitosan can be best utilized as safe antibacterial agent for textiles but there is always a limitation of its durability. The chitin containing shellfish waste is available in huge quantities, but very low quantities are utilized for extraction of high value products like chitosan. In the current work chitosan was extracted from shrimp shells and then used as antibacterial exhaust finishing agent for grafted bamboo rayon. Chitosan bound bamboo rayon was then evaluated for antibacterial activity against both gram positive and gram negative bacteria. The product showed antibacterial activity against both types of bacterias which was durable till 30 washes. Copyright © 2012 Elsevier B.V. All rights reserved.

Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline.

PubMed

Flowers, Christopher R; Seidenfeld, Jerome; Bow, Eric J; Karten, Clare; Gleason, Charise; Hawley, Douglas K; Kuderer, Nicole M; Langston, Amelia A; Marr, Kieren A; Rolston, Kenneth V I; Ramsey, Scott D

2013-02-20

To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia. A literature search identified relevant studies published in English. Primary outcomes included: development of fever and/or infections in afebrile neutropenic outpatients and recovery without complications and overall mortality in febrile neutropenic outpatients. Secondary outcomes included: in afebrile neutropenic outpatients, infection-related mortality; in outpatients with fever and neutropenia, defervescence without regimen change, time to defervescence, infectious complications, and recurrent fever; and in both groups, hospital admissions, duration, and adverse effects of antimicrobials. An Expert Panel developed guidelines based on extracted data and informal consensus. Forty-seven articles from 43 studies met selection criteria. Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days, unless other factors increase risks for complications or mortality to similar levels. Inpatient treatment is standard to manage febrile neutropenic episodes, although carefully selected patients may be managed as outpatients after systematic assessment beginning with a validated risk index (eg, Multinational Association for Supportive Care in Cancer [MASCC] score or Talcott's rules). Patients with MASCC scores ≥ 21 or in Talcott group 4, and without other risk factors, can be managed safely as outpatients. Febrile neutropenic patients should receive initial doses of empirical antibacterial therapy within an hour of triage and should either be monitored for at least 4 hours to determine suitability for outpatient management or be admitted to the hospital. An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if penicillin allergic) is recommended as empiric therapy, unless fluoroquinolone prophylaxis was used before fever developed.

Effect of water-ageing on dentine bond strength and anti-biofilm activity of bonding agent containing new monomer dimethylaminododecyl methacrylate

PubMed Central

Zhang, Ke; Cheng, Lei; Wu, Eric J.; Weir, Michael D.; Bai, Yuxing; Xu, Hockin H. K.

2013-01-01

Objectives The objectives of this study were to develop bonding agent containing a new antibacterial monomer dimethylaminododecyl methacrylate (DMADDM) as well as nanoparticles of silver (NAg) and nanoparticles of amorphous calcium phosphate (NACP), and to investigate the effects of water-ageing for 6 months on dentine bond strength and anti-biofilm properties for the first time. Methods Four bonding agents were tested: Scotchbond Multi-Purpose (SBMP) Primer and Adhesive control; SBMP + 5% DMADDM; SBMP + 5% DMADDM + 0.1% NAg; and SBMP + 5% DMADDM + 0.1% NAg with 20% NACP in adhesive. Specimens were water-aged for 1 d and 6 months at 37 °C. Then the dentine shear bond strengths were measured. A dental plaque microcosm biofilm model was used to inoculate bacteria on water-aged specimens and to measure metabolic activity, colony-forming units (CFUs), and lactic acid production. Results Dentine bond strength showed a 35% loss in 6 months of water-ageing for SBMP control (mean ± sd; n = 10); in contrast, the new antibacterial bonding agents showed no strength loss. The DMADDM–NAg–NACP containing bonding agent imparted a strong antibacterial effect by greatly reducing biofilm viability, metabolic activity and acid production. The biofilm CFU was reduced by more than two orders of magnitude, compared to SBMP control. Furthermore, the DMADDM–NAg–NACP bonding agent exhibited a long-term antibacterial performance, with no significant difference between 1 d and 6 months (p > 0.1). Conclusions Incorporating DMADDM–NAg–NACP in bonding agent yielded potent and long-lasting antibacterial properties, and much stronger bond strength after 6 months of water-ageing than a commercial control. The new antibacterial bonding agent is promising to inhibit biofilms and caries at the margins. The method of DMADDM–NAg–NACP incorporation may have a wide applicability to other adhesives, cements and composites. PMID:23583528

Levofloxacin : a review of its use as a high-dose, short-course treatment for bacterial infection.

PubMed

Anderson, Vanessa R; Perry, Caroline M

2008-01-01

Levofloxacin (Levaquin) is a fluoroquinolone antibacterial that is the L-isomer of ofloxacin. A high-dose (750 mg) short-course (5 days) of once-daily levofloxacin is approved for use in the US in the treatment of community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract infections (UTI) and acute pyelonephritis (AP). The broad spectrum antibacterial profile of levofloxacin means that monotherapy is often a possibility in patients with CAP at times when other agents may require combination therapy, although levofloxacin can be used in combination therapy when necessary. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent bactericidal activity and may reduce the potential for resistance to emerge. In addition, this regimen lends itself to better compliance because of the shorter duration of treatment and the convenient once-daily administration schedule. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation; importantly, patients can transition between the formulations, which results in more options in regards to the treatment regimen and the potential for patients with varying degrees of illness to be treated. Levofloxacin has good tissue penetration and an adequate concentration can be maintained in the urinary tract to treat uropathogens. Levofloxacin is generally well tolerated and has good efficacy in the treatment of patients with CAP, ABS, complicated UTI and AP. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP, ABS and UTIs is well established, and the high-dose, short-course levofloxacin regimen has been shown to be noninferior to the 10-day regimen in CAP and ABS, and to have a similar tolerability profile. Similarly, the high-dose, short-course levofloxacin regimen is noninferior to ciprofloxacin in patients with complicated UTI or AP. Thus, levofloxacin is a valuable antimicrobial agent that has activity against a wide range of bacterial pathogens; however, its use should be considered carefully so that the potential for resistance selection can be minimized and its usefulness in severe infections and against a range of penicillin- and macrolide-resistant pathogens can be maintained.

Effects of NorA Inhibitors on In Vitro Antibacterial Activities and Postantibiotic Effects of Levofloxacin, Ciprofloxacin, and Norfloxacin in Genetically Related Strains of Staphylococcus aureus

PubMed Central

Aeschlimann, Jeffrey R.; Dresser, Linda D.; Kaatz, Glenn W.; Rybak, Michael J.

1999-01-01

NorA is a membrane-associated multidrug efflux protein that can decrease susceptibility to fluoroquinolones in Staphylococcus aureus. To determine the effect of NorA inhibition on the pharmacodynamics of fluoroquinolones, we evaluated the activities of levofloxacin, ciprofloxacin, and norfloxacin with and without various NorA inhibitors against three genetically related strains of S. aureus (SA 1199, the wild-type; SA 1199B, a NorA hyperproducer with a grlA mutation; and SA 1199-3, a strain that inducibly hyperproduces NorA) using susceptibility testing, time-kill curves, and postantibiotic effect (PAE) methods. Levofloxacin had the most potent activity against all three strains and was minimally affected by addition of NorA inhibitors. In contrast, reserpine, omeprazole, and lansoprazole produced 4-fold decreases in ciprofloxacin and norfloxacin MICs and MBCs for SA 1199 and 4- to 16-fold decreases for both SA 1199B and SA 1199-3. In time-kill experiments reserpine, omeprazole, or lansoprazole increased levofloxacin activity against SA 1199-3 alone by 2 log10 CFU/ml and increased norfloxacin and ciprofloxacin activities against all three strains by 0.5 to 4 log10 CFU/ml. Reserpine and omeprazole increased norfloxacin PAEs on SA 1199, SA 1199B, and SA 1199-3 from 0.9, 0.6, and 0.2 h to 2.5 to 4.5, 1.1 to 1.3, and 0.4 to 1.1 h, respectively; similar effects were observed with ciprofloxacin. Reserpine and omeprazole increased the levofloxacin PAE only on SA 1199B (from 1.6 to 5.0 and 3.1 h, respectively). In conclusion, the NorA inhibitors dramatically improved the activities of the more hydrophilic fluoroquinolones (norfloxacin and ciprofloxacin). These compounds may restore the activities of these fluoroquinolones against resistant strains of S. aureus or may potentially enhance their activities against sensitive strains. PMID:9925528

Novel cajaninstilbene acid derivatives as antibacterial agents.

PubMed

Geng, Zhi-Zhong; Zhang, Jian-Jun; Lin, Jing; Huang, Mei-Yan; An, Lin-Kun; Zhang, Hong-Bin; Sun, Ping-Hua; Ye, Wen-Cai; Chen, Wei-Min

2015-07-15

Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The antibacterial activities of these compounds against gram-negative and gram-positive bacteria, as well as nine strains of methicillin-resistant staphylococcus aureus (MRSA) bacteria are evaluated，and the related structure-activity relationships are discussed. Assays suggest that some of the synthetic cajaninstilbene acid derivatives exhibit potent antibacterial activity against gram-positive bacterial strains and MRSA. Among these compounds, 5b, 5c, 5j and 5k show better antibacterial activity than the positive control compounds. The results of MTT assays illustrate the low cytotoxicity of the active compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Mutations in the quinolone resistance determining region conferring resistance to fluoroquinolones in Mycoplasma agalactiae.

PubMed

Tatay-Dualde, Juan; Prats-van der Ham, Miranda; de la Fe, Christian; Paterna, Ana; Sánchez, Antonio; Corrales, Juan Carlos; Contreras, Antonio; Gómez-Martín, Ángel

2017-08-01

M. agalactiae is the main causative agent of contagious agalactia, against which antimicrobial treatment is the main applied control measure. Quinolones are an effective group of antimicrobials inhibiting the growth of M. agalactiae, but in the last years, various reports have demonstrated an increase of resistance in field isolates due to its massive use. Nevertheless, the molecular mechanisms involved in the acquisition of fluoroquinolones resistance in M. agalactiae have not been elucidated yet. Therefore, the aim of this work was to analyze the presence of DNA variations that could be related to changes in fluoroquinolone susceptibility. For this purpose, three M. agalactiae strains were selected to obtain in vitro resistant mutants against enrofloxacin, marbofloxacin and moxifloxacin and afterwards, partial sequences of their gyrA, gyrB, parC and parE genes were analyzed. In addition, a set of field isolates with different MIC values were also studied. Changes related to variations in fluoroquinolones susceptibility were found in gyrB, parC and parE. Specifically, gyrB genes were affected at the predicted amino acid position 424, four amino acid changes were detected in parC (positions 78, 79, 80 and 84) and two substitutions were reported in parE (amino acid positions 429 and 459). Mutations at predicted positions 424 of gyrB and 429 of parE are novel DNA changes which had not been previously described and, on the whole, parC was the first gene showing alterations when changes in susceptibility to fluoroquinolones occurred. Thus, this gene is the most suitable target for a rapid study of fluoroquinolone resistance in field isolates of M. agalactiae. Copyright © 2017 Elsevier B.V. All rights reserved.

Pleuromutilin and its derivatives-the lead compounds for novel antibiotics.

PubMed

Tang, Y-Z; Liu, Y-H; Chen, J-X

2012-01-01

Due to the rapid onset of resistance to most antibacterial drugs, research efforts are focusing on new classes of antibacterials with different mechanisms of action from clinically used antibacterials. Pleuromutilin derivatives have received more and more scientific attention for their unique mechanism of action. Two pleuromutilin derivatives, tiamulin and valnemulin have been successfully developed as antibiotics for veterinary use. Retapamulin, another pleuromutilin derivative has been approved for use in humans in April 2007 by Food and Drug Administration (FDA). It has been shown that there is rarely cross-resistance between pleuromutilin derivatives and other antimicrobial agents, and the development of resistance bacterial is still low. This review will demonstrate mechanism of action of pleuromutilin derivatives and reveal the structure-activity relationship (SAR) of pleuromutilin derivatives. Additionally, the pleuromutilin antibacterial derivative agents in the market, such as tiamulin, valnemulin and retapamulin, will be discussed. It is proposed that new antibacterial agents might be developed from pleuromutilin derivatives in the future.

Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents.

PubMed

Phan, Phuong-Thuy T; Nguyen, Thu-Trang T; Nguyen, Hong-Nhung T; Le, Bao-Khanh N; Vu, Thao T; Tran, Dong C; Pham, Tuan-Anh N

2017-04-25

In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis ( S. faecalis ) ATCC 29212) and one Gram-(-) strain ( Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap-Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O -ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis , MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06-0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM ( 8f ) and 0.12 mM ( 8h ). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.

The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I. An in vitro agar assay.

PubMed

Reagor, Lee; Gusman, Jean; McCoy, Lana; Carino, Edith; Heggers, John P

2002-06-01

Grapefruit-seed extract (GSE) Citricidal has, in recent reports, been reported to be successful in combating a variety of common infectious agents. In our study, drops of concentrated grapefruit-seed extract were tested for antibacterial properties against a number of gram-positive and gram-negative organisms. Sixty-seven (67) distinct biotypes were tested for their susceptibilities to the GSE as well as to 5 other topical antibacterials (Silvadene, Sulfamylon, Bactroban, Nitrofurazone, and Silvadene, Nystatin). Wells were punched into Mueller-Hinton agar plates, which were then inoculated with the organism to be tested; each well was then inoculated with one of the antibacterial agents. After an overnight incubation period, the plates were checked for zones of bacterial susceptibility around the individual wells, with a measured susceptibility zone diameter of 10 mm or more considered a positive result. The GSE was consistently antibacterial against all of the biotypes tested, with susceptibility zone diameters equal to or greater than 15 mm in each case. Our preliminary data thus suggest an antibacterial characteristic to GSE that is comparable to that of proven topical antibacterials. Although the GSE appeared to have a somewhat greater inhibitory effect on gram-positive organisms than on gram-negative organisms, its comparative effectiveness against a wide range of bacterial biotypes is significant.

[Sensitivity of microbial associations of periodontal lesions to antibacterial agents].

PubMed

Makeeva, I M; Daurova, F Yu; Byakova, S F; Ippolitov, E V; Gostev, M S; Polikushina, A O; Shubin, E V

2016-01-01

The aim of the study was the development of approaches to improve the effectiveness of antibiotic therapy in dental practice on the basis of determining the sensitivity of pathogenic microorganisms to antibiotics of different groups. The study included determination of the sensitivity of the microbial complexes from wound exudate of periodontal pocket and apical abscess to macrolides, quinolones, penicillins, lincosamides and 5-nitroimidazole. A survey of dentists and dental clinics patients to identify the cause and frequency of use of antibiotics and to identify possible adverse reactions was also conducted. Dentists prefer macrolide antibiotics, protected penicillins, and fluoroquinolone combined with 5-nitroimidazole. All patients have taken antibiotics themselves at least once a year. Microbial complexes in patients with acute and exacerbated apical periodontitis in 79% of cases are susceptible to amoxicillin/clavulanic acid, to azithromycin - 52%, lincomycin - 36%, 5-nitroimidazole - 68%, ciprofloxacin - 73.7%. In patients with apical abscess high rates of resistance of microbial complexes to all types of antibiotics was revealed (33% for lincomycin 76,1% for ciprofloxacin, 28,6% for 5-nitroimidazole). Patients with moderate to severe periodontitis in 90.5% are sensitive to amoxicillin/clavulanic acid and azithromycin, in 62.4% to lincomycin. Sensitivity to ciprofloxacin was detected in 85.7% of patients, in 14.3% - moderate resistance.

Use of antibacterial prophylaxis for patients with neutropenia. Australian Consensus Guidelines 2011 Steering Committee.

PubMed

Slavin, M A; Lingaratnam, S; Mileshkin, L; Booth, D L; Cain, M J; Ritchie, D S; Wei, A; Thursky, K A

2011-01-01

The use of oral prophylactic antibiotics in patients with neutropenia is controversial and not recommended by this group because of a lack of evidence showing a reduction in mortality and concerns that such practice promotes antimicrobial resistance. Recent evidence has demonstrated non-significant but consistent, improvement in all-cause mortality when fluoroquinolones (FQs) are used as primary prophylaxis. However, the consensus was that this evidence was not strong enough to recommend prophylaxis. The evidence base for FQ prophylaxis is presented alongside current consensus opinion to guide the appropriate and judicious use of these agents. Due consideration is given to patient risk, as it pertains to specific patient populations, as well as the net effect on selective pressure from antibiotics if FQ prophylaxis is routinely used in a target population. The potential costs and consequences of emerging FQ resistance, particularly among Escherichia coli, Clostridium difficile and Gram-positive organisms, are considered. As FQ prophylaxis has been advocated in some chemotherapy protocols, specific regard is given to whether FQ prophylaxis should be used to support these regimens. The group also provides recommendations for monitoring and surveillance of emerging resistance in those centres that have adopted FQ prophylaxis. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Similarities and Differences between Silver Ions and Silver in Nanoforms as Antibacterial Agents

PubMed Central

Kędziora, Anna; Speruda, Mateusz; Rybka, Jacek; Łukowiak, Anna; Bugla-Płoskońska, Gabriela

2018-01-01

Silver is considered as antibacterial agent with well-known mode of action and bacterial resistance against it is well described. The development of nanotechnology provided different methods for the modification of the chemical and physical structure of silver, which may increase its antibacterial potential. The physico-chemical properties of silver nanoparticles and their interaction with living cells differs substantially from those of silver ions. Moreover, the variety of the forms and characteristics of various silver nanoparticles are also responsible for differences in their antibacterial mode of action and probably bacterial mechanism of resistance. The paper discusses in details the aforementioned aspects of silver activity. PMID:29393866

Antibacterial activity in adhesive dentistry: a literature review.

PubMed

Shafiei, Fereshteh; Memarpour, Mahtab

2012-01-01

This literature review summarizes the published research regarding the antibacterial agents used in adhesive dentistry. This article provides information about the clinical applications, beneficial effects, and possible disadvantages of antibacterials when used in various bonding situations.

In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Zhang, Xin-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

2015-12-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays. The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments. ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25. ML and HL showed synergistic potentiation of antibacterial agents against clinical isolates of MRSA and warrant further pharmacological investigation.

Evaluation of the oxidation of enrofloxacin by permanganate and the antimicrobial activity of the products.

PubMed

Xu, Yongpeng; Liu, Shiyao; Guo, Fang; Zhang, Bo

2016-02-01

Permanganate [Mn(VII)] oxidation of the fluoroquinolone (FQ) antibiotic enrofloxacin (ENR) was investigated with respect to kinetics and mechanisms, and the products were evaluated for residual antibacterial activity. The degradation of ENR by Mn(VII) obeyed second-order kinetics. A modern liquid chromatography coupled to a hybrid quadrupole time-of-flight mass spectrometer (LC-Q-TOF) was used to determine the accurate mass of the measured degradation products. The structures of nine oxidation products were identified at a neutral pH, one of which was an N-oxide product formed from the oxidation of tertiary amines. One proposed plausible reaction pathway was that the oxidation occurred on the piperazine ring; the C-H adjacent to the amine group was attacked by Mn(VII). The identified products from ENR arose through four pathways involving two mechanisms of N-dealkylation, C-hydroxylation and the reactions of amine oxides. The quinolone core remained intact for all of the products. The residual antibacterial activity of the oxidative reaction byproducts against the nonresistant Escherichia coli (G(-)) reference strain DH5ɑ was evaluated by quantifying the bacterial colonies. The oxidation products exhibited reduced antibacterial activity compared with their parent compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

The biology of Mur ligases as an antibacterial target.

PubMed

Kouidmi, Imène; Levesque, Roger C; Paradis-Bleau, Catherine

2014-10-01

With antibiotic resistance mechanisms increasing in diversity and spreading among bacterial pathogens, the development of new classes of antibacterial agents against judiciously chosen targets is a high-priority task. The biochemical pathway for peptidoglycan biosynthesis is one of the best sources of antibacterial targets. Within this pathway are the Mur ligases, described in this review as highly suitable targets for the development of new classes of antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with the same catalytic mechanism and share conserved amino acid regions and structural features that can conceivably be exploited for the design of inhibitors that simultaneously target more than one enzyme. This would provide multi-target antibacterial weapons with minimized likelihood of target-mediated resistance development. © 2014 John Wiley & Sons Ltd.

[New antibacterial agents on the market and in the pipeline].

PubMed

Kern, W V

2015-11-01

After some years of stagnation there have been several new successful developments in the field of antibacterial agents. Most of these new developments have been in conventional antibacterial classes. New drugs among the beta-lactam agents are methicillin-resistant Staphylococcus aureus (MRSA) active cephalosporins (ceftaroline and ceftobiprole) and new combinations of beta-lactam with beta-lactamase inhibitors (ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam and meropenem/RPX7009). New developments can also be observed among oxazolidinones (tedizolid, radezolid, cadazolid and MRX-I), macrolides/ketolides (modithromycin and solithromycin), aminoglycosides (plazomicin), quinolones (nemonoxacin, delafloxacin and avarofloxacin), tetracyclines (omadacycline and eravacycline) as well as among glycopeptides and lipopeptides (oritavancin, telavancin, dalbavancin and surotomycin). New agents in a very early developmental phase are FabI inhibitors, endolysines, peptidomimetics, lipid A inhibitors, methionyl-tRNA synthetase inhibitors and teixobactin.

Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents

PubMed Central

Dewal, Mahender B.; Wani, Amit S.; Vidaillac, Celine; Oupicky, David; Rybak, Michael J.

2012-01-01

Several thieno[2,3-d]pyrimidinediones have been synthesized and examined for antibacterial activity against a range of Gram-positive and Gram-negative pathogens. Two compounds displayed potent activity (2–16 mg/L) against multi-drug resistant Gram-positive organisms, including methicillin, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) and vancomycin-resistant enterococci (VRE). Only one of these agents possessed moderate activity (16–32 mg/L) against Gram-negative strains. An examination of the cytotoxicity of these agents revealed that they displayed low toxicity (40–50 mg/L) against mammalian cell and very low hemolytic activity (2–7%). Taken together, these studies suggest that thieno[2,3-d]pyrimidinediones are interesting scaffolds for the development of novel Gram-positive antibacterial agents. PMID:22405289

In vitro killing of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin in combination with its active metabolite ciprofloxacin using clinically relevant drug concentrations in the dog and cat.

PubMed

Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J

2012-03-23

Enrofloxacin is a fluoroquinolone antibacterial agent used to treat infections in companion animals. Enrofloxacin's antimicrobial spectrum includes Gram positive and Gram-negative bacteria and demonstrates concentration-dependent bacteriocidal activity. In dogs and cats, enrofloxacin is partially metabolized to ciprofloxacin and both active agents circulate simultaneously in treated animals at ratios of approximately 60-70% enrofloxacin to 30-40% ciprofloxacin. We were interested in determining the killing of companion animal isolates of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin and ciprofloxacin combined using clinically relevant drug concentrations and ratios. For E. coli isolates exposed to 2.1 and 4.1μg/ml of enrofloxacin/ciprofloxacin at 50:50, 60:40 and 70:30 ratios, a 1.7-2.5log(10) reduction (94-99% kill) was seen following 20min of drug exposure; 0.89-1.7log(10) (92-99% kill) of S. pseudintermedius following 180min of drug exposure; 0.85-3.4log(10) (98-99% kill) of P. aeruginosa following 15min of drug exposure. Killing of S. pseudintermedius was enhanced in the presence of enrofloxacin whereas killing of P. aeruginosa was enhanced in the presence of ciprofloxacin. Antagonism was not seen when enrofloxacin and ciprofloxacin were used in kill assays. The unique feature of partial metabolism of enrofloxacin to ciprofloxacin expands the spectrum of enhanced killing of common companion animal pathogens. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparative in vitro susceptibilities and bactericidal activities of investigational fluoroquinolone ABT-492 and other antimicrobial agents against human mycoplasmas and ureaplasmas.

PubMed

Waites, Ken B; Crabb, Donna M; Duffy, Lynn B

2003-12-01

We determined in vitro susceptibilities for ABT-492 and other antimicrobials against Mycoplasma pneumoniae, Mycoplasma fermentans, Mycoplasma hominis, and Ureaplasma species. ABT-492 MICs were < or =1 microg/ml, and the agent was bactericidal against selected isolates of M. pneumoniae and M. hominis. ABT-492 has potential for treatment of infections due to these microorganisms.

Comparative In Vitro Susceptibilities and Bactericidal Activities of Investigational Fluoroquinolone ABT-492 and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas

PubMed Central

Waites, Ken B.; Crabb, Donna M.; Duffy, Lynn B.

2003-01-01

We determined in vitro susceptibilities for ABT-492 and other antimicrobials against Mycoplasma pneumoniae, Mycoplasma fermentans, Mycoplasma hominis, and Ureaplasma species. ABT-492 MICs were ≤1 μg/ml, and the agent was bactericidal against selected isolates of M. pneumoniae and M. hominis. ABT-492 has potential for treatment of infections due to these microorganisms. PMID:14638513

Recent Development of Benzimidazole-Containing Antibacterial Agents.

PubMed

Song, Di; Ma, Shutao

2016-04-05

Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. However, new antibacterial agents are currently being developed at a much slower pace than our growing need for such drugs. Given their diverse biological activities and clinical applications, many bioactive heterocyclic compounds containing a benzimidazole nucleus have been the focus of interest for many researchers. The benzimidazole nucleus is a structural isostere of naturally occurring nucleotides. This advantage allows benzimidazoles to readily interact with the various biopolymers found in living systems. In view of this situation, much attention has been given to the exploration of benzimidazole-based antibacterial agents, leading to the discovery of many new chemical entities with intriguing profiles. In this minireview we summarize novel benzimidazole derivatives active against various bacterial strains. In particular, we outline the relationship between the structures of variously modified benzimidazoles and their antibacterial activity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[The history of the development and changes of quinolone antibacterial agents].

PubMed

Takahashi, Hisashi; Hayakawa, Isao; Akimoto, Takeshi

2003-01-01

The quinolones, especially the new quinolones (the 6-fluoroquinolones), are the synthetic antibacterial agents to rival the Beta-lactam and the macrolide antibacterials for impact in clinical usage in the antibacterial therapeutic field. They have a broad antibacterial spectrum of activity against Gram-positive, Gram-negative and mycobacterial pathogens as well as anaerobes. Further, they show good-to-moderate oral absorption and tissue penetration with favorable pharmacokinetics in humans resulting in high clinical efficacy in the treatment of many kinds of infections. They also exhibit excellent safety profiles as well as those of oral Beta-lactam antibiotics. The bacterial effects of quinolones inhibit the function of bacterial DNA gyrase and topoisomerase IV. The history of the development of the quinolones originated from nalidixic acid (NA), developed in 1962. In addition, the breakthrough in the drug design for the scaffold and the basic side chains have allowed improvements to be made to the first new quinolone, norfloxacin (NFLX), patented in 1978. Although currently more than 10,000 compounds have been already synthesized in the world, only two percent of them were developed and tested in clinical studies. Furthermore, out of all these compounds, only twenty have been successfully launched into the market. In this paper, the history of the development and changes of the quinolones are described from the first quinolone, NA, via, the first new quinolone (6-fluorinated quinolone) NFLX, to the latest extended-spectrum quinolone antibacterial agents against multi-drug resistant bacterial infections. NA has only modest activity against Gram-negative bacteria and low oral absorption, therefore a suitable candidate for treatment of systemic infections (UTIs) is required. Since the original discovery of NA, a series of quinolones, which are referred to as the old quinolones, have been developed leading to the first new quinolone, NFLX, with moderate improvements in over all properties starting in 1962 through and continuing throughout the 1970's. Especially, the drug design for pipemidic acid (PPA) indicated one of the important breakthroughs that lead to NFLX. The introduction of a piperazinyl group, which ia a basic moiety at the C7-position of the quinolone nuclei, improved activity against Gram-negative organisms broadening the spectrum to include Pseudomonas aeruginosa. PPA also showed soem activity against Gram-positive bac teria. The basic piperazine ring, which can form the zwitterionic natrure with the carboxylic acid at the C3-position, has subsequently been shown to increase the ability of the drugs to penetrate the bacterial cells resulting in enhanced activity. Further, the zwitterionic forms resulted in significant tissue penetration in the pharmacokinetics. On the other hand, the first compound with a fluorine atom at the C6-position of the related quinolone scaffold was flumequine and the compound indicated that activity against Gram-positive bacteria could be improved in the old quinolones. The addition of a flourine atom at the C6-position is essential for the inhibition of target enzymes. The results show the poten antibacterial activity and the penetration of the quinolone molecule into the bacterial cells and human tissue. The real breakthrough came with the combination of these two features in NFLX, a 6-fluorinated quinolone having a piperazinyl group at the C7-position, NFLX features significant differences from the old quinolones in the activities and pharmacokinetics in humans, resulting in high clinical efficacy in the treatment of many kinds of infections including RTIs.Consequently, those great discoveries are rapidly superseded by even better compounds and NFLX proved to be just the beginning of a highly successful period of research into the modifications of the new quinolone antibacterials. Simce the chemical structure and important features of NFLX had become apparent in 1978, many compounds were patented in the next three years, several of which reached the market. Among the drugs, ofloxacin (OFLX) and ciprofloxacin (CPFX) are recognized as superior in several respects to the oral beta-lactam antibiotics as an antibacterial agent. With a focus on OFLX and CPFX, numerous research groups entered the antibacterial therapeutic field, triggering intense competition in the search to find newer, more effective quinolones. After NFLX was introduced in the market, while resulting by the end of today, eleven kinds of other new quinolones launched in Japan. They are enoxacin (ENX), OFLX, CPFX, lomefloxacin (LFLX), fleroxacin (FRLX), tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), gatifloxacin (GFLX), prulifloxacin (PULX) and also pazufloxacin (PZFX). The advantages of these compounds, e.g., LVFX, SPFX and GFLX, are that their spectrum includes Gram-positive bacteria species as well as Gram-negative bacteria and they improve bioavailability results when a daily dose is administered for systemic infections including RTIs. However, unexpected adverse reactions, such as the CNS reaction, the drug-drug interaction, phototoxicity, hepatotoxicity and cardiotoxicity such as the QTc interval prolongation of ECG, have been reported in the clinical evaluations or the post-marketing surveillance of several new quinolones. Moreover, the adverse reactions of arthropathy (the joint toxicity) predicated from studies in juvenile animals have never materialized in clinical use. Therefore, no drugs other than NFLX have yet been approved for pediatric use. Fortunately, the newer quinolones are being developed and tested to reduce these adverse reactions on the basis of recent studies. On the other hand, multi-drug resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphycolocci (MRCNS), penicillin-resistant Streptococcus pneumoniae (PRSP) and vancomycin-resistant enterococci (VRE) have been a serious problem in the medical community. Recently, the new quinolone antibacterials are highly successful class of antibacterial therapeutic field, however, the increased isolation of quinolone-resistant bacteria above them has become a normal outcome. These problems of multi-drug resistance have been the driving force for the development of newer quinolones. The next gereration of quinolone antibacterial agents will be potent against multi-drug resistant bacteria, such as MRSA, and provide a lower rate of emergence in resistance. Further, they should have favorable safety profiles to reduce the adverse reactions. The future of quinolones as the ultimate in pharmaceuticals must be handled cautiously if they are to realize their potential in the medical community.

Cost-effectiveness and Pricing of Antibacterial Drugs

PubMed Central

Verhoef, Talitha I; Morris, Stephen

2015-01-01

Growing resistance to antibacterial agents has increased the need for the development of new drugs to treat bacterial infections. Given increasing pressure on limited health budgets, it is important to study the cost-effectiveness of these drugs, as well as their safety and efficacy, to find out whether or not they provide value for money and should be reimbursed. In this article, we systematically reviewed 38 cost-effectiveness analyses of new antibacterial agents. Most studies showed the new antibacterial drugs were cost-effective compared to older generation drugs. Drug pricing is a complicated process, involving different stakeholders, and has a large influence on cost-effectiveness. Value-based pricing is a method to determine the price of a drug at which it can be cost-effective. It is currently unclear what the influence of value-based pricing will be on the prices of new antibacterial agents, but an important factor will be the definition of ‘value’, which as well as the impact of the drug on patient health might also include other factors such as wider social impact and the health impact of disease. PMID:25521641

Detection of antibacterial-like activity on a silica surface: fluoroquinolones and their environmental metabolites.

PubMed

Lewis, Gareth; Juhasz, Albert; Smith, Euan

2011-08-01

BACKGROUND, SCOPE, AND AIMS: Antibacterial fluoroquinolones (FQs) are third-generation antibiotics that are commonly used as therapeutic treatments of respiratory and urinary tract infections. They are used far less in intensively farmed animal production systems, though their use may be permitted in the veterinary treatments of flocks or in medicated feeds. When used, only a fraction of ingested parent FQ actually reaches the in vivo target site of infection, while the remainder is excreted as the parent FQ and its metabolized products. In many species' metabolism, enrofloxacin (EF) is converted into ciprofloxacin (CF) while both FQs are classified as parent FQs in human treatments. It is therefore likely that both FQs and their metabolic products will contribute to a common pool of metabolites in biological wastes. Wastes from intensive farming practices are either directly applied to agricultural land without treatment or may be temporarily stored prior to disposal. However, human waste is treated in sewage treatment plants (STPs) where it is converted into biosolids. In the storage or treatment process of STPs, FQs and their in vivo metabolites are further converted into other environmental metabolites (FQEMs) by ex vivo physicochemical processes that act and interact to produce complex mixtures of FQEMs, some of which have antibacterial-like activities. Biosolids are then often applied to agricultural land as a fertilizer amendment where FQs and FQEMs can be further converted into additional FQEMs by soil processes. It is therefore likely that FQ-contaminated biowaste-treated soils will contain complex mixtures of FQEMs, some of which may have antibacterial-like activities that may be expressed on bacteria endemic to the receiving agricultural soil environment. Concern has arisen in the scientific and in the general community that repeated use of FQ-contaminated biowaste as fertilizer amendments of nutrient-impoverished agricultural land may create a selective environment in which FQ-resistant bacteria might grow. The likelihood of this happening will depend, to some extent, on whether bioactive FQEMs are first synthesized from the parent FQs by the action and interaction of in vivo and ex vivo processes producing bioactive FQEMs in biowastes and biosolids. The postulated creation of a selective environment will also depend, in part, on whether such bioactive FQEMs are biologically available to bacteria, which may, in turn, be influenced by soil type, amendment regime, and the persistence of the bioactive FQEMs. Additionally, soil bacteria and soil processes may be affected in different ways or extents by bioactive FQEMs that could possibly act additively or synergistically at ecological targets in these non-target bacteria. This is an important consideration, since, while parent FQs have well-defined ecological targets (DNA gyrase and topoisomerase IV) and modes of bactericidal action, the FQEMs and their possible modes of action on the many different species of soil bacteria is less well studied. It is therefore understandable that there is a lack of conclusive evidence directly attributing biosolid usage to any increase in FQ-resistant bacteria detected in biowaste-amended agricultural soil. However, a lack of evidence may simply imply that a causal relationship between biosolid usage programs and any detection of low levels of FQ-resistant bacteria in soils has yet to be established, rather than an assumption of no relationship whatsoever. Based on results presented in this paper, the precautionary principle should be applied in the usage of FQ-contaminated biosolids as fertilizer amendments of agricultural land. The aim of this research was to test whether any bioactive FQEMs of EF could be synthesized by aerobic fermentation processes using Mycobacterium gilvum (American Tissue Culture Collection) and a mixed culture of microorganisms derived from an agricultural soil. High-performance thin-layer chromatography (HPTLC) and bioautography were tested as screening techniques in the detection and analysis of bioactive FQEMs. FQEMs derived from M. gilvum and mixed (soil) culture aerobic ferments were fractionated using preparative HPTLC. A standard strain of Escherichia coli was then used as the reporter organism in a bioautography assay in the detection of bioactive-FQEMs on a mid-section of the HPTLC plate. Plate sections were reassembled, and a photograph was taken under low-intensity ultraviolet (UV) light to reveal regions that contained analytes that had UV chromophores and antibacterial-like activities. Many fractionated FQEMs displayed antibacterial-like activity while bound to silica gel HPTLC plates. These results also provide evidence that sufficient quantities of biologically active FQEMs were biologically available from a silica gel surface to prevent the adherent growth of E. coli. Six to seven FQEMs derived from EF using aerobic fermentation processes had antibacterial-like activities, while two FQEMs were also detectable using UV light. Furthermore, similar banding patterns of antibacterial-like activity were observed in both the monoculture (M. gilvum) and mixed culture bioautography assays, indicating that similar processes operated in both aerobic fermentations, either producing similar biologically active FQEMs or biologically active FQEMs that had similar physicochemical properties in both ferments. The simplest explanation for these findings is that the tested agricultural soil also contained mycobacteria that metabolized EF in a similar way to the purchased standard monoculture M. gilvum. Additionally, the marked contrast between the bioautography results and the UV results indicated that the presence of UV chromophores is not a prerequisite for the detection of antibacterial-like activity. A reliance on spectrophotometric techniques in the detection of bioactive FQEMs in the environment may underestimate component antibacterial-like activity and, possibly, total antibacterial-like activity expressed by EF and its FQEMs. The described bioautography method provides a screening technique with which antibacterial-like activities derived from EF and possibly other FQs can be detected directly on silica gel HPTLC plates. It is recommended that both bioassay and instrumental analytical techniques be used in any measurement of hazard and risk relating to antibacterial-like activities in the environment that are derived from fluoroquinolone antibiotics and their environmental metabolites.

Application of cow milk-derived carbon dots/Ag NPs composite as the antibacterial agent

NASA Astrophysics Data System (ADS)

Han, Shuai; Zhang, He; Xie, Yujie; Liu, Liangliang; Shan, Changfu; Li, Xiangkai; Liu, Weisheng; Tang, Yu

2015-02-01

Cow milk-derived carbon dots (CMCDs) were prepared by hydrothermal treatment of cow milk, and the as-prepared CMCDs were further extracted by ethyl acetate to obtain amphiphilic CMCDs (ACMCDs). Using the ACMCDs both as a reducing agent and a template, the ACMCDs-supported silver nanoparticles (ACMCD-Ag nanocomposites) were prepared, which showed good biocidal effect on both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterias. After that, a novel ACMCD-Ag/polymethylmethacrylate nanocomposite antibacterial film was fabricated by solvent casting method. Due to the excellent antibacterial, light admitting, and flexible properties, the nanocomposite antibacterial film is considered to be of great potential in applications.

[Mutant prevention concentrations of antibacterial agents to ocular pathogenic bacteria].

PubMed

Liang, Qing-Feng; Wang, Zhi-Qun; Li, Ran; Luo, Shi-Yun; Deng, Shi-Jing; Sun, Xu-Guang

2009-01-01

To establish a method to measure mutant prevention concentration (MPC) in vitro, and to measure MPC of antibacterial agents for ocular bacteria caused keratitis. It was an experimental study. Forty strains of ocular bacteria were separated from cornea in Beijing Institute of Ophthalmology, which included 8 strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Pseudomonas aeruginosa and Klebsiella pneumoniae respectively. The minimal inhibitory concentration (MIC) of the levofloxacin (LVF), ofloxacin (OFL), ciprofloxacin (CIP), norfloxacin (NFL), tobramycin (TOB) and chloromycetin (CHL) were determined by agar dilution method from National Committee of Clinical Laboratory Standard (NCCLS). The MPC were measured by accumulate-bacterial methods with bacterial population inoculated more than 1.2 x 10(10) colony forming units per milliliter with Mueller-Hinton broth and tryptic soy agar plate. With the software of SPSS 11.0, the datum such as the range of MIC, MPC, MIC90 and MPC90 were calculated, and the selection index (MPC90/ MI90) and mutant selection window (MSW) were obtained. The MI90 of LVF and TOB (4 mg/L) to Staphylococcus aureus strains were the lowest. CIP showed the lowest MIC90 (0.25 mg/L) to Pseudomonas aeruginosa among six kinds of antibacterial agents. The MIC90 of LVF to Staphylococcus epidermidis (256 mg/L), Streptococcus pneumoniae (1 mg/L) and Klebsiella pneumoniae (0.25 mg/L) were lower than other antibacterial agents. The MPC90, MSW and the MPC90/MIC90 of levofloxacin showed lower values compared with other antibacterial medicines. From all the datum, the MIC90 of CHL was the highest and the activity was the weakest. Although the activity of LVF was higher to every kind of bacteria, CIP had the highest activity antibacterial to Pseudomonas aeruginosa. The capacity of CHL and TOB was weaker than Quinolones for restricting resistant mutants on ocular bacteria. LVF had the strongest capacity for restricting resistant mutants among Quinolones. LVF has better antibacterial effects and stronger capacity for restricting the selection of resistant mutants on ocular bacteria than other antibacterial agents.

Effect of salivary pellicle on antibacterial activity of novel antibacterial dental adhesives using a dental plaque microcosm biofilm model

PubMed Central

Li, Fang; Weir, Michael D.; Fouad, Ashraf F.; Xu, Hockin H.K.

2014-01-01

Objectives Antibacterial primer and adhesive are promising to inhibit biofilms and caries. Since restorations in vivo are exposed to saliva, one concern is the attenuation of antibacterial activity due to salivary pellicles. The objective of this study was to investigate the effects of salivary pellicles on bonding agents containing a new monomer dimethylaminododecyl methacrylate (DMADDM) or nanoparticles of silver (NAg) against biofilms for the first time. Methods DMADDM and NAg were synthesized and incorporated into Scotchbond Multi-Purpose adhesive and primer. Specimens were either coated or not coated with salivary pellicles. A microcosm biofilm model was used with mixed saliva from ten donors. Two types of culture medium were used: an artificial saliva medium (McBain), and Brain Heart Infusion (BHI) medium without salivary proteins. Metabolic activity, colony-forming units (CFU), and lactic acid production of plaque microcosm biofilms were measured (n = 6). Results Bonding agents containing DMADDM and NAg greatly inhibited biofilm activities, even with salivary pellicles. When using BHI, the pre-coating of salivary pellicles on resin surfaces significantly decreased the antibacterial effect (p < 0.05). When using artificial saliva medium, pre-coating of salivary pellicles on resin did not decrease the antibacterial effect. These results suggest that artificial saliva yielded medium-derived pellicles on resin surfaces, which provided attenuating effects on biofilms similar to salivary pellicles. Compared with the commercial control, the DMADDM-containing bonding agent reduced biofilm CFU by about two orders of magnitude. Significance Novel DMADDM- and NAg-containing bonding agents substantially reduced biofilm growth even with salivary pellicle coating on surfaces, indicating a promising usage in saliva-rich environment. DMADDM and NAg may be useful in a wide range of primers, adhesives and other restoratives to achieve antibacterial and anti-caries capabilities. PMID:24332270

Effect of salivary pellicle on antibacterial activity of novel antibacterial dental adhesives using a dental plaque microcosm biofilm model.

PubMed

Li, Fang; Weir, Michael D; Fouad, Ashraf F; Xu, Hockin H K

2014-02-01

Antibacterial primer and adhesive are promising to inhibit biofilms and caries. Since restorations in vivo are exposed to saliva, one concern is the attenuation of antibacterial activity due to salivary pellicles. The objective of this study was to investigate the effects of salivary pellicles on bonding agents containing a new monomer dimethylaminododecyl methacrylate (DMADDM) or nanoparticles of silver (NAg) against biofilms for the first time. DMADDM and NAg were synthesized and incorporated into Scotchbond Multi-Purpose adhesive and primer. Specimens were either coated or not coated with salivary pellicles. A microcosm biofilm model was used with mixed saliva from ten donors. Two types of culture medium were used: an artificial saliva medium (McBain), and Brain Heart Infusion (BHI) medium without salivary proteins. Metabolic activity, colony-forming units (CFU), and lactic acid production of plaque microcosm biofilms were measured (n=6). Bonding agents containing DMADDM and NAg greatly inhibited biofilm activities, even with salivary pellicles. When using BHI, the pre-coating of salivary pellicles on resin surfaces significantly decreased the antibacterial effect (p<0.05). When using artificial saliva medium, pre-coating of salivary pellicles on resin did not decrease the antibacterial effect. These results suggest that artificial saliva yielded medium-derived pellicles on resin surfaces, which provided attenuating effects on biofilms similar to salivary pellicles. Compared with the commercial control, the DMADDM-containing bonding agent reduced biofilm CFU by about two orders of magnitude. Novel DMADDM- and NAg-containing bonding agents substantially reduced biofilm growth even with salivary pellicle coating on surfaces, indicating a promising usage in saliva-rich environment. DMADDM and NAg may be useful in a wide range of primers, adhesives and other restoratives to achieve antibacterial and anti-caries capabilities. Published by Elsevier Ltd.

Preparation and characterization of silver chloride nanoparticles as an antibacterial agent

NASA Astrophysics Data System (ADS)

Duong Trinh, Ngoc; Thanh Binh Nguyen, Thi; Hai Nguyen, Thanh

2015-12-01

Silver chloride nanoparticles were prepared by the precipitation reaction between silver nitrate and sodium chloride in an aqueous solution containing poly(vinyl alcohol) as a stabilizing agent. Different characteristics of the nanoparticles in suspension and in lyophilized powder such as size, morphology, chemical nature, interaction with stabilizing agent and photo-stability were investigated. Biological tests showed that the obtained silver chloride nanoparticles displayed antibacterial activities against Escherichia coli and Staphylococcus aureus.

Antimicrobial resistance mechanisms among Campylobacter.

PubMed

Wieczorek, Kinga; Osek, Jacek

2013-01-01

Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

In vitro selection of resistance in Escherichia coli and Klebsiella spp. at in vivo fluoroquinolone concentrations

PubMed Central

2010-01-01

Background Fluoroquinolones are potent antimicrobial agents used for the treatment of a wide variety of community- and nosocomial- infections. However, resistance to fluoroquinolones in Enterobacteriaceae is increasingly reported. Studies assessing the ability of fluoroquinolones to select for resistance have often used antimicrobial concentrations quite different from those actually acquired at the site of infection. The present study compared the ability to select for resistance of levofloxacin, ciprofloxacin and prulifloxacin at concentrations observed in vivo in twenty strains of Escherichia coli and Klebsiella spp. isolated from patients with respiratory and urinary infections. The frequencies of spontaneous single-step mutations at plasma peak and trough antibiotic concentrations were calculated. Multi-step selection of resistance was evaluated by performing 10 serial cultures on agar plates containing a linear gradient from trough to peak antimicrobial concentrations, followed by 10 subcultures on antibiotic-free agar. E. coli resistant strains selected after multi-step selection were characterized for DNA mutations by sequencing gyrA, gyrB, parC and parE genes. Results Frequencies of mutations for levofloxacin and ciprofloxacin were less than 10-11 at peak concentration, while for prulifloxacin they ranged from <10-11 to 10-5. The lowest number of resistant mutants after multistep selection was selected by levofloxacin followed by ciprofloxacin and prulifloxacin. Both ciprofloxacin- and prulifloxacin-resistant mutants presented mutations in gyrA and parC, while levofloxacin resistance was found associated only to mutations in gyrA. Conclusions Among the tested fluoroquinolones, levofloxacin was the most capable of limiting the occurrence of resistance. PMID:20409341

Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents.

PubMed

Park, Seong-Cheol; Kim, Nam-Hong; Yang, Wonseok; Nah, Jae-Woon; Jang, Mi-Kyeong; Lee, Dongwon

2016-01-10

Reactive oxygen species (ROS) produced by host phagocytes exert antibacterial action against a variety of pathogens and ROS-induced oxidative stress is the governing mechanism for the antibacterial activity of major bactericidal antibiotics. In particular, hydroxyl radical is a strong and nonselective oxidant which can damage biomolecules such as DNA, proteins and lipids. Ferrous ion is known to convert mild oxidant hydrogen peroxide (H2O2) into highly reactive and toxic hydroxyl radicals, referred to as Fenton reaction. Herein, we report a new class of antibacterial agents based on Fenton reaction-performing nanostructures, composed of H2O2-generating polymer (PCAE) and iron-containing ferrocene. Amphiphilic PCAE was designed to incorporate H2O2-generating cinnamaldehyde through acid-cleavable linkages and self-assemble to form thermodynamically stable micelles which could encapsulate ferrocene in their hydrophobic core. All the experiments in vitro display that ferrocene-loaded PCAE micelles produce hydroxyl radicals to kill Escherichia coli and Pseudomonas aeruginosa through membrane damages. Intraperitoneally injected ferrocene-loaded PCAE micelles significantly reduced the lung damages and therefore increased the survival rate of mice infected with drug resistant P. aeruginosa. Given their potent antibacterial activity, ferrocene-loaded PCAE micelles hold great potential as a new class of ROS-manipulating antibacterial agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Enzyme-coated mesoporous silica nanoparticles as efficient antibacterial agents in vivo.

PubMed

Li, Li-Li; Wang, Hao

2013-10-01

Despite the fact that pathogenic infections are widely treated by antibiotics in the clinic nowadays, the increasing risk of multidrug-resistance associated with abuse of antibiotics is becoming a major concern in global public health. The increased death toll caused by pathogenic bacterial infection calls for effective antibiotic alternatives. Lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys) are reported as antibacterial agents that exhibit efficient antibacterial activity both in vitro and in vivo with low cytotoxicity and negligible hemolytic side effect. The Lys corona provides multivalent interaction between MSNs⊂Lys and bacterial walls and consequently raises the local concentration of Lys on the surface of cell walls, which promotes hydrolysis of peptidoglycans and increases membrane-perturbation abilities. The minimal inhibition concentration (MIC) of MSNs⊂Lys is fivefold lower than that of free Lys in vitro. The antibacterial efficacy of MSNs⊂Lys is evaluated in vivo by using an intestine-infected mouse model. Experimental results indicate that the number of bacteria surviving in the colon is three orders of magnitude lower than in the untreated group. These natural antibacterial enzyme-modified nanoparticles open up a new avenue for design and synthesis of next-generation antibacterial agents as alternatives to antibiotics. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibacterial activities of tellurium nanomaterials.

PubMed

Lin, Zong-Hong; Lee, Chia-Hsin; Chang, Hsin-Yun; Chang, Huan-Tsung

2012-05-01

We prepared four differently shaped Te nanomaterials (NMs) as antibacterial reagents against Escherichia coli. By controlling the concentrations of hydrazine (N(2)H(4)) as reducing agent, NaCl, and temperature, we prepared Te nanowires, nanopencils, nanorices, and nanocubes. These four Te NMs resulted in a live/dead ratio of E. coli cells of less than 0.1, which is smaller than that of Ag nanoparticles. The order of antibacterial activity against E. coli is nanocubes ≈ nanorices > nanopencils ≈ nanowires. This is in good agreement with the concentration order of tellurite (TeO(3)(2-)) ions released from Te NMs in E. coli cells, revealing that TeO(3)(2-) ions account for the antibacterial activity of the four Te NMs. We found that spherical Te nanoparticles (32 nm in diameter) with TeO(3)(2-) ions were formed in the E. coli cells. Compared to Ag nanoparticles that are commonly used as antibacterial reagents, Te NMs have higher antibacterial activity and lower toxicity. Thus, Te NMs hold great practical potential as a new and efficient antibacterial agent. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fabrication of Te and Te-Au Nanowires-Based Carbon Fiber Fabrics for Antibacterial Applications

PubMed Central

Chou, Ting-Mao; Ke, Yi-Yun; Tsao, Yu-Hsiang; Li, Ying-Chun; Lin, Zong-Hong

2016-01-01

Pathogenic bacteria that give rise to diseases every year remain a major health concern. In recent years, tellurium-based nanomaterials have been approved as new and efficient antibacterial agents. In this paper, we developed the approach to directly grow tellurium nanowires (Te NWs) onto commercial carbon fiber fabrics and demonstrated their antibacterial activity. Those Te NWs can serve as templates and reducing agents for gold nanoparticles (Au NPs) to deposit. Three different Te-Au NWs with varied concentration of Au NPs were synthesized and showed superior antibacterial activity and biocompability. These results indicate that the as-prepared carbon fiber fabrics with Te and Te-Au NWs can become antimicrobial clothing products in the near future. PMID:26861380

Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis.

PubMed

Borrero, Nicholas V; Bai, Fang; Perez, Cristian; Duong, Benjamin Q; Rocca, James R; Jin, Shouguang; Huigens, Robert W

2014-02-14

Nearly all clinically used antibiotics have been (1) discovered from microorganisms (2) using phenotype screens to identify inhibitors of bacterial growth. The effectiveness of these antibiotics is attributed to their endogenous roles as bacterial warfare agents against competing microorganisms. Unfortunately, every class of clinically used antibiotic has been met with drug resistant bacteria. In fact, the emergence of resistant bacterial infections coupled to the dismal pipeline of new antibacterial agents has resulted in a global health care crisis. There is an urgent need for innovative antibacterial strategies and treatment options to effectively combat drug resistant bacterial pathogens. Here, we describe the implementation of a Pseudomonas competition strategy, using redox-active phenazines, to identify novel antibacterial leads against Staphylococcus aureus and Staphylococcus epidermidis. In this report, we describe the chemical synthesis and evaluation of a diverse 27-membered phenazine library. Using this microbial warfare inspired approach, we have identified several bromophenazines with potent antibacterial activities against S. aureus and S. epidermidis. The most potent bromophenazine analogue from this focused library demonstrated a minimum inhibitory concentration (MIC) of 0.78-1.56 μM, or 0.31-0.62 μg mL(-1), against S. aureus and S. epidermidis and proved to be 32- to 64-fold more potent than the phenazine antibiotic pyocyanin in head-to-head MIC experiments. In addition to the discovery of potent antibacterial agents against S. aureus and S. epidermidis, we also report a detailed structure-activity relationship for this class of bromophenazine small molecules.

New Paradigm Shift for the Green Synthesis of Antibacterial Silver Nanoparticles Utilizing Plant Extracts

PubMed Central

2014-01-01

This review covers general information regarding the green synthesis of antibacterial silver nanoparticles. Owing to their antibacterial properties, silver nanoparticles are widely used in many areas, especially biomedical applications. In green synthesis practices, the chemical reducing agents are eliminated, and biological entities are utilized to convert silver ions to silver nanoparticles. Among the various biological entities, natural plant extracts have emerged as green reducing agents, providing eco-friendly routes for the preparation of silver nanomaterials. The most obvious merits of green synthesis are the increased biocompatibility of the resulting silver nanoparticles and the ease with which the reaction can be carried out. This review summarizes some of the plant extracts that are used to produce antibacterial silver nanoparticles. Additionally, background information regarding the green synthesis and antibacterial activity of silver nanoparticles is provided. Finally, the toxicological aspects of silver nanoparticles are briefly mentioned. PMID:25343010

Addition of doxycycline to ciprofloxacin for infection prophylaxis during autologous stem cell transplants for multiple myeloma.

PubMed

Sivik, J M; Davidson, J; Hale, C M; Drabick, J J; Talamo, G

2018-03-21

The most commonly used antibacterial prophylaxis during autologous stem cell transplants (ASCT) for multiple myeloma (MM) involves a fluoroquinolone, such as ciprofloxacin or levofloxacin. We assessed the impact of adding doxycycline to ciprofloxacin as routine antibacterial prophylaxis in these patients. We retrospectively reviewed electronic medical records and our ASCT database to analyze rates and types of bacterial infections in MM patients who underwent ASCT in our institution. Among 419 patients, 118 received ciprofloxacin alone (cipro group), and 301 ciprofloxacin and doxycycline (cipro-doxy group). Neutropenic fever (NF) developed in 63 (53%) and 108 (36%) patients of the cipro and cipro-doxy groups, respectively (p = 0.010). The number of documented bacteremic episodes was 13 (11%) and 14 (4.7%) in the two groups, respectively (p = 0.017). Antimicrobial resistance and Clostridium difficile infections were uncommon. Transplant-related mortality was 1% in both groups. The addition of doxycycline to standard prophylaxis with ciprofloxacin seems to reduce the number of NF episodes and documented bacterial infections in patients with MM undergoing ASCT, without increasing rate of serious complications.

Development of Novel Antibiotics for the Treatment of Acinetobacter and Related Pathogens

DTIC Science & Technology

2012-07-07

1 was determined against liquid culture of each bacterial strain as recommended by the CLSI guidelines.අ Figure 1. Antibacterial activity of ABTZ...to enhance antibacterial activity were incorporated into compounds 28 and 29, and those known to attenuate antibacterial activity were incorporated ...Project objectives Our objectives were to identify novel antibacterial agents and strategies for the treatment of problematic bacterial pathogens

Antibacterial efficiency of the Sudanese Roselle (Hibiscus sabdariffa L.), a famous beverage from Sudanese folk medicine.

PubMed

Abdallah, Emad Mohamed

2016-01-01

Hibiscus sabdariffa L. is a plant native to tropical Africa and intensively cultivated in Sudan. Its calyces are widely consumed with many uses in Sudanese folk medicine. The dried calyces of H. sabdariffa were subjected to soak in 80% v/v methanol to get the methanolic extract, which was tested against five Gram-negative and three Gram-positive referenced bacterial strains using disc diffusion method. Selected bioactive phytochemical compounds were also investigated using qualitative methods. The results of the antibacterial test indicate that the methanol extract of H. sabdariffa calyces contained effective antibacterial agent(s), revealed a considerable zone of inhibition against all tested Gram-negative and Gram-positive bacteria, and it was a competitor to gentamicin and greatly higher than penicillin which showed weak or no effect. The results of current investigation support the folk medicine application of this plant against different microbial ailments and suggest it as a promising source for new antibacterial agents.

Antibacterial efficiency of the Sudanese Roselle (Hibiscus sabdariffa L.), a famous beverage from Sudanese folk medicine

PubMed Central

Abdallah, Emad Mohamed

2016-01-01

Background: Hibiscus sabdariffa L. is a plant native to tropical Africa and intensively cultivated in Sudan. Its calyces are widely consumed with many uses in Sudanese folk medicine. Materials and Methods: The dried calyces of H. sabdariffa were subjected to soak in 80% v/v methanol to get the methanolic extract, which was tested against five Gram-negative and three Gram-positive referenced bacterial strains using disc diffusion method. Selected bioactive phytochemical compounds were also investigated using qualitative methods. Results: The results of the antibacterial test indicate that the methanol extract of H. sabdariffa calyces contained effective antibacterial agent(s), revealed a considerable zone of inhibition against all tested Gram-negative and Gram-positive bacteria, and it was a competitor to gentamicin and greatly higher than penicillin which showed weak or no effect. Conclusion: The results of current investigation support the folk medicine application of this plant against different microbial ailments and suggest it as a promising source for new antibacterial agents. PMID:27104041

Axinellamines as Broad-Spectrum Antibacterial Agents: Scalable Synthesis and Biology

PubMed Central

2015-01-01

Antibiotic-resistant bacteria present an ongoing challenge to both chemists and biologists as they seek novel compounds and modes of action to out-maneuver continually evolving resistance pathways, especially against Gram-negative strains. The dimeric pyrrole–imidazole alkaloids represent a unique marine natural product class with diverse primary biological activity and chemical architecture. This full account traces the strategy used to develop a second-generation route to key spirocycle 9, culminating in a practical synthesis of the axinellamines and enabling their discovery as broad-spectrum antibacterial agents, with promising activity against both Gram-positive and Gram-negative bacteria. While their detailed mode of antibacterial action remains unclear, the axinellamines appear to cause secondary membrane destabilization and impart an aberrant cellular morphology consistent with the inhibition of normal septum formation. This study serves as a rare example of a natural product initially reported to be devoid of biological activity surfacing as an active antibacterial agent with an intriguing mode of action. PMID:25328977

Cost-effectiveness and pricing of antibacterial drugs.

PubMed

Verhoef, Talitha I; Morris, Stephen

2015-01-01

Growing resistance to antibacterial agents has increased the need for the development of new drugs to treat bacterial infections. Given increasing pressure on limited health budgets, it is important to study the cost-effectiveness of these drugs, as well as their safety and efficacy, to find out whether or not they provide value for money and should be reimbursed. In this article, we systematically reviewed 38 cost-effectiveness analyses of new antibacterial agents. Most studies showed the new antibacterial drugs were cost-effective compared to older generation drugs. Drug pricing is a complicated process, involving different stakeholders, and has a large influence on cost-effectiveness. Value-based pricing is a method to determine the price of a drug at which it can be cost-effective. It is currently unclear what the influence of value-based pricing will be on the prices of new antibacterial agents, but an important factor will be the definition of 'value', which as well as the impact of the drug on patient health might also include other factors such as wider social impact and the health impact of disease. © 2015 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

Bismuth subsalicylate nanoparticles with anaerobic antibacterial activity for dental applications

NASA Astrophysics Data System (ADS)

Vega-Jiménez, A. L.; Almaguer-Flores, A.; Flores-Castañeda, M.; Camps, E.; Uribe-Ramírez, M.; Aztatzi-Aguilar, O. G.; De Vizcaya-Ruiz, A.

2017-10-01

In recent years, nanomaterials have been used in the medical-dental field as new alternative antimicrobial agents. Bismuth subsalicylate (BSS) has been used as an antimicrobial agent, but the effect of BSS in the form of nanoparticles (BSS-nano) as a potential antimicrobial agent has not been tested, in specific against bacteria responsible for periodontal disease. The aim of this study was to evaluate the antibacterial effect of BSS-nano against oral anaerobic bacteria and to assess the safety of BSS-nano by evaluating their cytotoxicity in human gingival fibroblast (HGF-1) cells. BSS-nano were synthesized by laser ablation and were previously physico-chemically characterized using in vitro assays. The antibacterial activity was measured using the tetrazolium-based XTT assay, and cytotoxicity was determined using lactate dehydrogenase (LDH) and MTS assays in HGF-1 cells. Transmission electron microscopy of HGF-1 exposed to BSS-nano was also performed. BSS-nano was shown to have a primary size of 4-22 nm and a polygonal shape. Among the tested bacterial strains, those with a greater sensitivity to BSS-nano (highest concentration of 21.7 μg ml-1) were A. actinomycetemcomitans, C. gingivalis, and P. gingivalis. BSS-nano at a concentration of 60 μg ml-1 showed low cytotoxicity (6%) in HFG-1 cells and was mainly localized intracellularly in acidic vesicles. Our results indicate that the concentration of BSS-nano used as an effective antibacterial agent does not induce cytotoxicity in mammalian cells; thus, BSS-nano can be applied as an antibacterial agent in dental materials or antiseptic solutions.

Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant Gram-negative bacteria.

PubMed

Jouda, Jean-Bosco; Tamokou, Jean-de-Dieu; Mbazoa, Céline Djama; Sarkar, Prodipta; Bag, Prasanta Kumar; Wandji, Jean

2016-09-01

The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., an endophytic fungus associated with leaves of Garcinia nobilis. The culture filtrate from the fermentation of Penicillium sp. was extracted and analyzed by liquid chromatography-mass spectrometry, and the major metabolites were isolated and identified by spectroscopic analyses and by comparison with published data. The antibacterial activity of the compounds was assessed by broth microdilution method while the anticancer activity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The fractionation of the crude extract afforded penialidin A-C (1-3), citromycetin (4), p-hydroxyphenylglyoxalaldoxime (5) and brefelfin A (6). All of the compounds tested here showed antibacterial activity (MIC = 0.50 - 128 µg/mL) against Gramnegative multi-drug resistance bacteria, Vibrio cholerae (causative agent of dreadful disease cholera) and Shigella flexneri (causative agent of shigellosis), as well as the significant anticancer activity (LC 50 = 0.88 - 9.21 µg/mL) against HeLa cells. The results obtained indicate that compounds 1-6 showed good antibacterial and anticancer activities with no toxicity to human red blood cells and normal Vero cells.

[The participation of the transport-barrier functions of the plasma membrane in the development of fluoroquinolone (ciprofloxacin) resistance in Acholeplasma laidlawii].

PubMed

Abramycheva, N Iu; Govorun, V M

2000-01-01

The role of transport activity of Acholeplasma laidlawii plasmatic membrane in the development of resistance to ciprofloxacin was investigated. It was shown that ethidium bromide used as fluoroquinolone analogue in plasmatic membrane efflux pump was accumulated in ciprofloxacin-resistant cells in much less amount. It was estimated that ethidium bromide efflux depended on temperature, glucose and transmembrane electro-chemical proton potential. Inhibitors of efflux systems--reserpine and verapamil enhanced the ethidium bromide accumulation much more intensively in ciprofloxacin resistant cells. The results of investigation allowed to consider the existence of active efflux system for toxic agents in acholeplasma; in the case of ciprofloxacin-resistant strain these systems are inducible.

Interaction of Silver Nanoparticles with Serum Proteins Affects Their Antimicrobial Activity In Vivo

PubMed Central

Gnanadhas, Divya Prakash; Ben Thomas, Midhun; Thomas, Rony; Raichur, Ashok M.

2013-01-01

The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes. PMID:23877702

Topological pattern for the search of new active drugs against methicillin resistant Staphylococcus aureus.

PubMed

Bueso-Bordils, Jose I; Perez-Gracia, Maria T; Suay-Garcia, Beatriz; Duart, Maria J; Martin Algarra, Rafael V; Lahuerta Zamora, Luis; Anton-Fos, Gerardo M; Aleman Lopez, Pedro A

2017-09-29

Molecular topology was used to develop a mathematical model capable of classifying compounds according to antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA). Topological indices were used as structural descriptors and their relation to antimicrobial activity was determined by using linear discriminant analysis. This topological model establishes new structure activity relationships which show that the presence of cyclopropyl, chlorine and ramification pairs at a distance of two bonds favor this activity, while the presence of tertiary amines decreases it. This model was applied to a combinatorial library of a thousand and one 6-fluoroquinolones, from which 117 theoretical active molecules were obtained. The compound 10 and five new quinolones were tested against MRSA. They all showed some activity against MRSA, although compounds 6, 8 and 9 showed anti-MRSA activity similar to ciprofloxacin. This model was also applied to 263 theoretical antibacterial agents described by us in a previous work, from which 34 were predicted as theoretically active. Anti-MRSA activity was found bibliographically in 9 of them (ensuring at least 26% of success), and from the rest, 3 compounds were randomly chosen and tested, finding mitomycin C to be more active than ciprofloxacin. The results demonstrate the utility of the molecular topology approaches for identifying new drugs active against MRSA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of photodegradation, phototoxicity and photogenotoxicity of ofloxacin in ointments with sunscreens and in solutions.

PubMed

Zgadzaj, Anna; Skrzypczak, Agata; Welenc, Ilona; Ługowska, Agnieszka; Parzonko, Andrzej; Siedlecka, Ewa; Sommer, Sylwester; Sikorska, Katarzyna; Nałęcz-Jawecki, Grzegorz

2015-03-01

Fluoroquinolones are widely used anti-bacterial agents that are known to exhibit moderate to severe phototoxicity. Furthermore some of them reveal photogenotoxicity under UV irradiation. Incidence of side effects due to light exposure may be augmented, if the medicament is used topically. The main goal of this work was to compare the extent of photodegradation of ofloxacin in ointments with various excipients: hydrated or non-hydrated base and the addition of sunscreens: bisoctrizole (Tinosorb M) and bemotrizinol (Tinosorb S). The next goal of present work was the analysis of phototoxicity and photogenotoxicity of ofloxacin photodegradation products in tested ointments and in solutions with the umu-test, the test of mitotic gene conversion with Saccharomyces cerevisiae D7 and the micronucleus assay with V79 Chinese hamster cell line. At the same time an attempt was made to determinate the photodegradation products of ofloxacin in different unguents variants. We observed a significant photoprotective effect in ointment with Tinosorb M. We did not evaluated relevant differences regarding the genotoxicity and toxicity of unguents. However, the pre-irradiated ofloxacin solutions in comparison to samples stored in the dark were significantly more genotoxic to bacteria, slightly increased the number of micronuclei in V79 cell line and were toxic to the yeast strain. Copyright © 2015 Elsevier B.V. All rights reserved.

Microbiological etiology and susceptibility of bacterial conjunctivitis isolates from clinical trials with ophthalmic, twice-daily besifloxacin.

PubMed

Haas, Wolfgang; Gearinger, Lynne S; Hesje, Christine K; Sanfilippo, Christine M; Morris, Timothy W

2012-05-01

Bacterial conjunctivitis is a contagious infection of the surface of the eye usually treated empirically with topical antibiotics. Since the etiologic agent is rarely identified, it is important to monitor which bacteria cause conjunctivitis and determine their antibacterial resistance profiles. A total of 496 bacterial samples were isolated during a randomized, double-masked, vehicle-controlled, parallel-group study conducted in the United States with besifloxacin ophthalmic suspension 0.6% dosed twice daily. Species were determined by standard biochemical and/or molecular identification methods. Minimum inhibitory concentrations were determined according to Clinical and Laboratory Standards Institute standards. The most prevalent species was Haemophilus influenzae, followed by Staphylococcus epidermidis, Staphylococcus aureus, the Streptococcus mitis group, and Streptococcus pneumoniae. One species identified in this study, which was not previously noted as a common cause of bacterial conjunctivitis, was Dolosigranulum pigrum. Ampicillin resistance was common among H. influenzae isolates, while macrolide resistance was high among S. pneumoniae, S. epidermidis, and S. aureus. The latter two species also included a number of isolates resistant to methicillin and ciprofloxacin. Antibiotic resistance among isolates remains a concern and the appearance of an emerging ocular pathogen, D. pigrum, suggests the need for continued observation. The topical ophthalmic fluoroquinolones continue to provide a good balance of low to moderate (i.e., manageable) levels of resistance plus broad-spectrum coverage for empiric treatment of ocular infections.

The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride.

PubMed

Tsai, Tzu-Yun; Chen, Ta-Ching; Wang, I-Jong; Yeh, Chao-Yuan; Su, Ming-Jai; Chen, Ruey-Hua; Tsai, Tzu-Hsun; Hu, Fung-Rong

2015-02-10

Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX. Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515). Another commonly used FQ, levofloxacin (LEV), and the most commonly used preservatives, benzalkonium chloride (BAC), were also used for comparison with MOX. Cell viability and morphologic changes after treatment were evaluated with trypan blue exclusion assay, propidium iodine/annexin V-FITC staining, and flow cytometry. Chemiluminescence immunoassay was used for ROS quantification. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, wound healing assay, and intracellular detections of oxidative stress were performed to evaluate the effects of resveratrol. The MOX group, similar to the BAC group, showed significant cell shrinkage and death compared with the LEV group. High ROS production in HCECs of MOX group was observed both by chemiluminescence immunoassay and intracellular images. Within the observations of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, live cell images, and wound healing process in vitro, the cytotoxic effects of the MOX and BAC groups were opposed by resveratrol. Human corneal epithelial cells pretreated with resveratrol demonstrated better cell viability and healing rate in the early stage. The protective effects of antioxidant agents indicate that MOX, similar to BAC, causes oxidative stress-related cell damage. The results also inspired us to think about a "supplementary regimen" to increase safety and decrease the adverse effect in the treatment of corneal infections. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Small Peptides Derived from Penetratin as Antibacterial Agents.

PubMed

Parravicini, Oscar; Somlai, Csaba; Andujar, Sebastián A; Garro, Adriana D; Lima, Beatriz; Tapia, Alejandro; Feresin, Gabriela; Perczel, Andras; Tóth, Gabor; Cascales, Javier López; Rodríguez, Ana M; Enriz, Ricardo D

2016-04-01

The synthesis, in vitro evaluation and conformational study of several small-size peptides acting as antibacterial agents are reported. Among the compounds evaluated, the peptides Arg-Gln-Ile-Lys-Ile-Trp-Arg-Arg-Met-Lys-Trp-Lys-Lys-NH2 , Arg-Gln-Ile-Lys-Ile-Arg-Arg-Met-Lys-Trp-Arg-NH2 , and Arg-Gln-Ile-Trp-Trp-Trp-Trp-Gln-Arg-NH2 exhibited significant antibacterial activity. These were found to be very active antibacterial compounds, considering their small molecular size. In order to better understand the antibacterial activity obtained for these peptides, an exhaustive conformational analysis was performed, using both theoretical calculations and experimental measurements. Molecular dynamics simulations using two different media (water and trifluoroethanol/water) were employed. The results of these theoretical calculations were corroborated by experimental circular dichroism measurements. A brief discussion on the possible mechanism of action of these peptides at molecular level is also presented. Some of the peptides reported here constitute very interesting structures to be used as starting compounds for the design of new small-size peptides possessing antibacterial activity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Cefazolin efficacy and antibiotic sensitivity against pathogenic bacteria in pediatric with acute upper urinary tract infection].

PubMed

Fuke, Toshiya; Abe, Yoshifusa; Hoshino, Akihiro; Oto, Hideyasu; Sakai, Naho; Murayama, Junichiro; Yoshida, Koichiro; Itabashi, Kazuo

2010-05-01

Acute upper urinary tract infection may cause sepsis, especially in neonates and infants, mandating the choice of appropriate, effective antibacterials minimizing increasing bacterial resistance. Frequently prescribing broad-spectrum cephalosporinin is one such example. Different antibacterial therapies are initiated clinically due to treatment protocol differences among institutions, disease severity, etc. We studied the efficacy of cefazolin (CEZ), a first-generation cephalosporin, as first-line parenteral treatment in acute upper urinary tract infection. We found that 88.9% of microbial infections have indications for CEZ. CEZ efficacy is 91.3%, and 97.2% of urine cultures show negative results. Escherichia coli sensitivity to antibacterial agents is 90.9% of the minimal inhibitory concentration (MIC) < 4 for CEZ, 93.9% of MIC < 1 for ceftazidime (CAZ), 63.6% of MIC < 4 for ampicillin, and 81.8% of MIC < 2 for gentamicin. CEZ thus has the same efficacy as CAZ and is more effective than other antibacterial agents against E. coli. We concluded that CEZ is an effective antibacterial in initial antibacterial pediatric therapy in acute upper urinary tract infection.

Preparing high-adhesion silver coating on APTMS modified polyethylene with excellent anti-bacterial performance

NASA Astrophysics Data System (ADS)

Li, Wenfei; Chen, Yunxiang; Wu, Song; Zhang, Jian; Wang, Hao; Zeng, Dawen; Xie, Changsheng

2018-04-01

Silver coating as a broad-spectrum antimicrobial agent was considered to alleviate the inflammation caused by intrauterine device (IUD) in endometrium. In this work, to avoid the damage of silver coating and ensure its antibacterial properties, 3-aminopropyltrimethoxysilane (APTMS) was introduced to modify the polyethylene (PE) substrate for the purpose of improving the adhesion of the silver coating. From the 90° peel test, it could be found that the adhesive strength of silver coating on the APTMS modified PE substrate was nearly 23 times stronger than the silver coating on substrate without surface modification. The dramatically enhanced adhesive strength could be attributed to the formation of continuous chemical bonds between the silver coatings and substrates after surface modification, which had been confirmed by the XPS. Moreover, the standard antibacterial test revealed that the silver coated samples against Staphylococcus aureus (S. aureus) exhibit excellent antibacterial efficacy. Considering the largely enhanced adhesion and the effective antibacterial property, it is reasonable to believe that the silver coating could be considered as a potential candidate for the antibacterial agent in IUD.

Deciphering the complexation process of a fluoroquinolone antibiotic, levofloxacin, with bovine serum albumin in the presence of additives

NASA Astrophysics Data System (ADS)

Kaur, Amandeep; Khan, Imran Ahmd; Banipal, Parampaul Kaur; Banipal, Tarlok Singh

2018-02-01

The current work aims to explore the thermodynamic and conformational aspects for the binding of fluoroquinolone antibacterial drug, levofloxacin (LFC), with bovine serum albumin (BSA) using calorimetric, spectroscopic (UV-visible, fluorescence, circular dichroism, and 1H NMR), dynamic light scattering (DLS) and computational methods (molecular docking). The binding of LFC with BSA at two sequential sites with higher affinity ( 103 M- 1) at the first site has been explored by calorimetry whereas the binding at a single site with affinity of the order of 104 M- 1 has been observed from fluorescence spectroscopy. The calorimetric study in the presence of additives along with docking analysis reveals the significant role of electrostatic, hydrogen bonding, and hydrophobic interactions in the association process. The slight conformational changes in protein as well as the changes in the water network structure around the binding cavity of protein have been observed from spectroscopic and DLS measurements. The LFC induced quenching of BSA fluorescence was observed to be initiated mainly through the static quenching process and this suggests the formation of ground state LFC-BSA association complex. The stronger interactions of LFC in the cavity of Sudlow site I (subdomain IIA) of protein have been explored from site marker calorimetric and molecular docking study.

Determination of quinolones and fluoroquinolones, tetracyclines and sulfonamides in bovine, swine and poultry liver using LC-MS/MS.

PubMed

Martins, Magda Targa; Barreto, Fabiano; Hoff, Rodrigo Barcelos; Jank, Louise; Arsand, Juliana Bazzan; Feijó, Tiago Correa; Schapoval, Elfrides Eva Scherman

2015-01-01

Antibacterials are widely used in veterinary medicine. Residues of these drugs can remain in food of animal origin, including bovine liver. This paper describes a fast and simple analytical method for the determination of quinolones and fluoroquinolones, tetracyclines and sulfonamides in bovine liver samples. Deuterated enrofloxacin, sulfapyridine and demeclocycline were used as internal standards. The homogenised liver samples were extracted with acidified acetonitrile. Steps of non-solid-phase extraction (SPE) clean-up and concentration were used in the presented method. The final extracts were analysed by sensitive and selective detection of all components in a single run using LC-MS/MS. Acceptable recoveries between 66% and 110% were obtained. Good linearity (r(2)) above 0.96, considering three different days, for all drugs was achieved in concentrations ranging from 0.0 to 2.0 × the maximum residue limit (MRL). Intraday precision with coefficient of variation (CV%) (n = 6) lower than 14.7% and inter-day precision lower than 18.8% in agreement with European Commission Decision 2002/657/EC were obtained in concentrations ranging from 0.5 to 1.5 MRL. Accuracy was between 86% and 110%. Limits of detection and quantitation, as well as decision limit (CCα) and detection capability (CCβ), were also evaluated.

Antimicrobial resistance of Shigella spp. from humans in Shanghai, China, 2004-2011.

PubMed

Zhang, Jianmin; Jin, Huiming; Hu, Jiayu; Yuan, Zhengan; Shi, Weimin; Yang, Xiaowei; Xu, Xuebin; Meng, Jianghong

2014-03-01

A retrospective study conducted on patients with diarrhea in Shanghai, China from 2004-2011, indicated that of 77,600 samples collected, 1,635 (2.1%) tested positive for Shigella. Species isolated included S. sonnei (1,066, 65.1%), S. flexneri (569, 34.7%), and S. boydii (3, 0.2%). Most of the Shigella isolates were found to be resistant to streptomycin (98.7%), trimethoprim (98.0%), ampicillin (92.1%), and nalidixic acid (91.7%). Additionally, many isolates were resistant to tetracycline (86.9%), trimethoprim + sulfamethoxazole (80.1%), sulfisoxazole (76.8%) and gentamicin (55.5%). Approximately 80% of the isolates were resistant to at least eight antimicrobial agents, 14% to at least ten antimicrobials tested and 10 isolates to fourteen antimicrobials, including sulfonamides, fluoroquinolones, tetracyclines, aminoglycosides and β-lactamases. Importantly, co-resistance to fluoroquinolones and the third- and fourth-generation cephalosporins was also identified. The high levels of resistance to antimicrobial agents commonly used in clinical medicine presents a great challenge to treating patients with shigellosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Hydrolysis of Synthetic Esters by the Antibacterial Agent in Serum

PubMed Central

Yotis, William W.

1966-01-01

Yotis, William W. (Loyola University, Chicago, Ill.). Hydrolysis of synthetic esters by the antibacterial agent in serum. J. Bacteriol. 91:488–493. 1966.—An antistaphylococcal serum agent was assayed colorimetrically, manometrically, and titrimetrically for esterase activity. p-Nitrophenol acetate, triacetin, l-lysine methyl and ethyl ester, and norleucine methyl ester were hydrolyzed by the antistaphylococcal agent. Acetylcholine and benzoylcholine esters, triolein, tristearin, and p-tosylarginine methyl ester were not attacked by this agent. With p-nitrophenol acetate as substrate, optimal activity occurred at pH 7.4. Incubation at 60 C for 30 min reduced drastically the esterase activity of the antistaphylococcal agent, and incubation at 75 C for 30 min abolished the esterase activity of this agent. Almost complete inhibition of esterase activity was observed with 0.001 m HgCl2, ZnSO4, and ethylenediaminetetraacetic acid (EDTA). EDTA inhibition could be reversed by the addition of CaCl2, but not MgCl2. Cysteine reversed the inhibition of HgCl2. NaF, atoxyl, diisopropyl fluorophosphate, quinine, and physostigmine did not influence the esterase activity of the antibacterial agent. The demonstration of esterase activity of both the antistaphylococcal agent and coagulase may shed further light on the reported ability of coagulase to neutralize the antistaphylococcal activity of this agent, or the prevention of absorption of the agent on the staphylococcal cell surface. In addition, the colorimetric procedure described in this report may be a convenient tool in assaying the potency of the antistaphylococcal agent. Images PMID:4956776

Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles

PubMed Central

Chen, Chen; Weir, Michael D.; Cheng, Lei; Lin, Nancy; Lin-Gibson, Sheng; Chow, Laurence C.; Zhou, Xuedong; Xu, Hockin H. K.

2015-01-01

Objectives Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Methods Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Results Adding 5% DMADDM and 10–40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p > 0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6–10 folds. Significance Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was “smart” and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent containing DMADDM and NACP may be promising to inhibit biofilms and remineralize tooth lesions thereby increasing the restoration longevity. PMID:24954647

Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles.

PubMed

Chen, Chen; Weir, Michael D; Cheng, Lei; Lin, Nancy J; Lin-Gibson, Sheng; Chow, Laurence C; Zhou, Xuedong; Xu, Hockin H K

2014-08-01

Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Adding 5% DMADDM and 10-40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p>0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6-10 folds. Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was "smart" and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent containing DMADDM and NACP may be promising to inhibit biofilms and remineralize tooth lesions thereby increasing the restoration longevity. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Chicken cathelicidin-2-derived peptides with enhanced immunomodulatory and antibacterial activities against biological warfare agents.

PubMed

Molhoek, E Margo; van Dijk, Albert; Veldhuizen, Edwin J A; Dijk-Knijnenburg, Helma; Mars-Groenendijk, Roos H; Boele, Linda C L; Kaman-van Zanten, Wendy E; Haagsman, Henk P; Bikker, Floris J

2010-09-01

Host defence peptides (HDPs) are considered to be excellent candidates for the development of novel therapeutic agents. Recently, it was demonstrated that the peptide C1-15, an N-terminal segment of chicken HDP cathelicidin-2, exhibits potent antibacterial activity while lacking cytotoxicity towards eukaryotic cells. In the present study, we report that C1-15 is active against bacteria such as Bacillus anthracis and Yersinia pestis that may potentially be used by bioterrorists. Substitution of single and multiple phenylalanine (Phe) residues to tryptophan (Trp) in C1-15 resulted in variants with improved antibacterial activity against B. anthracis and Y. pestis as well as decreased salt sensitivity. In addition, these peptides exhibited enhanced neutralisation of lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). The antibacterial and LPS-neutralising activities of these C1-15-derived peptides are exerted at concentrations far below the concentrations that are toxic to human PBMCs. Taken together, we show that Phe-->Trp substitutions in C1-15 variants enhances the antibacterial and LPS-neutralising activities against pathogenic bacteria, including those that may potentially be used as biological warfare agents. Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Synthesis and potent in vitro activity of novel 1H-benzimidazoles as anti-MRSA agents.

PubMed

Karataş, Hacer; Alp, Mehmet; Yildiz, Sulhiye; Göker, Hakan

2012-08-01

A new class of 1H-benzimidazolecarboxamidines was synthesized and evaluated for in vitro antibacterial and antifungal activities, including drug-resistant bacterial strains. The most potent compound (32) has the same ratio of anti-MRSA activity as Vancomycin (minimal inhibitory concentrations value 0.78 μg/mL). The mechanism of action for 1H-benzimidazolecarboxamidine appears to be different from existing antibacterial agents. These compounds have potential for development as a new class of potent anti-MRSA agent. © 2012 John Wiley & Sons A/S.

Synthesis and biological evaluation of 2-arylimino-3-pyridin-thiazolineone derivatives as antibacterial agents.

PubMed

Cai, Ming-Guang; Wu, Yang; Chang, Jun

2016-05-15

With an intention to find more potent antibacterial agents, four halogen disubstituted thiazolineone derivatives (2a-d), five halogen monosubstituted thiazolineone derivatives (2e-i), and eleven 2-arylimino-3-pyridin-thiazolineone derivatives (2j-t) were synthesized and screened for their antibacterial activity, bactericidal activity, cytotoxicity, and erythrocyte hemolysis. Most of the synthesized derivatives showed antibacterial activity in inhibiting the growth of S. epidermidis and MRSA, and exhibited safety in the cytotoxicity study on the Vero cells and hemolytic activities test on healthy human erythrocytes. 2-Arylimino-3-pyridin-thiazolineone derivatives not only improved the clog P, but also showed potent antibacterial activity in inhibiting the growth of S. epidermidis and MRSA. In particularly, several compounds (2f, 2i, 2r and 2t) showed bactericidal activity, in which compound 2r displayed the best inhibitory capacity among the synthesized compounds, and further druggability research is on going. Copyright © 2016 Elsevier Ltd. All rights reserved.

A simple fragment of cyclic acyldepsipeptides is necessary and sufficient for ClpP activation and antibacterial activity.

PubMed

Carney, Daniel W; Compton, Corey L; Schmitz, Karl R; Stevens, Julia P; Sauer, Robert T; Sello, Jason K

2014-10-13

The development of new antibacterial agents, particularly those with unique biological targets, is essential to keep pace with the inevitable emergence of drug resistance in pathogenic bacteria. We identified the minimal structural component of the cyclic acyldepsipeptide (ADEP) antibiotics that exhibits antibacterial activity. We found that N-acyldifluorophenylalanine fragments function via the same mechanism of action as ADEPs, as evidenced by the requirement of ClpP for the fragments' antibacterial activity, the ability of fragments to activate Bacillus subtilis ClpP in vitro, and the capacity of an N-acyldifluorophenylalanine affinity matrix to capture ClpP from B. subtilis cell lysates. N-acyldifluorophenylalanine fragments are much simpler in structure than the full ADEPs and are also highly amenable to structural diversification. Thus, the stage has been set for the development of non-peptide activators of ClpP that can be used as antibacterial agents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Silver Nanoparticles Synthesized Using Caesalpinia sappan Extract as Potential Novel Nanoantibiotics Against Methicillin-Resistant Staphylococcus aureus.

PubMed

Jun, Sang Hui; Cha, Song-Hyun; Kim, Jae-Hyun; Yoon, Minho; Cho, Seonho; Park, Youmie

2015-08-01

Silver nanoparticles (AgNPs) have been shown to be effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). In this study, AgNPs were synthesized using Caesalpinia sappan extract as a reducing agent to convert Ag+ to AgNPs. Seven stabilizers (surfactants and polymers) were added during the reduction step to increase the colloidal stability and to enhance the antibacterial activity of the AgNPs. Spherical and amorphous particles were primarily observed, with estimated diameters ranging from 30.2 to 47.5 nm. X-ray diffraction confirmed the face centered cubic structures of the AgNPs. Among the employed stabilizers, the cationic surfactant cetyltrimethylammonium bromide (CTAB) exhibited the highest antibacterial activity against 19 strains of MRSA, followed by polyvinylpyrrolidone (PVP, average molecular weight of 10,000). In contrast, the anionic surfactants sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (NaDDBS) did not exhibit any significant antibacterial activity, suggesting that the cationic surfactant head group contributed to the higher antibacterial activity of the AgNPs against MRSA.

Developpement d'un film antibacterien ayant des proprietes de glissement pour une meilleure processabilite

NASA Astrophysics Data System (ADS)

Silverwood, Richard

Product safety is of crucial importance for the food industry. The challenge of food safety is evidenced by the number of food poisoning in Canada and worldwide. An outbreak of listeriosis in 2008, having put the safety of Canadians at risk, has motivated the revision of the strategy for food safety in Canada. In this context, a collaboration between two major industrial players in Quebec and École Polytechnique de Montréal was initiated. This collaboration is supported by the creation of the Research Chair for safe, smart and sustainable food. One of the many forefront projects of this research chair is to develop a package having a bactericidal effect. Many compounds are currently available for incorporation into a finished product. Zinc Omadine™ by ArchChemicals and Irgaguard™ by BASF are some examples of products that have proven themselves. However, the incorporation of a bactericidal agent in a product having a direct contact with food must meet certain safety criteria. Thus, an overview of various antibacterial agents is made in terms of their effectiveness and their potential use in packaging a food product. To date, no technology allows easy incorporation of an antibacterial agent in a polymer matrix. Antibacterial constituents of the mixture with the polymer melt will provide the simplicity pursued. We chose nano zinc oxide as the main antibacterial agent for its mode of action, its great potential for sustainability and its ability not to migrate out of the polyethylene polymer matrix. Moreover, the effect of trace element at very low concentrations is validated. To increase efficiency, good dispersion is achieved by adding a polyethylene with maleic anhydride grafted groups. The increase in antibacterial properties by this change has been proven. Although these films exhibit a marked bactericidal effect, a lack of persistence of the antibacterial effect was noticed. This is probably due to a rearrangement of the molecular structure on the surface. This rearrangement, due to the polar nature of particles, inhibits the antibacterial effect of the particles, causing them to migrate to a critical distance, outside their scope. Furthermore, we evaluated briefly some other antibacterial agents. Calcium oxide (CaO) demonstrated, although lower than ZnO, an interesting antibacterial potential. The specificity of the bactericidal for gram-positive bacteria for this variance. The addition of iron oxide (Fe2O3) did not, by its hydrophilic properties, increase the bactericidal properties of CaO, simply by mixing them. Also, the use of thymol (component of essential oil of thyme) was effective, even at very low doses. A question mark hangs, however, the sustainability of such an agent. Its use in conjunction with a compatibilizer could result in a much more persistent bactericidal effect, slowing the process of migrating to the film surface. This effect is reduced when the bactericidal thymol is mixed with ZnO in the polyethylene matrix. Finally, a tool for optimizing slip additives was developed. To do this, a correlation that links the absorbance in infrared spectroscopy (ATR reflection) to the surface concentration of the lubricant was developed. By using this correlation, also called master curve, and an infrared spectrometer to test an unknown film, it is possible to find the initial concentration of slip additive. These studies highlight the potential use of zinc oxide and thymol as efficient bactericidal agent for the food industry. This work represents the first effort to develop an antibacterial film, involving nanoscale metal oxides and a polymer matrix of polyolefin.

The ATP-binding site of type II topoisomerases as a target for antibacterial drugs.

PubMed

Maxwell, Anthony; Lawson, David M

2003-01-01

DNA topoisomerases are essential enzymes in all cell types and have been found to be valuable drug targets both for antibacterial and anti-cancer chemotherapy. Type II topoisomerases possess a binding site for ATP, which can be exploited as a target for chemo-therapeutic agents. High-resolution structures of protein fragments containing this site complexed with antibiotics or an ATP analogue have provided vital information for the understanding of the action of existing drugs and for the potential development of novel anti-bacterial agents. In this article we have reviewed the structure and function of the ATPase domain of DNA gyrase (bacterial topoisomerase II), particularly highlighting novel information that has been revealed by structural studies. We discuss the efficacy and mode of action of existing drugs and consider the prospects for the development of novel agents.

Solvothermal synthesis of ZnO nanoparticles and anti-infection application in vivo.

PubMed

Bai, Xiangyang; Li, Linlin; Liu, Huiyu; Tan, Longfei; Liu, Tianlong; Meng, Xianwei

2015-01-21

Zinc oxide nanoparticles (ZnONPs) have been widely studied as the bacteriostatic reagents. However, synthesis of small ZnO nanoparticles with good monodispersion and stability in aqueous solution is still a challenge. Anti-infection research of ZnONPs used as antibacterial agent in vivo is rare. In this paper, a novel, sustainable, and simple method to synthesize ZnO nanoparticles with good monodispersion in aqueous low-temperature conditions and with a small molecule agent is reported. Inhibition zone test and the minimum inhibitory concentration test were performed to examine the antibacterial activity of ZnONPs against bacteria Staphylococcus aureus and Escherichia coli in vitro. For further application in vivo, low cytotoxicity and low acute toxicity in mice of ZnO were demonstrated. Finally, 4 nm ZnONPs combined with poly(vinyl alcohol) gel was used as antibacterial agent in rodent elytritis model, and significant anti-infection effect was proven. In one word, the present research would shed new light on the designing of antibacterial materials like ZnO with promising application in disinfection.

Current Technology in the Discovery and Development of Novel Antibacterials.

PubMed

Chung, Pooi Yin

2018-01-01

Bacterial resistance to antibiotics is one of the most serious challenge to global public health. The introduction of new antibiotics in clinical settings, i.e. agents that belong to a new class of antibacterials, act on new targets or has a novel mechanisms of action, may not be sufficient to cope with the emergence of multidrug-resistant pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Escherichia coli, which are increasingly prevalent in healthcare settings in Europe, the USA and Asia. Hence, coordinated efforts in minimizing the risk of spread of resistant bacteria and renewing research efforts in the search for novel antibacterial agents are urgently needed to manage this global crisis. This review highlights the challenges and potential in using current technologies in the discovery and development of novel antibacterial agents to keep up with the constantly evolving resistance in bacteria. With the explosion of bacterial genomic data and rapid development of new sequencing technologies, the understanding of bacterial pathogenesis and identification of novel antibiotic targets have significantly improved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Estimating the Effects of Global Patent Protection in Pharmaceuticals: A Case Study of Quinolones in India.

PubMed

Chaudhuri, Shubham; Goldberg, Pinelopi K; Jia, Panle

2006-12-01

Under the Agreement on Trade-Related Intellectual Property Rights, the World Trade Organization members are required to enforce product patents for pharmaceuticals. In this paper we empirically investigate the welfare effects of this requirement on developing countries using data for the fluoroquinolones subsegment of the systemic anti-bacterials segment of the Indian pharmaceuticals market. Our results suggest that concerns about the potential adverse welfare effects of TRIPS may have some basis. We estimate that the withdrawal of all domestic products in this subsegment is associated with substantial welfare losses to the Indian economy, even in the presence of price regulation. The overwhelming portion of this welfare loss derives from the loss of consumer welfare.

Design, synthesis and structure-activity relationship evaluation of novel LpxC inhibitors as Gram-negative antibacterial agents.

PubMed

Ding, Shi; Dai, Rui-Yang; Wang, Wen-Ke; Cao, Qiao; Lan, Le-Fu; Zhou, Xian-Li; Yang, Yu-She

2018-01-15

LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To develop novel LpxC inhibitors with good antibacterial activities and biological metabolism, we summarized the basic skeleton of reported LpxC inhibitors, designed and synthesized several series of compounds and tested their antibacterial activities against Escherichial coli and Pseudomonas aeruginosa in vitro. Structure-activity relationships have been discussed in this article. The metabolism stability of YDL-2, YDL-5, YDL-8, YDL-14, YDL-20-YDL-23 have been evaluated in liver microsomes, which indicated that the 2-amino isopropyl group may be a preferred structure than the 2-hydroxy ethyl group in the design of LpxC inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

PubMed

Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

2012-11-01

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

[The combination effects of antibacterial agents against clinical isolated multiple-drug resistant Pseudomonas aeruginosa].

PubMed

Maesaki, Shigefumi; Yamaguchi, Toshiyuki; Sasaki, Kazumasa; Hashikita, Giichi; Shibuya, Shunsuke; Watanabe, Masaharu; Takayama, Sadao; Kawakami, Sayoko; Nagasawa, Mitsuaki; Suzuki, Noriyasu; Uchida, Takashi; Okabe, Tadashi; Kobayashi, Sugako

2006-02-01

The effectiveness of antibacterial agents against 70 strains of clinically isolated multiple-drug resistant Pseudomonas aeruginosa (MDRP) was measured by the micro dilution method. Fifty of all strains (71%) produced metallo-beta-lactamase and the IMP-1 gene was detected by polymerase chain reaction (PCR). The MIC90 (the minimum inhibitory concentration of an antibiotic necessary to inhibit the growth of 90% of bacterial strains) values of biapenem (BIPM), meropenem (MEPM), tazobactam/piperacillin (TAZ/PIPC), sulbactam/ cefoperazone (SBT/CPZ), cefepime (CFPM), ciprofloxacin (CPFX), pazufloxacin (PZFX), amikacin (AMK) and aztreonam (AZT) were found to be 265, 512, 256, 512, 512, 64, 128, 128 and 128 microg/mL, respectively. The in vitro combination effects of antibacterial agents were examined against 62 strains of MDRP and the synergy or additive effects were evaluated by fractional inhibitory concentration (FIC) index calculated by the checkerboard method. The combination of AMK and AZT showed synergy effects on 15/59 (25.4%) strains of MDRP. The synergy and additive effects on the MDRP strains were also found by the other antibacterial agents combination such as TAZ/PIPC and AMK, CFPM and AMK, and SBT/CPZ and AZT. These results suggested the necessity of further investigation of clinical usefulness.

Time for a change: addressing R&D and commercialization challenges for antibacterials

PubMed Central

Payne, David J.; Miller, Linda Federici; Findlay, David; Anderson, James; Marks, Lynn

2015-01-01

The antibacterial therapeutic area has been described as the perfect storm. Resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. Major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. This paper examines these challenges and proposes approaches to address them. There is a need for a broader scientific agenda to explore new approaches to discover and develop antibacterial agents. Additionally, ideas of how industry and academia could be better integrated will be presented. While promising progress in the regulatory environment has been made, more streamlined regulatory paths are still required and the solutions will lie in global harmonization and clearly defined guidance. Creating the right incentives for antibacterial research and development is critical and a new commercial model for antibacterial agents will be proposed. One key solution to help resolve both the problem of antimicrobial resistance (AMR) and lack of new drug development are rapid, cost-effective, accurate point of care diagnostics that will transform antibacterial prescribing and enable more cost-effective and efficient antibacterial clinical trials. The challenges of AMR are too great for any one group to resolve and success will require leadership and partnerships among academia, industry and governments globally. PMID:25918443

Cyst infection in autosomal dominant polycystic kidney disease: causative microorganisms and susceptibility to lipid-soluble antibiotics.

PubMed

Suwabe, T; Araoka, H; Ubara, Y; Kikuchi, K; Hazue, R; Mise, K; Hamanoue, S; Ueno, T; Sumida, K; Hayami, N; Hoshino, J; Imafuku, A; Kawada, M; Hiramatsu, R; Hasegawa, E; Sawa, N; Takaichi, K

2015-07-01

Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD). Lipid-soluble antibiotics like fluoroquinolones show good penetration into cysts and are recommended for cyst infection, but causative microorganisms are often resistant to these agents. This study investigated the profile of the microorganisms causing cyst infection in ADPKD, their susceptibility to lipid-soluble antibiotics, and clinical outcomes. This retrospective study reviewed all ADPKD patients admitted to Toranomon Hospital with a diagnosis of cyst infection from January 2004 to March 2014. All patients who underwent cyst drainage and had positive cyst fluid cultures were enrolled. Patients with positive blood cultures who satisfied our criteria for cyst infection or probable infection were also enrolled. There were 99 episodes with positive cyst fluid cultures and 93 episodes with positive blood cultures. The majority of patients were on dialysis. The death rate was high when infection was caused by multiple microorganisms or when there were multiple infected cysts. Gram-negative bacteria accounted for 74-79 % of the isolates in all groups, except for patients with positive hepatic cyst fluid cultures. The susceptibility of Escherichia coli to fluoroquinolones was very low in patients with hepatic cyst infection, especially those with frequent episodes and those with hepatomegaly. Fungi were detected in two episodes. Fluoroquinolone-resistant microorganisms showed a high prevalence in cyst infection. It is important to identify causative microorganisms to avoid the overuse of fluoroquinolones and to improve the outcome of cyst infection in ADPKD.

Longitudinal trends and cross-sectional analysis of English national hospital antibacterial use over 5 years (2008-13): working towards hospital prescribing quality measures.

PubMed

Cooke, Jonathan; Stephens, Peter; Ashiru-Oredope, Diane; Charani, Esmita; Dryden, Mathew; Fry, Carole; Hand, Kieran; Holmes, Alison; Howard, Philip; Johnson, Alan P; Livermore, David M; Mansell, Paula; McNulty, Cliodna A M; Wellsteed, Sally; Hopkins, Susan; Sharland, Mike

2015-01-01

There is global concern that antimicrobial resistance is a major threat to healthcare. Antimicrobial use is a primary driver of resistance but little information exists about the variation in antimicrobial use in individual hospitals in England over time or comparative use between hospitals. The objective of this study was to collate, analyse and report issue data from pharmacy records of 158 National Health Service (NHS) acute hospitals. This was a cohort study of inpatient antibacterial use in acute hospitals in England analysed over 5 years through a data warehouse from IMS Health, a leading provider of information, services and technology for the healthcare industry. Around 98% of NHS hospitals were included in a country with a population of 50 million residents. There was a dramatic change in the usage of different groups of antibacterials between 2009 and 2013 with a marked reduction in the use of first-generation cephalosporins by 24.7% and second-generation cephalosporins by 41%, but little change in the use of third-generation cephalosporins (+5.7%) and fluoroquinolones (+1.6%). In contrast, use of co-amoxiclav, carbapenems and piperacillin/tazobactam increased by 60.1%, 61.4% and 94.8%, respectively. There was wide variation in the total and relative amounts of antibacterials used between individual hospitals. Longitudinal analysis of antibacterial use demonstrated remarkable changes in NHS hospitals, probably reflecting governmental and professional guidance to mitigate the risk of Clostridium difficile infection. The wide variation in usage between individual hospitals suggests potential for quality improvement and benchmarking. Quality measures of optimal hospital antimicrobial prescribing need urgent development and validation to support antimicrobial stewardship initiatives. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads.

PubMed

Bi, Yi; Liu, Xian-Xuan; Zhang, Heng-Yuan; Yang, Xiao; Liu, Ze-Yun; Lu, Jing; Lewis, Peter John; Wang, Chong-Zhi; Xu, Jin-Yi; Meng, Qing-Guo; Ma, Cong; Yuan, Chun-Su

2017-04-07

Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20( S )-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria ( B. subtilis 168 and MRSA USA300) and Gram-negative bacteria ( P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2-16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.

Characterization and interplay of bacteriocin and exopolysaccharide-mediated silver nanoparticles as an antibacterial agent.

PubMed

Ansari, Asma; Pervez, Sidra; Javed, Urooj; Abro, Muhammad Ishaque; Nawaz, Muhammad Asif; Qader, Shah Ali Ul; Aman, Afsheen

2018-04-22

Metallic nanoparticles have a substantial scientific interest because of their distinctive physicochemical and antimicrobial properties and the emergence of multidrug resistant pathogens could unlock the potential of nanoparticles to combat infectious diseases. The aim of the current study is to enhance the antibacterial potential of purified bacteriocin by combining bacteriocin and antibacterial silver nanoparticles (AgNPs). Hence, the interaction of natural antimicrobial compounds and antibacterial nanoparticles can be used as a potential tool for combating infectious diseases. In this study, a green, simple and effective approach is used to synthesize antibacterial AgNPs using fungal exopolysaccharide as both a reducing and stabilizing agent. The AgNPs were characterized by spectroscopic analysis, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray spectroscopy (EDX) and Dynamic Light Scattering (DLS). Furthermore, the synergistic effect of bacteriocin-AgNPs was determined against pathogenic strains. The histogram of AgNPs indicated well-dispersed, stabilized and negatively charged particles with variable size distribution. The combination of bacteriocin with nanoparticles found to be more effective due to broad antibacterial potential with possibly lower doses. The current study is imperative to provide an alternative for the chemical synthesis of silver nanoparticles. It showed environmental friendly and cost effective green synthesis of antibacterial nanoparticles. Copyright © 2018 Elsevier B.V. All rights reserved.

Surface modification of polypropylene mesh devices with cyclodextrin via cold plasma for hernia repair: Characterization and antibacterial properties

NASA Astrophysics Data System (ADS)

Sanbhal, Noor; Mao, Ying; Sun, Gang; Xu, Rui Fang; Zhang, Qian; Wang, Lu

2018-05-01

Light weight polypropylene (PP) mesh is the most widely used implant among all other synthetic meshes for hernia repair. However, infection is the complication associated to all synthetic meshes after hernia repair. Thus, to manage mesh related infection; antibacterial drug is generally loaded to surgical implants to supply drug locally in mesh implanted site. Nevertheless, PP mesh restricts the loading of antibacterial drug at operated area due to its low wettability. The aim of this study was to introduce a novel antimicrobial PP mesh modified with β-cyclodextrine (CD) and loaded with antimicrobial agent for infection prevention. A cold oxygen plasma treatment was able to activate the surfaces of polypropylene fibers, and then CD was incorporated onto the surfaces of PP fibers. Afterward, triclosan, as a model antibacterial agent, was loaded into CD cavity to provide desired antibacterial functions. The modified polypropylene mesh samples CD-Tric-1, CD-Tric-3 exhibited excellent inhibition zone and continuous antibacterial efficacy against E. coli and S. aureus up to 6 and 7 days respectively. Results of AFM, SEM, FTIR and antibacterial tests evidenced that oxygen plasma process is necessary to increase chemical connection between CD molecules and PP fibers. The samples were also characterized by using EDX, XRD, TGA, DSC and water contact angle.

Effects of dual antibacterial agents MDPB and nano-silver in primer on microcosm biofilm, cytotoxicity and dentin bond properties

PubMed Central

Zhang, Ke; Cheng, Lei; Imazato, Satoshi; Antonucci, Joseph M.; Lin, Nancy J.; Lin-Gibson, Sheng; Bai, Yuxing; Xu, Hockin H. K.

2013-01-01

Objectives The objective of this study was to investigate the effects of dentin primer containing dual antibacterial agents, namely, 12-methacryloyloxydodecylpyridinium bromide (MDPB) and nanoparticles of silver (NAg), on dentin bond strength, dental plaque microcosm biofilm response, and fibroblast cytotoxicity for the first time. Methods Scotchbond Multi-Purpose (SBMP) was used as the parent bonding agent. Four primers were tested: SBMP primer control (referred to as “P”), P+5%MDPB, P+0.05%NAg, and P+5%MDPB+0.05%NAg. Dentin shear bond strengths were measured using extracted human teeth. Biofilms from the mixed saliva of 10 donors were cultured to investigate metabolic activity, colony-forming units (CFU), and lactic acid production. Human fibroblast cytotoxicity of the four primers was tested in vitro. Results Incorporating MDPB and NAg into primer did not reduce dentin bond strength compared to control (p>0.1). SEM revealed well-bonded adhesive-dentin interfaces with numerous resin tags. MDPB or NAg each greatly reduced biofilm viability and acid production, compared to control. Dual agents MDPB+NAg had a much stronger effect than either agent alone (p<0.05), increasing inhibition zone size and reducing metabolic activity, CFU and lactic acid by an order of magnitude, compared to control. There was no difference in cytotoxicity between commercial control and antibacterial primers (p>0.1). Conclusions The method of using dual agents MDPB+NAg in the primer yielded potent antibacterial properties. Hence, this method may be promising to combat residual bacteria in tooth cavity and invading bacteria at the margins. The dual agents MDPB+NAg may have wide applicability to other adhesives, composites, sealants and cements to inhibit biofilms and caries. PMID:23402889

Methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.

PubMed

Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

2015-01-01

The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.

Antibacterial and Antifungal Activities of Spices

PubMed Central

Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin

2017-01-01

Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices—such as clove, oregano, thyme, cinnamon, and cumin—possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives. PMID:28621716

Antibacterial and Antifungal Activities of Spices.

PubMed

Liu, Qing; Meng, Xiao; Li, Ya; Zhao, Cai-Ning; Tang, Guo-Yi; Li, Hua-Bin

2017-06-16

Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices-such as clove, oregano, thyme, cinnamon, and cumin-possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens , pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives.

Prevention of febrile neutropenia: use of prophylactic antibiotics.

PubMed

Cullen, M; Baijal, S

2009-09-01

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated.

Prevention of febrile neutropenia: use of prophylactic antibiotics

PubMed Central

Cullen, M; Baijal, S

2009-01-01

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated. PMID:19756000

Biosynthesis of silver nanoparticles using citrus sinensis peel extract and its antibacterial activity.

PubMed

Kaviya, S; Santhanalakshmi, J; Viswanathan, B; Muthumary, J; Srinivasan, K

2011-08-01

Biosynthesis of silver nanoparticles (AgNPs) was achieved by a novel, simple green chemistry procedure using citrus sinensis peel extract as a reducing and a capping agent. The effect of temperature on the synthesis of silver nanoparticles was carried out at room temperature (25°C) and 60°C. The successful formation of silver nanoparticles has been confirmed by UV-vis, FTIR, XRD, EDAX, FESEM and TEM analysis and their antibacterial activity against Escherichia coli, Pseudomonas aeruginosa (gram-negative), and Staphylococcus aureus (gram-positive) has been studied. The results suggest that the synthesized AgNPs act as an effective antibacterial agent. Copyright © 2011 Elsevier B.V. All rights reserved.

Cobalt Complexes as Antiviral and Antibacterial Agents

DTIC Science & Technology

2010-01-01

observed. Complex 26 has antibacterial activity against E. coli, S. aureus and Micrococcus lysodeikiticus, showing better growth inhibitory activity in...complexes exhibited activity towards E. coli, B. subtilis, S. aureus and Micrococcus lysodeikiticus. Figure 15. Selenium containing and

Antibacterial household products: cause for concern.

PubMed Central

Levy, S. B.

2001-01-01

The recent entry of products containing antibacterial agents into healthy households has escalated from a few dozen products in the mid-1990s to more than 700 today. Antibacterial products were developed and have been successfully used to prevent transmission of disease-causing microorganisms among patients, particularly in hospitals. They are now being added to products used in healthy households, even though an added health benefit has not been demonstrated. Scientists are concerned that the antibacterial agents will select bacteria resistant to them and cross-resistant to antibiotics. Moreover, if they alter a person's microflora, they may negatively affect the normal maturation of the T helper cell response of the immune system to commensal flora antigens; this change could lead to a greater chance of allergies in children. As with antibiotics, prudent use of these products is urged. Their designated purpose is to protect vulnerable patients. PMID:11485643

Antibacterial household products: cause for concern.

PubMed

Levy, S B

2001-01-01

The recent entry of products containing antibacterial agents into healthy households has escalated from a few dozen products in the mid-1990s to more than 700 today. Antibacterial products were developed and have been successfully used to prevent transmission of disease-causing microorganisms among patients, particularly in hospitals. They are now being added to products used in healthy households, even though an added health benefit has not been demonstrated. Scientists are concerned that the antibacterial agents will select bacteria resistant to them and cross-resistant to antibiotics. Moreover, if they alter a person's microflora, they may negatively affect the normal maturation of the T helper cell response of the immune system to commensal flora antigens; this change could lead to a greater chance of allergies in children. As with antibiotics, prudent use of these products is urged. Their designated purpose is to protect vulnerable patients.

Antioxidant, antibacterial and anti-aging activities of intracellular zinc polysaccharides from Grifola frondosa SH-05.

PubMed

Zhang, Chen; Gao, Zheng; Hu, Chunlong; Zhang, Jianjun; Sun, Xinyi; Rong, Chengbo; Jia, Le

2017-02-01

In present work, the strain of Grifola frondosa SH-05 was used as a vector of zinc biotransformation to produce the IZPS. The bioactivities including antioxidant and antibacterial activities in vitro and anti-aging properties in vivo of IZPS were investigated comparing with the IPS. The results which were in consistent with the results of histopathology assay demonstrated that the IZPS had superior antioxidant and anti-aging activities by scavenging the hydroxyl and DPPH radicals, increasing enzyme activities, decreasing the MDA contents and ameliorating the anile condition of mice. Besides, the IZPS also showed potential antibacterial activities. The IZPS with higher bioactivities was composed of were Rha, Ino and Glu with a molar ratio of 4.7:3.6:1. These conclusions indicated that the IZPS might be a potential source of natural antioxidant, antibacterial agent and anti-aging agent. Copyright © 2016 Elsevier B.V. All rights reserved.

Combating resistance: application of the emerging science of pharmacokinetics and pharmacodynamics.

PubMed

Jacobs, Michael R

2007-12-01

During the last 10-15 years understanding of relationships between pharmacokinetic (PK) and pharmacodynamic (PD) parameters and bacteriological and clinical outcomes has expanded allowing correlation between in vitro potency and in vivo efficacy. PK and PD principles can be applied to development of new antibacterials and formulation of existing agents to help address the increasing prevalence of antibacterial resistance. For beta-lactams, such as penicillins, the unbound serum concentration of the drug exceeding the minimum inhibitory concentration of the causative pathogen for 40-50% of the dosing interval is predictive of bacteriologic efficacy (bacterial eradication) and can be used to determine a PK/PD breakpoint for that specific dosing regimen. Amoxicillin/clavulanate was one of the earliest antibacterials to use the unique approach of PK/PD principles to develop new and enhanced formulations, allowing it to remain a significant antibacterial agent in the management of respiratory tract infections.

A simple, fast and cheap non-SPE screening method for antibacterial residue analysis in milk and liver using liquid chromatography-tandem mass spectrometry.

PubMed

Martins, Magda Targa; Melo, Jéssica; Barreto, Fabiano; Hoff, Rodrigo Barcellos; Jank, Louise; Bittencourt, Michele Soares; Arsand, Juliana Bazzan; Schapoval, Elfrides Eva Scherman

2014-11-01

In routine laboratory work, screening methods for multiclass analysis can process a large number of samples in a short time. The main challenge is to develop a methodology to detect as many different classes of residues as possible, combined with speed and low cost. An efficient technique for the analysis of multiclass antibacterial residues (fluoroquinolones, tetracyclines, sulfonamides and trimethoprim) was developed based on simple, environment-friendly extraction for bovine milk, cattle and poultry liver. Acidified ethanol was used as an extracting solvent for milk samples. Liver samples were treated using EDTA-washed sand for cell disruption, methanol:water and acidified acetonitrile as extracting solvent. A total of 24 antibacterial residues were detected and confirmed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), at levels between 10, 25 and 50% of the maximum residue limit (MRL). For liver samples a metabolite (sulfaquinoxaline-OH) was also monitored. A validation procedure was conducted for screening purposes in accordance with European Union requirements (2002/657/EC). The detection capability (CCβ) false compliant rate was less than 5% at the lowest level for each residue. Specificity and ruggedness were also discussed. Incurred and routine samples were analyzed and the method was successfully applied. The results proved that this method can be an important tool in routine analysis, since it is very fast and reliable. Copyright © 2014. Published by Elsevier B.V.

Biodegradable Polymer Releasing Antibiotic Developed for Drainage Catheter of Cerebrospinal Fluid: In Vitro Results

PubMed Central

Han, Song Yup; Cho, Ki Hong; Cho, Han Jin; An, Jeong Ho; Ra, Young Sin

2005-01-01

The authors developed a biodegradable polymer that releases an antibiotic (nalidixic acid) slowly and continuously, for prevention of catheter-induced infection during drainage of cerebrospinal fluid. We investigated the in vitro antibiotic releasing characteristics and bacterial killing effects of the new polymer against E. coli. The novel fluoroquinolone polymer was prepared using diisopropylcarbodiimide, poly (e-caprolactone) diol, and nalidixic acid. FT-IR, mass spectrometry, and elemental analysis proved that the novel antibacterial polymer was prepared successfully without any side products. Negative MS showed that the released drug has a similar molecular weight (M.W.=232, 350) to pure drug (M.W.=232). In high pressure liquid chromatography, the released drug and drug-oligomer showed similar retention times (about 4.5-5 min) in comparison to pure drug (4.5 min). The released nalidixic acid and nalidixic acid derivatives have antibacterial characteristics against E. coli, Staphylococcus aureus, and Salmonella typhi, of more than 3 months duration. This study suggests the possibility of applying this new polymer to manufacture drainage catheters that resist catheter-induced infection, by delivering antibiotics for a longer period of more than 1 month. PMID:15832004

Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿

PubMed Central

Yacoby, Iftach; Bar, Hagit; Benhar, Itai

2007-01-01

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug. PMID:17404004

Synthesis and structure-activity relationship of amidine derivatives of 3,4-ethylenedioxythiophene as novel antibacterial agents.

PubMed

Stolić, Ivana; Čipčić Paljetak, Hana; Perić, Mihaela; Matijašić, Mario; Stepanić, Višnja; Verbanac, Donatella; Bajić, Miroslav

2015-01-27

Current antibacterial chemotherapeutics are facing an alarming increase in bacterial resistance pressuring the search for novel agents that would expand the available therapeutic arsenal against resistant bacterial pathogens. In line with these efforts, a series of 9 amidine derivatives of 3,4-ethylenedioxythiophene were synthesized and, together with 18 previously synthesized analogs, evaluated for their relative DNA binding affinity, in vitro antibacterial activities and preliminary in vitro safety profile. Encouraging antibacterial activity of several subclasses of tested amidine derivatives against Gram-positive (including resistant MRSA, MRSE, VRE strains) and Gram-negative bacterial strains was observed. The bis-phenyl derivatives were the most antibacterially active, while compound 19 from bis-benzimidazole class exhibited the widest spectrum of activity (with MIC of 4, 2, 0.5 and ≤0.25 μg/ml against laboratory strains of Staphyloccocus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, respectively and 4-32 μg/ml against clinical isolates of sensitive and resistant S. aureus, Staphylococcus epidermidis and Enterococcus faecium) and also demonstrated the strongest DNA binding affinity (ΔTm of 15.4 °C). Asymmetrically designed compounds and carboxamide-amidines were, in general, less active. Molecular docking indicated that the shape of the 3,4-ethylenedioxythiophene derivatives and their ability to form multiple electrostatic and hydrogen bonds with DNA, corresponds to the binding modes of other minor-groove binders. Herein reported results encourage further investigation of this class of compounds as novel antibacterial DNA binding agents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Time for a change: addressing R&D and commercialization challenges for antibacterials.

PubMed

Payne, David J; Miller, Linda Federici; Findlay, David; Anderson, James; Marks, Lynn

2015-06-05

The antibacterial therapeutic area has been described as the perfect storm. Resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. Major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. This paper examines these challenges and proposes approaches to address them. There is a need for a broader scientific agenda to explore new approaches to discover and develop antibacterial agents. Additionally, ideas of how industry and academia could be better integrated will be presented. While promising progress in the regulatory environment has been made, more streamlined regulatory paths are still required and the solutions will lie in global harmonization and clearly defined guidance. Creating the right incentives for antibacterial research and development is critical and a new commercial model for antibacterial agents will be proposed. One key solution to help resolve both the problem of antimicrobial resistance (AMR) and lack of new drug development are rapid, cost-effective, accurate point of care diagnostics that will transform antibacterial prescribing and enable more cost-effective and efficient antibacterial clinical trials. The challenges of AMR are too great for any one group to resolve and success will require leadership and partnerships among academia, industry and governments globally. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Quaternary ammonium salts substituted by 5-phenyl-1,3,4-oxadiazole-2-thiol as novel antibacterial agents with low cytotoxicity.

PubMed

Wang, Chun-Hua; Xie, Xian-Rui; Liu, Wen-Shuai; Hou, Gui-Ge; Sun, Ju-Feng; Zhao, Feng; Cong, Wei; Li, Hong-Juan; Xin, Wen-Yu

2017-11-01

Twenty-one novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) substituted N-hydroxyethyl quaternary ammonium salts (6a-g, 7a-g, 8a-g) were prepared and characterized by FTIR, NMR, and elemental analysis. Compounds 6a, 6c, and 8a were confirmed by X-ray single-crystal diffraction. They display the unsurpassed antibacterial activity against Staphylococcus aureus, α-H-tococcus, Escherichia coli, P. aeruginosa, Proteus vulgaris, Canidia Albicans, especially 6g, 7g, 8g with dodecyl group. Compounds 8a-d with N,N-dihydroxyethyl and POT groups display unsurpassed antibacterial activity and non-toxicity. The structure-activity relationships indicate that POT and flexible dihydroxyethyl group in QAS are necessary for antibacterial activity and cytotoxicity. SEM and TEM images of E. coli morphologies of 8d show the antibacterial agents can adhere to membrane surfaces to inhibit bacterial growth by disrupting peptidoglycan formation and releasing bacterial cytoplasm from cell membranes. © 2017 John Wiley & Sons A/S.

Antibacterial resistance in sub-Saharan Africa: an underestimated emergency

PubMed Central

Kariuki, Samuel; Dougan, Gordon

2014-01-01

Antibacterial resistance–associated infections are known to increase morbidity and mortality and cost of treatment and to potentially put others in the community at higher risk of infections. In high-income countries, where the burden of infectious diseases is relatively modest, resistance to first-line antibacterial agents is usually overcome by use of second- and third-line agents. However, in developing countries where the burden of infectious diseases is high, patients with antibacterial-resistant infections may be unable to obtain or afford effective second-line treatments. In sub-Saharan Africa (SSA), the situation is aggravated by poor hygiene, unreliable water supplies, civil conflicts, and increasing numbers of immunocompromised people, such as those with HIV, which facilitate both the evolution of resistant pathogens and their rapid spread in the community. Due to limited capacity for disease detection and surveillance, the burden of illnesses due to treatable bacterial infections, their specific etiologies, and the awareness of antibacterial resistance is less well established in most of SSA, and therefore the ability to mitigate their consequences is significantly limited. PMID:24628272

Virtual Screening Approach of Bacterial Peptide Deformylase Inhibitors Results in New Antibiotics.

PubMed

Merzoug, Amina; Chikhi, Abdelouahab; Bensegueni, Abderrahmane; Boucherit, Hanane; Okay, Sezer

2018-03-01

The increasing resistance of bacteria to antibacterial therapy poses an enormous health problem, it renders the development of new antibacterial agents with novel mechanism of action an urgent need. Peptide deformylase, a metalloenzyme which catalytically removes N-formyl group from N-terminal methionine of newly synthesized polypeptides, is an important target in antibacterial drug discovery. In this study, we report the structure-based virtual screening of ZINC database in order to discover potential hits as bacterial peptide deformylase enzyme inhibitors with more affinity as compared to GSK1322322, previously known inhibitor. After virtual screening, fifteen compounds of the top hits predicted were purchased and evaluated in vitro for their antibacterial activities against one Gram positive (Staphylococcus aureus) and three Gram negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella. pneumoniae) bacteria in different concentrations by disc diffusion method. Out of these, three compounds, ZINC00039650, ZINC03872971 and ZINC00126407, exhibited significant zone of inhibition. The results obtained were confirmed using the dilution method. Thus, these proposed compounds may aid the development of more efficient antibacterial agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Screening for Antibacterial and Antioxidant Activities and Phytochemical Analysis of Oroxylum indicum Fruit Extracts.

PubMed

Sithisarn, Patchima; Nantateerapong, Petcharat; Rojsanga, Piyanuch; Sithisarn, Pongtip

2016-04-07

Oroxylum indicum, which is called Pheka in Thai, is a traditional Thai plant in the Bignoniaceae family with various ethnomedical uses such as as an astringent, an anti-inflammatory agent, an anti-bronchitic agent, an anti-helminthic agent and an anti-microbial agent. The young fruits of this plant have also been consumed as vegetables. However, there has been no report concerning its antibacterial activities, especially activities related to clinically isolated pathogenic bacteria and the in vitro antioxidant effects of this plant. Therefore, the extracts from O. indicum fruits and seeds collected from different provinces in Thailand were prepared by decoction and maceration with ethanol and determined for their in vitro antibacterial effects on two clinically isolated bacteria, Streptococcus suis and Staphylococcus intermedius, using disc diffusion assay. Ethanol extracts from O. indicum fruits collected from Nakorn Pathom province at the concentration of 1000 mg/mL exhibited intermediate antibacterial activity against S. intermedius with an inhibition zone of 15.11 mm. Moreover, it promoted moderate inhibitory effects on S. suis with an inhibition zone of 14.39 mm. The extracts prepared by maceration with ethanol promoted higher antibacterial activities than those prepared with water. The ethanol extract from the seeds of this plant, purchased in Bangkok, showed stronger in vitro antioxidant activities than the other extracts, with an EC50 value of 26.33 µg/mL. Phytochemical analysis suggested that the seed ethanol extract contained the highest total phenolic and flavonoid contents (10.66 g% gallic acid equivalent and 7.16 g% quercetin equivalent, respectively) by a significant amount. Thin layer chromatographic analysis of the extracts showed the chromatographic band that could correspond to a flavonoid baicalein. From the results, extracts from O. indicum fruits have an in vitro antioxidant effect, with antibacterial potential, on clinically pathologic bacteria and they contain an antioxidant flavonoid which could be developed for medicinal and pharmaceutical purposes in the future.

Enabling virtual screening of potent and safer antimicrobial agents against noma: mtk-QSBER model for simultaneous prediction of antibacterial activities and ADMET properties.

PubMed

Speck-Planche, Alejandro; Cordeiro, M N D S

2015-01-01

Neglected diseases are infections that thrive mainly among underdeveloped countries, particularly those belonging to regions found in Asia, Africa, and America. One of the most complex diseases is noma, a dangerous health condition characterized by a polymicrobial and opportunistic nature. The search for potent and safer antibacterial agents against this disease is therefore a goal of particular interest. Chemoinformatics can be used to rationalize the discovery of drug candidates, diminishing time and financial resources. However, in the case of noma, there is no in silico model available for its use in the discovery of efficacious antibacterial agents. This work is devoted to report the first mtk-QSBER model, which integrates dissimilar kinds of chemical and biological data. The model was generated with the aim of simultaneously predicting activity against bacteria present in noma, and ADMET (absorption, distribution, metabolism, elimination, toxicity) parameters. The mtk-QSBER model was constructed by employing a large and heterogeneous dataset of chemicals and displayed accuracies higher than 90% in both training and prediction sets. We confirmed the practical applicability of the model by predicting multiple profiles of the investigational antibacterial drug delafloxacin, and the predictions converged with the experimental reports. To date, this is the first model focused on the virtual search for desirable anti-noma agents.

Facile Synthesis of Efficient Antibacterial Agent as CoFe₂O₄/Ag Composite Material Against Both Gram-Negative Escherichia coli and Gram-Positive Bacillus subtilis Bacteria.

PubMed

Gankhuyag, Sukhbayar; Lee, Kyoung; Bae, Dong Sik

2018-09-01

We have suggested that a facile synthesis of CoFe2O4/Ag composite material as an antibacterial agent for substitution of a chlorination agent for microbial infected wastewater treatment. The CoFe2O4/Ag was synthesized by an impregnation method in assistance with trisodium citrate as a reducing agent. The as-prepared uncalcined CoFe2O4 (CFG), calcined CoFe2O4 (CFG600), and calcined CoFe2O4/Ag (CFG600/Ag) composites were characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FE-SEM) and Energy Dispersive X-ray (EDX) techniques. Antibacterial activities were also determined in liquid culture by measuring the minimum inhibitory concentrations (MIC) against Gram-negative Escherichia coli (E. coli) and Gram-positive Bacillus subtilis (B. subtilis) bacteria in vitro. Results showed that CFG600/Ag composites had an excellent antibacterial activity in comparison with CFG and CFG600 composites. The CFG600/Ag composites have completely inhibited the growth of both E. coli and B. subtilis bacteria from concentrations of more than 0.25 mg/ml. Furthermore, the FE-SEM study demonstrated the physical damage of bacteria when treated with CFG600/Ag composite material at a concentration of 0.10 mg/ml.

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or “Immuno-Fairy Tales”?

PubMed Central

Labro, Marie-Thérése

2000-01-01

Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general. PMID:11023961

Potential Mechanism of Action of 3'-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus.

PubMed

Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María del Rayo

2015-07-08

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

Potential mechanism of action of 3'-demethoxy-6-O-demethyl-isoguaiacin on methicillin resistant Staphylococcus aureus.

PubMed

Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María Del Rayo

2015-07-08

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

Antibacterial and synergy of berberines with antibacterial agents against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Li, Yang; Han, Jun; Wang, Gen-Chun; Zhang, Yun-Ling; Bian, Zhong-Qi

2012-08-29

Antibacterial activity of berberine (Ber) and 8-acetonyl-dihydroberberine (A-Ber) alone and combined uses with antibacterial agents ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (μg/mL) ranges were 32-128/64-256 (Ber) and 32-128/128-512 (A-Ber). Significant synergies were observed for the Ber (A-Ber)/AZM and Ber (A-Ber)/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs) values ranged from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

Characterization of plasma treated surfaces for food safety by terahertz spectroscopy

NASA Astrophysics Data System (ADS)

Sulovská, Kateřina; Lehocký, Marián.

2014-10-01

A physico-chemical approach to modify surfaces not only for use in medicine, but also for preservation of food is nowadays widely studied to lower the risks of increased number of bacterial pathogens that are in a direct contact with people. Food safety is very important part of preserving sustainability during crises, especially after the enterohaemorrhagic Escherichia coli outbreak in Europe in 2011. One of the possibility how we can protect food against various pathogens is the modification of packing materials that are directly in contact with preserved food. This contribution deals with the characterization of modified surfaces with antibacterial properties via Terahertz spectroscopy. For the purpose of this paper, three monomers were used for grafting onto air radiofrequency plasma activated low density polyethylene surface, which created a brush-like structure. Next, the antibacterial agents, Irgasan and Chlorhexidine, were anchored to these surfaces. These antibacterial agents were selected for supposed effect on two most frequently occurring bacterial strains - Escherichia coli and Staphylococcus aureus. Materials were further tested for the presence of antibacterial agent molecules, in our case by means of terahertz spectroscopy. Each material was tested on two spectroscopes - the SPECTRA and the OSCAT terahertz instruments.

Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates.

PubMed

Asbell, Penny A; Colby, Kathryn A; Deng, Sophie; McDonnell, Peter; Meisler, David M; Raizman, Michael B; Sheppard, John D; Sahm, Daniel F

2008-06-01

Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. Laboratory investigation. Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.

In Vitro Studies on a Microfluidic Sensor with Embedded Obstacles Using New Antibacterial Synthetic Compounds (1-TDPPO) Mixed Prop-2-en-1-one with Difluoro Phenyl.

PubMed

Roh, Changhyun; Lee, Jaewoong; Kinger, Mayank; Kang, Chankyu

2017-04-08

This paper describes the use of an analytical microfluidic sensor for accelerating chemo-repellent response and strong anti-bacterial 1-(Thien-2-yl)-3-(2, 6-difluoro phenyl) prop-2-en-1-one (1-TDPPO). The chemically-synthesized antimicrobial agent, which included prop-2-en-1-one and difluoro phenyl groups, was moving through an optically transparent polydimethylsiloxane (PDMS) microfluidic sensor with circular obstacles arranged evenly. The response, growth and distribution of fluorescent labeling Pseudomonas aeruginosa PAO1 against the antimicrobial agent were monitored by confocal laser scanning microscope (CLSM). The microfluidic sensor along with 1-TDPPOin this study exhibits the following advantages: (i) Real-time chemo-repellent responses of cell dynamics; (ii) Rapid eradication of biofilm by embedded obstacles and powerful antibacterial agents, which significantly reduce the response time compared to classical methods; (iii) Minimal consumption of cells and antimicrobial agents; and (iv) Simplifying the process of the normalization of the fluorescence intensity and monitoring of biofilm by captured images and datasets.

Synthesis and antibacterial evaluation of calcinated Ag-doped nano-hydroxyapatite with dispersibility.

PubMed

Furuzono, Tsutomu; Motaharul, Mazumder; Kogai, Yasumichi; Azuma, Yoshinao; Sawa, Yoshiki

2015-05-01

Dispersible hydroxyapatite (HAp) nanoparticles are very useful for applying a monolayer to implantable medical devices using the nano-coating technique. To improve tolerance to infection on implanted medical devices, silver-doped HAp (Ag-HAp) nanoparticles with dispersiblity and crystallinity were synthesized, avoiding calcination-induced sintering, and evaluated for antibacterial activity. The Ca10-xAgx(PO4)6(OH)2 with x = 0 and 0.2 were prepared by wet chemical processing at 100°C. Before calcination at 700°C for 2 h, two kinds of anti-sintering agents, namely a Ca(NO3)2 (Ca salt) and a polyacrylic acid/Ca salt mixture (PAA-Ca), were used. Escherichia coli was used to evaluate the antibacterial activity of the nanopowder. When PAA-Ca was used as an anti-sintering agent in calcination to prepare the dispersible nanoparticles, strong metallic Ag peaks were observed at 38.1° and 44.3° (2θ) in the X-ray diffraction (XRD) profile. However, the Ag peak was barely observed when Ca salt was used alone as the anti-sintering agent. Thus, using Ca salt alone was more effective for preparation of dispersible Ag-HAp than PAA-Ca. The particle average size of Ag-HAp with 0.5 mol% of Ag content was found to be 325 ± 70 nm when the formation of large particleaggregations was prevented, as determined by dynamic light scattering instrument. The antibacterial activity of the Ag-HAp nanoparticles possessing 0.5 mol% against E. coli was greater than 90.0%. Dispersible and crystalline nano Ag-HAp can be obtained by using Ca salt alone as an anti-sintering agent. The nanoparticles showed antibacterial activity.

In Vitro Susceptibilities of Mycoplasma putrefaciens Field Isolates▿

PubMed Central

Antunes, N. T.; Tavío, M. M.; Mercier, P.; Ayling, R. D.; Al-Momani, W.; Assunção, P.; Rosales, R. S.; Poveda, J. B.

2007-01-01

MICs were determined for 15 antimicrobial agents against 37 Mycoplasma putrefaciens isolates. The most effective antimicrobial drug classes were the fluoroquinolones, the tetracyclines, the lincosamide lincomycin, and the macrolides. The susceptibility profile of the isolates correlated with the geographic origin. This is the first report of decreased susceptibility to the macrolides, lincomycin, and the tetracyclines in M. putrefaciens strains. PMID:17638695

Empirical treatment of bacterial keratitis: an international survey of corneal specialists.

PubMed

Austin, Ariana; Schallhorn, Julie; Geske, Mike; Mannis, Mark; Lietman, Tom; Rose-Nussbaumer, Jennifer

2017-08-01

New antibiotic agents and changing susceptibility patterns may have changed the empirical treatment of bacterial keratitis. Our objective in this study was to survey cornea specialists' practice patterns in the initial treatment of bacterial ulcers. This study consisted of a short online survey emailed to members of the Cornea Society listserv for an international sample of cornea specialists. Data collection began July 2014 and ended October 2014. A total of 1009 surveys were emailed, and we received 140 (14%) responses. The majority of US clinicians surveyed (n=83, 80%) chose fortified antibiotics empirically, with 55% (n=57) selecting fortified vancomycin and 16% (n=17) using fluoroquinolone alone. International respondents were twice as likely to use fluoroquinolone monotherapy (31%, n=11, p=0.07) and less likely to use fortified vancomycin (33%, n=12, p=0.03). Forty-five per cent (n=46) of US respondents reported that their initial antibiotic choice covered methicillin-resistant Staphylococcus aureus , compared with 22% (n=8) of international respondents (p<0.01). Overall, respondents who were concerned about availability of antibiotics and toxicity were 20.86 (p<0.001) and 7.48 (p<0.001) times more likely to choose fluoroquinolone monotherapy, respectively. If respondents' primary considerations were broad spectrum coverage or antibiotic resistance they had 7.10 (p<0.001) and 12.51 (p<0.001) times the odds of using fortified vancomycin, respectively. Practice patterns for the initial treatment of bacterial keratitis vary with clinicians in the USA being more likely to use fortified antibiotics versus fluoroquinolone monotherapy and more concerned with resistant organisms than their international peers.

Methyl-Hydroxylamine as an Efficacious Antibacterial Agent That Targets the Ribonucleotide Reductase Enzyme

PubMed Central

Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

2015-01-01

The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme. PMID:25782003

Influence of Moxifloxacin on Hepatic Redox Status and Plasma Biomarkers of Hepatotoxicity and Nephrotoxicity in Rat

PubMed Central

Olayinka, Ebenezer Tunde

2015-01-01

Moxifloxacin is a broad spectrum fluoroquinolone antibacterial agent. We examined the hepatic redox status and plasma biomarkers of nephrotoxicity and hepatotoxicity in rat following administration of moxifloxacin (MXF). Twenty-four Wistar rats, 180–200 g, were randomized into four groups (I–IV). Animals in group I (control) received 1 mL of distilled water, while animals in groups II, III, and IV received 1 mL each of MXF equivalent to 4 mg/kg b.w., 8 mg/kg b.w., and 16 mg/kg b.w., respectively. After seven days, plasma urea, bilirubin, and creatinine were significantly (P < 0.05) elevated in the MXF-treated animals. Activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were significantly increased in the plasma of MXF-treated animals compared to control. Also plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides increased significantly in the MXF-treated groups relative to control. Moreover, MXF triggered a significant decrease in hepatic catalase, superoxide dismutase, and glutathione-S transferase activities. Likewise, MXF caused a decrease in the hepatic levels of glutathione and vitamin C. A significant increase in hepatic MDA content was also observed in the MXF-treated animals relative to control. Overall, our data suggest that the half-therapeutic, therapeutic, and twice the therapeutic dose of MXF induced nephrotoxicity, hepatotoxicity, and altered hepatic redox balance in rats. PMID:26550491

Side Chain Degradable Cationic-Amphiphilic Polymers with Tunable Hydrophobicity Show in Vivo Activity.

PubMed

Uppu, Divakara S S M; Samaddar, Sandip; Hoque, Jiaul; Konai, Mohini M; Krishnamoorthy, Paramanandham; Shome, Bibek R; Haldar, Jayanta

2016-09-12

Cationic-amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic-amphiphilic polymers. Optimal hydrophobicity of cationic-amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic-amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions keeping constant cationic charge density for developing potent membrane-active antibacterial polymers with minimal toxicity to mammalian cells.

Mur Ligase Inhibitors as Anti-bacterials: A Comprehensive Review.

PubMed

Sangshetti, Jaiprakash N; Joshi, Suyog S; Patil, Rajendra H; Moloney, Mark G; Shinde, Devanand B

2017-01-01

Exploring a new target for antibacterial drug discovery has gained much attention because of the emergence of Multidrug Resistance (MDR) strains of bacteria. To overcome this problem the development of novel antibacterial was considered as highest priority task and was one of the biggest challenge since multiple factors were involved. The bacterial peptidoglycan biosynthetic pathway has been well documented in the last few years and has been found to be imperative source for the development of novel antibacterial agents with high target specificity as they are essential for bacterial survival and have no homologs in humans. We have therefore reviewed the process of peptidoglycan biosynthesis which involves various steps like formation of UDP-Nacetylglucosamine (GlcNAc), UDP-N-acetylmuramic acid (MurNAc) and lipid intermediates (Lipid I and Lipid II) which are controlled by various enzymes like GlmS, GlmM, GlmU enzyme, followed by Mur Ligases (MurAMurF) and finally by MraY and MurG respectively. These four amide ligases MurC-MurF can be used as the source for the development of novel multi-target antibacterial agents as they shared and conserved amino acid regions, catalytic mechanisms and structural features. This review begins with the need for novel antibacterial agents and challenges in their development even after the development of bacterial genomic studies. An overview of the peptidoglycan monomer formation, as a source of disparity in this process is presented, followed by detailed discussion of structural and functional aspects of all Mur enzymes and different chemical classes of their inhibitors along with their SAR studies and inhibitory potential. This review finally emphasizes on different patents and novel Mur inhibitors in the development phase. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

PubMed Central

Hong, Wei; Gao, Xiang; Qiu, Peng; Yang, Jie; Qiao, Mingxi; Shi, Hong; Zhang, Dexian; Tian, Chunlian; Niu, Shengli; Liu, Mingchun

2017-01-01

Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly (d,l-lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers. PMID:28721045

Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo.

PubMed

Hong, Wei; Gao, Xiang; Qiu, Peng; Yang, Jie; Qiao, Mingxi; Shi, Hong; Zhang, Dexian; Tian, Chunlian; Niu, Shengli; Liu, Mingchun

2017-01-01

Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly (d,l-lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA 5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers.

Natural Pathogen Control Chemistry to Replace Toxic Treatment of Microbes and Biofilm in Cooling Towers

PubMed Central

Brouse, Lon; Brouse, Richard; Brouse, Daniel

2017-01-01

Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms that grow in evaporative cooling water systems, but can adversely affect the environment and human health. However, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years to inhibit microorganisms with excellent results. The water chemistry method concentrates natural minerals in highly-softened water to produce elevated pH and dissolved solids, while maintaining low calcium and magnesium content. The method provides further benefits in water conservation, and generates a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This report describes the antimicrobial effects of these chemistry modifications in the cooling water environment and the resultant collective inhibition of microbes, biofilm, and pathogen growth. This article also presents a novel perspective of parasitic microbiome functional relationships, including “Trojan Protozoans” and biofilms, and the function of polyvalent metal ions in the formation and inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Concurrently, scientists have concluded that discharge of antibacterial agents plays a key role in development of pathogen resistance to antimicrobials as well as antibiotics. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner. PMID:28420074

Susceptibilities of Legionella spp. to Newer Antimicrobials In Vitro

PubMed Central

Schülin, T.; Wennersten, C. B.; Ferraro, M. J.; Moellering, R. C.; Eliopoulos, G. M.

1998-01-01

The in vitro activities of 13 antimicrobial agents against 30 strains of Legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC90s], ≤0.008 μg/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC90s, 0.03 to 0.06 μg/ml) were more active than erythromycin A or roxithromycin. The MIC90s of dalfopristin-quinupristin and linezolid were 0.5 and 8 μg/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of Legionella infections. PMID:9624509

Myeloperoxidase-Halide-Hydrogen Peroxide Antibacterial System

PubMed Central

Klebanoff, Seymour J.

1968-01-01

An antibacterial effect of myeloperoxidase, a halide, such as iodide, bromide, or chloride ion, and H2O2 on Escherichia coli or Lactobacillus acidophilus is described. When L. acidophilus was employed, the addition of H2O2 was not required; however, the protective effect of catalase suggested that, in this instance, H2O2 was generated by the organisms. The antibacterial effect was largely prevented by preheating the myeloperoxidase at 80 C or greater for 10 min or by the addition of a number of inhibitors; it was most active at the most acid pH employed (5.0). Lactoperoxidase was considerably less effective than was myeloperoxidase when chloride was the halide employed. Myeloperoxidase, at high concentrations, exerted an antibacterial effect on L. acidophilus in the absence of added halide, which also was temperature- and catalase-sensitive. Peroxidase was extracted from intact guinea pig leukocytes by weak acid, and the extract with peroxidase activity had antibacterial properties which were similar, in many respects, to those of the purified preparation of myeloperoxidase. Under appropriate conditions, the antibacterial effect was increased by halides and by H2O2 and was decreased by catalase, as well as by cyanide, azide, Tapazole, and thiosulfate. This suggests that, under the conditions employed, the antibacterial properties of a weak acid extract of guinea pig leukocytes is due, in part, to its peroxidase content, particularly if a halide is present in the reaction mixture. A heat-stable antibacterial agent or agents also appear to be present in the extract. PMID:4970226

ANTIBACTERIAL ACTIVITY OF DRACONTOMELON DAO EXTRACTS ON METHICILLIN-RESISTANT S. AUREUS (MRSA) AND E. COLI MULTIPLE DRUG RESISTANCE (MDR).

PubMed

Yuniati, Yuniati; Hasanah, Nurul; Ismail, Sjarif; Anitasari, Silvia; Paramita, Swandari

2018-01-01

Staphylococcus aureus , methicillin-resistant and Escherichia coli , multidrug-resistant included in the list of antibiotic-resistant priority pathogens from WHO. As multidrug-resistant bacteria problem is increasing, it is necessary to probe new sources for identifying antimicrobial compounds. Medicinal plants represent a rich source of antimicrobial agents. One of the potential plants for further examined as antibacterial is Dracontomelon dao (Blanco) Merr. & Rolfe. The present study designed to find the antibacterial activity of D. dao stem bark extracts on Methicillin-resistant S. aureus (MRSA) and E. coli Multiple Drug Resistance (MDR), followed by determined secondary metabolites with antibacterial activity and determined the value of MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration). D. dao stem bark extracted using 60% ethanol. Disc diffusion test methods used to find the antibacterial activity, following by microdilution methods to find the value of MIC and MBC. Secondary metabolites with antibacterial activity determined by bioautography using TLC (thin layer chromatography) methods. D. dao stem bark extracts are sensitive to MSSA, MRSA and E.coli MDR bacteria. The inhibition zone is 16.0 mm in MSSA, 11.7 mm in MRSA and 10.7 mm in E. coli MDR. The entire MBC/MIC ratios for MSSA, MRSA and E.coli MDR is lower than 4. The ratio showed bactericidal effects of D. dao stem bark extracts. In TLC results, colorless bands found to be secondary metabolites with antibacterial activity. D. dao stem bark extracts are potential to develop as antibacterial agent especially against MRSA and E. coli MDR strain.

Nano-ZnO/ZnO-HAPw prepared via sol-gel method and antibacterial activities of inorganic agents on six bacteria associated with oral infections

NASA Astrophysics Data System (ADS)

Jin, Jianfeng; Liu, Wenying; Zhang, Wenyun; Chen, Qinghua; Yuan, Yanbo; Yang, Lidou; Wang, Qintao

2014-10-01

The antibacterial activity of zinc oxide (ZnO) and the strengthening of hydroxylapatite whiskers (HAPws) have been widely studied and applied. However, the antibacterial properties of ZnO-HAPws have scarcely been researched. The aim of this study was to further investigate several types of nano-ZnO morphologies of ZnO-HAPws that were prepared using the sol-gel method at different pondus hydrogenii (pH) values and temperatures. The four morphologies of ZnO-HAPws that were investigated here were granule, triangle, short rod and disc type, and these morphologies were investigated at 70 °C at pH 6.4, 37 °C at pH 6.6, 70 °C at pH 6.6 and 70 °C at pH 6.6, respectively. Next, the antibacterial activity of ZnO-HAPw was compared to that of nano-ZnO, commercially available ZnO and tetrapod-like ZnO whiskers (T-ZnOw) with six bacteria that are associated with oral infections: Streptococcus mutans, Lactobacillus casei, Candida albicans, Actinomyces viscosus, Staphylococcus aureus and Escherichia coli. The results of examinations of the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) showed that the antibacterial activity of ZnO-HAPw exceeded that of the commercially available ZnO and T-ZnOw. Additionally, analysis of variance (ANOVA) analysis of the MBCs revealed that the four tested antibacterial agents had significantly different effects on S. mutans ( F = 8.940; P = 0.006), S. aureus ( F = 6.924; P = 0.013) and E. coli ( F = 4.468; P = 0.04). ANOVA analyses of the MICs revealed that the four tested antibacterial agents had significantly different effects on S. mutans ( F = 6.183; P = 0.018), A. viscosus ( F = 4.531; P = 0.039) and S. aureus ( F = 18.976; P = 0.001).

Synthesis and Bioactivity Evaluation of N-Arylsulfonylindole Analogs Bearing a Rhodanine Moiety as Antibacterial Agents.

PubMed

Song, Ming-Xia; Li, Song-Hui; Peng, Jiao-Yang; Guo, Ting-Ting; Xu, Wen-Hui; Xiong, Shao-Feng; Deng, Xian-Qing

2017-06-14

Due to the rapidly growing bacterial resistance to antibiotics and the scarcity of novel agents under development, bacterial infections are still a pressing global problem, making new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, urgently needed. In this paper, seven series of N -arylsulfonylindole analogs 5 - 11 bearing rhodanine moieties were synthesized, characterized, and evaluated for antibacterial activity. According to the in vitro antimicrobial results, half of the synthesized compounds showed potent inhibition against four Gram-positive bacteria, with MIC values in the range of 0.5-8 µg/mL. For multidrug-resistant strains, compounds 6a and 6c were the most potent, with MIC values of 0.5 µg/mL, having comparable activity to gatifloxacin, moxiflocaxin and norfloxacin and being 128-fold more potent than oxacillin (MIC = 64 µg/mL) and 64-fold more active than penicillin (MIC = 32 µg/mL) against Staphylococcus aureus ATCC 43300 .

[In vitro comparison of antibacterial properties of antiseptics used in periodontology].

PubMed

Bezdenezhnykh, D S; Rusanova, E V; Nikitin, A A; Malychenko, N V

2012-01-01

Antibacterial properties of antiseptics most commonly used in periodontology were examined in vitro showing al agents containing chlorhexidine to be the most effective against gram-negative (E. coli), gram-positive (staphylococcus, streptococcus, enterococcus) germs as well as а C. аlbicans.

Modification of titanium surfaces by adding antibiotic-loaded PHB spheres and PEG for biomedical applications.

PubMed

Rodríguez-Contreras, Alejandra; Marqués-Calvo, María Soledad; Gil, Francisco Javier; Manero, José María

2016-08-01

Novel researches are focused on the prevention and management of post-operative infections. To avoid this common complication of implant surgery, it is preferable to use new biomaterials with antibacterial properties. Therefore, the aim of this work is to develop a method of combining the antibacterial properties of antibiotic-loaded poly(3-hydroxybutyrate) (PHB) nano- and micro-spheres and poly(ethylene glycol) (PEG) as an antifouling agent, with titanium (Ti), as the base material for implants, in order to obtain surfaces with antibacterial activity. The Ti surfaces were linked to both PHB particles and PEG by a covalent bond. This attachment was carried out by firstly activating the surfaces with either Oxygen plasma or Sodium hydroxide. Further functionalization of the activated surfaces with different alkoxysilanes allows the reaction with PHB particles and PEG. The study confirms that the Ti surfaces achieved the antibacterial properties by combining the antibiotic-loaded PHB spheres, and PEG as an antifouling agent.

Novel substituted (pyridin-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility.

PubMed

Reck, Folkert; Zhou, Fei; Eyermann, Charles J; Kern, Gunther; Carcanague, Dan; Ioannidis, Georgine; Illingworth, Ruth; Poon, Grace; Gravestock, Michael B

2007-10-04

Oxazolidinones represent a new and promising class of antibacterial agents. Current research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Oxazolidinones bearing a (pyridin-3-yl)phenyl moiety (e.g., 3) generally show improved antibacterial activity compared to linezolid but suffer from potent monoamine oxidase A (MAO-A) inhibition and low solubility. We now disclose the finding that new analogues of 3 with acyclic substituents on the pyridyl moiety exhibit excellent activity against Gram-positive pathogens, including linezolid-resistant Streptococcus pneumoniae. Generally, more bulky substituents yielded significantly reduced MAO-A inhibition relative to the unsubstituted compound 3. The MAO-A SAR can be rationalized on the basis of docking studies using a MAO-A/MAO-B homology model. Solubility was enhanced with incorporation of polar groups. One optimized analogue, compound 13, showed low clearance in the rat and efficacy against S. pneumoniae in a mouse pneumonia model.

Design and evaluation of anacardic acid derivatives as anticavity agents.

PubMed

Green, Ivan R; Tocoli, Felismino E; Lee, Sang Hwa; Nihei, Ken-ichi; Kubo, Isao

2008-06-01

On the basis of antibacterial anacardic acids, 6-pentadecenylsalicylic acids, isolated from the cashew apple, Anacardium occidentale L. (Anacardiaceae), a series of 6-alk(en)ylsalicylic acids were synthesized and tested for their antibacterial activity against Streptococcus mutans ATCC 25175. Among them, 6-(4',8'-dimethylnonyl)salicylic acid was found to exhibit the most potent antibacterial activity against this cariogenic bacterium with the minimum inhibition concentration (MIC) of 0.78 microg/ml.

Antibacterial effect of cationic porphyrazines and anionic phthalocyanine and their interaction with plasmid DNA

NASA Astrophysics Data System (ADS)

Hassani, Leila; Hakimian, Fatemeh; Safaei, Elham; Fazeli, Zahra

2013-11-01

Resistance to antibiotics is a public health issue and identification of new antibacterial agents is one of the most important goals of pharmacological research. Among the novel developed antibacterial agents, porphyrin complexes and their derivatives are ideal candidates for use in medical applications. Phthalocyanines differ from porphyrins by having nitrogen atoms link the individual pyrrol units. The aza analogues of the phthalocyanines (azaPcs) such as tetramethylmetalloporphyrazines are heterocyclic Pc analogues. In this investigation, interaction of an anionic phthalocyanine (Cu(PcTs)) and two cationic tetrapyridinoporphyrazines including [Cu(2,3-tmtppa)]4+ and [Cu(3,4-tmtppa)]4+ complexes with plasmid DNA was studied using spectroscopic and gel electrophoresis methods. In addition, antibacterial effect of the complexes against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was investigated using dilution test method. The results indicated that both porphyrazines have significant antibacterial properties, but Cu(PcTs) has weak antibacterial effect. Compairing the binding of the phthalocyanine and the porphyrazines to DNA demonstrated that the interaction of cationic porphyrazines is stronger than the anionic phthalocyanine remarkably. The extent of hypochromicity and red shift of absorption spectra indicated preferential intercalation of the two porphyrazine into the base pairs of DNA helix. Gel electrophoresis result implied Cu(2,3-tmtppa) and Cu(3,4-tmtppa) are able to perform cleavage of the plasmid DNA. Consequently, DNA binding and cleavage might be one of the antibacterial mechanisms of the complexes.

Functional gold nanoparticle-based antibacterial agents for nosocomial and antibiotic-resistant bacteria.

PubMed

Kuo, Yen-Ling; Wang, Sin-Ge; Wu, Ching-Yi; Lee, Kai-Chieh; Jao, Chan-Jung; Chou, Shiu-Huey; Chen, Yu-Chie

2016-10-01

Medical treatments for bacterial-infections have become challenging because of the emergence of antibiotic-resistant bacterial strains. Thus, new therapeutics and antibiotics must be developed. Arginine and tryptophan can target negatively-charged bacteria and penetrate bacterial cell membrane, respectively. Synthetic-peptides containing arginine, tryptophan and cysteine termini, in other words, (DVFLG)2REEW4C and (DVFLG)2REEW2C, as starting materials were mixed with aqueous tetrachloroauric acid to generate peptide-immobilized gold nanoparticles (i.e., [DVFLG]2REEW4C-AuNPs and [DVFLG]2REEW2C-AuNPs) through one-pot reactions. The peptide immobilized AuNPs exhibit targeting capacity and antibacterial activity. Furthermore, (DVFLG)2REEW4C-AuNPs immobilized with a higher number of tryptophan molecules possess more effective antibacterial capacity than (DVFLG)2REEW2C-AuNPs. Nevertheless, they are not harmful for animal cells. The feasibility of using the peptide-AuNPs to inhibit the cell growth of bacterium-infected macrophages was demonstrated. These results suggested that the proposed antibacterial AuNPs are effective antibacterial agents for Staphylococci, Enterococci and antibiotic-resistant bacterial strains. [Formula: see text].

In vitro activities of sitafloxacin (DU-6859a) and six other fluoroquinolones against 8,796 clinical bacterial isolates.

PubMed

Milatovic, D; Schmitz, F J; Brisse, S; Verhoef, J; Fluit, A C

2000-04-01

The in vitro activities of sitafloxacin, ciprofloxacin, trovafloxacin, levofloxacin, clinafloxacin, gatifloxacin, and moxifloxacin against 5,046 gram-negative bacteria, 3,344 gram-positive cocci, and 406 anaerobes were determined. Sitafloxacin was the most active agent against gram-positive cocci and anaerobes. Against Enterobacteriaceae and nonfermenters, its activity was either equivalent to or better than that of clinafloxacin.

New target for inhibition of bacterial RNA polymerase: 'switch region'.

PubMed

Srivastava, Aashish; Talaue, Meliza; Liu, Shuang; Degen, David; Ebright, Richard Y; Sineva, Elena; Chakraborty, Anirban; Druzhinin, Sergey Y; Chatterjee, Sujoy; Mukhopadhyay, Jayanta; Ebright, Yon W; Zozula, Alex; Shen, Juan; Sengupta, Sonali; Niedfeldt, Rui Rong; Xin, Cai; Kaneko, Takushi; Irschik, Herbert; Jansen, Rolf; Donadio, Stefano; Connell, Nancy; Ebright, Richard H

2011-10-01

A new drug target - the 'switch region' - has been identified within bacterial RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new target serves as the binding site for compounds that inhibit bacterial RNA synthesis and kill bacteria. Since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. Since the new target is different from targets of other antibacterial agents, compounds that bind to the new target are not cross-resistant with other antibacterial agents. Four antibiotics that function through the new target have been identified: myxopyronin, corallopyronin, ripostatin, and lipiarmycin. This review summarizes the switch region, switch-region inhibitors, and implications for antibacterial drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents.

PubMed

Liu, Jia-Jia; Zhao, Meng-Yue; Zhang, Xin; Zhao, Xin; Zhu, Hai-Liang

2013-11-01

Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

Thymbra capitata essential oil as potential therapeutic agent against Gardnerella vaginalis biofilm-related infections.

PubMed

Machado, Daniela; Gaspar, Carlos; Palmeira-de-Oliveira, Ana; Cavaleiro, Carlos; Salgueiro, Lígia; Martinez-de-Oliveira, José; Cerca, Nuno

2017-04-01

To evaluate the antibacterial activity of Thymbra capitata essential oil and its main compound, carvacrol, against Gardnerella vaginalis grown planktonically and as biofilms, and its effect of vaginal lactobacilli. Minimal inhibitory concentration, minimal lethal concentration determination and flow cytometry analysis were used to assess the antibacterial effect against planktonic cells. Antibiofilm activity was measured through quantification of biomass and visualization of biofilm structure by confocal laser scanning microscopy. T. capitata essential oil and carvacrol exhibited a potent antibacterial activity against G. vaginalis cells. Antibiofilm activity was more evident with the essential oil than carvacrol. Furthermore, vaginal lactobacilli were significantly more tolerant to the essential oil. T. capitata essential oil stands up as a promising therapeutic agent against G. vaginalis biofilm-related infections.

Antibacterial agents in composite restorations for the prevention of dental caries.

PubMed

Pereira-Cenci, Tatiana; Cenci, Maximiliano S; Fedorowicz, Zbys; Azevedo, Marina

2013-12-17

Dental caries is a multifactorial disease in which the fermentation of food sugars by bacteria from the biofilm (dental plaque) leads to localised demineralisation of tooth surfaces, which may ultimately result in cavity formation. Resin composites are widely used in dentistry to restore teeth. These restorations can fail for a number of reasons, such as secondary caries, and restorative material fracture and other minor reasons. From these, secondary caries, which are caries lesions developed adjacent to restorations, is the main cause for restorations replacement. The presence of antibacterials in both the filling material and the bonding systems would theoretically be able to affect the initiation and progression of caries adjacent to restorations. This is an update of the Cochrane review published in 2009. To assess the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 23 July 2013) and EMBASE via OVID (1980 to 23 July 2013). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov), the metaRegister of Controlled Trials (www.controlled-trials.com) and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing resin composite restorations containing antibacterial agents with composite restorations not containing antibacterial agents. Two review authors conducted screening of studies in duplicate and independently, and although no eligible trials were identified, the two authors had planned to extract data independently and assess trial quality using standard Cochrane Collaboration methodologies. We retrieved 308 references to studies, none of which matched the inclusion criteria for this review and all of which were excluded. We were unable to identify any randomised controlled trials on the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. The absence of high level evidence for the effectiveness of this intervention emphasises the need for well designed, adequately powered, randomised controlled clinical trials. Thus, conclusions remain the same as the previously published review, with no included clinical trials.

In Vitro Activity of Delafloxacin Tested against Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

PubMed Central

Rhomberg, Paul R.; Huband, Michael D.; Farrell, David J.

2016-01-01

Delafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested. MIC50 and MIC90 values against all S. pneumoniae isolates were 0.008 and 0.015 μg/ml. Delafloxacin susceptibility was not affected by β-lactamase status against H. influenzae and M. catarrhalis. PMID:27458220

Synthesis, anti-MRSA, and anti-VRE activity of hemin conjugates with amino acids and branched peptides.

PubMed

Okorochenkov, Sergei A; Zheltukhina, Galina A; Mirchink, Elena P; Isakova, Elena B; Feofanov, Alexey V; Nebolsin, Vladimir E

2013-10-01

The increasing prevalence of antibiotic-resistant bacterial strains has necessitated the synthesis of novel antibacterial agents. It was previously shown that naturally occurring metalloporphyrin hemin possesses dark antibacterial activity against Gram-positive bacteria. To improve hemin antibacterial activity, we synthesized a number of hemin conjugates with amino acids and branched peptides. Arginine-containing hemin conjugates demonstrated high antibacterial activity against Gram-positive bacteria including methicillin- and vancomycin-resistant strains in vitro. Most of the synthesized conjugates showed low toxicity against human erythrocytes and leukocytes. © 2013 John Wiley & Sons A/S.

Efficacy of Management for Rational Use of Antibiotics in Surgical Departments at a Multi-Disciplinary Hospital: Results of a 7-year Pharmacoepidemiological Research.

PubMed

Korableva, A A; Yudina, E V; Ziganshina, L E

Irrational medicine use including excessive use and abuse of antibiotics remains a crucial problem for the healthcare systems. In this regard, studies examining approaches to improving the clinical use of medicines are highly important. to assess the efficacy rate of management for the rational use of antibiotics in surgical departments of a multi-disciplinary hospital. The intervention complex combined the research, educational, and methodological activities: local protocols for perioperative antibiotic prophylaxis (PABP) for various surgical departments were developed; local PABP protocols were discussed with the physicians of specialized surgical departments; official order on implementation of PABP was issued; the list of drug prescriptions for registration of the first pre-operative antibiotic dose was changed; audit and feedback processes were introduced as well as consultations of a clinical pharmacologist were implemented. We assessed the efficacy rate of the interventions basing on the changes in consumption of antibiotics (both quantitatively and qualitatively) at surgical departments of a hospital using ATC/DDD methodology. Comparison of the studied outcomes was performed before and after the intervention implementation and between the departments (vascular and abdominal surgery). The consumption of antibacterial agents (ATCJ01) was measured as a number of defined daily doses (DDD) per 100 bed-days (DDD/100 bed-days, indicator recommended by the World Health Organization, WHO) and DDD per 100 treated patients (DDD/100 treated patients). From 2006 to 2012, a decrease in antibacterial consumption in surgical departments by 188 DDD/100 treated patients was observed. We obtained the opposite results when using an indicator of DDD/100 bed-days (increase by 2.5 DDD/100 bed-days) which could be explained by the dependence on indices of overall hospital work and its changes during the examined period. Observed changes in antibacterial consumption varied in different surgical departments. The most pronounced positive changes were noted in the department of vascular surgery: decrease in total antibacterial consumption by 298 DDD/100 treated patients, decrease in the use of cephalosporins of the III generation from 141 to 38 DDD/100 treated patients. These positive changes were accompanied by the same (low) level of consumption/use of reserve antibiotics. In the department of abdominal surgery, there was no decrease in total antibiotic consumption, as well as in consumption of broad-spectrum cephalosporins of the III generation and fluoroquinolones, and we observed an increase in the use of reserve antibiotics (carbapenems) during the study period. Positive changes in antibiotic consumption were associated with the positive attitude of the manager/head of the department towards interventions: we observed the most pronounced decrease in antibiotic consumption straight after the publication of the administrative order on perioperative antibacterial prophylaxis. The combination of scientific, educational, and methodological interventions is effective for improving antibiotic application. The study results provide the rationale for analyzing the drug consumption using the DDD/100 treated patients measure in addition to the WHO-recommended indicator of DDD/100 bed-days which depends on overall hospital performance.

Simultaneous Delivery of Multiple Antibacterial Agents from Additively Manufactured Porous Biomaterials to Fully Eradicate Planktonic and Adherent Staphylococcus aureus.

PubMed

Bakhshandeh, S; Gorgin Karaji, Z; Lietaert, K; Fluit, A C; Boel, C H E; Vogely, H C; Vermonden, T; Hennink, W E; Weinans, H; Zadpoor, A A; Amin Yavari, S

2017-08-09

Implant-associated infections are notoriously difficult to treat and may even result in amputation and death. The first few days after surgery are the most critical time to prevent those infections, preferably through full eradication of the micro-organisms entering the body perioperatively. That is particularly important for patients with a compromised immune system such as orthopedic oncology patients, as they are at higher risk for infection and complications. Full eradication of bacteria is, especially in a biofilm, extremely challenging due to the toxicity barrier that prevents delivery of high doses of antibacterial agents. This study aimed to use the potential synergistic effects of multiple antibacterial agents to prevent the use of toxic levels of these agents and achieve full eradication of planktonic and adherent bacteria. Silver ions and vancomycin were therefore simultaneously delivered from additively manufactured highly porous titanium implants with an extremely high surface area incorporating a bactericidal coating made from chitosan and gelatin applied by electrophoretic deposition (EPD). The presence of the chitosan/gelatin (Ch+Gel) coating, Ag, and vancomycin (Vanco) was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The release of vancomycin and silver ions continued for at least 21 days as measured by inductively coupled plasma (ICP) and UV-spectroscopy. Antibacterial behavior against Staphylococcus aureus, both planktonic and in biofilm, was evaluated for up to 21 days. The Ch+Gel coating showed some bactericidal behavior on its own, while the loaded hydrogels (Ch+Gel+Ag and Ch+Gel+Vanco) achieved full eradication of both planktonic and adherent bacteria without causing significant levels of toxicity. Combining silver and vancomycin improved the release profiles of both agents and revealed a synergistic behavior that further increased the bactericidal effects.

Simultaneous Delivery of Multiple Antibacterial Agents from Additively Manufactured Porous Biomaterials to Fully Eradicate Planktonic and Adherent Staphylococcus aureus

PubMed Central

2017-01-01

Implant-associated infections are notoriously difficult to treat and may even result in amputation and death. The first few days after surgery are the most critical time to prevent those infections, preferably through full eradication of the micro-organisms entering the body perioperatively. That is particularly important for patients with a compromised immune system such as orthopedic oncology patients, as they are at higher risk for infection and complications. Full eradication of bacteria is, especially in a biofilm, extremely challenging due to the toxicity barrier that prevents delivery of high doses of antibacterial agents. This study aimed to use the potential synergistic effects of multiple antibacterial agents to prevent the use of toxic levels of these agents and achieve full eradication of planktonic and adherent bacteria. Silver ions and vancomycin were therefore simultaneously delivered from additively manufactured highly porous titanium implants with an extremely high surface area incorporating a bactericidal coating made from chitosan and gelatin applied by electrophoretic deposition (EPD). The presence of the chitosan/gelatin (Ch+Gel) coating, Ag, and vancomycin (Vanco) was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The release of vancomycin and silver ions continued for at least 21 days as measured by inductively coupled plasma (ICP) and UV-spectroscopy. Antibacterial behavior against Staphylococcus aureus, both planktonic and in biofilm, was evaluated for up to 21 days. The Ch+Gel coating showed some bactericidal behavior on its own, while the loaded hydrogels (Ch+Gel+Ag and Ch+Gel+Vanco) achieved full eradication of both planktonic and adherent bacteria without causing significant levels of toxicity. Combining silver and vancomycin improved the release profiles of both agents and revealed a synergistic behavior that further increased the bactericidal effects. PMID:28696671

New treatment options for lower respiratory tract infections.

PubMed

Kocsis, Bela; Szabo, Dora

2017-09-01

Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are among the most frequent lower respiratory tract infections (LRTIs). They represent an increased morbidity and mortality rate in adults. Areas covered: This review describes recent advances regarding solithromycin, zabofloxacin and delafoxacin antibacterial agents that have been recently developed for treatment of CAP and in AECOPD. All of them have been introduced into phase III clinical trials. We will be summarising chemical structures, pharmacokinetics, antibacterial efficacy and toxicity of these agents. The manuscript has been prepared based on available scientific publications. Expert opinion: Novel agents of known antimicrobial classes have been developed that demonstrate treatment options in CAP and in AECOPD. Antimicrobials discussed in this review showed bactericide effect against major respiratory tract pathogens. Each has multiple targets in bacteria, thus enabling them for more potency, even against strains exhibiting resistance to commonly used antibiotics. Solithromycin, delafloxacin and zabofloxcian demonstrate broad-spectrum antibacterial activity together with other beneficial features like intracellular accumulation, anti-inflammatory effect and inhibition of biofilm production. These agents showed moderately severe or mild adverse events and demonstrated favourable tissue penetration. These features can make solithromycin, zabofloxacin and delafloxacin treatment options in LRTIs.

In Vitro Evaluation of Delafloxacin Activity when Tested Against Contemporary community-Acquired Bacterial Respiratory Tract Infection Isolates (2014–2016): Results from the Sentry Antimicrobial Surveillance Program

PubMed Central

Shortridge, Dee; Streit, Jennifer M; Huband, Michael D; Rhomberg, Paul R; Flamm, Robert K

2017-01-01

Abstract Background Delafloxacin (DLX) is a broad-spectrum fluoroquinolone (FQ) antibacterial that has completed clinical development (oral and intravenous formulations) with the new drug application currently under the Food and Drug Administration review for the treatment of acute bacterial skin and skin structure infections (ABSSSI). DLX is also in clinical trials for community-acquired bacterial pneumonia. In this study, in vitro susceptibility results for DLX and comparator agents were determined for clinical isolates from community-acquired respiratory tract infections (CA-RTI) collected in medical centers in the United States and Europe participating in the SENTRY surveillance program during 2014–2016. Methods A total of 3,093 isolates that included 1,673 Streptococcus pneumoniae (SPN), 805 Haemophilus influenzae (HI) and 555 Moraxella catarrhalis (MC) were collected during 2014–2016 and included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI reference broth microdilution methodology, and results were interpreted per CLSI (2017) breakpoints. Other antibacterials tested included levofloxacin (LVX) and penicillin. Β-lactamase production for HI and MC was determined by the nitrocephin disk test. Results DLX demonstrated potent in vitro activity against SPN (MIC50/90 0.015/0.03 mg/L). Activity remained the same for penicillin-intermediate or -resistant isolates. For 23 LVX nonsusceptible SPN, the DLX MIC50/90 were 0.12/0.25 mg/L with all isolates having DLX MIC values ≤1 mg/L. For HI, the DLX MIC50/90 were ≤0.001/0.004 mg/L, and for MC the MIC50/90 were 0.008/0.008 mg/L. DLX activity was unaffected by the presence of β-lactamase for either HI or MC. Activity of DLX was similar for US and European isolates. Conclusion Delafloxacin demonstrated potent in vitro antibacterial activity against CA-RTI pathogens, including SPN, HI, and MC. These data support the continued study of DLX as a potential treatment for community-acquired pneumonia. Disclosures D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant; J. M. Streit, Melinta Therapeutics: Research Contractor, Research grant; M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant; P. R. Rhomberg, Melinta Therapeutics: Research Contractor, Research grant; R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant

Design and Solution-Phase Synthesis of Membrane-Targeting Lipopeptides with Selective Antibacterial Activity.

PubMed

Konai, Mohini M; Adhikary, Utsarga; Haldar, Jayanta

2017-09-18

Designing selective antibacterial molecules remains an unmet goal in the field of membrane-targeting agents. Herein, we report the rational design and synthesis of a new class of lipopeptides, which possess highly selective bacterial killing over mammalian cells. The selective interaction with bacterial over mammalian membranes was established through various spectroscopic, as well as microscopic experiments, including biophysical studies with the model membranes. A detailed antibacterial structure-activity relationship was delineated after preparing a series of molecules consisting of the peptide moieties with varied sequence of amino acids, such as d-phenylalanine, d-leucine, and d-lysine. Antibacterial activity was found to vary with the nature and positioning of hydrophobicity in the molecules, as well as number of positive charges. Optimized lipopeptide 9 did not show any hemolytic activity even at 1000 μg mL -1 and displayed >200-fold and >100-fold selectivity towards S. aureus and E. coli, respectively. More importantly, compound 9 was found to display good antibacterial activity (MIC 6.3-12.5 μg mL -1 ) against the five top most critical bacteria according to World Health Organization (WHO) priority pathogens list. Therefore, the results suggested that this new class of lipopeptides bear real promises for the development as future antibacterial agents. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of quaternary ammonium-containing with nano-silver-containing adhesive in antibacterial properties and cytotoxicity

PubMed Central

Li, Fang; Weir, Michael D.; Chen, Jihua; Xu, Hockin H. K.

2013-01-01

Objective Antibacterial primer and adhesive are promising to help combat biofilms and recurrent caries. The objectives of this study were to compare novel bonding agent containing quaternary ammonium dimethacrylate (QADM) with bonding agent containing nanoparticles of silver (NAg) in antibacterial activity, contact-inhibition vs. long-distance inhibition, glucosyltransferases (gtf) gene expressions, and cytotoxicity for the first time. Methods QADM and NAg were incorporated into Scotchbond Multi-Purpose adhesive and primer. Microtensile dentin bond strength was measured. Streptococcus mutans (S. mutans) biofilm on resin surface (contact-inhibition) as well as S. mutans in culture medium away from the resin surface (long-distance inhibition) were tested for metabolic activity, colony-forming units (CFU), lactic acid production, and gtf gene expressions. Eluents from cured primer/adhesive samples were used to examine cytotoxicity against human gingival fibroblasts. Results Bonding agent with QADM greatly reduced CFU and lactic acid of biofilms on the resin surface (p < 0.05), while having no effect on S. mutans in culture medium away from the resin surface. In contrast, bonding agent with NAg inhibited not only S. mutans on the resin surface, but also S. mutans in culture medium away from the resin surface. Bonding agent with QADM suppressed gtfB, gtfC and gtfD gene expressions of S. mutans on its surface, but not away from its surface. Bonding agent with NAg suppressed S. mutans gene expressions both on its surface and away from its surface. Bonding agents with QADM and NAg did not adversely affect microtensile bond strength or fibroblast cytotoxicity, compared to control (p > 0.1). Significance QADM-containing adhesive had contact-inhibition and inhibited bacteria on its surface, but not away from its surface. NAg-containing adhesive had long-distance killing capability and inhibited bacteria on its surface and away from its surface. The novel antibacterial adhesives are promising for caries-inhibition restorations, and QADM and NAg could be complimentary agents in inhibiting bacteria on resin surface as well as away from resin surface. PMID:23428077

Diversity of Endophytic Bacteria in a Fern Species Dryopteris uniformis (Makino) Makino and Evaluation of Their Antibacterial Potential Against Five Foodborne Pathogenic Bacteria.

PubMed

Das, Gitishree; Park, Seonjoo; Baek, Kwang-Hyun

2017-05-01

The fern plant Dryopteris uniformis has traditionally been used in herbal medicine and possesses many biological activities. This study was conducted to explore the endophytic bacterial diversity associated with D. uniformis and evaluate their antibacterial potential against foodborne pathogenic bacteria (FPB). Among 51 isolated endophytic bacteria (EB), 26 EB were selected based on their morphological characteristics and identified by 16S rRNA gene analysis. The distribution of EB was diverse in the leaf and the stem/root tissues. When the EB were screened for antibacterial activity against five FPB, Listeria monocytogenes, Salmonella Typhimurium, Bacillus cereus, Staphylococcus aureus, and Escherichia coli O157:H7, four EB Bacillus sp. cryopeg, Paenibacillus sp. rif200865, Staphylococcus warneri, and Bacillus psychrodurans had a broad spectrum of antibacterial activity (9.58 ± 0.66 to 21.47 ± 0.27 mm inhibition zone). The butanol solvent extract of B. sp. cryopeg and P. sp. rif200865 displayed effective antibacterial activity against the five FPB, which was evident from the scanning electron microscopy with irregular or burst cell morphology in the EB-treated bacteria compared to smooth and regular cells in case of the control bacteria. The minimum inhibitory concentration and minimum bactericidal concentration values ranged between 250-500 μg/mL and 500-100 μg/mL, respectively. The above outcomes signify the huge prospective of the selected EB in the food industry. Overall, the above results suggested that D. uniformis contains several culturable EB that possess effective antibacterial compounds, and that EB can be utilized as a source of natural antibacterial agents for their practical application in food industry to control the spread of FPB as a natural antibacterial agent.

In vitro antibacterial and cytotoxicity assessments of an orthodontic bonding agent containing benzalkonium chloride.

PubMed

Saito, Kayo; Hayakawa, Tohru; Kawabata, Rihito; Meguro, Daijiro; Kasai, Kazutaka

2009-03-01

To assess the antibacterial activity and cytotoxicity of an orthodontic bonding material containing an antibacterial agent. Superbond C&B (4-methacryloxyethyl trimellitate anhydride/methyl methacrylate-tri-n-butyl borane [4-META/MMA-TBB]) resin was mixed with benzalkonium chloride (BAC) to obtain final BAC concentrations of 0.25%, 0.75%, 1.25%, 1.75%, 2.5%, and 5.0% (wt/ wt). Antibacterial activity against Streptococcus mutans and Streptococcus sobrinus was evaluated by soaking the BAC-resin in distilled water at 37 degrees C for periods of 30, 90, and 180 days. Antibacterial activity of the BAC-resin was measured by the disk diffusion method, and the inhibition zone around each sample was measured and recorded. For evaluation of cytotoxicity, BAC-resin samples were put into cell culture inserts placed above human gingival cells and were incubated at 37 degrees C for 1, 3, and 6 days. Cytotoxicity was assessed with a tetrazolium bromide reduction assay. The antibacterial activity of BAC-incorporated resin samples decreased significantly after immersion in water for 180 days, regardless of BAC concentration. The antibacterial activity of nonimmersed resin containing 0.25% or 1.75% BAC was comparable with that of 5.0% BAC-resin immersed for 180 days. In cytotoxicity tests, most cells died when exposed to resins containing 1.75%, 2.5%, and 5% BAC. No difference was observed between resins containing 0.25% and 0.75% BAC at 1, 3, and 6 days of culture. The addition of BAC to 4-META/MMA-TBB resin confers an antibacterial effect even after immersion in water, and 4-META/MMA-TBB resin containing 0.25% to 0.75% BAC has no significant cytotoxic effect.

Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones.

PubMed

Jeannot, Frédéric; Taillier, Thomas; Despeyroux, Pierre; Renard, Stéphane; Rey, Astrid; Mourez, Michaël; Poeverlein, Christoph; Khichane, Imène; Perrin, Marc-Antoine; Versluys, Stéphanie; Stavenger, Robert A; Huang, Jianzhong; Germe, Thomas; Maxwell, Anthony; Cao, Sha; Huseby, Douglas L; Hughes, Diarmaid; Bacqué, Eric

2018-04-26

In our quest for new antibiotics able to address the growing threat of multidrug resistant infections caused by Gram-negative bacteria, we have investigated an unprecedented series of non-quinolone bacterial topoisomerase inhibitors from the Sanofi patrimony, named IPYs for imidazopyrazinones, as part of the Innovative Medicines Initiative (IMI) European Gram Negative Antibacterial Engine (ENABLE) organization. Hybridization of these historical compounds with the quinazolinediones, a known series of topoisomerase inhibitors, led us to a novel series of tricyclic IPYs that demonstrated potential for broad spectrum activity, in vivo efficacy, and a good developability profile, although later profiling revealed a genotoxicity risk. Resistance studies revealed partial cross-resistance with fluoroquinolones (FQs) suggesting that IPYs bind to the same region of bacterial topoisomerases as FQs and interact with at least some of the keys residues involved in FQ binding.

1-(1H-indol-3-yl)ethanamine derivatives as potent Staphylococcus aureus NorA efflux pump inhibitors.

PubMed

Hequet, Arnaud; Burchak, Olga N; Jeanty, Matthieu; Guinchard, Xavier; Le Pihive, Emmanuelle; Maigre, Laure; Bouhours, Pascale; Schneider, Dominique; Maurin, Max; Paris, Jean-Marc; Denis, Jean-Noël; Jolivalt, Claude

2014-07-01

The synthesis of 37 1-(1H-indol-3-yl)ethanamine derivatives, including 12 new compounds, was achieved through a series of simple and efficient chemical modifications. These indole derivatives displayed modest or no intrinsic anti-staphylococcal activity. By contrast, several of the compounds restored, in a concentration-dependent manner, the antibacterial activity of ciprofloxacin against Staphylococcus aureus strains that were resistant to fluoroquinolones due to overexpression of the NorA efflux pump. Structure-activity relationships studies revealed that the indolic aldonitrones halogenated at position 5 of the indole core were the most efficient inhibitors of the S. aureus NorA efflux pump. Among the compounds, (Z)-N-benzylidene-2-(tert-butoxycarbonylamino)-1-(5-iodo-1H-indol-3-yl)ethanamine oxide led to a fourfold decrease of the ciprofloxacin minimum inhibitory concentration against the SA-1199B strain when used at a concentration of 0.5 mg L(-1) . To the best of our knowledge, this activity is the highest reported to date for an indolic NorA inhibitor. In addition, a new antibacterial compound, tert-butyl (2-(3-hydroxyureido)-2-(1H-indol-3-yl)ethyl)carbamate, which is not toxic for human cells, was also found. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

PubMed

Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

2003-10-01

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P. fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64 micrograms/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possible decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.

Effects of water-aging for 6 months on the durability of a novel antimicrobial and protein-repellent dental bonding agent.

PubMed

Zhang, Ning; Zhang, Ke; Weir, Michael D; Xu, David J; Reynolds, Mark A; Bai, Yuxing; Xu, Hockin H K

2018-06-21

Biofilms at the tooth-restoration bonded interface can produce acids and cause recurrent caries. Recurrent caries is a primary reason for restoration failures. The objectives of this study were to synthesize a novel bioactive dental bonding agent containing dimethylaminohexadecyl methacrylate (DMAHDM) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to inhibit biofilm formation at the tooth-restoration margin and to investigate the effects of water-aging for 6 months on the dentin bond strength and protein-repellent and antibacterial durability. A protein-repellent agent (MPC) and antibacterial agent (DMAHDM) were added to a Scotchbond multi-purpose (SBMP) primer and adhesive. Specimens were stored in water at 37 °C for 1, 30, 90, or 180 days (d). At the end of each time period, the dentin bond strength and protein-repellent and antibacterial properties were evaluated. Protein attachment onto resin specimens was measured by the micro-bicinchoninic acid approach. A dental plaque microcosm biofilm model was used to test the biofilm response. The SBMP + MPC + DMAHDM group showed no decline in dentin bond strength after water-aging for 6 months, which was significantly higher than that of the control (P < 0.05). The SBMP + MPC + DMAHDM group had protein adhesion that was only 1/20 of that of the SBMP control (P < 0.05). Incorporation of MPC and DMAHDM into SBMP provided a synergistic effect on biofilm reduction. The antibacterial effect and resistance to protein adsorption exhibited no decrease from 1 to 180 d (P > 0.1). In conclusion, a bonding agent with MPC and DMAHDM achieved a durable dentin bond strength and long-term resistance to proteins and oral bacteria. The novel dental bonding agent is promising for applications in preventive and restorative dentistry to reduce biofilm formation at the tooth-restoration margin.

Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants.

PubMed

Lan, Shih-Feng; Kehinde, Timilehin; Zhang, Xiangming; Khajotia, Sharukh; Schmidtke, David W; Starly, Binil

2013-06-01

Dental implants provide support for dental crowns and bridges by serving as abutments for the replacement of missing teeth. To prevent bacterial accumulation and growth at the site of implantation, solutions such as systemic antibiotics and localized delivery of bactericidal agents are often employed. The objective of this study was to demonstrate a novel method of controlled localized delivery of antibacterial agents to an implant site using a biodegradable custom fabricated ring. The study involved incorporating a model antibacterial agent (metronidazole) into custom designed poly-ε-caprolactone/alginate (PCL/alginate) composite rings to produce the intended controlled release profile. The rings can be designed to fit around the body of any root form dental implants of various diameters, shapes and sizes. In vitro release studies indicate that pure (100%) alginate rings exhibited an expected burst release of metronidazole in the first few hours, whereas Alginate/PCL composite rings produced a medium burst release followed by a sustained release for a period greater than 4 weeks. By varying the PCL/alginate weight ratios, we have shown that we can control the amount of antibacterial agents released to provide the minimal inhibitory concentration (MIC) needed for adequate protection. The fabricated composite rings have achieved a 50% antibacterial agent release profile over the first 48 h and the remaining amount slowly released over the remainder of the study period. The PCL/alginate agent release characteristic fits the Ritger-Peppas model indicating a diffusion-based mechanism during the 30-day study period. The developed system demonstrates a controllable drug release profile and the potential for the ring to inhibit bacterial biofilm growth for the prevention of diseases such as peri-implantitis resulting from bacterial infection at the implant site. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Graphene Oxide-Based Nanocomposites Decorated with Silver Nanoparticles as an Antibacterial Agent

NASA Astrophysics Data System (ADS)

Jaworski, Sławomir; Wierzbicki, Mateusz; Sawosz, Ewa; Jung, Anna; Gielerak, Grzegorz; Biernat, Joanna; Jaremek, Henryk; Łojkowski, Witold; Woźniak, Bartosz; Wojnarowicz, Jacek; Stobiński, Leszek; Małolepszy, Artur; Mazurkiewicz-Pawlicka, Marta; Łojkowski, Maciej; Kurantowicz, Natalia; Chwalibog, André

2018-04-01

One of the most promising methods against drug-resistant bacteria can be surface-modified materials with biocidal nanoparticles and nanocomposites. Herein, we present a nanocomposite with silver nanoparticles (Ag-NPs) on the surface of graphene oxide (GO) as a novel multifunctional antibacterial and antifungal material. Ultrasonic technologies have been used as an effective method of coating polyurethane foils. Toxicity on gram-negative bacteria ( Escherichia coli), gram-positive bacteria ( Staphylococcus aureus and Staphylococcus epidermidis), and pathogenic yeast ( Candida albicans) was evaluated by analysis of cell morphology, assessment of cell viability using the PrestoBlue assay, analysis of cell membrane integrity using the lactate dehydrogenase assay, and reactive oxygen species production. Compared to Ag-NPs and GO, which have been widely used as antibacterial agents, our nanocomposite shows much higher antimicrobial efficiency toward bacteria and yeast cells.

Graphene Oxide-Based Nanocomposites Decorated with Silver Nanoparticles as an Antibacterial Agent.

PubMed

Jaworski, Sławomir; Wierzbicki, Mateusz; Sawosz, Ewa; Jung, Anna; Gielerak, Grzegorz; Biernat, Joanna; Jaremek, Henryk; Łojkowski, Witold; Woźniak, Bartosz; Wojnarowicz, Jacek; Stobiński, Leszek; Małolepszy, Artur; Mazurkiewicz-Pawlicka, Marta; Łojkowski, Maciej; Kurantowicz, Natalia; Chwalibog, André

2018-04-23

One of the most promising methods against drug-resistant bacteria can be surface-modified materials with biocidal nanoparticles and nanocomposites. Herein, we present a nanocomposite with silver nanoparticles (Ag-NPs) on the surface of graphene oxide (GO) as a novel multifunctional antibacterial and antifungal material. Ultrasonic technologies have been used as an effective method of coating polyurethane foils. Toxicity on gram-negative bacteria (Escherichia coli), gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), and pathogenic yeast (Candida albicans) was evaluated by analysis of cell morphology, assessment of cell viability using the PrestoBlue assay, analysis of cell membrane integrity using the lactate dehydrogenase assay, and reactive oxygen species production. Compared to Ag-NPs and GO, which have been widely used as antibacterial agents, our nanocomposite shows much higher antimicrobial efficiency toward bacteria and yeast cells.

Evaluation of Antibacterial Activity of Three Selected Fruit Juices on Clinical Endodontic Bacterial Strains

PubMed Central

Behera, Subasish; Khetrapal, Prashant; Punia, Sandhya Kapoor; Agrawal, Deepak; Khandelwal, Minal; Lohar, Jitendra

2017-01-01

Introduction: The increasing problem of antibiotic drug resistance by pathogenic microorganisms in the past few decades has recently led to the continuous exploration of natural plant products for new antibiotic agents. Many consumable food materials have good as well as their bad effects, good effect includes their antibacterial effects on different microorganisms present in the oral cavity. Recently, natural products have been evaluated as source of antimicrobial agent with efficacies against a variety of microorganisms. Methodology: The present study describes the antibacterial activity of three selected fruit juices (Apple, Pomegranate and Grape) on endodontic bacterial strains. Antimicrobial activity of fruit juices were tested by wel l diffusion assay by an inhibition zone surrounding the well. The aim of the study was to evaluate the antibacterial activity of three fruit juises on different endodontic strains. Result: Agar well diffusion method was adopted for determining antibacterial potency. Antibacterial activity present on the plates was indicated by an inhibition zone surrounding the well containing the fruit juice. The zone of inhibition was measured by measuring scale in millimeter. Comparision between antibacterial efficacy of all three fruit juices against Enterococcus feacalis and Streptococcus mutans was observed with significant value of P ≤ 0.05. Conclusion: The results obtained in this study clearly demonstrated a significant antimicrobial effect of apple fruit juice against Enterococcus fecalis and Streptococcus mutans. However, preclinical and clinical trials are needed to evaluate biocompatibility & safety before apple can conclusively be recommended in endodontic therapy, but in vitro observation of apple effectiveness appears promising. PMID:29284967

Consumption of antibacterial molecules in broiler production in Morocco.

PubMed

Rahmatallah, Naoufal; El Rhaffouli, Hicham; Lahlou Amine, Idriss; Sekhsokh, Yassine; Fassi Fihri, Ouafaa; El Houadfi, Mohammed

2018-05-01

Monitoring the use of antibacterial agents in food-producing animals is crucial in order to reduce antimicrobial resistance, selection and dissemination of resistant bacterial strains, and drug residues in the animal food products. The broiler production sector is considered a great consumer of antibacterials and incriminated in the rise of antimicrobial resistance level in zoonotic bacterial pathogens such as Escherichia coli, Salmonella and Campylobacter. Following recommendations from the OIE and WHO, a survey was conducted about the use and consumption of several antibacterial agents in Moroccan broiler flocks. More than 5 million broilers were randomly surveyed at the prescriber level, that is, via the veterinary clinics involved in their health management. The results showed that 93% of the flocks received at least one antibacterial treatment of minimum 3 days duration. Enrofloxacin, colistin and trimethoprim/sulphonamides were the most used antibacterials followed by oxytetracycline, florfenicol and amoxicillin. Oxytetracycline, enrofloxacin and colistin were overdosed in most of the administration, while amoxicillin and the combination of trimethoprim/sulphonamides were under-dosed. The total amount of antibacterial consumed in the survey was 63.48 mg/kg and the Animal Level of Exposure to Antimicrobials (ALEA) was 94.45%. The reasons for this frequent use were related mainly to the poor quality of broiler production management. Chicks and animal feed provided to producers were of variable quality. Management of rearing stock density was often poor and biosecurity inadequate, and broilers were challenged by a high prevalence of infectious diseases. © 2018 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.

Vibrio sp. DSM 14379 pigment production--a competitive advantage in the environment?

PubMed

Starič, Nejc; Danevčič, Tjaša; Stopar, David

2010-10-01

The ability to produce several antibacterial agents greatly increases the chance of producer's survival. In this study, red-pigmented Vibrio sp. DSM 14379 and Bacillus sp., both isolated from the same sampling volume from estuarine waters of the Northern Adriatic Sea, were grown in a co-culture. The antibacterial activity of the red pigment extract was tested on Bacillus sp. in microtiter plates. The MIC(50) for Bacillus sp. was estimated to be around 10⁻⁵ mg/L. The extract prepared form the nonpigmented mutant of Vibrio sp. had no antibacterial effect. The pigment production of Vibrio sp. was studied under different physicochemical conditions. There was no pigment production at high or low temperatures, high or low salt concentrations in peptone yeast extract (PYE) medium, low glucose concentration in mineral growth medium or high glucose concentration in PYE medium. This indicates that the red pigment production is a luxurious good that Vibrio sp. makes only under favorable conditions. The Malthusian fitness of Bacillus sp. in a co-culture with Vibrio sp. under optimal environmental conditions dropped from 4.0 to -7.6, which corresponds to three orders of magnitude decrease in the number of CFU relative to the monoculture. The nonpigmented mutant of Vibrio sp. in a co-culture with Bacillus sp. had a significant antibacterial activity. This result shows that studying antibacterial properties in isolation (i.e. pigment extract only) may not reveal full antibacterial potential of the bacterial strain. The red pigment is a redundant antibacterial agent of Vibrio sp.

Outbreak of fluoroquinolone-resistant Escherichia coli infections after transrectal ultrasound-guided biopsy of the prostate.

PubMed

Dumford, Donald; Suwantarat, Nuntra; Bhasker, Vineet; Kundrapu, Sirisha; Zabarsky, Trina F; Drawz, Paul; Zhu, Hui; Donskey, Curtis J

2013-03-01

We conducted an investigation after identifying a cluster of 4 serious infections following transrectal ultrasound-guided biopsy of the prostate (TRUBP) during a 2-month period. Veterans Affairs medical center. Patients with urinary tract infection (UTI) after TRUBP and time-matched controls with no evidence of infection. The incidence of UTI within 30 days after TRUBP was calculated from 2002 through 2010. We evaluated the correlation between infection with fluoroquinolone-resistant gram-negative bacilli (GNB) and fluoroquinolone resistance in outpatient Escherichia coli urinary isolates and performed a case-control study to determine risk factors for infection with fluoroquinolone-resistant GNB. Processes for TRUBP prophylaxis, procedures, and equipment sterilization were reviewed. An outbreak of UTI due to fluoroquinolone-resistant E. coli after TRUBP began 2 years before the cluster was identified and was correlated with increasing fluoroquinolone resistance in outpatient E. coli. No deficiencies were identified in equipment processing or biopsy procedures. Fluoroquinolone-resistant E. coli UTI after TRUBP was independently associated with prior infection with fluoroquinolone-resistant GNB (adjusted odds ratio, 20.8; P=.005). A prediction rule including prior UTI, hospitalization in the past year, and previous infection with fluoroquinolone-resistant GNB identified only 17 (49%) of 35 cases. The outbreak of fluoroquinolone-resistant E. coli infections after TRUBP closely paralleled rising rates of fluoroquinolone resistance among outpatient E. coli isolates. The delayed detection of the outbreak and the absence of sensitive predictors of infection suggest that active surveillance for infection after TRUBP is necessary in the context of increasing fluoroquinolone resistance in the United States.

Colloidal silver nanoparticles/rhamnolipid (SNPRL) composite as novel chemotactic antibacterial agent.

PubMed

Bharali, P; Saikia, J P; Paul, S; Konwar, B K

2013-10-01

The antibacterial activity of silver nanoparticles and rhamnolipid are well known individually. In the present research, antibacterial and chemotactic activity due to colloidal silver nanoparticles (SNP), rhamnolipid (RL) and silver nanoparticles/rhamnolipid composite (SNPRL) were evaluated using Staphylococcus aureus (MTCC3160), Escherichia coli (MTCC40), Pseudomonas aeruginosa (MTCC8163) and Bacillus subtilis (MTCC441) as test strains. Further, the SNPRL nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The observation clearly indicates that SNPRL shows prominent antibacterial and chemotactic activity in comparison to all of its individual precursor components. Copyright © 2013 Elsevier B.V. All rights reserved.

Modulation of the multidrug efflux pump EmrD-3 from Vibrio cholerae by Allium sativum extract and the bioactive agent allyl sulfide plus synergistic enhancement of antimicrobial susceptibility by A. sativum extract.

PubMed

Bruns, Merissa M; Kakarla, Prathusha; Floyd, Jared T; Mukherjee, Mun Mun; Ponce, Robert C; Garcia, John A; Ranaweera, Indrika; Sanford, Leslie M; Hernandez, Alberto J; Willmon, T Mark; Tolson, Grace L; Varela, Manuel F

2017-10-01

The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts in synergy with antimicrobials and that a main bioactive component allyl sulfide inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum lowered the MICs of multiple antibacterials. We conclude that A. sativum and allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances antibacterial agents.

Marine sponge alkaloids as a source of anti-bacterial adjuvants

PubMed Central

Melander, Roberta J.; Liu, Hong-bing; Stephens, Matthew D.; Bewley, Carole A.; Melander, Christian

2018-01-01

Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofilm formation and suppress antibiotic resistance. PMID:27876320

Fabrication of silver nanoparticle sponge leather with durable antibacterial property.

PubMed

Liu, Gongyan; Haiqi, Gao; Li, Kaijun; Xiang, Jun; Lan, Tianxiang; Zhang, Zongcai

2018-03-15

Leather product with durable antibacterial property is of great interest both from industry and consumer's point of view. To fabricate such functional leather, gallic acid modified silver nanoparticles (GA@AgNPs) were first in situ synthesized with a core-shell structure and an average size of 15.3nm. Due to its hydrophilic gallic acid surface, the GA@AgNPs possessed excellent stability and dispersibility in wide pH range from 3 to 12 and also showed effective antibacterial activity with a minimum inhibitory concentration (MIC) of around 10μgmL -1 . Then, such GA@AgNPs were used as retanning agent to be successfully filled into leather matrix during the leather manufacturing process. Moreover, taking the advantage of its high surface density of carboxyl groups, these GA@AgNPs could be further chemically cross-linked onto collagen fibers by chrome tanning agent. After retanning, the resultant leather was given a "AgNPs sponge" feature with high payload of silver nanoparticles against laundry, exhibiting high and durable antibacterial activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of linoleic acid, a main component of the n-hexane fraction from Dryopteris crassirhizoma, as an anti-Streptococcus mutans biofilm agent.

PubMed

Jung, Ji-Eun; Pandit, Santosh; Jeon, Jae-Gyu

2014-01-01

Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown the potential of this plant as an agent for the control of cariogenic biofilms. In this study, the main antibacterial components of the plant were identified by correlating gas chromatography-mass spectrometry data with the antibacterial activity of chloroform and n-hexane fractions and then evaluating the activity of the most potent antibacterial component against Streptococcus mutans UA159 biofilms. The most potent antibacterial component was linoleic acid, a main component of the n-hexane fraction. Linoleic acid reduced viability in a dose dependent manner and reduced biofilm accumulation during initial and mature biofilm formation. Furthermore, when the biofilms were briefly treated with linoleic acid (10 min/treatment, a total of six times), the dry weight of the biofilms was significantly diminished. In addition, the anti-biofilm activity of the n-hexane fraction was similar to that of linoleic acid. These results suggest that the n-hexane fraction of D. crassirhizoma and linoleic acid may be useful for controlling cariogenic biofilms.

Study on antibacterial activity of silver nanoparticles synthesized by gamma irradiation method using different stabilizers

NASA Astrophysics Data System (ADS)

Van Phu, Dang; Quoc, Le Anh; Duy, Nguyen Ngoc; Lan, Nguyen Thi Kim; Du, Bui Duy; Luan, Le Quang; Hien, Nguyen Quoc

2014-04-01

Colloidal solutions of silver nanoparticles (AgNPs) were synthesized by gamma Co-60 irradiation using different stabilizers, namely polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), alginate, and sericin. The particle size measured from TEM images was 4.3, 6.1, 7.6, and 10.2 nm for AgNPs/PVP, AgNPs/PVA, AgNPs/alginate, and AgNPs/sericin, respectively. The influence of different stabilizers on the antibacterial activity of AgNPs was investigated. Results showed that AgNPs/alginate exhibited the highest antibacterial activity against Escherichia coli ( E. coli) among the as-synthesized AgNPs. Handwash solution has been prepared using Na lauryl sulfate as surfactant, hydroxyethyl cellulose as binder, and 15 mg/L of AgNPs/alginate as antimicrobial agent. The obtained results on the antibacterial test of handwash for the dilution to 3 mg AgNPs/L showed that the antibacterial efficiency against E. coli was of 74.6%, 89.8%, and 99.0% for the contacted time of 1, 3, and 5 min, respectively. Thus, due to the biocompatibility of alginate extracted from seaweed and highly antimicrobial activity of AgNPs synthesized by gamma Co-60 irradiation, AgNPs/alginate is promising to use as an antimicrobial agent in biomedicine, cosmetic, and in other fields.

The Mechanism Underlying the Antibacterial Activity of Shikonin against Methicillin-Resistant Staphylococcus aureus

PubMed Central

Lee, Dae-Young; Kim, Yeon Bok; Lee, Sang-Won; Cha, Seon-Woo; Park, Hong-Woo; Kim, Geum-Soog; Kwon, Dong-Yeul; Lee, Min-Ho; Han, Sin-Hee

2015-01-01

Shikonin (SKN), a highly liposoluble naphthoquinone pigment isolated from the roots of Lithospermum erythrorhizon, is known to exert antibacterial, wound-healing, anti-inflammatory, antithrombotic, and antitumor effects. The aim of this study was to examine SKN antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The SKN was analyzed in combination with membrane-permeabilizing agents Tris and Triton X-100, ATPase inhibitors sodium azide and N,N′-dicyclohexylcarbodiimide, and S. aureus-derived peptidoglycan; the effects on MRSA viability were evaluated by the broth microdilution method, time-kill test, and transmission electron microscopy. Addition of membrane-permeabilizing agents or ATPase inhibitors together with a low dose of SKN potentiated SKN anti-MRSA activity, as evidenced by the reduction of MRSA cell density by 75% compared to that observed when SKN was used alone; in contrast, addition of peptidoglycan blocked the antibacterial activity of SKN. The results indicate that the anti-MRSA effect of SKN is associated with its affinity to peptidoglycan, the permeability of the cytoplasmic membrane, and the activity of ATP-binding cassette (ABC) transporters. This study revealed the potential of SKN as an effective natural antibiotic and of its possible use to substantially reduce the use of existing antibiotic may also be important for understanding the mechanism underlying the antibacterial activity of natural compounds. PMID:26265924

Selective antibacterial effects of mixed ZnMgO nanoparticles

NASA Astrophysics Data System (ADS)

Vidic, Jasmina; Stankic, Slavica; Haque, Francia; Ciric, Danica; Le Goffic, Ronan; Vidy, Aurore; Jupille, Jacques; Delmas, Bernard

2013-05-01

Antibiotic resistance has impelled the research for new agents that can inhibit bacterial growth without showing cytotoxic effects on humans and other species. We describe the synthesis and physicochemical characterization of nanostructured ZnMgO whose antibacterial activity was compared to its pure nano-ZnO and nano-MgO counterparts. Among the three oxides, ZnO nanocrystals—with the length of tetrapod legs about 100 nm and the diameter about 10 nm—were found to be the most effective antibacterial agents since both Gram-positive ( B. subtilis) and Gram-negative ( E. coli) bacteria were completely eradicated at concentration of 1 mg/mL. MgO nanocubes (the mean cube size 50 nm) only partially inhibited bacterial growth, whereas ZnMgO nanoparticles (sizes corresponding to pure particles) revealed high specific antibacterial activity to Gram-positive bacteria at this concentration. Transmission electron microscopy analysis showed that B. subtilis cells were damaged after contact with nano-ZnMgO, causing cell contents to leak out. Our preliminary toxicological study pointed out that nano-ZnO is toxic when applied to human HeLa cells, while nano-MgO and the mixed oxide did not induce any cell damage. Overall, our results suggested that nanostructured ZnMgO, may reconcile efficient antibacterial efficiency while being a safe new therapeutic for bacterial infections.

Sodium alginate/carboxymethyl cellulose films containing pyrogallic acid: physical and antibacterial properties.

PubMed

Han, Yingying; Wang, Lijuan

2017-03-01

Antibacterial films were prepared using sodium alginate (SA) and carboxymethyl cellulose (CMC) as a matrix, glycerin as a plasticizer and CaCl 2 as a cross-linking agent, and by incorporating the natural antibacterial agent pyrogallic acid (PA). The present study describes the microstructure and the physical, barrier, mechanical, optical and antibacterial properties of blended films prepared by incorporating different concentrations of PA into the SA/CMC matrix. The microstructure of the films was investigated by Fourier transform infrared spectroscopy and scanning electron microscopy, which revealed that PA interacts with the SA/CMC matrix through hydrogen bonding. Moreover, the incorporation of PA increased the moisture content, water vapor permeability and oxygen permeability of SA/CMC films. Films containing 40 g kg -1 of PA had the highest elongation at break result (39.60%). Compared with pure SA/CMC films, the incorporation of PA improved the barrier properties against ultraviolet light; however, it decreased the color parameter L* value and increased the a* and b* values of the films. Furthermore, films with PA, especially at higher concentrations, were more effective against Escherichia coli and Staphylococcus aureus. Antibacterial SA/CMC films incorporating PA appear to have good potential to enhance the safety of foods and food products. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Screening Antibacterial Agent from Crude Extract of Marine-Derived Fungi Associated with Soft Corals against MDR-Staphylococcus haemolyticus

NASA Astrophysics Data System (ADS)

Sabdaningsih, A.; Cristianawati, O.; Sibero, M. T.; Nuryadi, H.; Radjasa, O. K.; Sabdono, A.; Trianto, A.

2017-02-01

Multidrug resistant Staphylococcus haemolyticus is a Gram-positive bacteria and member of coagulase negative staphylococci (CoNS) which has the highest level of antimicrobial resistance. This nosocomial pathogen due to skin or soft tissue infections, bacteremia, septicemia, peritonitis, otitis media, meningitis and urinary tract infections. The ability to produce enterotoxins, hemolysins, biofilm, and cytotoxins could be an important characteristic for the successful of infection. Marine-derived fungi have potency as a continuous supply of bioactive compound. The aim of this research was screening antibacterial agent from crude extracts of marine-derived fungi associated with soft corals against MDR-S. haemolyticus. Among 23 isolates of marine-derived fungi isolated from 7 soft corals, there were 4 isolates active against MDR-S. haemolyticus. The screening was conducted by using agar plug diffusion method. Isolate PPSC-27-A4 had the highest antibacterial activity with diameter 23±9,6 mm. The crude extract from this isolate had been confirmed to antibacterial susceptibility test and it had the highest antibacterial activity in 12.2 mm with concentration of 300μg/ml from mycelia extract. PPSC-27-A4 had been characterized in molecular, based on the sequence analysis of 18S rRNA, PPSC-27-A4 isolate was identified as Trichoderma longibrachiatum.

Timber industry waste-teak ( Tectona grandis Linn.) leaf extract mediated synthesis of antibacterial silver nanoparticles

NASA Astrophysics Data System (ADS)

Devadiga, Aishwarya; Shetty, K. Vidya; Saidutta, M. B.

2015-08-01

The current research article emphasizes efficacious use of teak leaves, an agro -biowaste from world's premier hardwood timber industry, for "green" synthesis of silver nanoparticles (AgNPs). Bioactive compounds of the leaves act as prolific reducing and stabilizing agents in AgNP synthesis. The characterization of the AgNPs synthesized using teak leaves revealed that the particles are spherical with an average size of 28 nm and the presence of bioactive compounds present in teak leaf extract as capping agents on the nanoparticles. A prominent decrease in the content of bioactive compounds such as polyphenols, antioxidants and flavonoids after the biosynthesis of AgNPs signifies that these class of compounds act as reductants and stabilizers during biosynthesis. The biosynthesized silver nanoparticles were also successfully evaluated for their antibacterial characteristics against waterborne pathogens, E. coli and S. aureus, with minimum inhibitory concentration of 25.6 μg/mL. Exploitation of agrowaste resources for synthesis of AgNPs curtails indiscriminate usage of food and commercial plant materials, rather contributing a sustainable way for effective plant waste biomass utilization and management. The biosynthesized AgNps have potential application in water purifiers, antibacterial fabrics, sports wear and in cosmetics as antibacterial agent and the process used for its synthesis being greener is highly beneficial from environmental, energy consumption and economic perspectives.

Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation.

PubMed

Gabardi, Steven; Waikar, Sushrut S; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

2010-07-01

Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

Effect of Two Cancer Chemotherapeutic Agents on the Antibacterial Activity of Three Antimicrobial Agents

PubMed Central

Moody, Marcia R.; Morris, Maureen J.; Young, Viola Mae; Moyé, Lemuel A.; Schimpff, Stephen C.; Wiernik, Peter H.

1978-01-01

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside. PMID:103494

Antibacterial screening of traditional herbal plants and standard antibiotics against some human bacterial pathogens.

PubMed

Awan, Uzma Azeem; Andleeb, Saiqa; Kiyani, Ayesha; Zafar, Atiya; Shafique, Irsa; Riaz, Nazia; Azhar, Muhammad Tehseen; Uddin, Hafeez

2013-11-01

Chloroformic and isoamyl alcohol extracts of Cinnnamomum zylanicum, Cuminum cyminum, Curcuma long Linn, Trachyspermum ammi and selected standard antibiotics were investigated for their in vitro antibacterial activity against six human bacterial pathogens. The antibacterial activity was evaluated and based on the zone of inhibition using agar disc diffusion method. The tested bacterial strains were Streptococcus pyogenes, Staphylococcus epidermidis, Klebsiella pneumonia, Staphylococcus aurues, Serratia marcesnces, and Pseudomonas aeruginosa. Ciprofloxacin showed highly significant action against K. pneumonia and S. epidermidis while Ampicillin and Amoxicillin indicated lowest antibacterial activity against tested pathogens. Among the plants chloroform and isoamyl alcohol extracts of C. cyminum, S. aromaticum and C. long Linn had significant effect against P. aeruginosa, S. marcesnces and S. pyogenes. Comparison of antibacterial activity of medicinal herbs and standard antibiotics was also recorded via activity index. Used medicinal plants have various phytochemicals which reasonably justify their use as antibacterial agent.

[Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2000--I. Gram-positive bacteria].

PubMed

Suzuki, Yumiko; Nishinari, Chisato; Endo, Harumi; Tamura, Chieko; Jinbo, Keiko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

2002-04-01

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2000 were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, and penicillins. Fifteen species, 1,062 strains, of Gram-positive bacteria were isolated from the clinical materials annually collected from January to December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA; n = 127), methicillin-resistant Staphylococcus aureus (MRSA; n = 123), Staphylococcus epidermidis (n = 104), Staphylococcus haemolyticus (n = 58), Streptococcus pyogenes (n = 100), Streptococcus agalactiae (n = 50), Streptococcus pneumoniae (n = 125), Enterococcus faecalis (n = 150), Enterococcus faecium (n = 50), Enterococcus avium (n = 50), and Peptostreptococcus spp. (P. anaerobius, P. asaccharolyticus, P. magnus, P. micros, P. prevotii; n = 125). CZOP possessed stable antibacterial activities against all strains tested throughout 5 years. The MIC90 of CZOP against MRSA and S. haemolyticus tended to decrease while against S. pneumoniae and Peptostreptococcus spp., tended to increase year by year. However, the MIC90 just changed a little and were consistent with the results from the studies performed until the new drug application approval. Increases in the MIC90 against S. pneumoniae were also observed with cefpirome (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also observed with ceftazidime (CAZ), CPR, CFPM, FMOX, SBT/CPZ, and IPM. The decreases in the sensitivities were not always considered to depend upon generation of resistant bacteria because the annual MIC range of each antibacterial agent was almost generally wide every year and the annual sensitivity of each strain to the agents extremely varied. In conclusion, the annual antibacterial activities of CZOP against the Gram-positive bacteria did not considerably change. It, therefore, was suggested that CZOP had maintained high antibacterial activity during 5 years of post-marketing.

Investigation of antibacterial mode of action for traditional and amphiphilic aminoglycosides.

PubMed

Udumula, Venkatareddy; Ham, Young Wan; Fosso, Marina Y; Chan, Ka Yee; Rai, Ravi; Zhang, Jianjun; Li, Jie; Chang, Cheng-Wei Tom

2013-03-15

Aminoglycoside represents a class of versatile and broad spectrum antibacterial agents. In an effort to revive the antibacterial activity against aminoglycoside resistant bacteria, our laboratory has developed two new classes of aminoglycoside, pyranmycin and amphiphilic neomycin (NEOF004). The former resembles the traditional aminoglycoside, neomycin. The latter, albeit derived from neomycin, appears to exert antibacterial action via a different mode of action. In order to discern that these aminoglycoside derivatives have distinct antibacterial mode of action, RNA-binding affinity and fluorogenic dye were employed. These studies, together with our previous investigation, confirm that pyranmycin exhibit the traditional antibacterial mode of action of aminoglycosides by binding toward the bacterial rRNA. On the other hand, the amphiphilic neomycin, NEOF004 disrupts the bacterial cell wall. In a broader perspective, it verifies that structurally modified neomycin can exert different antibacterial mode of action leading to the revival of activity against aminoglycoside resistant bacteria. Copyright © 2013 Elsevier Ltd. All rights reserved.

Size-dependent bacterial growth inhibition and mechanism of antibacterial activity of zinc oxide nanoparticles.

PubMed

Raghupathi, Krishna R; Koodali, Ranjit T; Manna, Adhar C

2011-04-05

The antibacterial properties of zinc oxide nanoparticles were investigated using both gram-positive and gram-negative microorganisms. These studies demonstrate that ZnO nanoparticles have a wide range of antibacterial activities toward various microorganisms that are commonly found in environmental settings. The antibacterial activity of the ZnO nanoparticles was inversely proportional to the size of the nanoparticles in S. aureus. Surprisingly, the antibacterial activity did not require specific UV activation using artificial lamps, rather activation was achieved under ambient lighting conditions. Northern analyses of various reactive oxygen species (ROS) specific genes and confocal microscopy suggest that the antibacterial activity of ZnO nanoparticles might involve both the production of reactive oxygen species and the accumulation of nanoparticles in the cytoplasm or on the outer membranes. Overall, the experimental results suggest that ZnO nanoparticles could be developed as antibacterial agents against a wide range of microorganisms to control and prevent the spreading and persistence of bacterial infections.

Fluoroquinolones and Tendinopathy: A Guide for Athletes and Sports Clinicians and a Systematic Review of the Literature

PubMed Central

Lewis, Trevor; Cook, Jill

2014-01-01

Context: Fluoroquinolone antibiotics have been used for several decades and are effective antimicrobials. Despite their usefulness as antibiotics, a growing body of evidence has accumulated in the peer-reviewed literature that shows fluoroquinolones can cause pathologic lesions in tendon tissue (tendinopathy). These adverse effects can occur within hours of commencing treatment and months after discontinuing the use of these drugs. In some cases, fluoroquinolone usage can lead to complete rupture of the tendon and substantial subsequent disability. Objective: To discuss the cause, pharmacology, symptoms, and epidemiology of fluoroquinolone-associated tendinopathy and to discuss the clinical implications with respect to athletes and their subsequent physiotherapy. Data Sources: We searched MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), Allied and Complementary Medicine Database (AMED), and SPORTDiscus databases for available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture) published from 1966 to 2012. Search terms were fluoroquinolones or quinolones and tendinopathy, adverse effects, and tendon rupture. Included studies were written in or translated into English. Non—English–language and non-English translations of abstracts from reports were not included (n = 1). Study Selection: Eligible studies were any available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture). Both animal and human histologic studies were included. Any papers not focusing on the tendon-related side effects of fluoroquinolones were excluded (n = 71). Data Extraction: Data collected included any cases of fluoroquinolone-related tendinopathy, the particular tendon affected, type of fluoroquinolone, dosage, and concomitant risk factors. Any data outlining the adverse histologic effects of fluoroquinolones also were collected. Data Synthesis: A total of 175 papers, including 89 case reports and 8 literature reviews, were identified. Conclusions: Fluoroquinolone tendinopathy may not respond well to the current popular eccentric training regimes and may require an alternative, staged treatment approach. Clinicians, athletes, athletic trainers, and their medical support teams should be aware of the need to discuss and possibly discontinue these antibiotics if adverse effects arise. PMID:24762232

Antibacterial potential of Calotropis procera (flower) extract against various pathogens.

PubMed

Ali, Abid; Ansari, Asma; Qader, Shah Ali Ul; Mumtaz, Majid; Saied, Sumayya; Mahboob, Tabassum

2014-09-01

Increased bacterial resistance towards commonly used antibiotics has become a debated issue all over the world in a last few decades. Due to this, consumer demand towards natural anti-microbial agents is increasing day by day. Natural anti-microbial agents have gained enormous attention as an alternative therapeutic agent in pharmaceutical industry. Current study is an effort to explore and identify a bactericidal potential of various solvent extracts of Calotropis procera flower. Flowers of C. procera were extracted with hexane, butanol, ethyl acetate and aqua to evaluate the antibacterial activity by agar well diffusion method against the various human pathogens. The microorganisms used in this study includes Salmonella typhi, Escherichia coli (O157:H7), Micrococcus luteus KIBGE-IB20 (Gen Bank accession: JQ250612) and methicillin resistant Staphylococcus aureus (MRSA) KIBGE-IB23 (Gen Bank accession: KC465400). Zones of inhibition were observed against all four pathogenic strains. Fraction soluble in hexane showed broad spectrum of inhibition against all the studied pathogens. However, fractions soluble in ethyl acetate inhibited the growth of E. coli, MRSA, and M. luteus. In case of butanol and aqueous extracts only growth of M. luteus was inhibited. Results revealed that the flower extracts of C. procera have a potential to be used as an antibacterial agent against these pathogenic organisms.

Revitalizing the drug pipeline: AntibioticDB, an open access database to aid antibacterial research and development.

PubMed

Farrell, L J; Lo, R; Wanford, J J; Jenkins, A; Maxwell, A; Piddock, L J V

2018-06-11

The current state of antibiotic discovery, research and development is insufficient to respond to the need for new treatments for drug-resistant bacterial infections. The process has changed over the last decade, with most new agents that are in Phases 1-3, or recently approved, having been discovered in small- and medium-sized enterprises or academia. These agents have then been licensed or sold to large companies for further development with the goal of taking them to market. However, early drug discovery and development, including the possibility of developing previously discontinued agents, would benefit from a database of antibacterial compounds for scrutiny by the developers. This article describes the first free, open-access searchable database of antibacterial compounds, including discontinued agents, drugs under pre-clinical development and those in clinical trials: AntibioticDB (AntibioticDB.com). Data were obtained from publicly available sources. This article summarizes the compounds and drugs in AntibioticDB, including their drug class, mode of action, development status and propensity to select drug-resistant bacteria. AntibioticDB includes compounds currently in pre-clinical development and 834 that have been discontinued and that reached varying stages of development. These may serve as starting points for future research and development.

Foodborne Pathogens Prevention and Sensory Attributes Enhancement in Processed Cheese via Flavoring with Plant Extracts.

PubMed

Tayel, Ahmed A; Hussein, Heba; Sorour, Noha M; El-Tras, Wael F

2015-12-01

Cheese contaminations with foodborne bacterial pathogens, and their health outbreaks, are serious worldwide problems that could happen from diverse sources during cheese production or storage. Plants, and their derivatives, were always regarded as the potential natural and safe antimicrobial alternatives for food preservation and improvement. The extracts from many plants, which are commonly used as spices and flavoring agents, were evaluated as antibacterial agents against serious foodborne pathogens, for example Listeria monocytogenes, Salmonella Typhimurium, Staphylococcus aureus, and Escherichia coli O157:H7, using qualitative and quantitative assaying methods. Dairy-based media were also used for evaluating the practical application of plant extracts as antimicrobial agents. Most of the examined plant extracts exhibited remarkable antibacterial activity; the extracts of cinnamon, cloves, garden cress, and lemon grass were the most powerful, either in synthetic or in dairy-based media. Flavoring processed cheese with plant extracts resulted in the enhancement of cheese sensory attributes, for example odor, taste, color, and overall quality, especially in flavored samples with cinnamon, lemon grass, and oregano. It can be concluded that plant extracts are strongly recommended, as powerful and safe antibacterial and flavoring agents, for the preservation and sensory enhancement of processed cheese. © 2015 Institute of Food Technologists®

Chiral lactic hydrazone derivatives as potential bioactive antibacterial agents: Synthesis, spectroscopic, structural and molecular docking studies

NASA Astrophysics Data System (ADS)

Noshiranzadeh, Nader; Heidari, Azam; Haghi, Fakhri; Bikas, Rahman; Lis, Tadeusz

2017-01-01

A series of novel chiral lactic-hydrazone derivatives were synthesized by condensation of (S)-lactic acid hydrazide with salicylaldehyde derivatives and characterized by elemental analysis and spectroscopic studies (FT-IR, 1H NMR and 13C NMR spectroscopy). The structure of one compound was determined by single crystal X-ray analysis. Antibacterial activity of the synthesized compounds was studied against Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli and Pseudomonas aeruginosa as bacterial cultures by broth microdilution method. All of the synthesized compounds showed good antibacterial activity with MIC range of 64-512 μg/mL. Compounds (S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene)propanehydrazide (5) and (S,E)-2-hydroxy-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)propanehydrazide (7) were the most effective antibacterial derivatives against S. aureus and E. coli respectively with a MIC value of 64 μg/mL. Bacterial biofilm formation assay showed that these compounds significantly inhibited biofilm formation of P. aeruginosa. Also, in silico molecular docking studies were performed to show lipoteichoic acid synthase (LtaS) inhibitory effect of lactic hydrazone derivatives. The association between electronic and structural effects of some substituents on the benzylidene moiety and the biological activity of these chiral compounds were studied. Structural studies show that compound with higher hydrogen bonding interactions show higher antibacterial activity. The results show chiral hydrazone derivatives based on lactic acid hydrazide could be used as potential lead compounds for developing novel antibacterial agents.

Does implant coating with antibacterial-loaded hydrogel reduce bacterial colonization and biofilm formation in vitro?

PubMed

Drago, Lorenzo; Boot, Willemijn; Dimas, Kostantinos; Malizos, Kostantinos; Hänsch, Gertrud M; Stuyck, Jos; Gawlitta, Debby; Romanò, Carlo L

2014-11-01

Implant-related infections represent one of the most severe complications in orthopaedics. A fast-resorbable, antibacterial-loaded hydrogel may reduce or prevent bacterial colonization and biofilm formation of implanted biomaterials. We asked: (1) Is a fast-resorbable hydrogel able to deliver antibacterial compounds in vitro? (2) Can a hydrogel (alone or antibacterial-loaded) coating on implants reduce bacterial colonization? And (3) is intraoperative coating feasible and resistant to press-fit implant insertion? We tested the ability of Disposable Antibacterial Coating (DAC) hydrogel (Novagenit Srl, Mezzolombardo, Italy) to deliver antibacterial agents using spectrophotometry and a microbiologic assay. Antibacterial and antibiofilm activity were determined by broth microdilution and a crystal violet assay, respectively. Coating resistance to press-fit insertion was tested in rabbit tibias and human femurs. Complete release of all tested antibacterial compounds was observed in less than 96 hours. Bactericidal and antibiofilm effect of DAC hydrogel in combination with various antibacterials was shown in vitro. Approximately 80% of the hydrogel coating was retrieved on the implant after press-fit insertion. Implant coating with an antibacterial-loaded hydrogel reduces bacterial colonization and biofilm formation in vitro. A fast-resorbable, antibacterial-loaded hydrogel coating may help prevent implant-related infections in orthopaedics. However, further validation in animal models and properly controlled human studies is required.

In Vitro Activity of Delafloxacin Tested against Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

PubMed

Flamm, Robert K; Rhomberg, Paul R; Huband, Michael D; Farrell, David J

2016-10-01

Delafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested. MIC50 and MIC90 values against all S. pneumoniae isolates were 0.008 and 0.015 μg/ml. Delafloxacin susceptibility was not affected by β-lactamase status against H. influenzae and M. catarrhalis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[Etiology of acute and chronic pyelonephritis in children in Khabarovsk region].

PubMed

Kozlova, E A; Kholodok, G N; Alekseeva, I N; Kozlov, V K

2008-01-01

Microflora of urinary tract was studied in 419 children aged 1 - 17 years and hospitalized due to acute or chronic pyelonephritis. Etiology of inflammatory process was established in 57.8% of cases. According to our study, etiologic structure of causative agents of pyelonephritis did not differ from all-Russian data. The leading positions belonged to Gram-negative microorganisms from Enterobacteriaceae family: Escherichia coli, Proteus mirabilis, and Klebsiella spp. Results of the study point to high susceptibility of main causative agents of pyelonephritis to cephalosporins, aminoglycosides, and fluoroquinolones. High resistance to aminopenicillines was noted. In several isolates from Enterobacteriaceae family significant resistance to nalidixic acid and furazidin was observed.

Current perspectives of nanoparticles in medical and dental biomaterials

PubMed Central

Mohamed Hamouda, Ibrahim

2012-01-01

Nanotechnology is gaining tremendous impetus due to its capability of modulating metals into their nanosize, which drastically changes the chemical, physical and optical properties of metals. Nanoparticles have been introduced as materials with good potential to be extensively used in biological and medical applications. Nanoparticles are clusters of atoms in the size range of 1-100 nm. Inorganic nanoparticles and their nano-composites are applied as good antibacterial agents. Due to the outbreak of infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance, pharmaceutical companies and researchers are searching for new antibacterial agents. The metallic nanoparticles are the most promising as they show good antibacterial properties due to their large surface area to volume ratios, which draw growing interest from researchers due to increasing microbial resistance against metal ions, antibiotics and the development of resistant strains. Metallic nanoparticles can be used as effective growth inhibitors in various microorganisms and thereby are applicable to diverse medical devices. Nanotechnology discloses the use of elemental nanoparticles as active antibacterial ingredient for dental materials. In dentistry, both restorative materials and oral bacteria are believed to be responsible for restoration failure. Secondary caries is found to be the main reason to restoration failure. Secondary caries is primarily caused by invasion of plaque bacteria (acid-producing bacteria) such as Streptococcus mutans and lactobacilli in the presence of fermentable carbohydrates. To make long-lasting restorations, antibacterial materials should be made. The potential of nanoparticles to control the formation of biofilms within the oral cavity is also coming under increasing scrutiny. Possible uses of nanoparticles as topically applied agents within dental materials and the application of nanoparticles in the control of oral infections are also reviewed. PMID:23554743

Quick identification of kuraridin, a noncytotoxic anti-MRSA (methicillin-resistant Staphylococcus aureus) agent from Sophora flavescens using high-speed counter-current chromatography.

PubMed

Chan, Ben Chung-Lap; Yu, Hua; Wong, Chun-Wai; Lui, Sau-Lai; Jolivalt, Claude; Ganem-Elbaz, Carine; Paris, Jean-Marc; Morleo, Barbara; Litaudon, Marc; Lau, Clara Bik-San; Ip, Margaret; Fung, Kwok-Pui; Leung, Ping-Chung; Han, Quan-Bin

2012-01-01

Bacterial resistance to antibiotics has become a serious problem of public health that concerns almost all currently used antibacterial agents and that manifests in all fields of their application. To find more antibacterial agents from natural resources is all the time considered as an important strategy. Sophora flavescens is a popularly used antibacterial herb in Chinese Medicine, from which prenylated flavones were reported as the antibacterial ingredients but with a major concern of toxicity. In our screening on the antibacterial activities of various chemicals of this herb, 18 fractions were obtained from 8 g of 50% ethanol extract on a preparative high-speed counter-current chromatography (HSCCC, 1000 ml). The system of n-hexane/ethyl acetate/methanol/water (1:1:1:1) was used as the two-phase separation solvent. A chalcone named kuraridin was isolated from the best anti-MRSA fraction, together with sophoraflavanone G, a known active ingredient of S. flavescens. Their structures were elucidated by analysis of the NMR spectra. Both compounds exhibited significant anti-MRSA effects, compared to baicalein that is a well known anti-MRSA natural product. More important, kuraridin showed no toxicity on human peripheral blood mononuclear cells (PBMC) at the concentration up to 64 μg/ml while sophoraflavanone G inhibited over 50% of cellular activity at 4 μg/ml or higher concentration. These data suggested that opening of ring A of the prenylated flavones might decrease the toxicity and remain the anti-MRSA effect, from a viewpoint of structure-activity relationship. Copyright © 2011 Elsevier B.V. All rights reserved.

Disinfection of Water with Quaternary Ammonium Salts Insolubilized on a Porous Glass Surface

PubMed Central

Nakagawa, Yoshihiro; Hayashi, Hiroyuki; Tawaratani, Takahiko; Kourai, Hiroki; Horie, Tokunaru; Shibasaki, Isao

1984-01-01

Insoluble quaternary ammonium salts bound to porous glass showed antibacterial activity. An agent designated as G12, which had a dodecyl alkyl chain, was selected for some antibacterial tests on comparison of it with the agent reported previously. The antibacterial activity of G12 toward Escherichia coli was mainly due to the adsorption of cells and therefore gradually decreased during continuous treatment of a cell suspension. The lost G12 activity was completely recovered by washing with ethanol, and the activity of refreshed G12 decreased in the same manner as that of fresh G12. The lost activity was, however, always recovered only by ethanol treatment. This indicated that G12 might interact with cells more strongly by means of a hydrophobic force than an electrostatic one. The antimicrobial spectrum showed that G12 was effective against not only bacteria but also yeasts. PMID:16346491

Phytochemical analysis of Andrographis paniculata and Orthosiphon stamineus leaf extracts for their antibacterial and antioxidant potential.

PubMed

Malahubban, M; Alimon, A R; Sazili, A Q; Fakurazi, S; Zakry, F A

2013-09-01

Leaves of Andrographis paniculata and Orthosiphon stamineus were extracted with water, ethanol, methanol and chloroform to assess their potential as antibacterial and antioxidant agents. High performance liquid chromatography analysis showed that the methanolic extracts of A. paniculata and O. stamineus leaves gave the highest amounts of andrographolide and rosmarinic acid, respectively. These leaf extracts exhibited antimicrobial and antioxidant activities and, at the highest concentration tested (200 mg/mL), showed greater inhibitory effects against the Gram positive bacteria Bacillus cereus and Staphylococcus aureus than 10% acetic acid. Andrographis paniculata and O. stamineus methanolic and ethanolic leaf extracts also showed the strongest antioxidant activity as compared with the other extracts tested. The bioactive compounds present in these leaf extracts have the potential to be developed into natural antibacterial and antioxidant agents that may have applications in animal and human health.

ESKAPEing the labyrinth of antibacterial discovery.

PubMed

Tommasi, Ruben; Brown, Dean G; Walkup, Grant K; Manchester, John I; Miller, Alita A

2015-08-01

Antimicrobial drug resistance is a growing threat to global public health. Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - is of particular concern because they are responsible for many serious infections in hospitals. Although some promising agents are in the pipeline, there is an urgent need for new antibiotic scaffolds. However, antibacterial researchers have struggled to identify new small molecules with meaningful cellular activity, especially those effective against multidrug-resistant Gram-negative pathogens. This difficulty ultimately stems from an incomplete understanding of efflux systems and compound permeation through bacterial membranes. This Opinion article describes findings from target-based and phenotypic screening efforts carried out at AstraZeneca over the past decade, discusses some of the subsequent chemistry challenges and concludes with a description of new approaches comprising a combination of computational modelling and advanced biological tools which may pave the way towards the discovery of new antibacterial agents.

Laboratory Evaluation of 3-(5-Tetrazolyl)Penam, a New Semisynthetic Beta-Lactam Antibacterial Agent with Extended Broad-Spectrum Activity

PubMed Central

English, Arthur R.; Retsema, James A.; Lynch, John E.

1976-01-01

In the new agent 3-(5-tetrazolyl)penam, hereafter referred to as CP-35,587, the carboxyl function at C3 in the penicillin nucleus has been replaced with the 5-tetrazolyl moiety. Marked changes in spectrum and resistance to gram-negative β-lactamases, particularly with regard to Klebsiella pneumoniae isolates, were conferred by this modification. The anti-Klebsiella activity clearly distinguishes the antibacterial spectrum of CP-35,587 from any known broad-spectrum penicillin. Compared to orally active cephalosporins, the spectrum advantage of CP-35,587 encompasses Enterobacter, Serratia marcescens, Citrobacter, Providencia, Haemophilus influenzae, and Streptococcus faecalis, both in vitro and in murine infections produced by many of the above-named microorganisms. Thus, CP-35,587 combines and extends the antibacterial activity of broad-spectrum penicillins and orally active cephalosporins. PMID:984745

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia.

PubMed

Aspa, Javier; Rajas, Olga; de Castro, Felipe Rodríguez

2008-02-01

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (beta-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.

Antibacterial activity of nitric oxide releasing silver nanoparticles

NASA Astrophysics Data System (ADS)

Seabra, Amedea B.; Manosalva, Nixson; de Araujo Lima, Bruna; Pelegrino, Milena T.; Brocchi, Marcelo; Rubilar, Olga; Duran, Nelson

2017-06-01

Silver nanoparticles (AgNPs) are well known potent antimicrobial agents. Similarly, the free radical nitric oxide (NO) has important antibacterial activity, and due to its instability, the combination of NO and nanomaterials has been applied in several biomedical applications. The aim of this work was to synthesize, characterize and evaluate the antibacterial activity of a new NO-releasing AgNPs. Herein, AgNPs were synthesized by the reduction of silver ions (Ag+) by catechin, a natural polyphenol and potent antioxidant agent, derived from green tea extract. Catechin acts as a reducing agent and as a capping molecule on the surface of AgNPs, minimizing particle agglomeration. The as-synthesized nanoparticles were characterized by different techniques. The results showed the formation of AgNPs with average hydrodynamic size of 44 nm, polydispersity index of 0.21, and zeta potential of -35.9 mV. X-ray diffraction and Fourier transform infrared spectroscopy revealed the presence of the AgNP core and cathecin as capping agent. The low molecular weight mercaptosuccinic acid (MSA), which contain free thiol group, was added on the surface of catechin-AgNPs, leading to the formation of MSA-catechin-AgNPs (the NO precursor nanoparticle). Free thiol groups of MSA-catechin-AgNPs were nitrosated leading to the formation of S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), the NO donor. The amount of 342 ± 16 µmol of NO was released per gram of S-nitroso-MSA-catechin-AgNPs. The antibacterial activities of catechin-AgNPs, MSA-catechin-AgNPs, and S-nitroso-MSA-catechin-AgNPs were evaluated towards different resistant bacterial strains. The results demonstrated an enhanced antibacterial activity of the NO-releasing AgNP. For instance, the minimal inhibitory concentration values for Pseudomonas aeruginosa (ATCC 27853) incubated with AgNPs-catechin, AgNPs-catechin-MSA, and AgNPs-catechin-S-nitroso-MSA were found to be 62, 125 and 3 µg/mL, respectively. While in the case of Klebsiella pneumoniae (ATCC 700603) the minimum bactericidal concentration values for treatments with AgNPs-catechin, AgNPs-catechin-MSA, and AgNPs-catechin-S-nitroso-MSA were found to be 1000, 500, and 125 µg/mL, respectively. The antibacterial actions of the NO-releasing nanoparticle were superior in comparison with the antibacterial effects of AgNPs, in most of the tested antibiotic resistant bacteria strains. These results highlight the promising uses of NO-releasing AgNPs against resistant bacteria in several biomedical applications.

Evaluation of Fluoroquinolones for the Prevention of BK Viremia after Renal Transplantation

PubMed Central

Waikar, Sushrut S.; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K.; Tullius, Stefan G.; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

2010-01-01

Background and objectives: Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. Design, setting, participants, & measurements: This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. Results: A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. Conclusions: This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation. PMID:20507960

Fluorescence and electron paramagnetic resonance studies of norfloxacin and N-donor mixed-ligand ternary copper(II) complexes: Stability and interaction with SDS micelles

NASA Astrophysics Data System (ADS)

Vignoli Muniz, Gabriel S.; Incio, Jimmy Llontop; Alves, Odivaldo C.; Krambrock, Klaus; Teixeira, Letícia R.; Louro, Sonia R. W.

2018-01-01

The stability of ternary copper(II) complexes of a heterocyclic ligand, L (L being 2,2‧-bipyridine (bipy) or 1,10-phenanthroline (phen)) and the fluorescent antibacterial agent norfloxacin (NFX) as the second ligand was studied at pH 7.4 and different ionic strengths. Fluorescence quenching upon titration of NFX with the binary complexes allowed to obtain stability constants for NFX binding, Kb, as a function of ionic strength. The Kb values vary by more than two orders of magnitude when buffer concentration varies from 0.5 to 100 mM. It was observed that previously synthesized ternary complexes dissociate in buffer according with the obtained stability constants. This shows that equimolar solutions of NFX and binary complexes are equivalent to solutions of synthesized ternary complexes. The interaction of the ternary copper complexes with anionic SDS (sodium dodecyl sulfate) micelles was studied by fluorescence and electron paramagnetic resonance (EPR). Titration of NFX-loaded SDS micelles with the complexes Cu:L allowed to determine the stability constants inside the micelles. Fluorescence quenching demonstrated that SDS micelles increase the stability constants by factors around 50. EPR spectra gave details of the copper(II) local environment, and demonstrated that the structure of the ternary complexes inside SDS micelles is different from that in buffer. Mononuclear ternary complexes formed inside the micelles, while in buffer most ternary complexes are binuclear. The results show that anionic membrane interfaces increase formation of copper fluoroquinolone complexes, which can influence bioavailability, membrane diffusion, and mechanism of action of the antibiotics.

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

PubMed

Kimura, Shun-Ichi; Fujita, Hiroyuki; Kato, Hideaki; Hiramoto, Nobuhiro; Hosono, Naoko; Takahashi, Tsutomu; Shigeno, Kazuyuki; Hatsumi, Naoko; Minamiguchi, Hitoshi; Miyatake, Junichi; Handa, Hiroshi; Akiyama, Nobu; Kanda, Yoshinobu; Yoshida, Minoru; Kiyoi, Hitoshi; Miyazaki, Yasushi; Naoe, Tomoki

2017-11-01

We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

Comparison of the antibacterial activity of chelating agents using the agar diffusion method

USDA-ARS?s Scientific Manuscript database

The agar diffusion assay was used to examine antibacterial activity of 2 metal chelators. Concentrations of 0 to 40 mM of ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N,N’-disuccinic acid (EDDS) were prepared in 1.0 M potassium hydroxide (KOH). The pH of the solutions was adjusted to 1...

Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity.

PubMed

Nehme, Hassan; Saulnier, Patrick; Ramadan, Alyaa A; Cassisa, Viviane; Guillet, Catherine; Eveillard, Matthieu; Umerska, Anita

2018-01-01

Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs) on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC) assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio), the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.

Benzaldehyde Schiff bases regulation to the metabolism, hemolysis, and virulence genes expression in vitro and their structure-microbicidal activity relationship.

PubMed

Xia, Lei; Xia, Yu-Fen; Huang, Li-Rong; Xiao, Xiao; Lou, Hua-Yong; Liu, Tang-Jingjun; Pan, Wei-Dong; Luo, Heng

2015-06-05

There is an urgent need to develop new antibacterial agents because of multidrug resistance by bacteria and fungi. Schiff bases (aldehyde or ketone-like compounds) exhibit intense antibacterial characteristics, and are therefore, promising candidates as antibacterial agents. To investigate the mechanism of action of newly designed benzaldehyde Schiff bases, a series of high-yielding benzaldehyde Schiff bases were synthesized, and their structures were determined by NMR and MS spectra data. The structure-microbicidal activity relationship of derivatives was investigated, and the antibacterial mechanisms were investigated by gene assays for the expression of functional genes in vitro using Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The active compounds were selective for certain active groups. The polar substitution of the R2 group of the amino acids in the Schiff bases, affected the antibacterial activity against E. coli and S. aureus; specific active group at the R3 or R4 groups of the acylhydrazone Schiff bases could improve their inhibitory activity against these three tested organisms. The antibacterial mechanism of the active benzaldehyde Schiff bases appeared to regulate the expression of metabolism-associated genes in E. coli, hemolysis-associated genes in B. subtilis, and key virulence genes in S. aureus. Some benzaldehyde Schiff bases were bactericidal to all the three strains and appeared to regulate gene expression associated with metabolism, hemolysis, and virulence, in vitro. The newly designed benzaldehyde Schiff bases possessed unique antibacterial activity and might be potentially useful for prophylactic or therapeutic intervention of bacterial infections. Copyright © 2015. Published by Elsevier Masson SAS.

Impact of fluoroquinolone administration on the emergence of fluoroquinolone-resistant gram-negative bacilli from gastrointestinal flora.

PubMed

Richard, P; Delangle, M H; Raffi, F; Espaze, E; Richet, H

2001-01-01

We assessed the risk factors for acquisition of fluoroquinolone-resistant, gram-negative organisms in the gastrointestinal tract of hospitalized patients. We analyzed stool samples from 204 patients and recovered fluoroquinolone-resistant, gram-negative organisms from 63. Receipt of fluoroquinolone during the month preceding admission was the only risk factor identified, whereas female sex, duration of hospitalization, exposure to indwelling devices, admission from another hospital, and history of infection were risk factors for fecal colonization after day 4.

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa.

PubMed

Takeoka, Yusuke; Tanino, Tetsuya; Sekiguchi, Mitsuaki; Yonezawa, Shuji; Sakagami, Masahiro; Takahashi, Fumiyo; Togame, Hiroko; Tanaka, Yoshikazu; Takemoto, Hiroshi; Ichikawa, Satoshi; Matsuda, Akira

2014-05-08

It is urgent to develop novel anti-Pseudomonas agents that should also be active against multidrug resistant P. aeruginosa. Expanding the antibacterial spectrum of muraymycins toward P. aeruginosa was investigated by the systematic structure-activity relationship study. It was revealed that two functional groups, a lipophilic side chain and a guanidino group, at the accessory moiety of muraymycins were important for the anti-Pseudomonas activity, and analogue 29 exhibited antibacterial activity against a range of P. aeruginosa strains with the minimum inhibitory concentration values of 4-8 μg/mL.

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa

PubMed Central

2014-01-01

It is urgent to develop novel anti-Pseudomonas agents that should also be active against multidrug resistant P. aeruginosa. Expanding the antibacterial spectrum of muraymycins toward P. aeruginosa was investigated by the systematic structure–activity relationship study. It was revealed that two functional groups, a lipophilic side chain and a guanidino group, at the accessory moiety of muraymycins were important for the anti-Pseudomonas activity, and analogue 29 exhibited antibacterial activity against a range of P. aeruginosa strains with the minimum inhibitory concentration values of 4–8 μg/mL. PMID:24900879

Synthesis and biological evaluation of novel 5-aryl-4-(5-nitrofuran-2-yl)-pyrimidines as potential anti-bacterial agents.

PubMed

Verbitskiy, Egor V; Baskakova, Svetlana A; Gerasimova, Natal'ya A; Evstigneeva, Natal'ya P; Zil'berberg, Natal'ya V; Kungurov, Nikolay V; Kravchenko, Marionella A; Skornyakov, Sergey N; Pervova, Marina G; Rusinov, Gennady L; Chupakhin, Oleg N; Charushin, Valery N

2017-07-01

A facile two-step synthetic approach to fluorinated and non-fluorinated 5-aryl-4-(5-nitrofuran-2-yl)-pyrimidines from readily available 5-bromo-4-(furan-2-yl)pyrimidine has been developed. All synthesized compounds were screened in vitro for their antibacterial activities against twelve various bacterial strains. It is demonstrated that some of these compounds exhibited significant antibacterial activities against strains Neisseria gonorrhoeae and Staphylococcus aureus, comparable and even higher with that commercial drug Spectinomycin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isolation of NDM-1-producing multidrug-resistant Pseudomonas putida from a paediatric case of acute gastroenteritis, India.

PubMed

Bhattacharya, D; Dey, S; Kadam, S; Kalal, S; Jali, S; Koley, H; Sinha, R; Nag, D; Kholkute, S D; Roy, S

2015-05-01

Pseudomonas putida is an uncommon opportunistic pathogen, usually susceptible to antimicrobial agents. Data concerning resistance to antimicrobial agents in clinical P. putida isolates are limited. To the best of our knowledge we report for the first time the isolation of NDM-1-producing multidrug-resistant P. putida from a case of acute gastroenteritis. The isolate showed resistance to a wide range of antimicrobials, including fluoroquinolones, third-generation cephalosporins and carbapenems. The isolate also exhibited multiple mutations in the quinolone resistance determining region and showed the presence of qepA, bla TEM , bla OXA1 and bla OXA7 genes. The present study highlights the importance of looking for the relatively rare aetiological agents in clinical samples that do not yield common pathogens.

Isolation of NDM-1-producing multidrug-resistant Pseudomonas putida from a paediatric case of acute gastroenteritis, India

PubMed Central

Bhattacharya, D.; Dey, S.; Kadam, S.; Kalal, S.; Jali, S.; Koley, H.; Sinha, R.; Nag, D.; Kholkute, S.D.; Roy, S.

2015-01-01

Pseudomonas putida is an uncommon opportunistic pathogen, usually susceptible to antimicrobial agents. Data concerning resistance to antimicrobial agents in clinical P. putida isolates are limited. To the best of our knowledge we report for the first time the isolation of NDM-1-producing multidrug-resistant P. putida from a case of acute gastroenteritis. The isolate showed resistance to a wide range of antimicrobials, including fluoroquinolones, third-generation cephalosporins and carbapenems. The isolate also exhibited multiple mutations in the quinolone resistance determining region and showed the presence of qepA, blaTEM, blaOXA1 and blaOXA7 genes. The present study highlights the importance of looking for the relatively rare aetiological agents in clinical samples that do not yield common pathogens. PMID:25893095

High prevalence of fluoroquinolone-nonsusceptible Streptococcus pyogenes emm12 in Taiwan.

PubMed

Lin, Jiun-Nong; Chang, Lin-Li; Lai, Chung-Hsu; Huang, Yi-Han; Chen, Wei-Fang; Yang, Chih-Hui; Hsu, Janine; Lin, Hsi-Hsun; Chen, Yen-Hsu

2015-10-01

Fluoroquinolone-nonsusceptible Streptococcus pyogenes has rapidly emerged in several countries. The aim of this study was to survey the epidemiology and molecular characteristics of fluoroquinolone-nonsusceptible S. pyogenes in Taiwan. A total of 350 consecutive S. pyogenes isolates were collected between January 2005 and December 2012, including 152 (43.4%) invasive and 198 (56.6%) noninvasive isolates. Thirty-nine isolates (11.1%) of S. pyogenes were nonsusceptible to fluoroquinolones, including one emm1/ST28, 4 emm4/ST39, 33 emm12/ST36, and 1 emm87/ST62. Of all the isolates, emm12 (50%) demonstrated the highest prevalence of fluoroquinolone nonsusceptibility. Alterations of Ser79Phe and Ala12Val in ParC were the most frequently mutations in fluoroquinolone-nonsusceptible S. pyogenes isolates. There were no amino acid substitutions in GyrB, and 1 emm87 isolate exhibited 3 nonsynonymous mutations in ParE. Our study reveals the emergence of fluoroquinolone-nonsusceptible S. pyogenes emm12/ST36 in Taiwan. Regular surveillance of fluoroquinolone susceptibility in S. pyogenes is suggested. Copyright © 2015 Elsevier Inc. All rights reserved.

Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

PubMed Central

Dalhoff, Axel

2012-01-01

This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum β-lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from <10% in rural areas to >30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller's diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever. PMID:23097666

Fluoroquinolones (FQs) in the environment: A review on their abundance, sorption and toxicity in soil.

PubMed

Riaz, Luqman; Mahmood, Tariq; Khalid, Azeem; Rashid, Audil; Ahmed Siddique, Muhammad Bashir; Kamal, Atif; Coyne, Mark S

2018-01-01

The use of fluoroquinolones (FQs) antibiotics as therapeutic agents and growth promoters is increasing worldwide; however their extensive uses are also resulting in antibiotic resistance among world communities. FQs have also become one of the major contaminants in the waste water bodies, which are not even completely removed during the treatment processes. Furthermore, their abundance in agricultural resources, such as the irrigation water, the bio-solids and the livestock manure can also affect the soil micro-environment. These antibiotics in soil tend to interact in several different ways to affect soil flora and fauna. The current review endeavors to highlight the some critical aspects of FQs prevalence in the environment. The review presents a detailed discussion on the pathways and abundance of FQs in soil. The discussion further spans the issue of sorption and FQs transformation into the soil better understand of their behavior and their toxicity to soil flora and fauna. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53

PubMed Central

York, D.; Withers, S. S.; Watson, K. D.; Seo, K. W.; Rebhun, R. B.

2016-01-01

Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity. PMID:27333821

Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.

PubMed

York, D; Withers, S S; Watson, K D; Seo, K W; Rebhun, R B

2017-09-01

Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity. © 2016 John Wiley & Sons Ltd.

Report: Studies on antibacterial activity of some traditional medicinal plants used in folk medicine.

PubMed

Israr, Fozia; Hassan, Fouzia; Naqvi, Baqir Shyum; Azhar, Iqbal; Jabeen, Sabahat; Hasan, S M Farid

2012-07-01

Ethanolic extracts of eight medicinal plants commonly used in folk medicine were tested for their antibacterial activity against four Gram positive strains (Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis and, Streptococcus pneumoniae) and six Gram negative strains (Escherichia coli, Proteus vulgaris, Proteus mirabilis. Salmonella typhi para A, Salmonella typhi para B and Shigella dysenteriae) that were obtained from different pathological laboratories located in Karachi, Pakistan. Disc diffusion method was used to analyze antibacterial activity. Out of eight, five medicinal plants showed antibacterial activity against two or more than two microbial species. The most effective antimicrobial plant found to be Punica granatum followed by Curcuma zedoaria Rosc, Grewia asiatica L and Carissa carandas L, Curcuma caesia Roxb respectively. From these results, it is evident that medicinal plants could be used as a potential source of new antibacterial agents.

Antibiotic-loaded, silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections.

PubMed

Wang, Yao; Ding, Xiali; Chen, Yuan; Guo, Mingquan; Zhang, Yan; Guo, Xiaokui; Gu, Hongchen

2016-09-01

Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical and mineralogical characteristics of French green clays used for healing

USGS Publications Warehouse

Williams, Lynda B.; Haydel, Shelley E.; Giese, Rossman F.; Eberl, Dennis D.

2008-01-01

The worldwide emergence of infectious diseases, together with the increasing incidence of antibiotic-resistant bacteria, elevate the need to properly detect, prevent, and effectively treat these infections. The overuse and misuse of common antibiotics in recent decades stimulates the need to identify new inhibitory agents. Therefore, natural products like clays, that display antibacterial properties, are of particular interest.The absorptive properties of clay minerals are well documented for healing skin and gastrointestinal ailments. However, the antibacterial properties of clays have received less scientific attention. French green clays have recently been shown to heal Buruli ulcer, a necrotic or ‘flesh-eating’ infection caused by Mycobacterium ulcerans. Assessing the antibacterial properties of these clays could provide an inexpensive treatment for Buruli ulcer and other skin infections.Antimicrobial testing of the two clays on a broad-spectrum of bacterial pathogens showed that one clay promotes bacterial growth (possibly provoking a response from the natural immune system), while another kills bacteria or significantly inhibits bacterial growth. This paper compares the mineralogy and chemical composition of the two French green clays used in the treatment of Buruli ulcer.Mineralogically, the two clays are dominated by 1Md illite and Fe-smectite. Comparing the chemistry of the clay minerals and exchangeable ions, we conclude that the chemistry of the clay, and the surface properties that affect pH and oxidation state, control the chemistry of the water used to moisten the clay poultices and contribute the critical antibacterial agent(s) that ultimately debilitate the bacteria.

ent-Copalic acid antibacterial and anti-biofilm properties against Actinomyces naeslundii and Peptostreptococcus anaerobius.

PubMed

Souza, Maria Gorete Mendes de; Leandro, Luís Fernando; Moraes, Thaís da Silva; Abrão, Fariza; Veneziani, Rodrigo Cassio Sola; Ambrosio, Sergio Ricardo; Martins, Carlos Henrique Gomes

2018-05-28

Diterpenes are an important class of plant metabolites that can be used in the search for new antibacterial agents. ent-Copalic acid (CA), the major diterpene in Copaifera species exudates, displays several pharmacological properties. This study evaluates the CA antibacterial potential against the anaerobic bacteria Peptostreptococcus anaerobius and Actinomyces naeslundii. Antimicrobial assays included time-kill and biofilm inhibition and eradication assays. Time-kill assays conducted for CA concentrations between 6.25 and 12.5 μg/mL evidenced bactericidal activity within 72 h. CA combined with chlorhexidine dihydrochloride (CHD) exhibited bactericidal action against P. anaerobius within 6 h of incubation. As for A. naeslundii, the same combination reduced the number of microorganisms by over 3 log10 at 24 h and exerted a bactericidal effect at 48 h of incubation. CA at 500 and 2000 μg/mL inhibited P. anaerobius and A. naeslundii biofilm formation by at least 50%, respectively. CA at 62.5 and 1.000 μg/mL eradicated 99.9% of pre-formed P. anaerobius and A. naeslundii biofilms, respectively. These results indicated that CA presents in vitro antibacterial activity and is a potential biofilm inhibitory agent. This diterpene may play an important role in the search for novel sources of agents that can act against anaerobic bacteria. Copyright © 2018 Elsevier Ltd. All rights reserved.

Discovery of 2-aminothiazolyl berberine derivatives as effectively antibacterial agents toward clinically drug-resistant Gram-negative Acinetobacter baumanii.

PubMed

Gao, Wei-Wei; Gopala, Lavanya; Bheemanaboina, Rammohan R Yadav; Zhang, Guo-Biao; Li, Shuo; Zhou, Cheng-He

2018-02-25

Aminothiazolyl berberine derivatives as potentially antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. The antimicrobial assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens, and the aminothiazole and Schiff base moieties were helpful structural fragments for aqueous solubility and antibacterial activity. Especially, aminothiazolyl 9-hexyl berberine 9c and 2,4-dichlorobenzyl derivative 18a exhibited good activities (MIC = 2 nmol/mL) against clinically drug-resistant Gram-negative Acinetobacter baumanii with low cytotoxicity to hepatocyte LO2 cells, rapidly bactericidal effects and quite slow development of bacterial resistance toward A. baumanii. Molecular modeling indicated that compounds 9c and 18a could bind with GLY-102, ARG-136 and/or ALA-100 residues of DNA gyrase through hydrogen bonds. It was found that compounds 9c and 18a were able to disturb the drug-resistant A. baumanii membrane effectively, and molecule 9c could not only intercalate but also cleave bacterial DNA isolated from resistant A. baumanii, which might be the preliminary antibacterial action mechanism of inhibiting the growth of A. baumanii strain. In particular, the combination use of compound 9c with norfloxacin could enhance the antibacterial activity, broaden antibacterial spectrum and overcome the drug resistance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Intensity and duration of in-vitro antibacterial activity of different adhesives used in orthodontics.

PubMed

Passariello, Claudio; Sannino, Gianpaolo; Petti, Stefano; Gigola, Pierangelo

2014-04-01

This work investigated the antibacterial activity of 14 bonding agents to predict their ability to inhibit white-spot development during orthodontic treatment. Standardized, sterilized disks of each material were continuously rinsed (for up to 180 d) in a flow of sterile saline. At predetermined time points, the residual ability of each material to inhibit bacterial growth (determined by measuring the size of inhibition halos around disks placed onto appropriate culture media seeded with Streptococcus gordonii DSM6777, Streptococcus sanguinis DSM20567, Streptococcus mutans DSM20523, or Lactobacillus acidophilus DSM20079) and biofilm formation (determined by measuring the numbers of bacteria adherent to disks following incubation in appropriate broths) was tested in triplicate and compared with the baseline activities of freshly prepared materials. Overall antibacterial and anti-biofilm activities, adjusted for exposure time and strain of bacteria, were assessed. The decrease of antibacterial activity was faster (30-60 d) and complete for fluoride-enriched materials, but slower (90 d) and partial for antimicrobial-containing materials (benzalkonium chloride, zinc oxide, chlorexidine, or MDPB). Materials enriched with benzalkonium chloride, chlorexidine, or MDPB showed the highest antibacterial activities. Anti-biofilm assays yielded similar results. These data could be helpful for clinicians in the choice of the best performing bonding agent also in light of duration of the clinical application. © 2014 Eur J Oral Sci.

Triceps Ruptures After Fluoroquinolone Antibiotics: A Report of 2 Cases.

PubMed

Shybut, Theodore B; Puckett, Ernest R

Rupture of the triceps brachii tendon is exceedingly rare, and surgical repair is generally indicated. Fluoroquinolone antibiotics have been implicated in tendon pathology, including tendon ruptures. Triceps rupture has not been previously reported in the setting of fluoroquinolone antibiotic therapy. We present 2 cases of triceps tendon rupture after treatment with fluoroquinolones. In both cases, triceps repair was performed with good outcomes. These cases highlight a risk of fluoroquinolone-induced tendinopathy to athletes. The sports medicine team should be aware of this risk and consider it when choosing antibiotics to treat athletes.

Nanotechnology: A Valuable Strategy to Improve Bacteriocin Formulations

PubMed Central

Fahim, Hazem A.; Khairalla, Ahmed S.; El-Gendy, Ahmed O.

2016-01-01

Bacteriocins are proteinaceous antibacterial compounds, produced by diverse bacteria, which have been successfully used as: (i) food biopreservative; (ii) anti-biofilm agents; and (iii) additives or alternatives to the currently existing antibiotics, to minimize the risk of emergence of resistant strains. However, there are several limitations that challenge the use of bacteriocins as biopreservatives/antibacterial agents. One of the most promising avenues to overcome these limitations is the use of nanoformulations. This review highlights the practical difficulties with using bacteriocins to control pathogenic microorganisms, and provides an overview on the role of nanotechnology in improving the antimicrobial activity and the physicochemical properties of these peptides. PMID:27695440

Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents.

PubMed

Shah, Syed Shoaib Ahmad; Rivera, Gildardo; Ashfaq, Muhammad

2013-01-01

Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.

In Situ Synthesis of Silver Nanoparticles in a Hydrogel of Carboxymethyl Cellulose with Phthalated-Cashew Gum as a Promising Antibacterial and Healing Agent.

PubMed

Lustosa, Ana Karina Marques Fortes; de Jesus Oliveira, Antônia Carla; Quelemes, Patrick Veras; Plácido, Alexandra; da Silva, Francilene Vieira; Oliveira, Irisdalva Sousa; de Almeida, Miguel Peixoto; Amorim, Adriany das Graças Nascimento; Delerue-Matos, Cristina; de Oliveira, Rita de Cássia Meneses; da Silva, Durcilene Alves; Eaton, Peter; de Almeida Leite, José Roberto de Souza

2017-11-12

Silver nanoparticles have been shown to possess considerable antibacterial activity, but in vivo applications have been limited due to the inherent, but low, toxicity of silver. On the other hand, silver nanoparticles could provide cutaneous protection against infection, due to their ability to liberate silver ions via a slow release mechanism, and their broad-spectrum antimicrobial action. Thus, in this work, we describe the development of a carboxymethyl cellulose-based hydrogel containing silver nanoparticles. The nanoparticles were prepared in the hydrogel in situ, utilizing two variants of cashew gum as a capping agent, and sodium borohydride as the reducing agent. This gum is non-toxic and comes from a renewable natural source. The particles and gel were thoroughly characterized through using rheological measurements, UV-vis spectroscopy, nanoparticles tracking analysis, and transmission electron microscopy analysis (TEM). Antibacterial tests were carried out, confirming antimicrobial action of the silver nanoparticle-loaded gels. Furthermore, rat wound-healing models were used and demonstrated that the gels exhibited improved wound healing when compared to the base hydrogel as a control. Thus, these gels are proposed as excellent candidates for use as wound-healing treatments.

In Situ Synthesis of Silver Nanoparticles in a Hydrogel of Carboxymethyl Cellulose with Phthalated-Cashew Gum as a Promising Antibacterial and Healing Agent

PubMed Central

Lustosa, Ana Karina Marques Fortes; de Jesus Oliveira, Antônia Carla; Quelemes, Patrick Veras; Plácido, Alexandra; da Silva, Francilene Vieira; Oliveira, Irisdalva Sousa; de Almeida, Miguel Peixoto; Amorim, Adriany das Graças Nascimento; Delerue-Matos, Cristina; de Oliveira, Rita de Cássia Meneses; da Silva, Durcilene Alves

2017-01-01

Silver nanoparticles have been shown to possess considerable antibacterial activity, but in vivo applications have been limited due to the inherent, but low, toxicity of silver. On the other hand, silver nanoparticles could provide cutaneous protection against infection, due to their ability to liberate silver ions via a slow release mechanism, and their broad-spectrum antimicrobial action. Thus, in this work, we describe the development of a carboxymethyl cellulose-based hydrogel containing silver nanoparticles. The nanoparticles were prepared in the hydrogel in situ, utilizing two variants of cashew gum as a capping agent, and sodium borohydride as the reducing agent. This gum is non-toxic and comes from a renewable natural source. The particles and gel were thoroughly characterized through using rheological measurements, UV-vis spectroscopy, nanoparticles tracking analysis, and transmission electron microscopy analysis (TEM). Antibacterial tests were carried out, confirming antimicrobial action of the silver nanoparticle-loaded gels. Furthermore, rat wound-healing models were used and demonstrated that the gels exhibited improved wound healing when compared to the base hydrogel as a control. Thus, these gels are proposed as excellent candidates for use as wound-healing treatments. PMID:29137157

Pathogenic bacteria carried by companion animals and their susceptibility to antibacterial agents.

PubMed

Buma, Ryoko; Maeda, Takuya; Kamei, Masaharu; Kourai, Hiroki

2006-03-01

Results of the investigation showed that there was a difference in the bacteria isolated from dogs, cats and their living environment. The number and species isolated from the hair and front paw samples from dogs kept outdoors and from cats were greater and more varied than those from the samples from dogs kept indoors. Staphylococcus, Micrococcus and Bacillus were frequently detected from skin surfaces. On the other hand, Escherichia, Pseudomonas, Proteus and others were detected on each sampling area on dogs kept outdoors and on cats. About 60% of the bacteria commonly causes infectious diseases and carries a risk of food poisoning. Moreover, Pasteurella multocida, which causes pasteurellasis, a kind of zoonosis, was isolated from dogs and cats. These pathogenic bacteria were transmitted from animals to humans by direct contact. This result suggests that direct contact with dogs and cats and contact with aerosols can possibly transmit infectious diseases. Most of the isolates (75.9%, 60/79) were resistant to antibacterial agents. We then investigated the effect of household detergents and pet care deodorant sprays containing antibacterial agents on isolates from dogs and cats. They were effective in preventing the transmission of pathogens from dogs and cats to humans.

[Special characteristics of antibiotic therapy in the elderly].

PubMed

Stock, Ingo

2012-03-01

The ever-increasing proportion of elderly people in the general population represents physicians and pharmacists with new challenges. Older people suffer more frequently than younger persons from bacterial diseases, and they have a higher tendency to develop more severe or progressive forms of these illnesses. Bacterial diseases of the urinary tract, respiratory tract, skin and soft tissues are especially common in old age. In general, most antibacterial agents are also promising agents for the therapy of bacterial diseases in the elderly. Prior to initiating therapy, however, the modified organ functions of the elderly have to be considered carefully. Depending on the individual and the antibacterial agent, a dose adjustment may be necessary. To reduce the high mortality rate characteristic for many infectious diseases in the elderly, antibacterial therapy ought to be carefully calculated and initiated as quickly as possible. It has to be born in mind that some side effects of antibiotics are more common and more severe in old age. Since older people often take several drugs simultaneously, the probability for the occurrence of side effects and drug interactions in this population is greatly increased. Significant compliance problems may also arise.

Evaluation of the antibacterial activity of a conventional orthodontic composite containing silver/hydroxyapatite nanoparticles.

PubMed

Sodagar, Ahmad; Akhavan, Azam; Hashemi, Ehsan; Arab, Sepideh; Pourhajibagher, Maryam; Sodagar, Kosar; Kharrazifard, Mohammad Javad; Bahador, Abbas

2016-12-01

One of the most important complications of fixed orthodontic treatment is the formation of white spots which are initial carious lesions. Addition of antimicrobial agents into orthodontic adhesives might be a wise solution for prevention of white spot formation. The aim of this study was to evaluate the antibacterial properties of a conventional orthodontic adhesive containing three different concentrations of silver/hydroxyapatite nanoparticles. One hundred and sixty-two Transbond XT composite discs containing 0, 1, 5, and 10 % silver/hydroxyapatite nanoparticles were prepared and sterilized. Antibacterial properties of these composite groups against Streptococcus mutans, Lactobacillus acidophilus, and Streptococcus sanguinis were investigated using three different antimicrobial tests. Disk agar diffusion test was performed to assess the diffusion of antibacterial agent on brain heart infusion agar plate by measuring bacterial growth inhibition zones. Biofilm inhibition test showed the antibacterial capacity of composite discs against resistant bacterial biofilms. Antimicrobial activity of eluted components from composite discs was investigated by comparing the viable counts of bacteria after 3, 15, and 30 days. Composite discs containing 5 and 10 % silver/hydroxyapatite nanoparticles were capable of producing growth inhibition zones for all bacterial types. Results of biofilm inhibition test showed that all of the study groups reduced viable bacterial count in comparison to the control group. Antimicrobial activity of eluted components from composite discs was immensely diverse based on the bacterial type and the concentration of nanoparticles. Transbond XT composite discs containing 5 and 10 % silver/hydroxyapatite nanoparticles produce bacterial growth inhibition zones and show antibacterial properties against biofilms.

Tannic acid-mediated green synthesis of antibacterial silver nanoparticles.

PubMed

Kim, Tae Yoon; Cha, Song-Hyun; Cho, Seonho; Park, Youmie

2016-04-01

The search for novel antibacterial agents is necessary to combat microbial resistance to current antibiotics. Silver nanoparticles (AgNPs) have been reported to be effective antibacterial agents. Tannic acid is a polyphenol compound from plants with antioxidant and antibacterial activities. In this report, AgNPs were prepared from silver ions by tannic acid-mediated green synthesis (TA-AgNPs). The reaction process was facile and involved mixing both silver ions and tannic acid. The absorbance at 423 nm in the UV-Visible spectra demonstrated that tannic acid underwent a reduction reaction to produce TA-AgNPs from silver ions. The synthetic yield of TA-AgNPs was 90.5% based on inductively coupled plasma mass spectrometry analysis. High-resolution transmission electron microscopy and atomic force microscopy images indicated that spherical-shaped TA-AgNPs with a mean particle size of 27.7-46.7 nm were obtained. Powder high-resolution X-ray diffraction analysis indicated that the TA-AgNP structure was face-centered cubic with a zeta potential of -27.56 mV. The hydroxyl functional groups of tannic acid contributed to the synthesis of TA-AgNPs, which was confirmed by Fourier transform infrared spectroscopy. The in vitro antibacterial activity was measured using the minimum inhibitory concentration (MIC) method. The TA-AgNPs were more effective against Gram-negative bacteria than Gram-positive bacteria. The MIC for the TA-AgNPs in all of the tested strains was in a silver concentration range of 6.74-13.48 μg/mL. The tannic acid-mediated synthesis of AgNPs afforded biocompatible nanocomposites for antibacterial applications.

Antibacterial properties and mechanisms of gold-silver nanocages

NASA Astrophysics Data System (ADS)

Wang, Yulan; Wan, Jiangshan; Miron, Richard J.; Zhao, Yanbin; Zhang, Yufeng

2016-05-01

Despite the number of antibiotics used in routine clinical practice, bacterial infections continue to be one of the most important challenges faced in humans. The main concerns arise from the continuing emergence of antibiotic-resistant bacteria and the difficulties faced with the pharmaceutical development of new antibiotics. Thus, advancements in the avenue of novel antibacterial agents are essential. In this study, gold (Au) was combined with silver (Ag), a well-known antibacterial material, to form silver nanoparticles producing a gold-silver alloy structure with hollow interiors and porous walls (gold-silver nanocage). This novel material was promising in antibacterial applications due to its better biocompatibility than Ag nanoparticles, potential in photothermal effects and drug delivery ability. The gold-silver nanocage was then tested for its antibacterial properties and the mechanism involved leading to its antibacterial properties. This study confirms that this novel gold-silver nanocage has broad-spectrum antibacterial properties exerting its effects through the destruction of the cell membrane, production of reactive oxygen species (ROS) and induction of cell apoptosis. Therefore, we introduce a novel gold-silver nanocage that serves as a potential nanocarrier for the future delivery of antibiotics.

Are Fluoroquinolones Appropriate for the Treatment of Extended-Spectrum β-Lactamase-Producing Gram-Negative Bacilli?

PubMed Central

Wiener, Emily S.; Heil, Emily L.; Hynicka, Lauren M.; Johnson, J. Kristie

2015-01-01

Objective: To review the data analyzing the role of fluoroquinolones in the treatment of extended-spectrum β-lactamase (ESBL)-producing infections and rates and methods of co-transmission of resistance. Data Sources: A MEDLINE literature search was performed using the search terms extended-spectrum beta-lactamase, fluoroquinolone, ciprofloxacin, levofloxacin, plasmid transmission, and resistance from 1996 to June 2015. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language retrospective studies, prospective studies, and meta-analyses assessing efficacy of fluoroquinolone use in ESBL infections, assessing methods of resistance transmission, or analyzing patient risk factors were reviewed. Data Synthesis: A total of 18 studies that analyzed fluoroquinolone resistance and association to ESBL producing bacteria from either molecular or clinical perspectives were idenitifed. Four studies evaluated the genetic association between ESBL transmission and fluoroquinolone resistance. Plasmid mediated quinolone resistance was found in higher rates in ESBL-producing bacteria. Numerous studies analyzed the risk factors of co-occurring resistance identifying nosocomial acquired infections, recent hospitalization, long-term care facility residence, and intensive care unit stay as the most common. Conclusive clinical data are lacking; however, a meta-analysis showed fluoroquinolones had higher odds of all-cause mortality when used empirically to treat ESBL bacteremia compared with carbapenems. Conclusions: Fluoroquinolone resistance may be co-transmitted in ESBL-producing Enterobacteriaceae. There are limited data on the efficacy for fluoroquinolones in the treatment of ESBL-producing infections. Additional prospective trials are needed to definitively determine the role of fluoroquinolones in ESBL infections.

Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India.

PubMed

Banerjee, Tuhina; Anupurba, Shampa

2016-10-01

Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

The investigation of antibacterial activity of selected native plants from North of Iran.

PubMed

Koohsari, H; Ghaemi, E A; Sadegh Sheshpoli, M; Jahedi, M; Zahiri, M

2015-01-01

Plant derived products have been used for medicinal purposes during centuries. Bacterial resistance to currently used antibiotics has become a concern to public health. The development of bacterial super resistant strains has resulted in the currently used antibiotic agents failing to end many bacterial infections. For this reason, the search is ongoing for new antimicrobial agents, both by the design and by the synthesis of new agents, or through the search of natural sources for yet undiscovered antimicrobial agents. Herbal medications in particular have seen a revival of interest due to a perception that there is a lower incidence of adverse reactions to plant preparations compared to synthetic pharmaceuticals. Coupled with the reduced costs of plant preparations, this makes the search for natural therapeutics an attractive option. This research was carried out to assess the antibacterial activity aqueous and ethanolic extracts of six Azadshahr township Native plants in north of Iran against six species of pathogen bacteria by using three methods of Disk diffusion, Well method and MBC. The results of this research indicated that the effect of ethanol extracts were more than aqueous extract and among six plants, Lippia citriodora and Plantago major ethanol extract had the most antibacterial activity in any of the three methods. Gram-positive bacteria were more sensitive than gram-negative bacteria. Staphylococcus epidermidis and Staphylococcus aureus were the most susceptible Gram-positive bacteria.

Combined effect of zinc ions and cationic antibacterial agents on intraoral volatile sulphur compounds (VSC).

PubMed

Young, A; Jonski, G; Rölla, G

2003-08-01

Volatile sulphur compounds (VSC) are major components of oral malodour. As both zinc ions and cationic antibacterial agents inhibit the formation of oral VSC, this study aimed to determine whether these agents combined have synergistic anti-VSC actions. Baseline oral VSC measurements of mouth air from 10 volunteers following cysteine rinsing (6mM, pH 7.2) were obtained using gas chromatography (GC). Subjects rinsed for 1 min with 10ml of the test solutions, 0.3% zinc acetate (Zn), 0.025% chlorhexidine (CHX), 0.025% cetyl pyridinium (CPC), and the combinations Zn+CHX and Zn+CPC. Cysteine rinses were repeated at 1h, 2h and 3h and VSC measurements recorded. Three subjects rinsed with the Zn+CHX combination and fasted for 9h, undergoing cysteine rinses and VSC measurements at 3h intervals. 10 microl of the test solutions were also added to 1ml aliquots of human whole saliva (n=8). Following incubation at 37 degrees C for 24h VSC levels in the saliva headspace were measured by GC. Inhibition of VSC formation and the fractional inhibitory index indicating synergy were calculated. Zn+CHX mouthrinse had a synergistic anti-VSC effect, and was effective for at least 9h. Zn+CPC mouthrinse was less effective. Both combinations showed a synergistic inhibiting effect in-vitro. Synergy between Zn and the antibacterial agents confirms different mechanisms of operation.

In vitro evaluation of the antibacterial activity of Arctium lappa as a phytotherapeutic agent used in intracanal dressings.

PubMed

Gentil, Marcelo; Pereira, Juliana Vianna; Sousa, Yara T Corrêa Silva; Pietro, Rosimeire; Neto, Manoel D Sousa; Vansan, Luiz Pascoal; de Castro França, Suzelei

2006-03-01

The discovery of natural biocomponents from plants with antibacterial activity on endodontic microbiota may lead to new therapies. This study evaluated the antibacterial activity of a phytotherapeutic agent prepared from an ethyl acetate fraction (AcOEt) extracted from Arctium lappa. This agent was compared with calcium hydroxide as an intracanal dressing. Twenty-seven maxillary canines were instrumented, sterilized and inoculated with a mixed bacterial suspension of Pseudomonas aeruginosa, Escherichia coli, Lactobacillus acidophilus, Streptococcus mutans and Candida albicans. The teeth were divided into three groups and their canals filled with: group 1, calcium hydroxide and propylene glycol; group 2, a paste containing AcOEt fraction of A. lappa and propylene glycol; group 3, propylene glycol (control). At 7, 14 and 30 days, three teeth from each group were opened and a paper point was placed in the root canal for 5 min. The paper points were transferred to Petri dishes with Brain Heart Infusion (BHI). The bacterial growth was classified. Mild bacterial growth was found in group 1 at all time intervals; in group 2 there was severe growth at 7 days, but no growth at 14 and 30 days. The phytotherapeutic agent extracted from an AcOEt fraction of A. lappa inhibited the growth of all the microorganisms in this study. Copyright 2006 John Wiley & Sons, Ltd.

Antibacterial activity of 3-methylbenzo[d]thiazol-methylquinolinium derivatives and study of their action mechanism.

PubMed

Sun, Ning; Du, Ruo-Lan; Zheng, Yuan-Yuan; Guo, Qi; Cai, Sen-Yuan; Liu, Zhi-Hua; Fang, Zhi-Yuan; Yuan, Wen-Chang; Liu, Ting; Li, Xiao-Mei; Lu, Yu-Jing; Wong, Kwok-Yin

2018-12-01

The increasing incidence of multidrug resistant bacterial infection renders an urgent need for the development of new antibiotics. To develop small molecules disturbing FtsZ activity has been recognized as promising approach to search for antibacterial of high potency systematically. Herein, a series of novel quinolinium derivatives were synthesized and their antibacterial activities were investigated. The compounds show strong antibacterial activities against different bacteria strains including MRSA, VRE and NDM-1 Escherichia coli. Among these derivatives, a compound bearing a 4-fluorophenyl group (A2) exhibited a superior antibacterial activity and its MICs to the drug-resistant strains are found lower than those of methicillin and vancomycin. The biological results suggest that these quinolinium derivatives can disrupt the GTPase activity and dynamic assembly of FtsZ, and thus inhibit bacterial cell division and then cause bacterial cell death. These compounds deserve further evaluation for the development of new antibacterial agents targeting FtsZ.

A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance.

PubMed

Germe, Thomas; Vörös, Judit; Jeannot, Frederic; Taillier, Thomas; Stavenger, Robert A; Bacqué, Eric; Maxwell, Anthony; Bax, Benjamin D

2018-05-04

Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA ('poisoning') in an analogous fashion to fluoroquinolones, but without the requirement for the water-metal-ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase-DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate. These involve movement at the GyrA interface and tilting of the TOPRIM domains toward the scissile phosphate coupled to capture of the catalytic metal ion. Our experiments show that these structural transitions are involved generally in poisoning of gyrase by therapeutic compounds and resemble those undergone by the enzyme during its adenosine triphosphate-coupled strand-passage cycle. In addition to resistance mutations affecting residues that directly interact with the compounds, we characterized a mutant (D82N) that inhibits formation of the cleavage complex by the unpoisoned enzyme. The D82N mutant appears to act by stabilizing the binary conformation of DNA gyrase with uncleaved DNA without direct interaction with the compounds. This provides general insight into the resistance mechanisms to antibiotics targeting bacterial type II topoisomerases.

A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance

PubMed Central

Germe, Thomas; Vörös, Judit; Jeannot, Frederic; Taillier, Thomas; Stavenger, Robert A; Bacqué, Eric; Bax, Benjamin D

2018-01-01

Abstract Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA (‘poisoning’) in an analogous fashion to fluoroquinolones, but without the requirement for the water–metal–ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase–DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate. These involve movement at the GyrA interface and tilting of the TOPRIM domains toward the scissile phosphate coupled to capture of the catalytic metal ion. Our experiments show that these structural transitions are involved generally in poisoning of gyrase by therapeutic compounds and resemble those undergone by the enzyme during its adenosine triphosphate-coupled strand-passage cycle. In addition to resistance mutations affecting residues that directly interact with the compounds, we characterized a mutant (D82N) that inhibits formation of the cleavage complex by the unpoisoned enzyme. The D82N mutant appears to act by stabilizing the binary conformation of DNA gyrase with uncleaved DNA without direct interaction with the compounds. This provides general insight into the resistance mechanisms to antibiotics targeting bacterial type II topoisomerases. PMID:29538767

Preparation of Calcium Carbonate (from Shellfish)/Magnesium Oxide Composites as an Antibacterial Agent

NASA Astrophysics Data System (ADS)

Jannah, Z.; Mubarok, H.; Syamsiyah, F.; Putri, A. A. H.; Rohmawati, L.

2018-05-01

We have performed research on antibacterial substance from a natural substance, one of them is calcite from shellfish (Anadara granosa) in Kenjeran Beach Surabaya. This calcite is composed of magnesium oxide using PEG 4000 (Polyethylene glycol) as a solvent and then heated at 800 °C for 30 minutes. Weight variety of calcite used was 80% wt, 85% wt, and 90 wt%. Subsequently, that composites characterized using XRD, antibacterial activity test (Escherichia coli and Staphylococcus aureus), and SEM. The result of antibacterial assay shows that composite of CaCO3/MgO with 80% wt composition have the best activity inhibitory of 31,96 mm for Escherichia coli bacteria and 32.26 mm for Staphylococcus aureus bacteria.

Preparation and antibacterial activity of oligosaccharides derived from dandelion.

PubMed

Qian, Li; Zhou, Yan; Teng, Zhaolin; Du, Chun-Ling; Tian, Changrong

2014-03-01

In this study, we prepared oligosaccharides from dandelion (Taraxacum officinale) by hydrolysis with hydrogen peroxide (H2O2) and investigated their antibacterial activity. The optimum hydrolysis conditions, as determined using the response surface methodology, were as follows: reaction time, 5.12h; reaction temperature, 65.53 °C and H2O2 concentration, 3.16%. Under these conditions, the maximum yield of the oligosaccharides reached 25.43%. The sugar content in the sample was 96.8%, and the average degree of polymerisation was approximately 9. The oligosaccharides showed high antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus, indicating that dandelion-derived oligosaccharides have the potential to be used as antibacterial agents. Copyright © 2013 Elsevier B.V. All rights reserved.

Ultra-high performance liquid chromatographic determination of levofloxacin in human plasma and prostate tissue with use of experimental design optimization procedures.

PubMed

Szerkus, O; Jacyna, J; Wiczling, P; Gibas, A; Sieczkowski, M; Siluk, D; Matuszewski, M; Kaliszan, R; Markuszewski, M J

2016-09-01

Fluoroquinolones are considered as gold standard for the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. However, recent studies reported that fluoroquinolone- resistant bacterial strains are responsible for gradually increasing number of infections after transrectal prostate biopsy. In daily clinical practice, antibacterial efficacy is evaluated only in vitro, by measuring the reaction of bacteria with an antimicrobial agent in culture media (i.e. calculation of minimal inhibitory concentration). Such approach, however, has no relation to the treated tissue characteristics and might be highly misleading. Thus, the objective of this study was to develop, with the use of Design of Experiments approach, a reliable, specific and sensitive ultra-high performance liquid chromatography- diode array detection method for the quantitative analysis of levofloxacin in plasma and prostate tissue samples obtained from patients undergoing prostate biopsy. Moreover, correlation study between concentrations observed in plasma samples vs prostatic tissue samples was performed, resulting in better understanding, evaluation and optimization of the fluoroquinolone-based antimicrobial prophylaxis during transrectal ultrasound guided prostate biopsy. Box-Behnken design was employed to optimize chromatographic conditions of the isocratic elution program in order to obtain desirable retention time, peak symmetry and resolution of levofloxacine and ciprofloxacine (internal standard) peaks. Fractional Factorial design 2(4-1) with four center points was used for screening of significant factors affecting levofloxacin extraction from the prostatic tissue. Due to the limited number of tissue samples the prostatic sample preparation procedure was further optimized using Central Composite design. Design of Experiments approach was also utilized for evaluation of parameter robustness. The method was found linear over the range of 0.030-10μg/mL for human plasma and 0.300-30μg/g for human prostate tissue samples. The intra-day and inter-day variability for levofloxacine from both plasma and prostate samples were less than 10%, with accuracies between 93 and 108% of the nominal values. The limit of detection and the limit of quantification for human plasma were 0.01μg/mL and 0.03μg/mL, respectively. For the prostate tissue, the limit of detection and the limit of quantification were 0.1μg/g and 0.3μg/g, respectively. The average recoveries of levofloxacin were in the range from 99 to 106%. Also, the method fulfills requirements of robustness what was determined and proved by Design of Experiments. The developed method was successfully applied to examine prostate tissue and plasma samples from 140 hospitalized patients enrolled into the clinical study, 12h after oral administration of LVF at a dose of 500mg. The mean (±SD) LVF concentration in prostate was 6.22±3.52μg/g and in plasma 2.54±1.14μg/mL. Due to simplicity of the method and relative small amount of sample needed for the assay, the method can be applied in clinical practice for monitoring of LVF concentrations in plasma and prostate gland. Copyright © 2016 Elsevier B.V. All rights reserved.

[Activity of macrolides and fluoroquinolones against intracellular Legionella pneumophila].

PubMed

Yu, Ling-ling; Hu, Bi-jie; Huang, Sheng-lei; Zhou, Zhao-yan; Tao, Li-li

2011-06-01

To evaluate the activity of macrolides and fluoroquinolones against Legionella pneumophila by intracellular susceptibility testing. Minimum inhibitory concentration (MIC) was determined by standard agar dilution test according to the CLSI. For intracellular assays, legionella pneumonia was used to infect human monocytic cell line THP-1. Erythromycin, azithromycin, levofloxacin and moxifloxacin at 1 × MIC, 4 × MIC, 8 × MIC were added following phagocytosis. Number of viable bacteria was enumerated at 24 h on BCYE (buffered charcoal yeast extract) agar in duplicates using standard plate count method. The result was expressed as percentage inhibition. Mann-Whitney U test was used to determine the significant differences in mean percentage inhibition between agents. Percentage inhibition at 24 h were as follows: Erythromycin 1 × MIC (50.18 ± 27.29)%, 4 × MIC (79.48 ± 20.08)%, 8 × MIC (91.46 ± 8.70)%; Azithromycin 1 × MIC (66.77 ± 26.18)%, 4 × MIC (91.73 ± 8.72)%, 8 × MIC (97.10 ± 3.37)%; Levofloxacin 1 × MIC (99.84 ± 0.25)%, 4 × MIC (99.99 ± 0.02)%, 8 × MIC (99.99 ± 0.01)%; Moxifloxacin 1 × MIC (99.90 ± 0.10)%, 4 × MIC (99.99 ± 0.03)%, 8 × MIC (99.99 ± 0.03)%. The fluoroquinolones showed greater inhibitory activity than macrolides against legionella pneumophila(u = 1.0, 2.0, 5.0, P < 0.05). Levofloxacin and moxifloxacin had the same intracellular activity against legionella pneumophila (u = 190, 183, 217, P > 0.05). Azithromycin was more effective than erythromycin in inhibiting intracellular legionella pneumophila (u = 132, 125, 128, P < 0.05). The fluoroquinolones were more active than macrolides against legionella pneumophila. The intracellular activity of levofloxacin against legionella pneumophila appeared to be similar to moxifloxacin. Azithromycin was demonstrated to have superior activity against legionella pneumophila compared with erythromycin.

Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives.

PubMed

Khan, Salman Ahmad; Kumar, Praveen; Joshi, Rajkumar; Iqbal, Prince F; Saleem, Kishwar

2008-09-01

We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR and mass spectroscopic data, to find an effective antibacterial agent. The antibacterial activity was first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds was determined. The results showed that the steroidal thiosemicarbazones derivatives inhibit growth of both types of the bacteria (Gram-positive and Gram-negative). The acetoxy and chloro derivatives of cyclopentyl and cyclohexyl amine thiosemicarbazones were found to have more antibacterial activity than the other derivatives.

Low Cost CaTiO3 Perovskite Synthesized from Scallop (Anadara granosa) Shell as Antibacterial Ceramic Material

NASA Astrophysics Data System (ADS)

Fatimah, Is; Nur Ilahi, Rico; Pratami, Rismayanti

2018-01-01

Research on perovskite CaTiO3 synthesis from scallop (Anadara granosa) shell and its test as material for antibacterial ceramic application have been conducted. The synthesis was performed by calcium extraction from the scallop shell followed by solid-solid reaction of obtained calcium with TiO2. Physicochemical character of the perovskite wasstudied by measurement of crystallinity using x-ray diffraction (XRD), diffuse-reflectance UV Visible spectrophotometry, scanning electrone microscope-energy dispersive x-ray (SEM-EDX) and Fourier-Transform InfraRed. Considering the future application of the perovskite as antibacterial agent, laboratory test of the peroskite as material in antibacterial ceramic preparation was also conducted. Result of research indicated that perovskite formation was obtained and the material demonstrated photocatalytic activity as identified by band gap energy (Eg) value. The significant activity was also reflected by the antibacterial action of formed ceramic.

Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa.

PubMed

Gurunathan, Sangiliyandi; Han, Jae Woong; Dayem, Ahmed Abdal; Eppakayala, Vasuki; Kim, Jin-Hoi

2012-01-01

Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO) and reduced graphene oxide (rGO) in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME), for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared. The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation. Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of cell viability, induced oxidative stress, and DNA fragmentation. The antibacterial activities of GO and rGO against P. aeruginosa were compared. The loss of P. aeruginosa viability increased in a dose- and time-dependent manner. Exposure to GO and rGO induced significant production of superoxide radical anion compared to control. GO and rGO showed dose-dependent antibacterial activity against P. aeruginosa cells through the generation of reactive oxygen species, leading to cell death, which was further confirmed through resulting nuclear fragmentation. The data presented here are novel in that they prove that GO and rGO are effective bactericidal agents against P. aeruginosa, which would be used as a future antibacterial agent.

Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa

PubMed Central

Gurunathan, Sangiliyandi; Han, Jae Woong; Dayem, Ahmed Abdal; Eppakayala, Vasuki; Kim, Jin-Hoi

2012-01-01

Background Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO) and reduced graphene oxide (rGO) in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME), for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared. Methods The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation. Results Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of cell viability, induced oxidative stress, and DNA fragmentation. Conclusion The antibacterial activities of GO and rGO against P. aeruginosa were compared. The loss of P. aeruginosa viability increased in a dose- and time-dependent manner. Exposure to GO and rGO induced significant production of superoxide radical anion compared to control. GO and rGO showed dose-dependent antibacterial activity against P. aeruginosa cells through the generation of reactive oxygen species, leading to cell death, which was further confirmed through resulting nuclear fragmentation. The data presented here are novel in that they prove that GO and rGO are effective bactericidal agents against P. aeruginosa, which would be used as a future antibacterial agent. PMID:23226696

Allergic, Immunological and Infectious Disease Problems in Aerospace Medicine Held in Rome, Italy on 21 - 25 October 1991 (Les Problemes Causes par les Maladies Allergiques, Immunologiques et Contagieuses en Mdecine Aerospatiale).

DTIC Science & Technology

1992-04-01

whose lymphocytes displayed, at the identified. When assays for antibacterial activity time of lowest immune responses, a surface IL2Ra were performed...with these two agents SSD demon- level around 50% of the first day level (Figure 5), strated superior antibacterial activity in in vitro tests the...day At day 30, a significative increase of direct antibacterial activity 0 and 28. The second group was treated with Ty2la (Neotif, Scla- was observed

Novel dental adhesive containing antibacterial agents and calcium phosphate nanoparticles

PubMed Central

Melo, Mary Anne S.; Cheng, Lei; Weir, Michael D.; Hsia, Ru-ching; Rodrigues, Lidiany K. A.; Xu, Hockin H. K.

2013-01-01

Secondary caries remains the main reason for dental restoration failure. Replacement of failed restorations accounts for 50-70% of all restorations performed. Antibacterial adhesives could inhibit biofilm acids at tooth-restoration margins, and calcium phosphate (CaP) ions could remineralize tooth lesions. The objectives of this study were to: (1) incorporate nanoparticles of silver (NAg), quaternary ammonium dimethacrylate (QADM), and nanoparticles of amorphous calcium phosphate (NACP) into bonding agent; and (2) investigate their effects on dentin bonding and microcosm biofilms. An experimental primer was made with pyromellitic glycerol dimethacrylate (PMGDM) and 2-hydroxyethyl methacrylate (HEMA). An adhesive was made with bisphenol-A-glycerolate dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA). NAg was incorporated into primer at 0.1wt%. The adhesive contained 0.1% NAg and 10% QADM, and 0-40% NACP. Incorporating NAg into primer and NAg-QADM-NACP into adhesive did not adversely affect dentin bond strength (p>0.1). SEM showed numerous resin tags, and TEM revealed NAg and NACP in dentinal tubules. Viability of human saliva microcosm biofilms on primer/adhesive/composite disks was substantially reduced via NAg and QADM. Metabolic activity, lactic acid, and colony-forming units of biofilms were much lower on the new bonding agents than control (p<0.05). In conclusion, novel dental bonding agents containing NAg, QADM and NACP were developed with the potential to kill residual bacteria in the tooth cavity and inhibit the invading bacteria along tooth-restoration margins, with NACP to remineralize tooth lesions. The novel method of combining antibacterial agents (NAg and QADM) with remineralizing agent (NACP) may have wide applicability to other adhesives for caries inhibition. PMID:23281264

Cost-Effectiveness Analysis of Fosfomycin for Treatment of Uncomplicated Urinary Tract Infections in Ontario

PubMed Central

Dahan, Sybil; Iliza, Ange Christelle; LeLorier, Jacques

2017-01-01

Background and Objective. Bacterial resistance to antibiotics traditionally used to treat uncomplicated urinary tract infections (uUTIs) is rising in Canada. We compared the cost-per-patient in Ontario of including fosfomycin (an antibiotic with a low resistance profile) as an option for first-line empirical treatment of uUTIs with current cost of treatment with sulfonamides, fluoroquinolones, and nitrofurantoin. Methods. A decision-tree model was used to perform a cost-minimization analysis. All possible outcomes of a uUTI caused by bacterial species treated with either sulfonamides, fluoroquinolones, nitrofurantoin, or fosfomycin were included. Results. In the base case analysis, the cost-per-patient for treating uUTI with fosfomycin was $105.12. This is similar to the cost-per-patient for each of the other currently reimbursed antibiotics (e.g., $96.19 for sulfonamides, $98.85 for fluoroquinolones, and $99.09 for nitrofurantoins). The weighted average cost-per-patient for treating uUTI was not substantially elevated with the inclusion of fosfomycin in the treatment landscape ($98.41 versus $98.29 with and without fosfomycin, resp.). The sensitivity analyses revealed that most (88.34%) of the potential variation in cost was associated with the probability of progressing to pyelonephritis and hospitalization for pyelonephritis. Conclusion. Fosfomycin in addition to being a safe and effective agent to treat uUTI has a low resistance profile, offers a single-dose treatment administration, and is similar in cost to other reimbursed antibiotics. PMID:28316632

Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease.

PubMed

Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim

2017-01-01

This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes ( sfp, ituC and bmyB ) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight ( p = 0.000) and the antibacterial activity in vitro ( p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol ( p = 0.004) and the reduction in gall weight ( p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo . Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens . These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains.

Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease

PubMed Central

Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim

2017-01-01

This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes (sfp, ituC and bmyB) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight (p = 0.000) and the antibacterial activity in vitro (p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol (p = 0.004) and the reduction in gall weight (p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo. Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens. These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains. PMID:28855909

Optimization of the central linker of dicationic bis-benzimidazole anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-07-01

A series of bis-benzimidazole diamidine compounds containing different central linkers has been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Seven compounds have shown potent antibacterial activities. The anti-MRSA and anti-VRE activities of compound 1h were more potent than that of the lead compound 1a and vancomycin.

Antibacterial activity, surface roughness, flexural strength, and solubility of conventional luting cements containing chlorhexidine diacetate/cetrimide mixtures.

PubMed

Korkmaz, Fatih Mehmet; Tüzüner, Tamer; Baygin, Ozgul; Buruk, Celal Kurtulus; Durkan, Rukiye; Bagis, Bora

2013-08-01

The failure of fixed dental restorations is commonly associated with caries. The use of conventional luting cements containing antibacterial agents may overcome this problem. The purpose of this study was to evaluate the antibacterial activity (ABA), surface roughness (Ra), flexural strength (FS), and solubility (SL) patterns of the conventional dental luting cements zinc phosphate (ZP), zinc polycarboxylate (PC), and glass ionomer (GIC) after the addition of 5% chlorhexidine diacetate/cetrimide (CHX+CT). Antibacterial agents with a total concentration of 5% (2.5% CHX+2.5% CT) were added to antibacterial agent-free conventional luting cement powders (ZPC, PCC, and GICC) and designated as experimental groups (ZPE, PCE, and GICE). ABA against Streptococcus mutans (SM) and Lactobacillus casei (LB) was examined by using the agar diffusion test method. Ra, FS, and SL values were obtained after storage in distilled water at 37°C for 24 hours. The Kruskal-Wallis and Mann Whitney U with Bonferroni correction tests were used to test for agar diffusion (α=.05) and 2-way ANOVA and Fisher Least Significant Difference (LSD) test were used to measure Ra, FS, and SL (α=.05). The control groups exhibited limited ABA. With the exception of PCE>PCC on day 1 for SM, all experimental groups showed significantly greater and longer-lasting protection against SM and LB bacteria for up to 180 days than their controls (P<.05). Ra values decreased (ZPC>ZPE; P>.05, PCC>PCE; P<.05) except that GICE>GICC (P>.05) when compared with their individual controls. Control groups exhibited higher FS values than did the experimental groups (ZPC>ZPE; P<.05, PCC>PCE; P<.05, GICC>GICE; P>.05). The experimental groups exhibited higher solubilities than did their controls in the ZPC (P>.05) and GICC groups (P<.05) but were lower in PCC group (P<.05). Incorporating a 5% CHX+CT mixture into conventional dental luting cements and altering their Ra, FS, and SL values may provide greater antibacterial protection against SM and LB. Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Cotton textiles modified with citric acid as efficient anti-bacterial agent for prevention of nosocomial infections

PubMed Central

Bischof Vukušić, Sandra; Flinčec Grgac, Sandra; Budimir, Ana; Kalenić, Smilja

2011-01-01

Aim To study the antimicrobial activity of citric acid (CA) and sodium hypophosphite monohydrate (SHP) against gram-positive and gram-negative bacteria, and to determine the influence of conventional and microwave thermal treatments on the effectiveness of antimicrobial treatment of cotton textiles. Method Textile material was impregnated with CA and SHP solution and thermally treated by either conventional or microwave drying/curing treatment. Antibacterial effectiveness was tested according to the ISO 20743:2009 standard, using absorption method. The surfaces were morphologically observed by scanning electron microscopy, while physical characteristics were determined by wrinkle recovery angles method (DIN 53 891), tensile strength (DIN 53 837), and whiteness degree method (AATCC 110-2000). Results Cotton fabric treated with CA and SHP showed significant antibacterial activity against MRSA (6.38 log10 treated by conventional drying and 6.46 log10 treated by microwave drying before washing, and 6.90 log10 and 7.86 log10, respectively, after 1 cycle of home domestic laundering washing [HDLW]). Antibacterial activity was also remarkable against S. aureus (4.25 log10 by conventional drying, 4.58 log10 by microwave drying) and against P. aeruginosa (1.93 log10 by conventional and 4.66 log10 by microwave drying). Antibacterial activity against P. aeruginosa was higher in samples subjected to microwave drying/curing than in those subjected to conventional drying/curing. As expected, antibacterial activity was reduced after 10 HDLW cycles but the compound was still effective. The surface of the untreated cotton polymer was smooth, while minor erosion stripes appeared on the surfaces treated with antimicrobial agent, and long and deep stripes were found on the surface of the washed sample. Conclusion CA can be used both for the disposable (non-durable) materials (gowns, masks, and cuffs for blood pressure measurement) and the materials that require durability to laundering. The current protocols and initiatives in infection control could be improved by the use of antimicrobial agents applied on cotton carbohydrate polymer. PMID:21328723

Early postoperative fluoroquinolone use is associated with an increased revision rate after arthroscopic rotator cuff repair.

PubMed

Cancienne, Jourdan M; Brockmeier, Stephen F; Rodeo, Scott A; Young, Chris; Werner, Brian C

2017-07-01

To evaluate the association of postoperative fluoroquinolone use following arthroscopic primary rotator cuff repair with failure requiring revision rotator cuff repair. An insurance database was queried for patients undergoing rotator cuff repair from 2007 to 2015. These patients were divided into three groups: (1) patients prescribed fluoroquinolones within 6 months postoperatively (divided into 0-2, 2-4, and 4-6 months), (2) a matched negative control cohort of patients not prescribed fluoroquinolones, and (3) a matched positive control cohort of patients prescribed fluoroquinolones between 6 and 18 months following rotator cuff repair. Rates of failure requiring revision rotator cuff repair were compared within 2 years. A total of 1292 patients were prescribed fluoroquinolones within 6 months after rotator cuff repair, including 442 within 2 months, 433 within 2 to 4 months, and 417 within 4 to 6 months, and were compared to 5225 matched negative controls and 1597 matched positive controls. The rate of revision rotator cuff repair was significantly higher in patients prescribed fluoroquinolones within 2 months (6.1 %) compared to matched negative (2.2 %, P = 0.0009) and positive controls (2.4 %, P = 0.0026). There were no significant differences in the rate of revision rotator cuff repair when fluoroquinolones were prescribed >2 months after rotator cuff repair. Early use of fluoroquinolones following rotator cuff repair was independently associated with significantly increased rates of failure requiring revision rotator cuff repair. This is the first clinical study examining the association of postoperative fluoroquinolone use with failure following arthroscopic rotator cuff repair. III.

Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α.

PubMed

Yassien, M A M; Elfaky, M A

2015-11-01

A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α.

4-Substituted thieno[2,3-d]pyrimidines as potent antibacterial agents: Rational design, microwave-assisted synthesis, biological evaluation and molecular docking studies.

PubMed

Gill, Rupinder K; Singh, Harpreet; Raj, Tilak; Sharma, Anuradha; Singh, Gagandeep; Bariwal, Jitender

2017-12-01

In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug-resistant problems, some novel 4-substituted thieno[2,3-d]pyrimidines have been synthesized via microwave-assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12b and 13c showed the promising inhibitory potencies against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MICs ranging from 2 to 10 μg/ml. Compound 13c was also found to be highly potent against methicillin-resistant S. aureus (MRSA) with MIC value of 4 μg/ml. Docking simulation studies have been performed to unravel the mode of action and association study indicate the binding of potent compounds with DHPS enzyme. In silico ADME studies suggest the drug-like characteristics of the potent compounds. © 2017 John Wiley & Sons A/S.

Novel Hybrid Virtual Screening Protocol Based on Molecular Docking and Structure-Based Pharmacophore for Discovery of Methionyl-tRNA Synthetase Inhibitors as Antibacterial Agents

PubMed Central

Liu, Chi; He, Gu; Jiang, Qinglin; Han, Bo; Peng, Cheng

2013-01-01

Methione tRNA synthetase (MetRS) is an essential enzyme involved in protein biosynthesis in all living organisms and is a potential antibacterial target. In the current study, the structure-based pharmacophore (SBP)-guided method has been suggested to generate a comprehensive pharmacophore of MetRS based on fourteen crystal structures of MetRS-inhibitor complexes. In this investigation, a hybrid protocol of a virtual screening method, comprised of pharmacophore model-based virtual screening (PBVS), rigid and flexible docking-based virtual screenings (DBVS), is used for retrieving new MetRS inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen the Specs (202,408 compounds) database, a structurally diverse chemical database. Fifteen hit compounds were selected from the final hits and shifted to experimental studies. These results may provide important information for further research of novel MetRS inhibitors as antibacterial agents. PMID:23839093

The frequency of antibiotic-resistant bacteria in homes differing in their use of surface antibacterial agents.

PubMed

Marshall, Bonnie M; Robleto, Eduardo; Dumont, Theresa; Levy, Stuart B

2012-10-01

Antibacterial agents are common in household cleaning and personal care products, but their long-range impacts on commensal and pathogenic household bacteria are largely unknown. In a one-time survey of 38 households from Boston, MA [19] and Cincinnati, OH [18], 13 kitchen and bathroom sites were sampled for total aerobic bacteria and screened for gram phenotype and susceptibility to six antibiotic drug families. The overall bacterial titers of both user (2 or more antibacterial cleaning or personal care products) and non-user (0 or 1 product) rooms were similar with sponges and sink drains consistently showing the highest overall titers and relatively high titers of antibiotic-resistant bacteria. The mean frequency of resistant bacteria ranged from ≤20 % to as high as 45 % and multi-drug resistance was common. However, no significant differences were noted between biocide users and non-users. The frequency of pathogen recovery was similar in both user and non-user groups.

Pseudomonas aeruginosa prevalence, antibiotic resistance and antimicrobial use in Chinese burn wards from 2007 to 2014

PubMed Central

Dou, Yi; Guo, Feng; Zhou, Zengding; Shi, Yan

2017-01-01

Objective To assess the application of antibacterial agents, alongside pathogen prevalence and Pseudomonas aeruginosa drug resistance, with the aim of understanding the impact of inappropriate antibacterial use. Methods This retrospective study assessed bacteria from wounds, catheters, blood, faeces, urine and sputum of hospitalized patients in burn wards between 2007 and 2014. The intensity of use of antibacterial agents and resistance of P. aeruginosa to common anti-Gram-negative antibiotics were measured. Results Annual detection rates of Staphylococcus aureus were significantly decreased, whereas annual detection rates of P. aeruginosa and Klebsiella pneumoniae were significantly increased. Multidrug-resistant strains of P. aeruginosa were increased. The intensity of use of some anti-Gramnegative antibiotics positively correlated with resistance rates of P. aeruginosa to similar antimicrobials. Conclusion In burn wards, more attention should be paid to P. aeruginosa and K. pneumoniae. The use of ciprofloxacin, ceftazidime and cefoperazone/sulbactam should be limited to counter the related increase in resistance levels. PMID:28443385

Combined antibacterial activity of phage lytic proteins holin and lysin from Streptococcus suis bacteriophage SMP.

PubMed

Shi, Yibo; Li, Ning; Yan, Yaxian; Wang, Hengan; Li, Yan; Lu, Chengping; Sun, Jianhe

2012-07-01

Development of novel antibacterial agents is required to control infection with multidrug-resistant Streptococcus suis. HolSMP and LySMP, the holin and lysin of S. suis serotype 2 bacteriophage, named SMP, are responsible for lysis of host cells and release of progeny phage. HolSMP and LySMP expressed in Escherichia coli BL21(DE3) exerted efficient activity at 37 °C, pH 5.2, with addition of 0.8 % β-mercaptoethanol. Lytic spectra of purified HolSMP, LySMP or HolSMP + LySMP mixture were investigated. HolSMP, exhibiting a narrow lytic spectrum, was effective against Staphylococcus aureus and Bacillus subtilis, which were insensitive to LySMP. Moreover, HolSMP was identified as a promising antibacterial agent which was able to extend the spectrum of LySMP. The data suggest that combined use of holin and lysin could be a candidate strategy for resolution of drug resistance.

Antibacterial activity of natural spices on multiple drug resistant Escherichia coli isolated from drinking water, Bangladesh

PubMed Central

2011-01-01

Background Spices traditionally have been used as coloring agents, flavoring agents, preservatives, food additives and medicine in Bangladesh. The present work aimed to find out the antimicrobial activity of natural spices on multi-drug resistant Escherichia coli isolates. Methods Anti-bacterial potentials of six crude plant extracts (Allium sativum, Zingiber officinale, Allium cepa, Coriandrum sativum, Piper nigrum and Citrus aurantifolia) were tested against five Escherichia coli isolated from potable water sources at kushtia, Bangladesh. Results All the bacterial isolates were susceptible to undiluted lime-juice. None of them were found to be susceptible against the aqueous extracts of garlic, onion, coriander, pepper and ginger alone. However, all the isolates were susceptible when subjected to 1:1:1 aqueous extract of lime, garlic and ginger. The highest inhibition zone was observed with lime (11 mm). Conclusion Natural spices might have anti-bacterial activity against enteric pathogens and could be used for prevention of diarrheal diseases. Further evaluation is necessary. PMID:21406097

Nanofabrication and characterization of PVA-organofiller/Ag nanocoatings on pMAD plasmids

NASA Astrophysics Data System (ADS)

Erdonmez, D.; Mosayyebi, S.; Erkan, K.; Salimi, K.; Nagizade, N.; Saglam, N.; Rzayev, Z. M. O.

2014-11-01

Nowadays, the most important problem in microbial researches is bacterial resistance which is carried out by DNA plasmids against antibacterial agents. The effect of antibacterial nanoparticles on bacteria is remarkable, but studies on the interactions of these particles with plasmids do not search or there are no adequate studies. We proposed that the nanoparticles, which are disrupted the self-assembled structure of plasmids, may decrease the resistance of bacteria, and therefore, increase the activity of utilized antibacterial agents. In this work, we synthesized polymer nanofiber webs samples by electrospinning technique from pure water solution of nanocomposites with different contents of silver nanoparticles, and surface morphology of nanofibers composites were characterized by SEM microscopy. Their interactions with pMAD DNA plasmids were investigated. It was demonstrated that the synthesized Ag-carrying nanohybrid composites with higher surface contacted areas were significantly inhibited the activity of plasmid DNA against bacterial resistance. Agreeing with obtained results, synthesized nanofiber coatings can be recommended for the widely applications in nanobiotechnology, nanomedicine, and bioengineering processing.

Antibacterial activity of natural spices on multiple drug resistant Escherichia coli isolated from drinking water, Bangladesh.

PubMed

Rahman, Shahedur; Parvez, Anowar Khasru; Islam, Rezuanul; Khan, Mahboob Hossain

2011-03-15

Spices traditionally have been used as coloring agents, flavoring agents, preservatives, food additives and medicine in Bangladesh. The present work aimed to find out the antimicrobial activity of natural spices on multi-drug resistant Escherichia coli isolates. Anti-bacterial potentials of six crude plant extracts (Allium sativum, Zingiber officinale, Allium cepa, Coriandrum sativum, Piper nigrum and Citrus aurantifolia) were tested against five Escherichia coli isolated from potable water sources at kushtia, Bangladesh. All the bacterial isolates were susceptible to undiluted lime-juice. None of them were found to be susceptible against the aqueous extracts of garlic, onion, coriander, pepper and ginger alone. However, all the isolates were susceptible when subjected to 1:1:1 aqueous extract of lime, garlic and ginger. The highest inhibition zone was observed with lime (11 mm). Natural spices might have anti-bacterial activity against enteric pathogens and could be used for prevention of diarrheal diseases. Further evaluation is necessary.

Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in the Czech Republic.

PubMed

Torumkuney, D; Zemlickova, H; Maruscak, M; Morrissey, I

2018-04-01

To determine the antibiotic susceptibility of isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from patients with community-acquired respiratory infections in the Czech Republic. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. S. pneumoniae isolates (n = 200) showed high rates of susceptibility (>95%) to amoxicillin, amoxicillin/clavulanic acid, penicillin [intravenous (iv) non-meningitis], ceftriaxone, cefuroxime and the fluoroquinolones using CLSI breakpoints. Susceptibility to cefaclor and trimethoprim/sulfamethoxazole was 94%-94.5%, to penicillin (oral) 91.5% and to the macrolides 89.5%. Susceptibility of H. influenzae (n = 197) to amoxicillin/clavulanic acid, ceftriaxone, cefuroxime, azithromycin and the fluoroquinolones was ≥98% by CLSI criteria. Rates of susceptibility to the remaining agents were ≥75% except for clarithromycin at 37.1%. Great variability was seen across breakpoints, especially for the macrolides, cefaclor and cefuroxime (oral), 98.0% of H. influenzae showing susceptibility to the latter by CLSI criteria, 69.5% by PK/PD and 1.5% by EUCAST standards. The β-lactamase rate was 13.7% with no β-lactamase-negative-ampicillin-resistant (BLNAR) isolates by CLSI criteria. Antibiotic resistance among the two major respiratory pathogens remained low in the Czech Republic. These findings support local clinicians in continuing the historically restrictive use of antibiotics in the Czech Republic, with selection of narrower-spectrum agents for the empirical therapy of community-acquired respiratory tract infections. This highlights one of the great benefits of continuous surveillance of antimicrobial resistance: knowledge of current local resistance patterns reduces the need to choose broad-spectrum agents that contribute to increasing resistance worldwide.

10 x '20 Progress--development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America.

PubMed

Boucher, Helen W; Talbot, George H; Benjamin, Daniel K; Bradley, John; Guidos, Robert J; Jones, Ronald N; Murray, Barbara E; Bonomo, Robert A; Gilbert, David

2013-06-01

Infections caused by antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's "10 × '20 Initiative."

Phenotypic and genotypic evaluation of fluoroquinolone resistance in clinical isolates of Staphylococcus aureus in Tehran

PubMed Central

Aligholi, Marzieh; Mirsalehian, Akbar; Halimi, Shahnaz; Imaneini, Hossein; Taherikalani, Morovat; Jabalameli, Fereshteh; Asadollahi, Parisa; Mohajer, Babak; Abdollahi, Alireza; Emaneini, Mohammad

2011-01-01

Summary Background Fluoroquinolones are broad-spectrum antibiotics widely used in the treatment of bacterial infections such as Staphylococcus aureus isolates. Resistance to these antibiotics is increasing. Material/Methods The occurrence of mutations in the grlA and gyrA loci were evaluated in 69 fluoroquinolone-resistant S. aureus isolates from 2 teaching hospitals of Tehran University of Medical Sciences. Results Out of the 165 S. aureus isolates, 87 (52.7%) were resistant to methicillin and 69 (41.8%) were resistant to fluoroquinolone. Fluoroquinolone-resistant S. aureus isolates had a mutation at codon 80 in the grlA gene and different mutational combinations in the gyrA gene. These mutational combinations included 45 isolates at codons 84 and 86, 23 isolates at codons 84, 86 and 106 and 1 isolate at codons 84, 86 and 90. Fluoroquinolone-resistant S. aureus isolates were clustered into 33 PFGE types. Conclusions The findings of this study show that the fluoroquinolone-resistant S. aureus strains isolated in the teaching hospitals in Tehran had multiple mutations in the QRDRs region of both grlA and gyrA genes. PMID:21873957

Phenotypic and genotypic evaluation of fluoroquinolone resistance in clinical isolates of Staphylococcus aureus in Tehran.

PubMed

Aligholi, Marzieh; Mirsalehian, Akbar; Halimi, Shahnaz; Imaneini, Hossein; Taherikalani, Morovat; Jabalameli, Fereshteh; Asadollahi, Parisa; Mohajer, Babak; Abdollahi, Alireza; Emaneini, Mohammad

2011-09-01

Fluoroquinolones are broad-spectrum antibiotics widely used in the treatment of bacterial infections such as Staphylococcus aureus isolates. Resistance to these antibiotics is increasing. The occurrence of mutations in the grlA and gyrA loci were evaluated in 69 fluoroquinolone-resistant S. aureus isolates from 2 teaching hospitals of Tehran University of Medical Sciences. Out of the 165 S. aureus isolates, 87 (52.7%) were resistant to methicillin and 69 (41.8%) were resistant to fluoroquinolone. Fluoroquinolone-resistant S. aureus isolates had a mutation at codon 80 in the grlA gene and different mutational combinations in the gyrA gene. These mutational combinations included 45 isolates at codons 84 and 86, 23 isolates at codons 84, 86 and 106 and 1 isolate at codons 84, 86 and 90. Fluoroquinolone-resistant S. aureus isolates were clustered into 33 PFGE types. The findings of this study show that the fluoroquinolone-resistant S. aureus strains isolated in the teaching hospitals in Tehran had multiple mutations in the QRDRs region of both grlA and gyrA genes.

Benzimidazole-Based Antibacterial Agents Against F. tularensis

PubMed Central

Kumar, Kunal; Awasthi, Divya; Lee, Seung-Yub; Cummings, Jason E.; Knudson, Susan E.; Slayden, Richard A.; Ojima, Iwao

2013-01-01

Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90 % growth inhibition at 1 µg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35–48.6 µg/mL after accurate MIC determination. In ex-vivo efficacy assays, four of these compounds exhibited 2–3 Log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 µg/mL. PMID:23623254

Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

PubMed

Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Buchman, Marek; Shah, Akshay A; Cen, Nicholas; McCurry, Megan D; Beabout, Kathryn; Shamoo, Yousif

2017-11-08

An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

Antibacterial gold nanoparticles-biomass assisted synthesis and characterization.

PubMed

Badwaik, Vivek D; Willis, Chad B; Pender, Dillon S; Paripelly, Rammohan; Shah, Monic; Kherde, Yogesh A; Vangala, Lakshmisri M; Gonzalez, Matthew S; Dakshinamurthy, Rajalingam

2013-10-01

Xylose is a natural monosaccharide found in biomass such as straw, pecan shells, cottonseed hulls, and corncobs. Using this monosaccharide, we report the facile, green synthesis and characterization of stable xylose encapsulated gold nanoparticles (Xyl-GNPs) with potent antibacterial activity. Xyl-GNPs were synthesized using the reduction property of xylose in an aqueous solution containing choloraurate anions carried out at room temperature and atmospheric pressure. These nanoparticles were stable and near spherical in shape with an average diameter of 15 +/- 5 nm. Microbiological assay results showed the concentration dependent antibacterial activity of these particles against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus epidermidis) bacteria. Thus the facile, environmentally friendly Xyl-GNPs have many potential applications in chemical and biomedical industries, particularly in the development of antibacterial agents in the field of biomedicine.

Effect of quaternary ammonium and silver nanoparticle-containing adhesives on dentin bond strength and dental plaque microcosm biofilms

PubMed Central

Zhang, Ke; Melo, Mary Anne S.; Cheng, Lei; Weir, Michael D.; Bai, Yuxing; Xu, Hockin H. K.

2012-01-01

Objectives Antibacterial bonding agents are promising to hinder the residual and invading bacteria at the tooth-restoration interfaces. The objectives of this study were to develop an antibacterial bonding agent by incorporation of quaternary ammonium dimethacrylate (QADM) and nanoparticles of silver (NAg), and to investigate the effect of QADM-NAg adhesive and primer on dentin bond strength and plaque microcosm biofilm response for the first time. Methods Scotchbond Multi-Purpose adhesive and primer were used as control. Experimental adhesive and primer were made by adding QADM and NAg into control adhesive and primer. Human dentin shear bond strengths were measured (n = 10). A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm metabolic activity, colony-forming unit (CFU) counts, lactic acid production, and live/dead staining assay (n = 6). Results Adding QADM and NAg into adhesive and primer did not compromise the dentin shear bond strength which ranged from 30 to 35 MPa (p > 0.1). Scanning electron microscopy (SEM) examinations revealed numerous resin tags, which were similar for the control and the QADM and NAg groups. Adding QADM or NAg markedly reduced the biofilm viability, compared to adhesive control. QADM and NAg together in the adhesive had a much stronger antibacterial effect than using each agent alone (p < 0.05). Adding QADM and NAg in both adhesive and primer had the strongest antibacterial activity, reducing metabolic activity, CFU, and lactic acid by an order of magnitude, compared to control. Significance Without compromising dentin bond strength and resin tag formation, the QADM and NAg containing adhesive and primer achieved strong antibacterial effects against microcosm biofilms for the first time. QADM-NAg adhesive and primer are promising to combat residual bacteria in tooth cavity and invading bacteria at the margins, thereby to inhibit secondary caries. QADM and NAg incorporation may have a wide applicability to other dental bonding systems. PMID:22592165

Development of novel dental adhesive with double benefits of protein-repellent and antibacterial capabilities.

PubMed

Zhang, Ning; Weir, Michael D; Romberg, Elaine; Bai, Yuxing; Xu, Hockin H K

2015-07-01

Secondary caries at the tooth-restoration margins remains a main reason for restoration failure. The objectives of this study were to: (1) combine protein-repellent 2-methacryloyloxyethyl phosphorylcholine (MPC) with quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM) to develop a new dental adhesive with double benefits of protein-repellent and antibacterial capabilities for the first time; and (2) investigate the effects on protein adsorption, anti-biofilm activity, and dentin bond strength. MPC and DMAHDM were incorporated into Scotchbond Multi-Purpose (SBMP) primer and adhesive. Dentin shear bond strengths were measured using extracted human molars. Protein adsorption onto the adhesive resin surfaces was determined by the micro bicinchoninic acid (BCA) method. A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm metabolic activity, colony-forming unit (CFU) counts, lactic acid production and live/dead staining of biofilms on resins. Incorporation of 7.5% MPC and 5% DMAHDM into primer and adhesive did not adversely affect the dentin shear bond strength (p>0.1). The resin with 7.5% MPC+5% DMAHDM had protein adsorption that was nearly 20-fold less than SBMP control (p<0.05). The resin with 7.5% MPC+5% DMAHDM had much stronger antibacterial effects than using MPC or DMAHDM alone (p<0.05). Biofilm CFU counts on the resin with 7.5% MPC+5% DMAHDM were reduced by more than 4 orders of magnitude, compared to SBMP control. The use of double agents (protein-repellent MPC+antibacterial DMAHDM) in dental adhesive achieved much stronger inhibition of biofilms than using each agent alone. The novel protein-repellent and antibacterial bonding agent is promising to reduce biofilm/plaque buildup and reduce recurrent caries at the tooth-restoration margins. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Citrus fruit extracts with carvacrol and thymol eliminated 7-log acid-adapted Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes: A potential of effective natural antibacterial agents.

PubMed

Chung, Doohyun; Cho, Tae Jin; Rhee, Min Suk

2018-05-01

Despite the widespread belief that citrus fruit extracts (CFEs) are microbiologically safe due to their acidity, limited bactericidal effect results in low applicability as antibacterial agent and outbreaks occurred by acid-adapted pathogens. Here, we examined the antibacterial effects of CFEs [lime (Citrus medica), lemon (Citrus limon), calamansi (Citrus microcarpa)] combined with essential oil components (EOCs; carvacrol and thymol) against non-acid-adapted/acid-adapted Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes under 22 °C for 5 min. CFEs (<20%) alone or small amounts of EOCs (2.0 mM; 0.032%) alone could not inactivate the target bacteria effectively. However, combined treatments exhibited marked synergy: CFE + EOCs eliminated all the bacteria (>6.9 log CFU/ml). Among the CFEs tested, the highest synergism was shown by calamansi, an exotic citrus fruit previously unrecognized as an antibacterial agent. Although acid-adaptation improved bacterial survival, calamansi (<20%) + EOCs (<0.032%) completely inactivated even the most resistant pathogen (E. coli O157:H7). Validation test also showed that all tested commercial juice products also eliminated acid-adapted pathogens when used with EOCs. Physicochemical analysis of tested CFEs (pH measurement and HPLC analysis of components) revealed that low pH and flavanone (hesperidin) did not contribute to the synergistic bactericidal effects. Rather, the high citric acid content is likely to contribute to the strong synergistic effect with EOCs by damaging susceptible bacterial membranes. Sensory scores for CFEs were not altered by addition of EOCs at concentrations up to 1.5 mM. This study provides new insight into the utility of CFEs with EOCs to improve not only the microbiological safety of food products containing CFEs but also their applicability as natural antibacterial complex. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of quaternary ammonium and silver nanoparticle-containing adhesives on dentin bond strength and dental plaque microcosm biofilms.

PubMed

Zhang, Ke; Melo, Mary Anne S; Cheng, Lei; Weir, Michael D; Bai, Yuxing; Xu, Hockin H K

2012-08-01

Antibacterial bonding agents are promising to hinder the residual and invading bacteria at the tooth-restoration interfaces. The objectives of this study were to develop an antibacterial bonding agent by incorporation of quaternary ammonium dimethacrylate (QADM) and nanoparticles of silver (NAg), and to investigate the effect of QADM-NAg adhesive and primer on dentin bond strength and plaque microcosm biofilm response for the first time. Scotchbond Multi-Purpose adhesive and primer were used as control. Experimental adhesive and primer were made by adding QADM and NAg into control adhesive and primer. Human dentin shear bond strengths were measured (n = 10). A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm metabolic activity, colony-forming unit (CFU) counts, lactic acid production, and live/dead staining assay (n = 6). Adding QADM and NAg into adhesive and primer did not compromise the dentin shear bond strength which ranged from 30 to 35MPa (p>0.1). Scanning electron microscopy (SEM) examinations revealed numerous resin tags, which were similar for the control and the QADM and NAg groups. Adding QADM or NAg markedly reduced the biofilm viability, compared to adhesive control. QADM and NAg together in the adhesive had a much stronger antibacterial effect than using each agent alone (p<0.05). Adding QADM and NAg in both adhesive and primer had the strongest antibacterial activity, reducing metabolic activity, CFU, and lactic acid by an order of magnitude, compared to control. Without compromising dentin bond strength and resin tag formation, the QADM and NAg containing adhesive and primer achieved strong antibacterial effects against microcosm biofilms for the first time. QADM-NAg adhesive and primer are promising to combat residual bacteria in tooth cavity and invading bacteria at the margins, thereby to inhibit secondary caries. QADM and NAg incorporation may have a wide applicability to other dental bonding systems. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Economic consequences of the demography of MRSA patients and the impact of broad-spectrum antimicrobials.

PubMed

Kaier, K; Moog, S

2012-07-01

Studies have determined the societal impact of methicillin-resistant Staphylococcus aureus (MRSA) by modelling its impact on labour supply and productivity. In addition, most of the studies on the topic conclude that the problem of resistance should be counteracted on the macro level by reducing overall antibacterial consumption. Two major questions have been raised in the present work. Firstly, is MRSA impairing labour supply and productivity? Secondly, is it the overall use of antibacterials that may be seen as crucial to the spread of MRSA infections? The age distribution of MRSA patients is compared with the age distribution of the entire patient population at a German teaching hospital. In addition, the age distribution of MRSA patients was applied to the age distribution of the German population in the year 2050 in order to identify the effects of the double-ageing process on the spread of MRSA. Furthermore, recent epidemiological studies were reviewed on the impact of overall antibacterial consumption on MRSA infection rates. Based on available data, we show that patients infected or colonized with MRSA are, for the most part, beyond retirement age and thus not responsible for changes in labour supply or productivity. Application of age distribution of MRSA patients to the age distribution of the German population in the year 2050 gives a 24% increase in the number of MRSA cases to a total of 182 778 due to an ageing population. In addition, we show that a 32% reduction in the cost of MRSA to the German healthcare system could be reached if use of fluoroquinolones and third-generation cephalosporins was reduced by just 10% and, correspondingly, use of antiseptics for hand disinfection was increased by 10%. MRSA is a phenomenon that, to a larger degree, affects the elderly population rather than the labour force. When it comes to policy options to counteract MRSA on the macro level, most economic research on the topic is biased in assuming that the overall use of antibacterials is responsible for the spread of MRSA infections.

Green-Tea and Epigallocatechin-3-Gallate are Bactericidal against Bacillus anthracis

DTIC Science & Technology

2017-06-13

EGCG, catechins such 245 as epigallocatechin and epicatechin gallate are also antibacterial agents. Moreover, the 246 bactericidal activity of green...Sharma A, Gupta S, Sarethy IP, Dang S, Gabrani R. 2012. Green tea extract: possible mechanism 285 and antibacterial activity on skin pathogens. Food...was shown to be responsible for this activity , against 30 both the attenuated B. anthracis ANR and the virulent, encapsulated strain B. anthracis

Antibacterial kaolinite/urea/chlorhexidine nanocomposites: Experiment and molecular modelling

NASA Astrophysics Data System (ADS)

Holešová, Sylva; Valášková, Marta; Hlaváč, Dominik; Madejová, Jana; Samlíková, Magda; Tokarský, Jonáš; Pazdziora, Erich

2014-06-01

Clay minerals are commonly used materials in pharmaceutical production both as inorganic carriers or active agents. The purpose of this study is the preparation and characterization of clay/antibacterial drug hybrids which can be further included in drug delivery systems for treatment oral infections. Novel nanocomposites with antibacterial properties were successfully prepared by ion exchange reaction from two types of kaolinite/urea intercalates and chlorhexidine diacetate. Intercalation compounds of kaolinite were prepared by reaction with solid urea in the absence of solvents (dry method) as well as with urea aqueous solution (wet method). The antibacterial activity of two prepared samples against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was evaluated by finding the minimum inhibitory concentration (MIC). Antibacterial studies of both samples showed the lowest MIC values (0.01%, w/v) after 1 day against E. faecalis, E. coli and S. aureus. A slightly worse antibacterial activity was observed against P. aeruginosa (MIC 0.12%, w/v) after 1 day. Since samples showed very good antibacterial activity, especially after 1 day of action, this means that these samples can be used as long-acting antibacterial materials. Prepared samples were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental data are supported by results of molecular modelling.

Phenolic Compounds and In Vitro Antibacterial and Antioxidant Activities of Three Tropic Fruits: Persimmon, Guava, and Sweetsop

PubMed Central

Lu, WenQing; Zhou, XiaoMin

2016-01-01

In our previous study, we have found that persimmon, guava, and sweetsop owned considerably high antioxidant activity and contained high total phenolic contents as well. In order to further supply information on the antibacterial and antioxidant activity of these three tropic fruits, they were extracted by 80% methanol. We then examined the extractions about their phenolic compounds and also studied the extractions and phenolic contents about their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against twelve targeted pathogens including 8 standard strains (Staphylococcus aureus, Bacillus cereus, Staphylococcus epidermidis, Monilia albican, Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Pseudomonas aeruginosa) and 4 multidrug-resistant strains (methicillin-resistant Staphylococcus aureus, ESBLs-producing Escherichia coli, carbapenems-resistant Pseudomonas aeruginosa, and multidrug-resistant Acinetobacter baumannii), which are common and comprehensive in clinic. We also employed two ways, that is, FRAP and TEAC, to evaluate their antioxidant activities, using ultraviolet and visible spectrophotometer. Our study indicated that the three tropical fruits possessed obvious antioxidant and antibacterial activity, which supported the possibility of developing the fruits into new natural resource food and functional food as well as new natural antimicrobial agent and food preservatives. Moreover, phenolic compounds detected in the fruits could be used as a potential natural antibacterial agent and antioxidant. PMID:27648444

Oxazolidinone antimicrobials: a patent review (2012-2015).

PubMed

Phillips, Oludotun A; Sharaf, Leyla H

2016-05-01

Antimicrobial resistance in Gram-positive bacteria is a major health care issue. This review summarizes patent publications from 2012 to 2015 that divulged novel oxazolidinones as antibacterial agents. A total of 25 patents obtained from Espacenet, WIPO Patentscope and FreePatentsOnline, and AcclaimIP search engines were reviewed. The patents were scrutinized based on the novelty of the compounds, their antibacterial activity (MIC, µg/mL), and the process of preparation. The oxazolidinones with promising antibacterial activity were classified according to the following structural diversities, as biaryl heterocyclic, fused heteroaryl rings containing oxazolidinones, and others. The biaryl heterocyclic, fused heteroaryl, benzoxazine, and the 1H-pyrazol-1-yl containing oxazolidinone derivatives demonstrated potent antibacterial activities superior to linezolid against Gram-positive bacteria. Some derivatives were effective against standard strains of Gram-negative bacteria, namely Moraxella catarrhalis ATCC A894, and Escherichia coli ATCC 25922. In addition, a patent disclosed a structural isomer of linezolid with marginal activity against the aerobic Gram-negative bacteria MDR Stenotrophomonas (Xanthomonas) maltophilia, while linezolid and vancomycin did not inhibit growth. Finally, some derivatives showed activity against respiratory infectious diseases' causative agents, such as B. anthracis, B. mallei, Y. pestis, and M. pneumoniae. Overall, there is limited in vivo data to support the potential clinical advancement of the currently reported novel derivatives.

Bacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus

PubMed Central

Younis, Waleed; Ezzat, Hany G.; Peters, Christine E.; AbdelKhalek, Ahmed; Cooper, Bruce; Pogliano, Kit; Pogliano, Joe; Mayhoub, Abdelrahman S.; Seleem, Mohamed N.

2017-01-01

Bacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including β-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 μg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents. PMID:28797064

Efficacy of silver diamine fluoride as an antibacterial as well as antiplaque agent compared to fluoride varnish and acidulated phosphate fluoride gel: an in vivo study.

PubMed

Shah, Shalin; Bhaskar, Vijay; Venkataraghavan, Karthik; Choudhary, Prashant; Ganesh, M; Trivedi, Krishna

2013-01-01

Silver diamine fluoride (SDF) is already proven as an antibacterial agent in vitro. Present study was formulated to compare the efficacy of SDF as an antibacterial as well as antiplaque agent in vivo with fluoride varnish and acidulated phosphate fluoride (APF) gel. Total 123 children (male = 82, female = 41) were included in the study for a period of 18 months. Children were divided into three different groups-Group 1: SDF; Group 2: fluoride varnish; and Group 3: APF gel. All subjects were evaluated via plaque score at 6 th, 12 th, and 18 th months as well as Streptococcus mutans counts in saliva at 72 h, 6 th, 12 th, and 18 th months of follow-up. Significant reduction was found in plaque score as well as S. mutans counts irrespective of group division. On intergroup comparison, no statistically significant difference was found in plaque score, but significant reduction in S. mutans counts was found in Group 1 as compared with Groups 2 and 3, while no significant difference was found between Groups 2 and 3. In vivo application of SDF on enamel significantly decreases S. mutans counts as compared to fluoride varnish and APF gel.

Ecology of Anti-Biofilm Agents I: Antibiotics versus Bacteriophages

PubMed Central

Abedon, Stephen T.

2015-01-01

Bacteriophages, the viruses that infect bacteria, have for decades been successfully used to combat antibiotic-resistant, chronic bacterial infections, many of which are likely biofilm associated. Antibiotics as anti-biofilm agents can, by contrast, be inefficacious against even genetically sensitive targets. Such deficiencies in usefulness may result from antibiotics, as naturally occurring compounds, not serving their producers, in nature, as stand-alone disruptors of mature biofilms. Anti-biofilm effectiveness by phages, by contrast, may result from a combination of inherent abilities to concentrate lytic antibacterial activity intracellularly via bacterial infection and extracellularly via localized population growth. Considered here is the anti-biofilm activity of microorganisms, with a case presented for why, ecologically, bacteriophages can be more efficacious than traditional antibiotics as medically or environmentally applied biofilm-disrupting agents. Four criteria, it can be argued, generally must be met, in combination, for microorganisms to eradicate biofilms: (1) Furnishing of sufficiently effective antibacterial factors, (2) intimate interaction with biofilm bacteria over extended periods, (3) associated ability to concentrate antibacterial factors in or around targets, and, ultimately, (4) a means of physically disrupting or displacing target bacteria. In nature, lytic predators of bacteria likely can meet these criteria whereas antibiotic production, in and of itself, largely may not. PMID:26371010

Preliminary investigations on the antibacterial activity of zinc oxide nanostructures

NASA Astrophysics Data System (ADS)

Ramani, Meghana; Ponnusamy, S.; Muthamizhchelvan, C.

2013-04-01

In this study, we present a systematic investigation on the evolution of nanorods of diameter 35-40 nm and 1-2 μm length from nanoparticles of diameter 30-35 nm by varying the concentration of 2,6-lutidine which acts as a shape-directing agent in the synthesis process. This variation in morphology was studied using transmission electron microscopy. The surface capping agent was subsequently removed by heating during the synthesis process and confirmed using Fourier Transform Infra-red spectroscopy. Sufficient quantity of surface defects in the form of oxygen vacancies was observed from the photoluminescence analysis of the synthesized nanostructures. The concentration of defects decreased as the shape transits from nanoparticles to nanorods. The synthesized samples were preliminarily studied for their antibacterial activity against four model (gram-positive and gram-negative) pathogens by disk diffusion method and growth curve analysis. The calculated generation time indicates higher activity for nanoparticles than nanorods. However, the difference in the activity against different pathogens and their dependence on the concentration of defects indicate oxidative stress in addition to mechanical membrane damage as the major toxicity mechanism. Overall, the experimental findings are preliminary evidence supporting the possibility of developing zinc oxide nanostructures as antibacterial agents against a wide range of microorganisms to control and prevent the spreading of bacterial infections.

Plasmin digest of κ-casein as a source of antibacterial peptides.

PubMed

Sedaghati, Marjaneh; Ezzatpanah, Hamid; Boojar, Masoud Mashhadi Akbar; Ebrahimi, Maryam Tajabadi; Aminafshar, Mehdi

2014-05-01

This study investigated the antibacterial properties of plasmin, the plasmin hydrolysis of bovine κ-casein and the fractions (named κC1, κC2, κC3, κC4, and κC5) liberated from it using RP-HPLC. The target bacteria were Escherichia coli, Staphylococcus aureus (pathogenic), Lactobacillus casei and Lactobacillus acidophilus (probiotic). Three peptides (kC1, kC3, and kC4) were found to have antibacterial activity, with κC3 peptide being the most active. The plasmin digest of bovine κ-casein proved to be stronger than any of its fractions in terms of antibacterial potential. Measurement of the minimum inhibitory concentration (MIC) showed that Gram-positive bacteria are generally more sensitive to antibacterial activity than Gram-negative bacteria. The MIC of nisin, as a bacteriocin peptide, was also measured. The three antibacterial peptides were identified using LC-Mass. The molecular mass of kC1, kC3, and kC4 corresponded to the f(17-21), f(22-24), and f(1-3) of bovine κ-casein, respectively. It was also found that the positive charge and hydrophobicity of a peptide are not key factors in antibacterial activity. On the whole, the present study demonstrated that the plasmin digest of κ-casein has a high antibacterial potential and can be considered as a natural antibacterial agent in the food chain.

Current Antimicrobial Usage for the Management of Neutropenic Fever in Korea: A Nationwide Survey

PubMed Central

Choi, Su-Mi; Park, Sun Hee; Lee, Dong-Gun; Choi, Jung-Hyun; Yoo, Jin-Hong

2008-01-01

A nationwide questionnaire-based survey was performed to evaluate the current clinical practices for the management of neutropenic fever in hematology units and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A 86.9% response rate was obtained from a total of 46 doctors and practical policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the sites responded that they used oral fluoroquinolone as prophylaxis for neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally, 42.4% of the sites responded that they used antifungal prophylaxis in the chemotherapy groups whereas 90.9% of the sites responded that they used antifungal prophylaxis in HSCT recipients. Approximately half of the responding sites prescribed combination regimen with 3rd or 4th cephalosporin plus aminoglycoside as a first-line therapy. Most of the sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line regimen, and they changed antibiotics to second-line regimens that varied widely among the sites. Twenty-seven sites (84.4%) responded that they considered adding an antifungal agent when fever persisted for 5-7 days despite antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line antifungal, which was probably due to the limitations of the national health insurance system. The role of oral antibiotics in the management of neutropenic fever still accounted for a small portion. To the best of our knowledge, this survey is the first report to examine the practical policies currently in place for the management of neutropenic fever in Korea and the results of this survey may help to establish a Korean guideline in the future. PMID:19119433

Cell-wall recycling and synthesis in Escherichia coli and Pseudomonas aeruginosa - their role in the development of resistance.

PubMed

Dhar, Supurna; Kumari, Hansi; Balasubramanian, Deepak; Mathee, Kalai

2018-01-01

The bacterial cell-wall that forms a protective layer over the inner membrane is called the murein sacculus - a tightly cross-linked peptidoglycan mesh unique to bacteria. Cell-wall synthesis and recycling are critical cellular processes essential for cell growth, elongation and division. Both de novo synthesis and recycling involve an array of enzymes across all cellular compartments, namely the outer membrane, periplasm, inner membrane and cytoplasm. Due to the exclusivity of peptidoglycan in the bacterial cell-wall, these players are the target of choice for many antibacterial agents. Our current understanding of cell-wall biochemistry and biogenesis in Gram-negative organisms stems mostly from studies of Escherichia coli. An incomplete knowledge on these processes exists for the opportunistic Gram-negative pathogen, Pseudomonas aeruginosa. In this review, cell-wall synthesis and recycling in the various cellular compartments are compared and contrasted between E. coli and P. aeruginosa. Despite the fact that there is a remarkable similarity of these processes between the two bacterial species, crucial differences alter their resistance to β-lactams, fluoroquinolones and aminoglycosides. One of the common mediators underlying resistance is the amp system whose mechanism of action is closely associated with the cell-wall recycling pathway. The activation of amp genes results in expression of AmpC β-lactamase through its cognate regulator AmpR which further regulates multi-drug resistance. In addition, other cell-wall recycling enzymes also contribute to antibiotic resistance. This comprehensive summary of the information should spawn new ideas on how to effectively target cell-wall processes to combat the growing resistance to existing antibiotics.

Effect of plasma superficial treatments on antibacterial functionalization and coloration of cellulosic fabrics

NASA Astrophysics Data System (ADS)

Ibrahim, Nabil A.; Eid, Basma M.; Abdel-Aziz, Mohamed S.

2017-01-01

Remarkable improvement in antibacterial activity and durability of different cellulosic substrates namely cotton, linen, viscose and lyocell was achieved by pre-surface modification using N2-plasma to create new active and binding sites, -NH2 groups, onto the modified fabric surfaces followed by subsequent loading of biosynthesized silver nanoparticles (Ag NPs) alone and in combination with certain antibiotics using exhaustion method. The imparted antibacterial activity against both G+ve (S. aureus) and G-ve (E. coli) pathogens was governed by type of substrate, extent of modification and subsequent loading of antibacterial agent, synergistic effect, and antibacterial activity as well as type of harmful bacteria. A remarkable antibacterial activity still retained even after 15 washings. In addition, incorporation of Ag NPs into pigment printing paste and into acid dyeing bath for combined coloration and functionalization of O2-plasma and N2-plasma pre-modified substrates respectively were successfully achieved. Moreover, both SEM images and EDS spectra of selected substrates revealed the change in surface morphology as well as the presence of the loaded Ag element onto the post-treated substrates.

Preparation and antibacterial properties of O-carboxymethyl chitosan/lincomycin hydrogels.

PubMed

He, Guanghua; Chen, Xiang; Yin, Yihua; Cai, Weiquan; Ke, Wanwan; Kong, Yahui; Zheng, Hua

2016-01-01

In this study, O-carboxymethyl chitosan (O-CMCS) was synthesized from chitosan and monochloroacetic acid. Then O-CMCS hydrogel was prepared by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in which the lincomycin was packaged. The Fourier transform infrared spectrum and scanning electron microscopy were adopted to characterize the structure and morphology of the product. The influences of dosage of EDC/NHS and concentration of O-CMCS on the swelling properties of the hydrogels were investigated. The hydrogels performed good swelling capacities and obvious pH-sensitive properties. The antibacterial activities of the hydrogels were tested against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Compared with pure O-CMCS hydrogels, the antibacterial activities of O-CMCS/lincomycin hydrogels were significantly improved with the increase in the concentration of lincomycin against E. coli and S. aureus. With the increase in dosage of crosslinking agent or concentration of O-CMCS, the antibacterial activities both decreased gradually against the two bacteria. O-CMCS/lincomycin hydrogel was expected to be used for antibacterial material in view of its significant antibacterial activities.

Antibacterial activity of vegetables and juices.

PubMed

Lee, Yee-Lean; Cesario, Thomas; Wang, Yang; Shanbrom, Edward; Thrupp, Lauri

2003-01-01

We evaluated the antibacterial activities of various fruit and vegetable extracts on common potential pathogens including antibiotic-resistant strains. Standardized bacterial inocula were added to serial dilutions of sterile vegetable and fruit extracts in broth, with final bacterial concentrations of 10(4-5) cells/mL. After overnight incubation at 35 degrees C, antibacterial activity was measured by minimum inhibitory and minimum bactericidal dilutions (for raw juices) or concentrations (for tea). Among the vegetable and fruit extracts tested, all green vegetables showed no antibacterial activity on Staphylococcus epidermidis and Klebsiella pneumoniae. All purple and red vegetable and fruit juices had antibacterial activities in dilutions ranging from 1:2 to 1:16. Garlic juice had significant activity, with bactericidal action in dilutions ranging up to 1:128 of the original juice. Tea also had significant activity, with bactericidal action in concentrations ranging up to 1.6 mg/mL, against a spectrum of pathogens including resistant strains such as methicillin- and ciprofloxacin-resistant staphylococci, vancomycin-resistant enterococci, and ciprofloxacin-resistant Pseudomonas aeruginosa. Tea and garlic have the potential for exploration of broader applications as antibacterial agents.

Pahangensin A and B, two new antibacterial diterpenes from the rhizomes of Alpinia pahangensis Ridley.

PubMed

Sivasothy, Yasodha; Ibrahim, Halijah; Paliany, Audra Shaleena; Alias, Siti Aisyah; Awang, Khalijah

2013-12-01

The rhizomes of Alpinia pahangensis Ridley yielded a new bis-labdanic diterpene for which the name pahangensin A (1) was proposed along with a new labdane diterpene, pahangensin B (2). Their structures were elucidated by spectroscopic methods including, 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Pahangensin A (1) was found to be an antibacterial agent against Staphylococcus aureus, Bacillus cereus and Bacillus subtilis with MIC values less than 100 μg/mL, respectively. Pahangensin B (2) exhibited antibacterial activity (MIC <100 μg/mL) against B. cereus. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis of 1-phenyl-3-(4'-nitrophenyl)-5-(3',4'-dimethoxy-6'-nitrophenyl)-2-pyrazoline and its antibacterial activity

NASA Astrophysics Data System (ADS)

Fauzi'ah, Lina; Wahyuningsih, Tutik Dwi

2017-03-01

Synthesis of pyrazoline substituted with nitro groups as antibacterial agent has been carried out by cycloaddition reaction. The compound was synthesized from chalcone and phenylhyrazine by refluxing them in 2-butanol for 24 h. The product was purified and characterized using FTIR and 1H-NMR spectrometers. The result showed that pyrazoline has been succesfully synthesized in 33.06% yield. The compund has antibacterial activity againts Bacillus subtilis and Shigella flexneri. However, it has tendency of activity for Gram-negative bacteria. In conclusion, the nitro groups that substituted in aromatic ring were predicted as a part of pharmacophore.

Enhancement of bismuth antibacterial activity with lipophilic thiol chelators.

PubMed Central

Domenico, P; Salo, R J; Novick, S G; Schoch, P E; Van Horn, K; Cunha, B A

1997-01-01

The antibacterial properties of bismuth are greatly enhanced when bismuth is combined with certain lipophilic thiol compounds. Antibacterial activity was enhanced from 25- to 300-fold by the following seven different thiols, in order of decreasing synergy: 1,3-propanedithiol, dimercaprol (BAL), dithiothreitol, 3-mercapto-2-butanol, beta-mercaptoethanol, 1-monothioglycerol, and mercaptoethylamine. The dithiols produced the greatest synergy with bismuth at optimum bismuth-thiol molar ratios of from 3:1 to 1:1. The monothiols were generally not as synergistic and required molar ratios of from 1:1 to 1:4 for optimum antibacterial activity. The most-active mono- or dithiols were also the most soluble in butanol. The intensity of the yellow formed by bismuth-thiol complexes reflected the degree of chelation and correlated with antibacterial potency at high molar ratios. The bismuth-BAL compound (BisBAL) was active against most bacteria, as assessed by broth dilution, agar diffusion, and agar dilution analyses. Staphylococci (MIC, 5 to 7 microM Bi3+) and Helicobacter pylori (MIC, 2.2 microM) were among the most sensitive bacteria. Gram-negative bacteria were sensitive (MIC, < 17 microM). Enterococci were relatively resistant (MIC, 63 microM Bi3+). The MIC range for anaerobes was 15 to 100 microM Bi3+, except for Clostridium difficile (MIC, 7.5 microM). Bactericidal activity averaged 29% above the MIC. Bactericidal activity increased with increasing pH and/or increasing temperature. Bismuth-thiol solubility, stability, and antibacterial activity depended on pH and the bismuth-thiol molar ratio. BisBAL was stable but ineffective against Escherichia coli at pH 4. Activity and instability (reactivity) increased with increasing alkalinity. BisBAL was acid soluble at a molar ratio of greater than 3:2 and alkaline soluble at a molar ratio of less than 2:3. In conclusion, certain lipophilic thiol compounds enhanced bismuth antibacterial activity against a broad spectrum of bacteria. The activity, solubility, and stability of BisBAL were strongly dependent on the pH, temperature, and molar ratio. Chelation of bismuth with certain thiol agents enhanced the solubility and lipophilicity of this cationic heavy metal, thereby significantly enhancing its potency and versatility as an antibacterial agent. PMID:9257744

Quantitative risk from fluoroquinolone-resistant Salmonella and Campylobacter due to treatment of dairy heifers with enrofloxacin for bovine respiratory disease.

PubMed

Hurd, H Scott; Vaughn, Michael B; Holtkamp, Derald; Dickson, James; Warnick, Lorin

2010-11-01

The objective of this study was to evaluate the human health impact of using fluoroquinolones to treat bovine respiratory disease (BRD) in dairy heifers less than 20 months of age. Specifically, this study quantified the probability of persistent symptoms in humans treated with a fluoroquinolone, for a fluoroquinolone-resistant Campylobacter, Salmonella, or multidrug-resistant (MDR) Salmonella infection acquired following the consumption of ground beef. To comply with a Food and Drug Administration requirement for approval of enrofloxacin use in dairy heifers, a binomial event tree was constructed following Food and Drug Administration guidance 152. Release was estimated from the slaughter of dairy cattle carrying fluoroquinolone-resistant bacteria attributed to the proposed use in dairy heifers. For exposure, human foodborne exposure to Campylobacter, Salmonella, and MDR Salmonella after consumption of ground beef was estimated. The consequence assessment included illness, fluoroquinolone treatment, and persistent symptoms in patients treated with a fluoroquinolone. Using best available data to estimate the parameters and probabilities of each event, stochastic simulation was used to represent uncertainty and variability in many of the parameters. A scenario analysis was performed to evaluate the uncertainty of the following parameters: (1) probability of resistance development in treated animals, (2) portion of illnesses attributable to ground beef, and (3) probability of persistent symptoms in patients 18 years of age and over treated with a fluoroquinolone. The population at risk was restricted to people 18 years of age and over, as fluoroquinolones are not labeled for treatment of gastroenteritis in children. The mean annual increased risk of cases in the U.S. population (18 years of age and over) where compromised fluoroquinolone treatment resulted in persistent symptoms was estimated to be 1 in 61 billion (one case every 293 years) for Salmonella, 1 in 33 billion (one case every 158 years) for MDR Salmonella, and 1 in 2.8 billion (one case every 13 years) for Campylobacter.

Fluoroquinolone Treatment and Susceptibility of Isolates From Bacterial Keratitis

PubMed Central

Ray, Kathryn J.; Prajna, Lalitha; Srinivasan, Muthiah; Geetha, Manoharan; Karpagam, Rajarathinam; Glidden, David; Oldenburg, Catherine E.; Sun, Catherine Q.; McLeod, Stephen D.; Acharya, Nisha R.; Lietman, Thomas M.

2013-01-01

Objective To analyze the relationship between fluoroquinolone use at presentation and minimum inhibitory concentration in bacterial keratitis. Methods The Steroids for Corneal Ulcers Trial was a randomized, double-masked, placebo-controlled trial assessing the effect of adjunctive topical corticosteroid treatment on outcomes in bacterial keratitis. After presentation, all patients were treated with moxifloxacin hydrochloride, 0.5%. We compare antibiotic use at presentation with minimum inhibitory concentration against moxifloxacin for all isolates. Separate analyses accounted for organism species and fluoroquinolone generation. Results Topical fluoroquinolone use at presentation was reported in 92 of 480 cases (19.2%). Causative organisms in the 480 cases included Streptococcus pneumoniae (247 cases [51.5%]), Pseudomonas aeruginosa (109 cases [22.7%]), and Nocardia species (55 cases [11.5%]). Isolates from patients who reported fluoroquinolone use at presentation had a 2.01-fold–higher minimum inhibitory concentration (95% CI, 1.39-fold to 2.91-fold; P <.001). Fourth-generation fluoroquinolones were associated with a 3.48-fold–higher minimum inhibitory concentration than those isolates that were not exposed to pretreatment at enrollment (95% CI, 1.99-fold to 6.06-fold; P <.001). Conclusion This study provides evidence that prior use of fluoroquinolones is associated with antibiotic resistance. PMID:23307105

Fluoroquinolone treatment and susceptibility of isolates from bacterial keratitis.

PubMed

Ray, Kathryn J; Prajna, Lalitha; Srinivasan, Muthiah; Geetha, Manoharan; Karpagam, Rajarathinam; Glidden, David; Oldenburg, Catherine E; Sun, Catherine Q; McLeod, Stephen D; Acharya, Nisha R; Lietman, Thomas M

2013-03-01

To analyze the relationship between fluoroquinolone use at presentation and minimum inhibitory concentration in bacterial keratitis. The Steroids for Corneal Ulcers Trial was a randomized, double-masked, placebo-controlled trial assessing the effect of adjunctive topical corticosteroid treatment on outcomes in bacterial keratitis. After presentation, all patients were treated with moxifloxacin hydrochloride, 0.5%. We compare antibiotic use at presentation with minimum inhibitory concentration against moxifloxacin for all isolates. Separate analyses accounted for organism species and fluoroquinolone generation. Topical fluoroquinolone use at presentation was reported in 92 of 480 cases (19.2%). Causative organisms in the 480 cases included Streptococcus pneumoniae (247 cases [51.5%]), Pseudomonas aeruginosa (109 cases [22.7%]), and Nocardia species (55 cases [11.5%]). Isolates from patients who reported fluoroquinolone use at presentation had a 2.01-fold-higher minimum inhibitory concentration (95% CI, 1.39-fold to 2.91-fold; P < .001). Fourth-generation fluoroquinolones were associated with a 3.48-fold-higher minimum inhibitory concentration than those isolates that were not exposed to pretreatment at enrollment (95% CI, 1.99-fold to 6.06-fold; P < .001). This study provides evidence that prior use of fluoroquinolones is associated with antibiotic resistance. clinicaltrials.gov Identifier: NCT00324168.

Clinicomicrobiological profile of endophthalmitis: A 10 year experience in a Tertiary Care Center in North India.

PubMed

Satpathy, Gita; Nayak, Niranjan; Wadhwani, Meenakshi; Venkwatesh, Pradeep; Kumar, Atul; Sharma, Yograj; Sreenivas, Vishnu

2017-01-01

To determine the clinicomicrobiological profile of infectious agents and their antibiotic susceptibility in different type of endophthalmitis. A retrospective review of clinical and microbiological records from January 2001 to December 2010, was performed in 1110 patients diagnosed with different type of endophthalmitis (postoperative, posttraumatic, endogenous and post keratitis) to record the demographic details, clinical presentations; microbiological agents isolated with their antimicrobial sensitivity pattern. Antimicrobial susceptibility testing for various culture positive isolates (bacterial/fungal) was performed by the disc diffusion technique. Out of the 1110 intra-ocular specimens processed, 384 (34.6%) were positive for bacteria. S epidermidis was the most predominant isolate accounting for 42.7% of all bacteria obtained, followed by Pseudomonas aeruginosa (24.5%). Besides Pseudomonas, Acinetobacter spp. were the next common gram negative bacilli detected (8.3%) followed by Klebsiella, E. coli, Enterobacter and Alkaligenes in 2.6%, 0.8%, 0.8% and 0.5% cases respectively. The predominant fungal species were Aspergillus spp., in 36.1%, followed by Fusarium spp. in 26.4% cases. Overall susceptibility pattern in our study showed that gram positive bacteria were most susceptible to glycopeptides like vancomycin (80-100%) and fluoroquinolones (87-91%). The sensitivity pattern of gram negative organisms like Pseudomonas and Klebsiella towards fluoroquinolones ranged between 61% - 82%. S epidermidis was the most common bacteria isolated in postoperative and posttraumatic endophthalmitis, Pseudomonas aeruginosa was the most common bacterial isolated in posttraumatic endophthalmitisAmongst fungi Aspergillus was the most common organism.

Antimicrobial resistance in zoonotic nontyphoidal Salmonella: an alarming trend?

PubMed

Michael, G B; Schwarz, S

2016-12-01

Zoonotic bacteria of the genus Salmonella have acquired various antimicrobial resistance properties over the years. The corresponding resistance genes are commonly located on plasmids, transposons, gene cassettes, or variants of the Salmonella Genomic Islands SGI1 and SGI2. Human infections by nontyphoidal Salmonella isolates mainly result from ingestion of contaminated food. The two predominantly found Salmonella enterica subsp. enterica serovars in the USA and in Europe are S. Enteritidis and S. Typhimurium. Many other nontyphoidal Salmonella serovars have been implicated in foodborne Salmonella outbreaks. Summary reports of the antimicrobial susceptibility patterns of nontyphoidal Salmonella isolates over time suggest a moderate to low level of antimicrobial resistance and multidrug-resistance. However, serovar-specific analyses showed in part a steady state, a continuous decline, or a recent increase in resistance to certain antimicrobial agents. Resistance to critically important antimicrobial agents, e.g. third-generation cephalosporins and (fluoro)quinolones is part of many monitoring programmes and the corresponding results confirm that extended-spectrum β-lactamases are still rarely found in nontyphoidal Salmonella serovars, whereas resistance to (fluoro)quinolones is prevalent at variable frequencies among different serovars from humans and animals in different countries. Although it is likely that nontyphoidal Salmonella isolates from animals represent a reservoir for resistance determinants, it is mostly unknown where and when Salmonella isolates acquired resistance properties and which exchange processes have happened since then. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study.

PubMed

Sode, Jacob; Obel, Niels; Hallas, Jesper; Lassen, Annmarie

2007-05-01

Several case-control studies have reported that the use of fluoroquinolone increases the risk of rupture of the Achilles tendon. Our aim was to estimate this risk by means of a population-based cohort approach. Data on Achilles tendon ruptures and fluoroquinolone use were retrieved from three population-based databases that include information on residents of Funen County (population: 470,000) in primary and secondary care during the period 1991-1999. A study cohort of all 28,262 first-time users of fluoroquinolone and all incident cases of Achilles tendon ruptures were identified. The incidence rate of Achilles tendon ruptures among users and non-users of fluoroquinolones and the standardised incidence rate ratio associating fluoroquinolon use with Achilles tendon rupture were the main outcome measures. Between 1991 and 2002 the incidence of Achilles tendon rupture increased from 22.1 to 32.6/100,000 person-years. Between 1991 and 1999 the incidence of fluoroquinolone users was 722/100,000 person-years, with no apparent trend over time. Within 90 days of their first use of fluoroquinolone, five individuals had a rupture of the Achilles tendon; the expected number was 1.6, yielding an age- and sex-standardised incidence ratio of 3.1 [(95% confidence interval (95%CI): 1.0-7.3). The 90-day cumulative incidence of Achilles tendon ruptures among fluoroquinolone users was 17.7/100,000 (95%CI: 5.7-41.3), which is an increase of 12.0/100,000 (95%CI: 0.0-35.6) compared to the background population. Fluoroquinolone use triples the risk of Achilles tendon rupture, but the incidence among users is low.

Molecular Evolution Perspectives on Intraspecific Lateral DNA Transfer of Topoisomerase and Gyrase Loci in Streptococcus pneumoniae, with Implications for Fluoroquinolone Resistance Development and Spread

PubMed Central

Stanhope, Michael J.; Walsh, Stacey L.; Becker, Julie A.; Italia, Michael J.; Ingraham, Karen A.; Gwynn, Michael N.; Mathie, Tom; Poupard, James A.; Miller, Linda A.; Brown, James R.; Amrine-Madsen, Heather

2005-01-01

Fluoroquinolones are an important class of antibiotics for the treatment of infections arising from the gram-positive respiratory pathogen Streptococcus pneumoniae. Although there is evidence supporting interspecific lateral DNA transfer of fluoroquinolone target loci, no studies have specifically been designed to assess the role of intraspecific lateral transfer of these genes in the spread of fluoroquinolone resistance. This study involves a comparative evolutionary perspective, in which the evolutionary history of a diverse set of S. pneumoniae clinical isolates is reconstructed from an expanded multilocus sequence typing data set, with putative recombinants excluded. This control history is then assessed against networks of each of the four fluoroquinolone target loci from the same isolates. The results indicate that although the majority of fluoroquinolone target loci from this set of 60 isolates are consistent with a clonal dissemination hypothesis, 3 to 10% of the sequences are consistent with an intraspecific lateral transfer hypothesis. Also evident were examples of interspecific transfer, with two isolates possessing a parE-parC gene region arising from viridans group streptococci. The Spain 23F-1 clone is the most dominant fluoroquinolone-nonsusceptible clone in this set of isolates, and the analysis suggests that its members act as frequent donors of fluoroquinolone-nonsusceptible loci. Although the majority of fluoroquinolone target gene sequences in this set of isolates can be explained on the basis of clonal dissemination, a significant number are more parsimoniously explained by intraspecific lateral DNA transfer, and in situations of high S. pneumoniae population density, such events could be an important means of resistance spread. PMID:16189113

Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

PubMed Central

Wacker, Evelin; Meister, Reinhard; Panse, Mary; Weber-Schoendorfer, Corinna; Oppermann, Marc; Schaefer, Christof

2014-01-01

Fluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [ORadj], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HRadj], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [ORcrude], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HRadj, 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered. PMID:24841264

Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs.

PubMed

KuKanich, K; KuKanich, B; Guess, S; Heinrich, E

2016-01-01

Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. Five healthy Greyhounds housed in a research colony. This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h μg/mL) compared to enrofloxacin (AUC 3.86-7.50 h μg/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%). A possible clinically relevant drug interaction for the relative bioavailability of ciprofloxacin with sucralfate was found. No significant difference in bioavailability was documented for enrofloxacin with sucralfate. Further research is warranted in fasted dogs and clinical cases requiring enrofloxacin or other approved fluoroquinolones in combination with sucralfate. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc on behalf of the American College of Veterinary Internal Medicine.

Role of fluoroquinolones in lower respiratory tract infections.

PubMed

Vellend, H

1989-02-01

Oral quinolones such as ciprofloxacin are promising agents in the treatment of serious bronchopulmonary infections due to susceptible gram-negative micro-organisms such as Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae and even Pseudomonas aeruginosa. Their moderative activity against Streptococcus pneumoniae may limit the use of these agents in the treatment of acute exacerbations of chronic bronchitis and in the empiric management of community-acquired bacterial pneumonia. Further prospectively designed studies are needed to address this issue. The ability of quinolones to effectively penetrate bronchial mucosa and to be concentrated within macrophages may afford additional advantage to these agents. They should not be used as a sole agent in the treatment of aspiration pneumonia nor anaerobic pleuropulmonary disease. Quinolones are very active in experimental models of Legionnaire's disease and deserve further clinical study. Ciprofloxacin is a promising alternative to standard parenteral drugs in the management of Pseudomonas aeruginosa infections in adults with cystic fibrosis. The potential for drug interactions with theophylline must be kept in mind for patients on both of these drugs.

Unearthing the Antibacterial Mechanism of Medicinal Clay: A Geochemical Approach to Combating Antibiotic Resistance

DOE PAGES

Morrison, Keith D.; Misra, Rajeev; Williams, Lynda B.

2016-01-08

Natural antibacterial clays, when hydrated and applied topically, kill human pathogens including antibiotic resistant strains proliferating worldwide. Only certain clays are bactericidal; those containing soluble reduced metals and expandable clay minerals that absorb cations, providing a capacity for extended metal release and production of toxic hydroxyl radicals. Here we show the critical antibacterial components are soluble Fe 2+ and Al 3+ that synergistically attack multiple cellular systems in pathogens normally growth-limited by Fe supply. This geochemical process is more effective than metal solutions alone and provides an alternative antibacterial strategy to traditional antibiotics. Advanced bioimaging methods and genetic show thatmore » Al 3+ misfolds cell membrane proteins, while Fe 2+ evokes membrane oxidation and enters the cytoplasm inflicting hydroxyl radical attack on intracellular proteins and DNA. The lethal reaction precipitates Fe 3+-oxides as biomolecular damage proceeds. In conclusion, discovery of this bactericidal mechanism demonstrated by natural clays should guide designs of new mineral-based antibacterial agents.« less

Unearthing the Antibacterial Mechanism of Medicinal Clay: A Geochemical Approach to Combating Antibiotic Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrison, Keith D.; Misra, Rajeev; Williams, Lynda B.

Natural antibacterial clays, when hydrated and applied topically, kill human pathogens including antibiotic resistant strains proliferating worldwide. Only certain clays are bactericidal; those containing soluble reduced metals and expandable clay minerals that absorb cations, providing a capacity for extended metal release and production of toxic hydroxyl radicals. Here we show the critical antibacterial components are soluble Fe 2+ and Al 3+ that synergistically attack multiple cellular systems in pathogens normally growth-limited by Fe supply. This geochemical process is more effective than metal solutions alone and provides an alternative antibacterial strategy to traditional antibiotics. Advanced bioimaging methods and genetic show thatmore » Al 3+ misfolds cell membrane proteins, while Fe 2+ evokes membrane oxidation and enters the cytoplasm inflicting hydroxyl radical attack on intracellular proteins and DNA. The lethal reaction precipitates Fe 3+-oxides as biomolecular damage proceeds. In conclusion, discovery of this bactericidal mechanism demonstrated by natural clays should guide designs of new mineral-based antibacterial agents.« less

Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

PubMed

Baig, Noorullah; Singh, Rajnish Prakash; Chander, Subhash; Jha, Prabhat Nath; Murugesan, Sankaranarayanan; Sah, Ajay K

2015-12-01

Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ.

PubMed

Li, Xin; Sheng, Juzheng; Huang, Guihua; Ma, Ruixin; Yin, Fengxin; Song, Di; Zhao, Can; Ma, Shutao

2015-06-05

In an attempt to discover potential antibacterial agents against the increasing bacterial resistance, novel cinnamaldehyde derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method, and their cell division inhibitory activity against four representative strains. In the in vitro antibacterial activity, the newly synthesized compounds generally displayed better efficacy against Staphylococcus aureus ATCC25923 than the others. In particular, compounds 3, 8 and 10 exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 μg/mL, over 256-fold better than all the reference drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Preparation, characterization, and antibacterial activity studies of silver-loaded poly(styrene-co-acrylic acid) nanocomposites.

PubMed

Song, Cunfeng; Chang, Ying; Cheng, Ling; Xu, Yiting; Chen, Xiaoling; Zhang, Long; Zhong, Lina; Dai, Lizong

2014-03-01

A simple method for preparing a new type of stable antibacterial agent was presented. Monodisperse poly(styrene-co-acrylic acid) (PSA) nanospheres, serving as matrices, were synthesized via soap-free emulsion polymerization. Field-emission scanning electron microscopy micrographs indicated that PSA nanospheres have interesting surface microstructures and well-controlled particle size distributions. Silver-loaded poly(styrene-co-acrylic acid) (PSA/Ag-NPs) nanocomposites were prepared in situ through interfacial reduction of silver nitrate with sodium borohydride, and further characterized by transmission electron microscopy and X-ray diffraction. Their effects on antibacterial activity including inhibition zone, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetics were evaluated. In the tests, PSA/Ag-NPs nanocomposites showed excellent antibacterial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. These nanocomposites are considered to have potential application in antibacterial coatings on biomedical devices to reduce nosocomial infection rates. Copyright © 2013 Elsevier B.V. All rights reserved.

Novel 3-Aminothiazolquinolones: Design, Synthesis, Bioactive Evaluation, SARs, and Preliminary Antibacterial Mechanism.

PubMed

Cui, Sheng-Feng; Addla, Dinesh; Zhou, Cheng-He

2016-05-26

A series of novel 3-aminothiazolquinolones as analogues of quinolone antibacterial agents were designed and synthesized in an effort to circumvent quinolone resistance. Among these 3-aminothiazolquinolones, 3-(2-aminothiazol-4-yl)-7-chloro-6-(pyrrolidin-1-yl) quinolone 12b exhibited potent antibacterial activity, low cytotoxicity to hepatocyte cells, strong inhibitory potency to DNA gyrase, and a broad antimicrobial spectrum including against multidrug-resistant strains. This active molecule 12b also induced bacterial resistance more slowly than norfloxacin. Analysis of structure-activity relationships (SARs) disclosed that the 2-aminothiazole fragment at the 3-position of quinolone plays an important role in exerting antibacterial activity. Molecular modeling and experimental investigation of aminothiazolquinolone 12b with DNA from a sensitive methicillin-resistant Staphylococcus aureus (MRSA) strain revealed that the possible antibacterial mechanism might be related to the formation of a compound 12b-Cu(2+)-DNA ternary complex in which the Cu(2+) ion acts as a bridge between the backbone of 3-aminothiazolquinolone and the phosphate group of the nucleic acid.

Unearthing the Antibacterial Mechanism of Medicinal Clay: A Geochemical Approach to Combating Antibiotic Resistance

PubMed Central

Morrison, Keith D.; Misra, Rajeev; Williams, Lynda B.

2016-01-01

Natural antibacterial clays, when hydrated and applied topically, kill human pathogens including antibiotic resistant strains proliferating worldwide. Only certain clays are bactericidal; those containing soluble reduced metals and expandable clay minerals that absorb cations, providing a capacity for extended metal release and production of toxic hydroxyl radicals. Here we show the critical antibacterial components are soluble Fe2+ and Al3+ that synergistically attack multiple cellular systems in pathogens normally growth-limited by Fe supply. This geochemical process is more effective than metal solutions alone and provides an alternative antibacterial strategy to traditional antibiotics. Advanced bioimaging methods and genetic show that Al3+ misfolds cell membrane proteins, while Fe2+ evokes membrane oxidation and enters the cytoplasm inflicting hydroxyl radical attack on intracellular proteins and DNA. The lethal reaction precipitates Fe3+-oxides as biomolecular damage proceeds. Discovery of this bactericidal mechanism demonstrated by natural clays should guide designs of new mineral-based antibacterial agents. PMID:26743034

Isolation, characterization and chromatography based purification of antibacterial compound isolated from rare endophytic actinomycetes Micrococcus yunnanensis.

PubMed

Ranjan, Ravi; Jadeja, Vasantba

2017-10-01

Endophytic actinomycetes are considered as one of the relatively unexplored potential sources in search of antibiotic producer against antibiotic resistant pathogens. A potent strain isolated from Catharanthus roseus that displays antibacterial potential against antibiotic resistant human pathogen Staphylococcus aureus was characterized and designated as Micrococcus yunnanensis strain rsk5. Rsk5 is capable of producing optimum antibacterial metabolites on starch casein medium at 30 °C, pH 5 and 2% NaCl condition. The crude antibacterial agent was extracted from fermentation broth by ethyl acetate and separated by TLC using chloroform-methanol (24:1, v/v) solvent system with R f value of 0.26. It was partially purified by flash chromatography, followed by HPLC and analyzed by ultraviolet visible spectrophotometer to get absorption maxima at 208.4 nm. The ESI-MS spectra showed molecular ion peaks at m / z 472.4 [M-H], which does not match with any known antibacterial compound.

Synthesis and Antibacterial Activities of Antibacterial Peptides with a Spiropyran Fluorescence Probe

PubMed Central

Chen, Lei; Zhu, Yu; Yang, Danling; Zou, Rongfeng; Wu, Junchen; Tian, He

2014-01-01

In this report, antibacterial peptides1-3 were prepared with a spiropyran fluorescence probe. The probe exhibits a change in fluorescence when isomerized from a colorless spiro-form (spiropyran, Sp) to a colored open-form (merocyanine, Mc) under different chemical environments, which can be used to study the mechanism of antimicrobial activity. Peptides 1-3 exhibit a marked decrease in antimicrobial activity with increasing alkyl chain length. This is likely due to the Sp-Mc isomers in different polar environments forming different aggregate sizes in TBS, as demonstrated by time-dependent dynamic light scattering (DLS). Moreover, peptides 1-3 exhibited low cytotoxicity and hemolytic activity. These probe-modified peptides may provide a novel approach to study the effect of structural changes on antibacterial activity, thus facilitating the design of new antimicrobial agents to combat bacterial infection. PMID:25358905

Synthesis of Some New Tetrahydropyrimidine Derivatives as Possible Antibacterial Agents.

PubMed

Foroughifar, Naser; Karimi Beromi, Somayeh; Pasdar, Hoda; Shahi, Masoumeh

2017-01-01

Heterocyclic compounds containing a pyrimidine nucleus are of special interests thanks to their applications in medicinal chemistry as they are the basic skeleton of several bioactive compounds such as antifungal, antibacterial, antitumor and antitubercular. As a part of our research in the synthesis of pyrimidine derivatives containing biological activities, some new tetrahydropyrimidine derivatives (1-10) were synthesized via Biginelli reaction using HCl or DABCO as a catalyst with good yields. All structures of products were confirmed by IR, 1 H NMR and 13 C NMR spectroscopy. The antibacterial activity of some synthesized compounds was investigated against Staphylococcus aureus (ATCC 6538), Staphylococcus epidermidis (ATCC 12228) , Bacillus cereus (ATCC14579) , Esherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 13883) and Pseudomonas aeruginosa (PAO1) bacteria. Some of these compounds such as 8 and 10 exhibited a good to significant antibacterial activity.

Synthesis of Some New Tetrahydropyrimidine Derivatives as Possible Antibacterial Agents

PubMed Central

Foroughifar, Naser; Karimi Beromi, Somayeh; Pasdar, Hoda; Shahi, Masoumeh

2017-01-01

Heterocyclic compounds containing a pyrimidine nucleus are of special interests thanks to their applications in medicinal chemistry as they are the basic skeleton of several bioactive compounds such as antifungal, antibacterial, antitumor and antitubercular. As a part of our research in the synthesis of pyrimidine derivatives containing biological activities, some new tetrahydropyrimidine derivatives (1-10) were synthesized via Biginelli reaction using HCl or DABCO as a catalyst with good yields. All structures of products were confirmed by IR, 1H NMR and 13C NMR spectroscopy. The antibacterial activity of some synthesized compounds was investigated against Staphylococcus aureus (ATCC 6538), Staphylococcus epidermidis (ATCC 12228), Bacillus cereus (ATCC14579), Esherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 13883) and Pseudomonas aeruginosa (PAO1) bacteria. Some of these compounds such as 8 and 10 exhibited a good to significant antibacterial activity. PMID:28979312

In silico modeling and synthesis of phenyl and thienyl analogs of chalcones for potential leads as anti-bacterial agents

NASA Astrophysics Data System (ADS)

Kar, Swayamsiddha; Mishra, Rohit Kumar; Pathak, Ashutosh; Dikshit, Anupam; Golakoti, Nageswara Rao

2018-03-01

In the recent times, the common diseases like food poisoning, pneumonia, diarrhea etc. have been observed to be drug resistant. The present study deals with the synthesis of known chalcone derivatives using the Claisen-Schmidt condensation and further characterization using UV-vis, IR, 1H NMR, 13C NMR and mass spectrometry. These derivatives were first simulated for their anti-bacterial efficacy in silico and consequently confirmed in vitro to confirm the findings. One of the chalcones, 4-NDM-2‧-HC showed excellent in-vitro antibacterial activity with an IC90 0.43 mg/mL against Vibrio cholerae as compared to commercially available antibiotic gentamicin as the standard. Further, all these tested chalcone derivatives fulfill Lipinski's parameters and show tremendous drug likeness score, confirming their potential as antibacterial leads.

Synthesis and Evaluation of Curcuminoid Analogues as Antioxidant and Antibacterial Agents.

PubMed

Emam, Dalia R; Alhajoj, Ahmad M; Elattar, Khaled M; Kheder, Nabila A; Fadda, Ahmed A

2017-06-11

Diazocoupling reaction of curcumin with different diazonium salts of p -toluidine, 2-aminopyridine, and 4-aminoantipyrine in pyridine yielded the arylhydrazones 2a - c . Arylhydrazone of p -toluidine reacted with urea, thiourea, and guanidine nitrate to produce 5,6-dihydropyrimidines. Further reaction of 2a with 2,3-diaminopyrdine in sodium ethoxide solution yielded 1 H -pyrido[2,3- b ][1,4]diazepine derivative. Bis (2,5-dihydroisoxazole) is obtained from the reaction of 2a with hydroxylamine hydrochloride, while its reactions with hydrazines afforded the respective 4,5-dihydro-1 H -pyrazoles. The target compounds were evaluated as antioxidant and antibacterial agents. The tested compounds showed good to moderate activities compared to ascorbic acid and chloramphenicol, respectively.

Comparison of the antibacterial activity of different self-etching primers and adhesives.

PubMed

Korkmaz, Yonca; Ozalp, Meral; Attar, Nuray

2008-11-01

The aim of this study was to evaluate the antibacterial effects of different one-step and two-step self-etching primer/adhesives on Streptococcus mutans (S. mutans), Lactobacillus casei (L. casei), and Lactobacillus acidophilus (L. acidophilus). The antibacterial effects of Clearfil Protect Bond Primer and Bonding agent; AdheSE Primer and Bonding agent; Adper Prompt L-Pop; Futurabond NR; Clearfil Tri S Bond; and Cervitec (positive control, 1% chlorhexidine varnish) were tested against standard strains of S. mutans, L. Casei, and L. acidophilus using the disk diffusion method. Standard filter paper disks (n=5) impregnated with 20 microL of each material were prepared. After incubation at 37 masculineC for 48 hours in a 5-10% CO2 atmosphere, the diameter of inhibition zones were measured in millimeters. Data were analyzed using one way analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA). Duncan's Multiple Range Test was used for pairwise comparison. The size of inhibition zones produced by primer/adhesives varied among the brands. AdheSE Primer: S. mutans (20.6+/-1.51); L. casei (14.8+/-1.78); L. acidophilus (11.4+/-0.54). Adper Prompt L-Pop: S. mutans (19.6+/-1.51); L. casei (13.8+/-1.64); L. acidophilus (13.8+/-1.09). Cervitec: S. mutans (23+/-0.00); L. casei (27+/-0.70); L. acidophilus (22.4+/-0.54). Clearfil Protect Bond Primer: S. mutans (17+/-0.00); L. casei (17.6+/-0.54); L. acidophilus (22.4+/-0.54). Futurabond NR was found effective only against S. mutans (14.6+/-1.67). Of all the materials tested, AdheSE Bonding agent, Clearfil Protect Bond Bonding agent, and Clearfil Tri S Bond exhibited no inhibition zone (-) for all bacteria tested. Among the adhesives tested Clearafil Protect Bond Primer based upon monomer methacryloyloxydodecylpyridiniium bromide (MDPB) was found to be the most potent material against L. acidophilus and L. casei. AdheSE Primer and Adper Prompt L-Pop are highly effective against S. mutans. Compared with other adhesive systems, Clearfil Protect Bond Primer (containing MDPB) showed a high antibacterial effect against all microorganizms tested. Two-step, self-etching primer/adhesive system Clearfil Protect Bond might be a suitable choice under minimally invasive restorations. The recently developed one-step, self-etching system Clearfil Tri S Bond showed no antibacterial effect against microorgazims tested.

Detection of a wide variety of human and veterinary fluoroquinolone antibiotics in municipal wastewater and wastewater-impacted surface water.

PubMed

He, Ke; Soares, Ana Dulce; Adejumo, Hollie; McDiarmid, Melissa; Squibb, Katherine; Blaney, Lee

2015-03-15

As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1-10 μg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900 ng/L for ciprofloxacin and 600 ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9-170 ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy: A prospective multicenter study.

PubMed

Chung, Ho Seok; Hwang, Eu Chang; Yu, Ho Song; Jung, Seung Il; Lee, Sun Ju; Lim, Dong Hoon; Cho, Won Jin; Choe, Hyun Sop; Lee, Seung-Ju; Park, Sung Woon

2018-03-01

To estimate the prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy and to identify the high-risk groups. From January 2015 to March 2016, rectal swabs of 557 men who underwent transrectal ultrasound-guided prostate needle biopsy were obtained from five institutions. Clinical variables, including demographics, rectal swab culture results and infectious complications, were evaluated. Univariable and multivariable analyses were used to identify the risk factors for fluoroquinolone resistance of rectal flora and infectious complications. The incidence of fluoroquinolone-resistant and extended-spectrum beta-lactamase production was 48.1 and 11.8%, respectively. The most common fluoroquinolone-resistant bacteria was Escherichia coli (81% of total fluoroquinolone-resistant bacteria, 39% of total rectal flora), and 16 (2.9%) patients had infectious complications. Univariable and multivariable analysis of clinical parameters affecting fluoroquinolone resistance showed no factor associated with fluoroquinolone resistance of rectal flora. The clinical parameter related to infectious complications after prostate biopsy was a history of operation within 6 months (relative risk 6.60; 95% confidence interval 1.99-21.8, P = 0.002). These findings suggest that a risk-based approach by history taking cannot predict antibiotic resistance of rectal flora, and physicians should consider targeted antibiotic prophylaxis or extended antibiotic prophylaxis for Korean patients undergoing transrectal ultrasound-guided prostate biopsy because of high antibiotic resistance of rectal flora. © 2017 The Japanese Urological Association.

10 × '20 Progress—Development of New Drugs Active Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America

PubMed Central

Boucher, Helen W.; Talbot, George H.; Benjamin, Daniel K.; Bradley, John; Guidos, Robert J.; Jones, Ronald N.; Murray, Barbara E.; Bonomo, Robert A.; Gilbert, David

2013-01-01

Infections caused by antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's “10 × '20 Initiative.” PMID:23599308

Furan-based benzene mono- and dicarboxylic acid derivatives as multiple inhibitors of the bacterial Mur ligases (MurC-MurF): experimental and computational characterization.

PubMed

Perdih, Andrej; Hrast, Martina; Pureber, Kaja; Barreteau, Hélène; Grdadolnik, Simona Golič; Kocjan, Darko; Gobec, Stanislav; Solmajer, Tom; Wolber, Gerhard

2015-06-01

Bacterial resistance to the available antibiotic agents underlines an urgent need for the discovery of novel antibacterial agents. Members of the bacterial Mur ligase family MurC-MurF involved in the intracellular stages of the bacterial peptidoglycan biosynthesis have recently emerged as a collection of attractive targets for novel antibacterial drug design. In this study, we have first extended the knowledge of the class of furan-based benzene-1,3-dicarboxylic acid derivatives by first showing a multiple MurC-MurF ligase inhibition for representatives of the extended series of this class. Steady-state kinetics studies on the MurD enzyme were performed for compound 1, suggesting a competitive inhibition with respect to ATP. To the best of our knowledge, compound 1 represents the first ATP-competitive MurD inhibitor reported to date with concurrent multiple inhibition of all four Mur ligases (MurC-MurF). Subsequent molecular dynamic (MD) simulations coupled with interaction energy calculations were performed for two alternative in silico models of compound 1 in the UMA/D-Glu- and ATP-binding sites of MurD, identifying binding in the ATP-binding site as energetically more favorable in comparison to the UMA/D-Glu-binding site, which was in agreement with steady-state kinetic data. In the final stage, based on the obtained MD data novel furan-based benzene monocarboxylic acid derivatives 8-11, exhibiting multiple Mur ligase (MurC-MurF) inhibition with predominantly superior ligase inhibition over the original series, were discovered and for compound 10 it was shown to possess promising antibacterial activity against S. aureus. These compounds represent novel leads that could by further optimization pave the way to novel antibacterial agents.

C8-Linked Pyrrolobenzodiazepine Monomers with Inverted Building Blocks Show Selective Activity against Multidrug Resistant Gram-Positive Bacteria.

PubMed

Andriollo, Paolo; Hind, Charlotte K; Picconi, Pietro; Nahar, Kazi S; Jamshidi, Shirin; Varsha, Amrit; Clifford, Melanie; Sutton, J Mark; Rahman, Khondaker Miraz

2018-02-09

Antimicrobial resistance has become a major global concern. Development of novel antimicrobial agents for the treatment of infections caused by multidrug resistant (MDR) pathogens is an urgent priority. Pyrrolobenzodiazepines (PBDs) are a promising class of antibacterial agents initially discovered and isolated from natural sources. Recently, C8-linked PBD biaryl conjugates have been shown to be active against some MDR Gram-positive strains. To explore the role of building block orientations on antibacterial activity and obtain structure activity relationship (SAR) information, four novel structures were synthesized in which the building blocks of previously reported compounds were inverted, and their antibacterial activity was studied. The compounds showed minimum inhibitory concentrations (MICs) in the range of 0.125-32 μg/mL against MDR Gram-positive strains with a bactericidal mode of action. The results showed that a single inversion of amide bonds reduces the activity while the double inversion restores the activity against MDR pathogens. All inverted compounds did not stabilize DNA and lacked eukaryotic toxicity. The compounds inhibit DNA gyrase in vitro, and the most potent compound was equally active against both wild-type and mutant DNA gyrase in a biochemical assay. The observed activity of the compounds against methicillin resistant S. aureus (MRSA) strains with equivalent gyrase mutations is consistent with gyrase inhibition being the mechanism of action in vivo, although this has not been definitively confirmed in whole cells. This conclusion is supported by a molecular modeling study showing interaction of the compounds with wild-type and mutant gyrases. This study provides important SAR information about this new class of antibacterial agents.

Furan-based benzene mono- and dicarboxylic acid derivatives as multiple inhibitors of the bacterial Mur ligases (MurC-MurF): experimental and computational characterization

NASA Astrophysics Data System (ADS)

Perdih, Andrej; Hrast, Martina; Pureber, Kaja; Barreteau, Hélène; Grdadolnik, Simona Golič; Kocjan, Darko; Gobec, Stanislav; Solmajer, Tom; Wolber, Gerhard

2015-06-01

Bacterial resistance to the available antibiotic agents underlines an urgent need for the discovery of novel antibacterial agents. Members of the bacterial Mur ligase family MurC-MurF involved in the intracellular stages of the bacterial peptidoglycan biosynthesis have recently emerged as a collection of attractive targets for novel antibacterial drug design. In this study, we have first extended the knowledge of the class of furan-based benzene-1,3-dicarboxylic acid derivatives by first showing a multiple MurC-MurF ligase inhibition for representatives of the extended series of this class. Steady-state kinetics studies on the MurD enzyme were performed for compound 1, suggesting a competitive inhibition with respect to ATP. To the best of our knowledge, compound 1 represents the first ATP-competitive MurD inhibitor reported to date with concurrent multiple inhibition of all four Mur ligases (MurC-MurF). Subsequent molecular dynamic (MD) simulations coupled with interaction energy calculations were performed for two alternative in silico models of compound 1 in the UMA/ d-Glu- and ATP-binding sites of MurD, identifying binding in the ATP-binding site as energetically more favorable in comparison to the UMA/ d-Glu-binding site, which was in agreement with steady-state kinetic data. In the final stage, based on the obtained MD data novel furan-based benzene monocarboxylic acid derivatives 8- 11, exhibiting multiple Mur ligase (MurC-MurF) inhibition with predominantly superior ligase inhibition over the original series, were discovered and for compound 10 it was shown to possess promising antibacterial activity against S. aureus. These compounds represent novel leads that could by further optimization pave the way to novel antibacterial agents.

Mechanism of MenE Inhibition by Acyl-Adenylate Analogues and Discovery of Novel Antibacterial Agents

PubMed Central

Sharma, Indrajeet; Lavaud, Lubens J.; Ngo, Stephen C.; Shek, Roger; Rajashankar, Kanagalaghatta R.; French, Jarrod B.; Tan, Derek S.; Tonge, Peter J.

2015-01-01

MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and is a promising target for the development of novel antibacterial agents. The enzyme catalyzes CoA ligation via an acyl-adenylate intermediate, and we have previously reported tight-binding inhibitors of MenE based on stable acyl-sulfonyladenosine analogues of this intermediate, including OSB-AMS (1) which has an IC50 value of ≤ 25 nM for the Escherichia coli MenE. Herein, we show that OSB-AMS reduces menaquinone levels in S. aureus, consistent with its proposed mechanism of action, despite the observation that the antibacterial activity of OSB-AMS is ~1000-fold lower than the IC50 for enzyme inhibition. To inform the synthesis of MenE inhibitors with improved antibacterial activity, we have undertaken a structure–activity relationship (SAR) study stimulated by the knowledge that OSB-AMS can adopt two isomeric forms in which the OSB side chain exists either as an open-chain keto acid or a cyclic lactol. These studies revealed that negatively charged analogues of the keto-acid form bind, while neutral analogues do not, consistent with the hypothesis that the negatively-charged keto-acid form of OSB-AMS is the active isomer. X-ray crystallography and site-directed mutagenesis confirm the importance of a conserved arginine for binding the OSB carboxylate. Although most lactol isomers tested were inactive, a novel difluoroindanediol inhibitor (11) with improved antibacterial activity was discovered, providing a pathway toward the development of optimized MenE inhibitors in the future. PMID:26394156

Mechanism of MenE inhibition by acyl-adenylate analogues and discovery of novel antibacterial agents.

PubMed

Matarlo, Joe S; Evans, Christopher E; Sharma, Indrajeet; Lavaud, Lubens J; Ngo, Stephen C; Shek, Roger; Rajashankar, Kanagalaghatta R; French, Jarrod B; Tan, Derek S; Tonge, Peter J

2015-10-27

MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and is a promising target for the development of novel antibacterial agents. The enzyme catalyzes CoA ligation via an acyl-adenylate intermediate, and we have previously reported tight-binding inhibitors of MenE based on stable acyl-sulfonyladenosine analogues of this intermediate, including OSB-AMS (1), which has an IC50 value of ≤25 nM for Escherichia coli MenE. Herein, we show that OSB-AMS reduces menaquinone levels in Staphylococcus aureus, consistent with its proposed mechanism of action, despite the observation that the antibacterial activity of OSB-AMS is ∼1000-fold lower than the IC50 for enzyme inhibition. To inform the synthesis of MenE inhibitors with improved antibacterial activity, we have undertaken a structure-activity relationship (SAR) study stimulated by the knowledge that OSB-AMS can adopt two isomeric forms in which the OSB side chain exists either as an open-chain keto acid or a cyclic lactol. These studies revealed that negatively charged analogues of the keto acid form bind, while neutral analogues do not, consistent with the hypothesis that the negatively charged keto acid form of OSB-AMS is the active isomer. X-ray crystallography and site-directed mutagenesis confirm the importance of a conserved arginine for binding the OSB carboxylate. Although most lactol isomers tested were inactive, a novel difluoroindanediol inhibitor (11) with improved antibacterial activity was discovered, providing a pathway toward the development of optimized MenE inhibitors in the future.

Antibacterial activity of crude extracts of some South African medicinal plants against multidrug resistant etiological agents of diarrhoea.

PubMed

Bisi-Johnson, Mary A; Obi, Chikwelu L; Samuel, Babatunde B; Eloff, Jacobus N; Okoh, Anthony I

2017-06-19

This study evaluated the antibacterial activity of some plants used in folklore medicine to treat diarrhoea in the Eastern Cape Province, South Africa. The acetone extracts of Acacia mearnsii De Wild., Aloe arborescens Mill., A. striata Haw., Cyathula uncinulata (Schrad.) Schinz, Eucomis autumnalis (Mill.) Chitt., E. comosa (Houtt.) Wehrh., Hermbstaedtia odorata (Burch. ex Moq.) T.Cooke, Hydnora africana Thunb, Hypoxis latifolia Wight, Pelargonium sidoides DC, Psidium guajava L and Schizocarphus nervosus (Burch.) van der Merwe were screened against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, multi-resistant Salmonella enterica serovar Isangi, S. typhi, S. enterica serovar Typhimurium, Shigella flexneri type 1b and Sh. sonnei phase II. A qualitative phytochemical screening of the plants extracts was by thin layer chromatography. Plants extracts were screened for antibacterial activity using serial dilution microplate technique and bioautography. The TLC fingerprint indicated the presence of terpenoids and flavonoids in the herbs. Most of the tested organisms were sensitive to the crude acetone extracts with minimum inhibitory concentration (MIC) values ranging from 0.018-2.5 mg/mℓ. Extracts of A. striata, C. uncinulata, E. autumnalis and P. guajava were more active against enteropathogens. S. aureus and Sh. flexneri were the most sensitive isolates to the crude extracts but of significance is the antibacterial activity of A. arborescens and P. guajava against a confirmed extended spectrum betalactamase positive S. enterica serovar Typhimurium. The presence of bioactive compounds and the antibacterial activity of some of the selected herbs against multidrug resistant enteric agents corroborate assertions by traditional healers on their efficacies.

In-vitro antibacterial study of zinc oxide nanostructures on Streptococcus sobrinus

NASA Astrophysics Data System (ADS)

Bakhori, Siti Khadijah Mohd; Mahmud, Shahrom; Ann, Ling Chuo; Sirelkhatim, Amna; Hasan, Habsah; Mohamad, Dasmawati; Masudi, Sam'an Malik; Seeni, Azman; Rahman, Rosliza Abd

2014-10-01

Zinc oxide nanostructures were prepared using a pilot plant of zinc oxide boiling furnace. Generally, it produced two types of nanostructures different in morphology; one is rod-like shaped (ZnO-1) and a plate-like shape (ZnO-2). The properties of ZnO were studied by structural, optical and morphological using XRD, PL and FESEM respectively. The XRD patterns confirmed the wurtzite structures of ZnO with the calculated crystallite size of 41 nm (ZnO-1) and 42 nm (ZnO-2) using Scherrer formula. The NBE peaks were determined by photoluminescence spectra which reveal peak at 3.25 eV and 3.23 eV for ZnO-1 and ZnO-2 respectively. Prior to that, the morphologies for both ZnO-1 and ZnO-2 were demonstrated from FESEM micrographs. Subsequently the antibacterial study was conducted using in-vitro broth dilution technique towards a gram positive bacterium Streptococcus sobrinus (ATCC 33478) to investigate the level of antibacterial effect of zinc oxide nanostructures as antibacterial agent. Gradual increment of ZnO concentrations from 10-20 mM affected the inhibition level after twenty four hours of incubation. In conjunction with concentration increment of ZnO, the percentage inhibition towards Streptococcus sobrinus was also increased accordingly. The highest inhibition occurred at 20 mM of ZnO-1 and ZnO-2 for 98% and 77% respectively. It showed that ZnO has good properties as antibacterial agent and relevancy with data presented by XRD, PL and FESEM were determined.

Carbon Nanoparticles decorated with cupric oxide Nanoparticles prepared by laser ablation in liquid as an antibacterial therapeutic agent

NASA Astrophysics Data System (ADS)

Khashan, Khawla S.; Jabir, Majid S.; Abdulameer, Farah A.

2018-03-01

Carbon nanoparticles (CNPs) decorated with cupric oxide nanoparticles (CuO NPs) were prepared by laser ablation in water, and their antibacterial activity was examined. X-ray diffraction measurements demonstrated the presence of carbon phases and different CuO phases, and results were confirmed by Fourier transform infrared analysis. Energy- Dispersive spectra showed the presence of C, O, and Cu in the final product. Transmission electron micrographs revealed that the CNPs were 10-80 nm in size and spherical; after being decorated with CuO NPs, particles became 5-50 nm in size and uniform in shape. The absorption spectrum of decorated Nanoparticles indicated the appearance of a new peak at 254-264 nm in addition to the fundamental peak at 228 nm. We then examined the antibacterial activity of the decorated CNPs for both gram-negative and -positive bacteria using the agar-well-diffusion method. The mode of action was determined using acridine orange-ethidium bromide staining to detect reactive oxygen species, and bacterial morphological change was studied by scanning electron microscopy. Results showed that CNPs decorated with 43% CuO NPs had the highest antibacterial activity for gram-positive bacteria. The CNPs acted on the cytoplasmic membrane and nucleic acid of bacteria, which led to a loss of cell-wall integrity, increased cell-wall permeability, and nucleic acid damage. The results offer a novel way to synthesis Carbon nanoparticles decorated with cupric oxide nanoparticles and could use them as novel antibacterial agent in future for pharmaceutical and biomedical applications.

Antibacterial and wound healing properties of chitosan/poly(vinyl alcohol)/zinc oxide beads (CS/PVA/ZnO).

PubMed

Gutha, Yuvaraja; Pathak, Janak L; Zhang, Weijiang; Zhang, Yaping; Jiao, Xu

2017-10-01

Treatment against bacterial infection is crucial for wound healing. Development of cost-effective antibacterial agent with wound healing properties is still in high demand. In this study we aimed to design chitosan/poly(vinyl alcohol)/zinc oxide (CS/PVA/ZnO) beads as novel antibacterial agent with wound healing properties. CS/PVA/ZnO beads were synthesized, and characterized by using XRD, FTIR, SEM, and TEM analysis. Pure chitosan exhibits two peaks at 2θ=10 and 20 and the CS/PVA polymer matrix exhibit the peaks at 2θ=19.7° and another of low intensity at 2θ=11.5°. Pure ZnO shows the characteristic peaks at (100), (002), (101), (102), (110), (103), (200), and (112) that were in good agreement with wurtzite ore having hexagonal lattice structure. The antibacterial activity of CS/PVA/ZnO against Escherichia coli, and Staphylococcus aureus were evaluated with the zone of inhibition method. Antibacterial activity of CS/PVA/ZnO was higher than that of chitosan (CS) and poly(vinyl alcohol (PVA). Hemocompatibility and biocompatibility of CS/PVA/ZnO were tested in in vitro. Wound healing properties of CS/PVA/ZnO were tested in mice skin wound. CS/PVA/ZnO showed strong antimicrobial, wound healing effect, hemocompatibility and biocompatibility. Hence the results strongly support the possibility of using this novel CS/PVA/ZnO material for the anti bacterial and wound healing application. Copyright © 2017 Elsevier B.V. All rights reserved.

Terbium-sensitized luminescence screening method for fluoroquinolones in beef serum

USDA-ARS?s Scientific Manuscript database

Enrofloxacin is one of only two fluoroquinolone antibiotics approved for use in cattle in the U.S. Microbial screening methods commonly used for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay was developed...

Assessment of antibacterial properties of newer dentin bonding agents: An in vitro study.

PubMed

Sampath, Pavitra B; Hegde, Mithra N; Hegde, Priyadarshini

2011-07-01

To evaluate and compare the antibacterial activity of newer dentin bonding agents on Streptococcus mutans using the direct contact test. Streptococcus mutans was used as test organism and a direct contact test was performed. The dentin bonding agents to be tested were grouped as Group I, Clearfil Protect Bond, Group II, Adper Easy One, and Group III, Prime and Bond NT. For the direct contact test, three microtiter plates consisting of 96 wells each were taken (288 wells). These wells were divided into three groups of 96 wells; 16 wells of a microtiter plate were utilized, of which four were designated as 'A' wells (with the dentin bonding agent and bacterial suspension), another four as 'B' wells (without the dentin bonding agent, but with the bacterial suspension), another four as the 'C' wells (with the tested material, but without bacteria, which served as the negative control), and the remaining four as the 'D' wells (without the dentin bonding agent, which served as the positive control). Each group was treated with their respective bonding agents as per the manufactures instructions. Broth of 15 μL was then transferred from the A wells into an adjacent set of B wells containing fresh medium (215 μL). This resulted in two sets of four wells for each tested material containing an equal volume of liquid medium, so that bacterial growth was monitored both in the presence and in the absence of the tested material. The plate was placed for incubation at 37°C in the microplate reader and the optical density in each well was measured at 600 nm. The readings were taken at regular intervals. (Every 30 minutes for 16 hours). The Dentin bonding agents evaluated in this study showed different inhibitory effects. Clearfil Protect Bond and Prime and Bond NT were most effective, and Adper Easy One was least effective against Streptococcus mutans. The Dentin bonding agents evaluated in this study showed different inhibitory effects. Clearfil Protect Bond and Prime and Bond NT were most effective, and Adper Easy One was the least effective against Streptococcus mutans. Hence, the incorporation of antibacterial agents into the dentin bonding agents may become an essential factor in inhibiting residual bacteria in the cavity and secondary caries.

Therapeutic options and emerging alternatives for multidrug resistant staphylococcal infections.

PubMed

Magana, Maria; Ioannidis, Anastasios; Magiorkinis, Emmanouil; Ursu, Oleg; Bologa, Cristian G; Chatzipanagiotou, Stylianos; Hamblin, Michael R; Tegos, George P

2015-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) remains the single biggest challenge in infectious disease in the civilized world. Moreover, vancomycin resistance is also spreading, leading to fears of untreatable infections as were common in ancient times. Molecular microbiology and bioinformatics have revealed many of the mechanisms involved in resistance development. Mobile genetic elements, up-regulated virulence factors and multi-drug efflux pumps have been implicated. A range of approved antibiotics from the glycopeptide, lipopeptide, pleuromutilin, macrolide, oxazolidinone, lincosamide, aminoglycoside, tetracycline, steptogramin, and cephalosporin classes has been employed to treat MRSA infections. The upcoming pipeline of drugs for MRSA includes some new compounds from the above classes, together with fluoroquinolones, antibacterial peptide mimetics, aminomethylciclines, porphyrins, peptide deformylase inhibitors, oxadiazoles, and diaminopyrimidines. A range of non-drug alternative approaches has emerged for MRSA treatment. Bacteriophage-therapy including purified lysins has made a comeback after being discovered in the 1930s. Quorum-sensing inhibitors are under investigation. Small molecule inhibitors of multi-drug efflux pumps may potentiate existing antibiotics. The relative failure of staphylococcal vaccines is being revisited by efforts with multi-valent vaccines and improved adjuvants. Photodynamic therapy uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species that can nonspecifically destroy bacteria while preserving host cells. Preparation of nanoparticles can kill bacteria themselves, as well as improve the delivery of anti-bacterial drugs. Anti-MRSA drug discovery remains an exciting field with great promise for the future.

Oxidation of fluoroquinolone antibiotics and structurally related amines by chlorine dioxide: Reaction kinetics, product and pathway evaluation.

PubMed

Wang, Pei; He, Yi-Liang; Huang, Ching-Hua

2010-12-01

Fluoroquinolones (FQs) are a group of widely prescribed antibiotics and have been frequently detected in the aquatic environment. The reaction kinetics and transformation of seven FQs (ciprofloxacin (CIP), enrofloxacin (ENR), norfloxacin (NOR), ofloxacin (OFL), lomefloxacin (LOM), pipemidic acid (PIP) and flumequine (FLU)) and three structurally related amines (1-phenylpiperazine (PP), N-phenylmorpholine (PM) and 4-phenylpiperidine (PD)) toward chlorine dioxide (ClO(2)) were investigated to elucidate the behavior of FQs during ClO(2) disinfection processes. The reaction kinetics are highly pH-dependent, can be well described by a second-order kinetic model incorporating speciation of FQs, and follow the trend of OFL > ENR > CIP ∼ NOR ∼ LOM > > PIP in reactivity. Comparison among FQs and related amines and product characterization indicate that FQs' piperazine ring is the primary reactive center toward ClO(2). ClO(2) likely attacks FQ's piperazinyl N4 atom followed by concerted fragmentation involving piperazinyl N1 atom, leading to dealkylation, hydroxylation and intramolecular ring closure at the piperazine moiety. While FQs with tertiary N4 react faster with ClO(2) than FQs with secondary N4, the overall reactivity of the piperazine moiety also depends strongly on the quinolone ring through electronic effects. The reaction rate constants obtained in clean water matrix can be used to model the decay of CIP by ClO(2) in surface water samples, but overestimate the decay in wastewater samples. Overall, transformation of FQs, particularly for those with tertiary N4 amines, could be expected under typical ClO(2) disinfection conditions. However, the transformation may not eliminate antibacterial activity because of little destruction at the quinolone ring. Copyright © 2010 Elsevier Ltd. All rights reserved.

Enantioselective degradation of ofloxacin and levofloxacin by the bacterial strains Labrys portucalensis F11 and Rhodococcus sp. FP1.

PubMed

Maia, Alexandra S; Tiritan, Maria Elizabeth; Castro, Paula M L

2018-07-15

Fluoroquinolones are a class of antibiotics widely prescribed in both human and veterinary medicine of high environmental concern and characterized as environmental micropollutants due to their ecotoxicity and persistence and antibacterial resistance potential. Ofloxacin and levofloxacin are chiral fluoroquinolones commercialized as racemate and in enantiomerically pure form, respectively. Since the pharmacological properties and toxicity of the enantiomers may be very different, understanding the stereochemistry of these compounds should be a priority in environmental monitoring. This work presents the biodegradation of racemic ofloxacin and its (S)-enantiomer levofloxacin by the bacterial strains Labrys portucalensis F11 and Rhodococcus sp. FP1 at a laboratory-scale microcosm following the removal and the behavior of the enantiomers. Strain F11 could degrade both antibiotics almost completely when acetate was supplied regularly to the cultures. Enrichment of the (R)-enantiomer was observed in FP1 and F11 cultures supplied with ofloxacin. Racemization was observed in the biodegradation of the pure (S)-ofloxacin (levofloxacin) by strain F11, which was confirmed by liquid chromatography - exact mass spectrometry. Biodegradation of ofloxacin at 450 µg L -1 by both bacterial strains expressed good linear fits (R 2 > 0.98) according to the Rayleigh equation. The enantiomeric enrichment factors were comprised between - 22.5% to - 9.1%, and - 18.7% to - 9.0% in the biodegradation of ofloxacin by strains F11 and FP1, respectively, with no significant differences for the two bacteria under the same conditions. This is the first time that enantioselective biodegradation of ofloxacin and levofloxacin by single bacteria is reported. Copyright © 2018 Elsevier Inc. All rights reserved.

Microgravity

NASA Image and Video Library

1989-02-03

(PCG) Protein Crystal Growth Gamma-Interferon. Stimulates the body's immune system and is used clinically in the treatment of cancer. Potential as an anti-tumor agent against solid tumors as well as leukemia's and lymphomas. It has additional utility as an anti-ineffective agent, including antiviral, anti-bacterial, and anti-parasitic activities. Principal Investigator on STS-26 was Charles Bugg.

Looking for the new preparations for antibacterial therapy III. New antimicrobial agents from the quinolones group in clinical trials.

PubMed

Karpiuk, Izabela; Tyski, Stefan

2013-01-01

There is an essential need for searching for the new compounds effective in the treatment of infections caused by multidrug-resistant bacteria. This paper is the third part of a series associated with the exploration of new antibacterial agents and it discusses the compounds belonging to the group of quinolones and substances possessing a hybrid structure composed of the quinolone molecule and other compounds. Eleven new substances at the stage of clinical trials are presented. Three of them belong to the group of non-fluorinated quinolone (nemonoxacin, ozenoxacin and KRP-AM 1977X), while six are the quinolones containing fluorine atom at 6 position of the carbon atom in the quinoline ring (zabofloxacin, finafloxacin, delafloxacin, JNJ-Q2, WCK771 and KPI-10). The remaining two compounds possess a hybrid construction composed of the quinolone structure and other molecules (cadazolid and CBR-2092). There is a chance in the near future, that the presented compounds can extend the range of existing antibacterial drugs and provide an alternative to currently available medicinal products.

Phenylthiazole Antibacterial Agents Targeting Cell Wall Synthesis Exhibit Potent Activity in Vitro and in Vivo against Vancomycin-Resistant Enterococci.

PubMed

Mohammad, Haroon; Younis, Waleed; Chen, Lu; Peters, Christine E; Pogliano, Joe; Pogliano, Kit; Cooper, Bruce; Zhang, Jianan; Mayhoub, Abdelrahman; Oldfield, Eric; Cushman, Mark; Seleem, Mohamed N

2017-03-23

The emergence of antibiotic-resistant bacterial species, such as vancomycin-resistant enterococci (VRE), necessitates the development of new antimicrobials. Here, we investigate the spectrum of antibacterial activity of three phenylthiazole-substituted aminoguanidines. These compounds possess potent activity against VRE, inhibiting growth of clinical isolates at concentrations as low as 0.5 μg/mL. The compounds exerted a rapid bactericidal effect, targeting cell wall synthesis. Transposon mutagenesis suggested three possible targets: YubA, YubB (undecaprenyl diphosphate phosphatase (UPPP)), and YubD. Both UPPP as well as undecaprenyl diphosphate synthase were inhibited by compound 1. YubA and YubD are annotated as transporters and may also be targets because 1 collapsed the proton motive force in membrane vesicles. Using Caenorhabditis elegans, we demonstrate that two compounds (1, 3, at 20 μg/mL) retain potent activity in vivo, significantly reducing the burden of VRE in infected worms. Taken altogether, the results indicate that compounds 1 and 3 warrant further investigation as novel antibacterial agents against drug-resistant enterococci.

Antimicrobial Activities of Three Medicinal Plants and Investigation of Flavonoids of Tripleurospermum disciforme.

PubMed

Tofighi, Zahra; Molazem, Maryam; Doostdar, Behnaz; Taban, Parisa; Shahverdi, Ahmad Reza; Samadi, Nasrin; Yassa, Narguess

2015-01-01

Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used as disinfectant agents and for treatment of some disease in folk medicine of Iran. The antimicrobial effects of different fractions of seeds extract of S. securidaca, petals extract of R. damascena and aerial parts extract of T. disciforme were examined against some gram positive, gram negative and fungi by cup plate diffusion method. The petroleum ether and chloroform fractions of S. securidaca showed antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects. R. damascena petals extract demonstrated antibacterial activities against Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects only against S. aureus and S. epidermidis. None of the fractions had any antifungal activities. Therefore, present study confirmed utility of these plants as disinfectant agents. Six flavonoids were isolated from T. disciforme: Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T. disciforme are reported for the first time.

Antimicrobial Activities of Three Medicinal Plants and Investigation of Flavonoids of Tripleurospermum disciforme

PubMed Central

Tofighi, Zahra; Molazem, Maryam; Doostdar, Behnaz; Taban, Parisa; Shahverdi, Ahmad Reza; Samadi, Nasrin; Yassa, Narguess

2015-01-01

Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used as disinfectant agents and for treatment of some disease in folk medicine of Iran. The antimicrobial effects of different fractions of seeds extract of S. securidaca, petals extract of R. damascena and aerial parts extract of T. disciforme were examined against some gram positive, gram negative and fungi by cup plate diffusion method. The petroleum ether and chloroform fractions of S. securidaca showed antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects. R. damascena petals extract demonstrated antibacterial activities against Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects only against S. aureus and S. epidermidis. None of the fractions had any antifungal activities. Therefore, present study confirmed utility of these plants as disinfectant agents. Six flavonoids were isolated from T. disciforme: Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T. disciforme are reported for the first time. PMID:25561928

Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.

PubMed

Fleeman, Renee; LaVoi, Travis M; Santos, Radleigh G; Morales, Angela; Nefzi, Adel; Welmaker, Gregory S; Medina-Franco, José L; Giulianotti, Marc A; Houghten, Richard A; Shaw, Lindsey N

2015-04-23

Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study, we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10000 and 750000 structural analogues for a total of >6 million compounds. From this, we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations <2 μM. In addition, these compounds were bactericidal, had antibiofilm effects, showed limited potential for the development of resistance, and displayed almost no toxicity when tested against human lung cells and erythrocytes. Using a murine model of peritonitis, we also demonstrate that these agents are highly efficacious in vivo.

Design and synthesis of some new pyrazolyl-pyrazolines as potential anti-inflammatory, analgesic and antibacterial agents.

PubMed

Viveka, Shivapura; Dinesha; Shama, Prasanna; Nagaraja, Gundibasappa Karikannar; Ballav, Shuvankar; Kerkar, Savita

2015-08-28

In the present study, an efficient synthesis of some new substituted pyrazoline derivatives linked to a substituted pyrazole scaffold was performed by a multistep reaction sequences and compounds were screened for their anti-inflammatory, analgesic and antibacterial activities. The preliminary results revealed that the N-acylated (5e, 5h) and nitro substituted N-phenyl (6f) pyrazolyl-pyrazolines derivatives exhibited a very promising anti-inflammatory activity whereas 5h, 6f were interesting analgesic agents. The compounds with halo substituted phenyl group at C-3 of the pyrazoline ring (4a, 5g, 5h, 6a and 6b) were found to be active against clinical bacterial pathogens with MIC in the range of 0.2-0.4 mg/mL. Compound containing N-propionyl pyrazolyl-pyrazoline (5h) could be identified as the most active member within this study with a dual anti-inflammatory and antibacterial profile. Taken together, this study has led to the development of promising compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting.

PubMed

Wang, Hao; Mann, Paul A; Xiao, Li; Gill, Charles; Galgoci, Andrew M; Howe, John A; Villafania, Artjohn; Barbieri, Christopher M; Malinverni, Juliana C; Sher, Xinwei; Mayhood, Todd; McCurry, Megan D; Murgolo, Nicholas; Flattery, Amy; Mack, Matthias; Roemer, Terry

2017-05-18

Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural elements that control gene expression of numerous metabolic pathways and transport functions essential for cell growth. As such, riboswitch inhibitors represent a new class of potential antibacterial agents. Recently, we identified ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an antimetabolite analog of RF, among medically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. We provide genetic, biophysical, computational, biochemical, and pharmacological evidence that ribocil-C and RoF specifically inhibit dual FMN riboswitches, separately controlling RF biosynthesis and uptake processes essential for MRSA growth and pathogenesis. Such a dual-targeting mechanism is specifically required to develop broad-spectrum Gram-positive antibacterial agents targeting RF metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Risk of Some Veterinary Antimicrobial Agents on Public Health Associated with Antimicrobial Resistance and their Molecular Basis

PubMed Central

Hao, Haihong; Sander, Pascal; Iqbal, Zahid; Wang, Yulian; Cheng, Guyue; Yuan, Zonghui

2016-01-01

The risk of antimicrobial agents used in food-producing animals on public health associated with antimicrobial resistance continues to be a current topic of discussion as related to animal and human public health. In the present review, resistance monitoring data, and risk assessment results of some important antimicrobial agents were cited to elucidate the possible association of antimicrobial use in food animals and antimicrobial resistance in humans. From the selected examples, it was apparent from reviewing the published scientific literature that the ban on use of some antimicrobial agents (e.g., avoparcin, fluoroquinolone, tetracyclines) did not change drug resistance patterns and did not mitigate the intended goal of minimizing antimicrobial resistance. The use of some antimicrobial agents (e.g., virginiamycin, macrolides, and cephalosporins) in food animals may have an impact on the antimicrobial resistance in humans, but it was largely depended on the pattern of drug usage in different geographical regions. The epidemiological characteristics of resistant bacteria were closely related to molecular mechanisms involved in the development, fitness, and transmission of antimicrobial resistance. PMID:27803693

Lipopeptides as the Antifungal and Antibacterial Agents: Applications in Food Safety and Therapeutics

PubMed Central

Meena, Khem Raj; Kanwar, Shamsher S.

2015-01-01

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of the Bacillus genus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families of Bacillus lipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activities, while Surfactin has broad range of potent antibacterial activities and this has also been used as larvicidal agent. Interestingly, lipopeptides being the molecules of biological origin are environmentally acceptable. PMID:25632392

[Dental plaque microcosm biofilm behavior on a resin composite incorporated with nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt].

PubMed

Junling, Wu; Qiang, Zhang; Ruinan, Sun; Ting, Zhu; Jianhua, Ge; Chuanjian, Zhou

2015-12-01

To develop a resin composite incorporated with nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt, and to measure its effect on human dental plaque microcosm biofilm. A novel nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt was synthesized according to methods introduced in previous research. Samples of the novel nano-antibacterial inorganic fillers were modified by a coupling agent and then added into resin composite at 0%, 5%, 10%, 15% or 20% mass fractions; 0% composite was used as control. A flexural test was used to measure resin composite mechanical properties. Results showed that a dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony-forming unit (CFU) counts, lactic acid production, and live/dead assay of biofilm on the resin composite were calculated to test the effect of the resin composite on human dental plaque microcosm biofilm. The incorporation of nano-antibacterial inorganic fillers with as much as 15% concentration into the resin composite showed no adverse effect on the mechanical properties of the resin composite (P > 0.05). Resin composite containing 5% or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilm, suggesting its strong antibacterial potency (P < 0.05). This novel resin composite exhibited a strong antibacterial property upon the addition of up to 5% nano-antibacterial inorganic fillers, thereby leading to effective caries inhibition in dental application.

Discovery and Optimization of Indolyl-Containing 4-Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-negative Bacteria.

PubMed

Gerasyuto, Aleksey I; Arnold, Michael A; Wang, Jiashi; Chen, Guangming; Zhang, Xiaoyan; Smith, Sean; Woll, Matthew G; Baird, John; Zhang, Nanjing; Almstead, Neil G; Narasimhan, Jana; Peddi, Srinivasa; Dumble, Melissa; Sheedy, Josephine; Weetall, Marla; Branstrom, Arthur A; Prasad, J V N; Karp, Gary M

2018-05-14

There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) bacterial infections, particularly those caused by Gram-negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of bacterial type II topoisomerases active against MDR Gram-negative bacteria. Herein, we report on the discovery and structure-activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antibacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC 90 values against Escherichia coli (0.5-1 μg/mL) and Acinetobacter baumannii (8-16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli.

Antibacterial Activity of AI-Hemocidin 2, a Novel N-Terminal Peptide of Hemoglobin Purified from Arca inflata.

PubMed

Li, Chunlei; Zhu, Jianhua; Wang, Yanqing; Chen, Yuyan; Song, Liyan; Zheng, Weiming; Li, Jingjing; Yu, Rongmin

2017-06-29

The continued emergence of antibiotic resistant bacteria in recent years is of great concern. The search for new classes of antibacterial agents has expanded to non-traditional sources such as shellfish. An antibacterial subunit of hemoglobin (Hb-I) was purified from the mantle of Arca inflata by phosphate extraction and ion exchange chromatography. A novel antibacterial peptide, AI-hemocidin 2, derived from Hb-I, was discovered using bioinformatics analysis. It displayed antibacterial activity across a broad spectrum of microorganisms, including several Gram-positive and Gram-negative bacteria, with minimal inhibitory concentration (MIC) values ranging from 37.5 to 300 μg/mL, and it exhibited minimal hemolytic or cytotoxic activities. The antibacterial activity of AI-hemocidin 2 was thermostable (25-100 °C) and pH resistant (pH 3-10). The cellular integrity was determined by flow cytometry. AI-hemocidin 2 was capable of permeating the cellular membrane. Changes in the cell morphology were observed with a scanning electron microscope. Circular dichroism spectra suggested that AI-hemocidin 2 formed an α-helix structure in the membrane mimetic environment. The results indicated that the anti-bacterial mechanism for AI-hemocidin 2 occurred through disrupting the cell membrane. AI-hemocidin 2 might be a potential candidate for tackling antibiotic resistant bacteria.

Microstructure, mechanical properties, bio-corrosion properties and antibacterial properties of Ti-Ag sintered alloys.

PubMed

Chen, Mian; Zhang, Erlin; Zhang, Lan

2016-05-01

In this research, Ag element was selected as an antibacterial agent to develop an antibacterial Ti-Ag alloy by a powder metallurgy. The microstructure, phase constitution, mechanical properties, corrosion resistance and antibacterial properties of the Ti-Ag sintered alloys have been systematically studied by X-ray diffraction (XRD), scanning electron microscope (SEM), compressive test, electrochemical measurements and antibacterial test. The effects of the Ag powder size and the Ag content on the antibacterial property and mechanical property as well as the anticorrosion property have been investigated. The microstructure results have shown that Ti-Ag phase, residual pure Ag and Ti were the mainly phases in Ti-Ag(S75) sintered alloy while Ti2Ag was synthesized in Ti-Ag(S10) sintered alloy. The mechanical test indicated that Ti-Ag sintered alloy showed a much higher hardness and the compressive yield strength than cp-Ti but the mechanical properties were slightly reduced with the increase of Ag content. Electrochemical results showed that Ag powder size had a significant effect on the corrosion resistance of Ti-Ag sintered alloy. Ag content increased the corrosion resistance in a dose dependent way under a homogeneous microstructure. Antibacterial tests have demonstrated that antibacterial Ti-Ag alloy was successfully prepared. It was also shown that the Ag powder particle size and the Ag content influenced the antibacterial activity seriously. The reduction in the Ag powder size was benefit to the improvement in the antibacterial property and the Ag content has to be at least 3wt.% in order to obtain a strong and stable antibacterial activity against Staphylococcus aureus bacteria. The bacterial mechanism was thought to be related to the Ti2Ag and its distribution. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of hydrogen peroxide on antibacterial activities of Canadian honeys.

PubMed

Brudzynski, Katrina

2006-12-01

Honey is recognized as an efficacious topical antimicrobial agent in the treatment of burns and wounds. The antimicrobial activity in some honeys depends on the endogenous hydrogen peroxide content. This study was aimed to determine whether honey's hydrogen peroxide level could serve as a honey-specific, activity-associated biomarker that would allow predicting and assessing the therapeutic effects of honey. Using a broth microdilution assay, I analyzed antibacterial activities of 42 Canadian honeys against two bacterial strains: Escherichia coli (ATCC 14948) and Bacillus subtilis (ATCC 6633). The MIC90 and MIC50 were established from the dose-response relationship between antibacterial activities and honey concentrations. The impact of H2O2 on antibacterial activity was determined (i) by measuring the levels of H2O2 before and after its removal by catalase and (ii) by correlating the results with levels of antibacterial activities. Canadian honeys demonstrated moderate to high antibacterial activity against both bacterial species. Both MIC90 and MIC50 revealed that the honeys exhibited a selective growth inhibitory activity against E. coli, and this activity was strongly influenced by endogenous H2O2 concentrations. Bacillus subtilis activity was marginally significantly correlated with H2O2 content. The removal of H2O2 by catalase reduced the honeys' antibacterial activity, but the enzyme was unable to completely decompose endogenous H2O2. The 25%-30% H2O2 "leftover" was significantly correlated with the honeys' residual antibacterial activity against E. coli. These data indicate that all Canadian honeys exhibited antibacterial activity, with higher selectivity against E. coli than B. subtilis, and that these antibacterial activities were correlated with hydrogen peroxide production in honeys. Hydrogen peroxide levels in honey, therefore, is a strong predictor of the honey's antibacterial activity.

Challenges of Antibacterial Discovery

PubMed Central

Silver, Lynn L.

2011-01-01

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

Novel dental adhesives containing nanoparticles of silver and amorphous calcium phosphate

PubMed Central

Melo, Mary Anne S.; Cheng, Lei; Zhang, Ke; Weir, Michael D.; Rodrigues, Lidiany K. A.; Xu, Hockin H. K.

2012-01-01

Objectives Secondary caries is the main reason for restoration failure, and replacement of the failed restorations accounts for 50–70% of all restorations. Antibacterial adhesives could inhibit residual bacteria in tooth cavity and invading bacteria along the margins. Calcium (Ca) and phosphate (P) ion release could remineralize the lesions. The objectives of this study were to incorporate nanoparticles of silver (NAg) and nanoparticles of amorphous calcium phosphate (NACP) into adhesive for the first time, and to investigate the effects on dentin bond strength and plaque microcosm biofilms. Methods Scotchbond Multi-Purpose adhesive was used as control. NAg were added into primer and adhesive at 0.1% by mass. NACP were mixed into adhesive at 10%, 20%, 30% and 40%. Microcosm biofilms were grown on disks with primer covering the adhesive on a composite. Biofilm metabolic activity, colony-forming units (CFU) and lactic acid were measured. Results Human dentin shear bond strengths (n=10) ranged from 26 to 34 MPa; adding NAg and NACP into adhesive did not decrease the bond strength (p > 0.1). SEM examination revealed resin tags from well-filled dentinal tubules. Numerous NACP infiltrated into the dentinal tubules. While NACP had little antibacterial effect, NAg in bonding agents greatly reduced the biofilm viability and metabolic activity, compared to the control (p < 0.05). CFU for total microorganisms, total streptococci, and mutans streptococci on bonding agents with NAg were an order of magnitude less than those of the control. Lactic acid production by biofilms for groups containing NAg was 1/4 of that of the control. Significance Dental plaque microcosm biofilm viability and acid production were greatly reduced on bonding agents containing NAg and NACP, without compromising dentin bond strength. The novel method of incorporating dual agents (remineralizing agent NACP and antibacterial agent NAg) may have wide applicability to other dental bonding systems. PMID:23138046

Preparation of 8-hydroxyquinoline derivatives as potential antibiotics against Staphylococcus aureus.

PubMed

Lam, Kim-Hung; Gambari, Roberto; Lee, Kenneth Ka-Ho; Chen, Yi-Xin; Kok, Stanton Hon-Lung; Wong, Raymond Siu-Ming; Lau, Fung-Yi; Cheng, Chor-Hing; Wong, Wai-Yeung; Bian, Zhao-Xiang; Chan, Albert Sun-Chi; Tang, Johnny Cheuk-On; Chui, Chung-Hin

2014-01-01

This work describes the preparation of quinoline compounds as possible anti-bacterial agents. The synthesized quinoline derivatives show anti-bacterial activity towards Staphylococcus aureus. It is interesting to observe that the synthetic 5,7-dibromo-2-methylquinolin-8-ol (4) shows a similar minimum inhibitory concentration of 6.25μg/mL as compared to that of methicillin (3.125μg/mL) against Staphylococcus aureus. Copyright © 2013 Elsevier Ltd. All rights reserved.

U.S. Army Institute of Surgical Research Annual Research Progress Report for Fiscal Year 1989

DTIC Science & Technology

1989-10-01

inhibits dihydropteroate synthase. Antimicrob Agents Chemother (in press). 3. Klotz IM and Morrison RT: The antibacterial activity of p-amino...mit sulfonamidwirkung. Chem Ber 75:711-9, 1942. 5. Misiek M, Buck RE, Pursiano TA, et al: Antibacterial activity of phosphanilic acid, alone and in...10, associated inhalation injury, survived. Seven were returned to active duty. Less than three months later, early on the morning of 4 June 1989, at a

Antibacterial activity of tannins isolated from Sapium baccatum extract and use for control of tomato bacterial wilt.

PubMed

Vu, Thuy Thu; Kim, Hun; Tran, Vu Khac; Vu, Hoang Dinh; Hoang, Tien Xuan; Han, Jae Woo; Choi, Yong Ho; Jang, Kyoung Soo; Choi, Gyung Ja; Kim, Jin-Cheol

2017-01-01

In the search for new antibacterial agents from natural sources, we revealed that a crude methanol extract of Sapium baccatum was highly active against Ralstonia solanacearum, a causal agent of a serious disease called bacterial wilt of tomato. The bioassay-guided fractionation of this extract resulted in the isolation of seven known active compounds, including gallic acid, methyl gallate, corilagin, tercatain, chebulagic acid, chebulinic acid, and quercetin 3-O-α-L-arabinopyranoside. Their chemical structures were determined by electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. An in vitro antibacterial bioassay using a broth microdilution method revealed that, except for quercetin 3-O-α-L-arabinopyranoside (MIC = 250 μg/mL), the isolated compounds exhibited strong antibacterial activity against R. solanacearum (MIC = 26-52 μg/mL). Among the seven compounds, methyl gallate exhibited the strongest broad-spectrum activity against most of the plant pathogenic bacteria tested (MIC = 26-250 μg/mL). In the in vivo experiments, the crude extract of S. baccatum at 2000 and 1000 μg/mL reduced the development of tomato bacterial wilt by 83 and 63%, respectively, under greenhouse conditions after 14 days of infection. The results suggested that the extracts of S. baccatum or isolated tannins could be used as natural bactericides for the control of bacterial wilt of tomato.

Antibacterial activity of tannins isolated from Sapium baccatum extract and use for control of tomato bacterial wilt

PubMed Central

Vu, Thuy Thu; Kim, Hun; Tran, Vu Khac; Vu, Hoang Dinh; Hoang, Tien Xuan; Han, Jae Woo; Choi, Yong Ho; Jang, Kyoung Soo; Choi, Gyung Ja

2017-01-01

In the search for new antibacterial agents from natural sources, we revealed that a crude methanol extract of Sapium baccatum was highly active against Ralstonia solanacearum, a causal agent of a serious disease called bacterial wilt of tomato. The bioassay-guided fractionation of this extract resulted in the isolation of seven known active compounds, including gallic acid, methyl gallate, corilagin, tercatain, chebulagic acid, chebulinic acid, and quercetin 3-O-α-L-arabinopyranoside. Their chemical structures were determined by electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. An in vitro antibacterial bioassay using a broth microdilution method revealed that, except for quercetin 3-O-α-L-arabinopyranoside (MIC = 250 μg/mL), the isolated compounds exhibited strong antibacterial activity against R. solanacearum (MIC = 26–52 μg/mL). Among the seven compounds, methyl gallate exhibited the strongest broad-spectrum activity against most of the plant pathogenic bacteria tested (MIC = 26–250 μg/mL). In the in vivo experiments, the crude extract of S. baccatum at 2000 and 1000 μg/mL reduced the development of tomato bacterial wilt by 83 and 63%, respectively, under greenhouse conditions after 14 days of infection. The results suggested that the extracts of S. baccatum or isolated tannins could be used as natural bactericides for the control of bacterial wilt of tomato. PMID:28742863

Chemical agents for the control of plaque and plaque microflora: an overview.

PubMed

Gaffar, A; Afflitto, J; Nabi, N

1997-10-01

This presentation provides an overview of the technologies available for the chemical control of plaque. It is generally accepted that the formation of dental plaque at the interfaces of tooth/gingiva is one of the major causes of gingival inflammation and dental caries. Several therapeutic approaches have been used to control dental plaque and supragingival infections. These include fluoride preparations such as stannous fluoride, oxygenating agents, anti-attachment agents, and cationic and non-cationic antibacterial agents. Among the fluoride preparations, stable stannous fluoride pastes and gels have been shown to reduce supragingival plaque, gingivitis, hypersensitivity and caries. The effect of the oxygenating agents on the supragingival plaque has been equivocal, but recent data indicate that a stable agent which provides sustained active oxygen release is effective in controlling plaque. A polymer, PVPA, which reduced attachment of bacteria to teeth was shown to significantly reduce plaque formation in humans. A new generation of antibacterials includes non-ionics such as triclosan, which in combination with a special polymer delivery system, has been shown to reduce plaque, gingivitis, supragingival calculus and dental caries in long-term studies conducted around the world. Unlike the first generation of agents, the triclosan/copolymer/sodium fluoride system is effective in long-term clinicals and does not cause staining of teeth, increase in calculus, or disturbance in the oral microbial ecology.

Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy.

PubMed

Alhamadi, Wisam; Al-Saigh, Rafal J; Al-Dabagh, Nebras N; Al-Humadi, Hussam W

2017-01-01

Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA. Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis. According to bliss independent interaction, the synergistic interactions depended on Δ E values that showed the best for CIP was with AMB (Δ E = 55.14) followed with KET (Δ E = 41.23) and lastly ITR (Δ E = 39.67) at CIP = 150 mg/L. DOX was optimal with KET (Δ E = 42.11) followed with AMB (Δ E = 40.77) and the lowest with ITR (Δ E = 9.12) at DOX = 75 mg/L. MET is the best with AMB (Δ E = 40.95) and then with ITR (Δ E = 35.45) and finally KET (Δ E = 15.15) at MET 200 mg/L. Moreover, usage of higher concentrations of antibacterial agents revealed inhibitory effects. This study uncovers the optimum antibiotic combination therapy against cariogenic candida with FOA by usage of low therapeutic concentrations.

Review of new insights into antimicrobial agents.

PubMed

Dehghan Esmatabadi, M J; Bozorgmehr, A; Hajjari, S N; Sadat Sombolestani, A; Malekshahi, Z V; Sadeghizadeh, M

2017-02-28

People have known the bacteria and have used various ways to deal with them, from a long time ago. Perhaps, natural antibiotics with have been the first step in fighting against pathogens. However, several factors, such as dealing with unfamiliar bacteria or emergence of drug-resistant species, have motivated us to discover new antibiotics or  even change previous types. In this regard, a variety of natural and synthetic antibiotics with different origins, mechanism of action, structures and functional spectrum, have been developed and used. Some impact on the synthesis of nucleic acids and some affect protein synthesis so destroy bacteria. There is a ring in the structure of most of the antibiotics which gives them special properties. However, despite their numerous advantages, antibiotics also have drawbacks ehich limit their use in all situations. Therefore, other approaches such as photodynamic therapy (PDT) and antibacterial peptides were considered as alternatives. Photodynamic therapy (PDT) is a treatment that uses photosensitizing agents, along with light, to kill bacteria. The photosensitizing agents only work after they have been activated by certain kinds of light. Antibacterial peptides are a unique and diverse group of molecules which have  between 12 and 50 amino acids in general.  In this paper, will reviewt hree mentioned topics, namely antibiotics, photodynamic therapy and antibacterial peptides and will discuss the advantages and disadvantages of each approach briefly.

Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as determined by isothermal microcalorimetry.

PubMed

Kong, Wei-Jun; Xing, Xiao-Yan; Xiao, Xiao-He; Zhao, Yan-Ling; Wei, Jian-He; Wang, Jia-Bo; Yang, Rui-Chuang; Yang, Mei-Hua

2012-10-01

The strong toxicity of pathogenic bacteria has resulted in high levels of morbidity and mortality in the general population. Developing effective antibacterial agents with high efficacy and long activity is in great demand. In this study, the microcalorimetric technique based on heat output of bacterial metabolism was applied to evaluate the effect of berberine on Escherichia coli, Bacillus subtilis, individually and in a mixture of both using a multi-channel microcalorimeter. The differences in shape of the power-time fingerprints and thermokinetic parameters of microorganism growth were compared. The results revealed that low concentration (20 μg/mL) of berberine began to inhibit the growth of E. coli and mixed microorganisms, while promoting the growth of B. subtilis; high concentration of berberine (over 100 μg/mL) inhibited B. subtilis. The endurance of E. coli to berberine was obviously lower than B. subtilis, and E. coli could decrease the endurance of B. subtilis to berberine. The sequence of half-inhibitory concentration (IC(50)) of berberine was: B. subtilis (952.37 μg/mL) > mixed microorganisms (682.47 μg/mL) > E. coli (581.69 μg/mL). Berberine might be a good selection of antibacterial agent used in the future. The microcalorimetric method should be strongly suggested in screening novel antibacterial agents for fighting against pathogenic bacteria.

Volatile organic compounds produced by a soil-isolate, Bacillus subtilis FA26 induce adverse ultra-structural changes to the cells of Clavibacter michiganensis ssp. sepedonicus, the causal agent of bacterial ring rot of potato.

PubMed

Rajer, Faheem Uddin; Wu, Huijun; Xie, Yongli; Xie, Shanshan; Raza, Waseem; Tahir, Hafiz Abdul Samad; Gao, Xuewen

2017-04-01

Rhizobacterial volatile organic compounds (VOCs) play an important role in the suppression of soil-borne phytopathogens. In this study, the VOCs produced by a soil-isolate, Bacillus subtilis FA26, were evaluated in vitro for their antibacterial activity against Clavibacter michiganensis ssp. sepedonicus (Cms), the causal agent of bacterial ring rot of potato. The VOCs emitted by FA26 inhibited the growth of Cms significantly compared with the control. Scanning and transmission electron microscopy analyses revealed distorted colony morphology and a wide range of abnormalities in Cms cells exposed to the VOCs of FA26. Varying the inoculation strategy and inoculum size showed that the production and activity of the antibacterial VOCs of FA26 were dependent on the culture conditions. Headspace solid-phase microextraction/gas chromatography-mass spectrometry analyses revealed that FA26 produced 11 VOCs. Four VOCs (benzaldehyde, nonanal, benzothiazole and acetophenone) were associated with the antibacterial activity against Cms. The results suggested that the VOCs produced by FA26 could control the causal agent of bacterial ring rot of potato. This information will increase our understanding of the microbial interactions mediated by VOCs in nature and aid the development of safer strategies for controlling plant disease.

3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors

PubMed Central

Fang, Yajing; Lu, Yulin; Zang, Xixi; Wu, Ting; Qi, XiaoJuan; Pan, Siyi; Xu, Xiaoyun

2016-01-01

Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti-Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids. The cross-validated coefficient (q2) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents. PMID:27049530

Zinc

MedlinePlus

... Using toothpastes containing zinc, with or without an antibacterial agent, appears to prevent plaque and gingivitis. Some ... is some evidence that zinc has some antiviral activity against the herpes virus. Low zinc levels can ...

Antibacterial activity of sphagnum acid and other phenolic compounds found in Sphagnum papillosum against food-borne bacteria.

PubMed

Mellegård, H; Stalheim, T; Hormazabal, V; Granum, P E; Hardy, S P

2009-07-01

To identify the phenolic compounds in the leaves of Sphagnum papillosum and examine their antibacterial activity at pH appropriate for the undissociated forms. Bacterial counts of overnight cultures showed that whilst growth of Staphylococcus aureus 50084 was impaired in the presence of milled leaves, the phenol-free fraction of holocellulose of S. papillosum had no bacteriostatic effect. Liquid chromatography-mass spectrometry analysis of an acetone-methanol extract of the leaves detected eight phenolic compounds. Antibacterial activity of the four dominating phenols specific to Sphagnum leaves, when assessed in vitro as minimal inhibitory concentrations (MICs), were generally >2.5 mg ml(-1). MIC values of the Sphagnum-specific compound 'sphagnum acid' [p-hydroxy-beta-(carboxymethyl)-cinnamic acid] were >5 mg ml(-1). No synergistic or antagonistic effects of the four dominating phenols were detected in plate assays. Sphagnum-derived phenolics exhibit antibacterial activity in vitro only at concentrations far in excess of those found in the leaves. We have both identified the phenolic compounds in S. papillosum and assessed their antibacterial activity. Our data indicate that phenolic compounds in isolation are not potent antibacterial agents and we question their potency against food-borne pathogens.

New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins

PubMed Central

Dias, Susana A.; Freire, João M.; Pérez-Peinado, Clara; Domingues, Marco M.; Gaspar, Diana; Vale, Nuno; Gomes, Paula; Andreu, David; Henriques, Sónia T.; Castanho, Miguel A. R. B.; Veiga, Ana S.

2017-01-01

The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Pseudomonas aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of P. aeruginosa cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties. PMID:28522994

Synthesis and structure-activity relationship studies of novel [6,6,5] tricyclic oxazolidinone derivatives as potential antibacterial agents.

PubMed

Xue, Tao; Ding, Shi; Guo, Bin; Chu, Wenjing; Wang, Hui; Yang, Yushe

2015-01-01

In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate 2. In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6,6,5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds 54, 58, 59 and 63. In vitro liver microsomal stability was further evaluated and the results manifested that compounds 54 and 58 were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phytochemical screening and in-vitro evaluation of pharmacological activities of peels of Musa sapientum and Carica papaya fruit.

PubMed

Siddique, Sarmad; Nawaz, Shamsa; Muhammad, Faqir; Akhtar, Bushra; Aslam, Bilal

2018-06-01

Aqueous, absolute and 80% ethanolic extract of fruit peels of Musa sapientum and Carica papaya were investigated for their antibacterial activity, measured by disc diffusion method and antioxidant activity, measured by four different methods. Papaya and banana peels were found to contain terpenoids, tannins, alkaloids, saponins steroid, phenols, fixed oils and fats. 80% ethanolic extract of banana peel was found to contain highest total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity but in papaya peel, highest TPC and reducing activity was shown by water extract while, TFC and radical scavenging activity was given by 80% ethanolic extract. In banana, water extract showed highest antibacterial activity against tested bacteria while in case of papaya, absolute ethanolic extract showed highest antibacterial activity. The present study revealed that peels of banana and papaya fruits are potentially good source of antioxidant and antibacterial agents.

Antibacterial Potential of Northeastern Portugal Wild Plant Extracts and Respective Phenolic Compounds

PubMed Central

Ferreira, Isabel C. F. R.; Barros, Lillian; Carvalho, Ana Maria; Soares, Graça; Henriques, Mariana

2014-01-01

The present work aims to assess the antibacterial potential of phenolic extracts, recovered from plants obtained on the North East of Portugal, and of their phenolic compounds (ellagic, caffeic, and gallic acids, quercetin, kaempferol, and rutin), against bacteria commonly found on skin infections. The disk diffusion and the susceptibility assays were used to identify the most active extracts and phenolic compounds. The effect of selected phenolic compounds on animal cells was assessed by determination of cellular metabolic activity. Gallic acid had a higher activity, against gram-positive (S. epidermidis and S. aureus) and gram-negative bacteria (K. pneumoniae) at lower concentrations, than the other compounds. The caffeic acid, also, showed good antibacterial activity against the 3 bacteria used. The gallic acid was effective against the 3 bacteria without causing harm to the animal cells. Gallic and caffeic acid showed a promising applicability as antibacterial agents for the treatment of infected wounds. PMID:24804249

Novel semisynthetic antibiotics from caprazamycins A-G: caprazene derivatives and their antibacterial activity.

PubMed

Takahashi, Yoshiaki; Igarashi, Masayuki; Miyake, Toshiaki; Soutome, Hiromi; Ishikawa, Kanae; Komatsuki, Yasuhiro; Koyama, Yoshiko; Nakagawa, Naoko; Hattori, Seiko; Inoue, Kunio; Doi, Norio; Akamatsu, Yuzuru

2013-03-01

Acidic treatment of a mixture of caprazamycins (CPZs) A-G isolated from a screen of novel antimycobacterial agents gave caprazene, a core structure of CPZs, in high yield. Chemical modification of the resulting caprazene was performed to give its various derivatives. The structure-activity relationships of the caprazene derivatives against several mycobacterial species and pathogenic Gram-positive and Gram-negative bacteria were studied. Although caprazene showed no antibacterial activity, the antibacterial activity was restored for its 1'''-alkylamide, 1'''-anilide and 1'''-ester derivatives. Compounds 4b (CPZEN-45), 4d (CPZEN-48), 4f and 4g (CPZEN-51) exhibited more potent activities against Mycobacterium tuberculosis and M. avium complex strains than CPZ-B. These results suggest that caprazene would be a good precursor from which novel semisynthetic antibacterial antibiotics can be designed for the treatment of mycobacterial diseases such as tuberculosis and M. avium complex infection.

Trichoderma koningii assisted biogenic synthesis of silver nanoparticles and evaluation of their antibacterial activity

NASA Astrophysics Data System (ADS)

Tripathi, R. M.; Gupta, Rohit Kumar; Shrivastav, Archana; Singh, M. P.; Shrivastav, B. R.; Singh, Priti

2013-09-01

The present study demonstrates the biosynthesis of silver nanoparticles using Trichoderma koningii and evaluation of their antibacterial activity. Trichoderma koningii secretes proteins and enzymes that act as reducing and capping agent. The biosynthesized silver nanoparticles (AgNPs) were characterized by UV-Vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and x-ray diffraction (XRD). UV-Vis spectra showed absorbance peak at 413 nm corresponding to the surface plasmon resonance of silver nanoparticles. DLS was used to find out the size distribution profile. The size and morphology of the AgNPs was determined by TEM, which shows the formation of spherical nanoparticles in the size range of 8-24 nm. X-ray diffraction showed intense peaks corresponding to the crystalline silver. The antibacterial activity of biosynthesized AgNPs was evaluated by growth curve and inhibition zone and it was found that the AgNPs show potential effective antibacterial activity.

Shrink-induced superhydrophobic and antibacterial surfaces in consumer plastics.

PubMed

Freschauf, Lauren R; McLane, Jolie; Sharma, Himanshu; Khine, Michelle

2012-01-01

Structurally modified superhydrophobic surfaces have become particularly desirable as stable antibacterial surfaces. Because their self-cleaning and water resistant properties prohibit bacteria growth, structurally modified superhydrophobic surfaces obviate bacterial resistance common with chemical agents, and therefore a robust and stable means to prevent bacteria growth is possible. In this study, we present a rapid fabrication method for creating such superhydrophobic surfaces in consumer hard plastic materials with resulting antibacterial effects. To replace complex fabrication materials and techniques, the initial mold is made with commodity shrink-wrap film and is compatible with large plastic roll-to-roll manufacturing and scale-up techniques. This method involves a purely structural modification free of chemical additives leading to its inherent consistency over time and successive recasting from the same molds. Finally, antibacterial properties are demonstrated in polystyrene (PS), polycarbonate (PC), and polyethylene (PE) by demonstrating the prevention of gram-negative Escherichia coli (E. coli) bacteria growth on our structured plastic surfaces.

Preparation, characterization and antibacterial activity of oxidized κ-carrageenan.

PubMed

Zhu, Mingjin; Ge, Liming; Lyu, Yongbo; Zi, Yaxin; Li, Xinying; Li, Defu; Mu, Changdao

2017-10-15

The oxidized κ-carrageenans with different oxidation levels were prepared through the hydrogen peroxide and copper sulfate redox system. The oxidation level of oxidized κ-carrageenan was successfully controlled by adjusting the dosage of hydrogen peroxide. The results showed that the microtopography of oxidized κ-carrageenan changed from rough granules to smooth flakes, mainly resulting from the easily melting property of oxidized κ-carrageenan induced by introduced carboxyl and aldehyde groups. Especially, the antibacterial activity of oxidized κ-carrageenans against Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) was systematically investigated. The results showed that the oxidized κ-carrageenan could damage the bacterial cell wall and cytoplasmic membrane and suppress the growth of both Gram-positive and Gram-negative bacteria. The oxidized κ-carrageenan possessed broad-spectrum antibacterial activity, which may be used as a new antibacterial agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

PubMed Central

Pitart, C.; Marco, F.; Keating, T. A.; Nichols, W. W.

2015-01-01

Ceftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200 Enterobacteriaceae and 25 Pseudomonas aeruginosa strains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistant Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBL Escherichia coli (MIC90 of 0.25 mg/liter), ESBL Klebsiella pneumoniae (MIC90 of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90 of 1 mg/liter), non-ESBL E. coli (MIC90 of ≤0.125 mg/liter), non-ESBL K. pneumoniae (MIC90 of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90 of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant P. aeruginosa strains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90 of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtained in vitro from two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90 values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains of Enterobacteriaceae and P. aeruginosa were ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affect Enterobacteriaceae and P. aeruginosa susceptibility to ceftazidime-avibactam; that is, there is no cross-resistance. PMID:25753646

Using pullulan-based edible coatings to extend shelf-life of fresh-cut 'Fuji' apples.

PubMed

Wu, Shengjun; Chen, Jinhua

2013-04-01

Pullulan is a thickener that can form semipermeable films, and glutathione is an effective reducing agent, while chitooligosaccharide has antibacterial activity. In this study, effect of pullulan-based coatings in combination with antibrowning and antibacterial agents (1% pullulan; 0.8% glutathione+1% chitooligosaccharides; and 0.8% glutathione+1% chitooligosaccharides+1% pullulan) on apple slices was investigated during hypothermia storage. Pullulan-coating treatments effectively retarded enzymatic browning, maintained firmness, decreased weight loss, and inhibited microbial growth and respiration rate of apple slices during hypothermia storage compared with that of the control (p<0.05). Results indicate that using pullulan-based coatings in combination with glutathione and chitooligosaccharides is a promising way to extend the shelf-life of apple slices. Copyright © 2013 Elsevier B.V. All rights reserved.

Recent advances on antimicrobial wound dressing: A review.

PubMed

Simões, Déborah; Miguel, Sónia P; Ribeiro, Maximiano P; Coutinho, Paula; Mendonça, António G; Correia, Ilídio J

2018-06-01

Skin and soft tissue infections (SSTIs) have high rates of morbidity and mortality associated. Despite the successful treatment of some SSTIs, those affecting the subcutaneous tissue, fascia, or muscle delay the healing process and can lead to life-threatening conditions. Therefore, more effective treatments are required to deal with such pathological situations. Recently, wound dressings loaded with antimicrobial agents emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this review, an overview of the most prominent antibacterial agents incorporated in wound dressings along with their mode of action is provided. Furthermore, the recent advances in the therapeutic approaches used in the clinic and some future perspectives regarding antibacterial wound dressings are also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Echinacea plants as antioxidant and antibacterial agents: From traditional medicine to biotechnological applications.

PubMed

Sharifi-Rad, Mehdi; Mnayer, Dima; Morais-Braga, Maria Flaviana Bezerra; Carneiro, Joara Nályda Pereira; Bezerra, Camila Fonseca; Coutinho, Henrique Douglas Melo; Salehi, Bahare; Martorell, Miquel; Del Mar Contreras, María; Soltani-Nejad, Azam; Uribe, Yoshie Adriana Hata; Yousaf, Zubaida; Iriti, Marcello; Sharifi-Rad, Javad

2018-05-10

The genus Echinacea consists of 11 taxa of herbaceous and perennial flowering plants. In particular, Echinacea purpurea (L.) Moench is widely cultivated all over the United States, Canada, and in Europe, exclusively in Germany, for its beauty and reported medicinal properties. Echinacea extracts have been used traditionally as wound healing to improve the immune system and to treat respiratory symptoms caused by bacterial infections. Echinacea extracts have demonstrated antioxidant and antimicrobial activities, and to be safe. This survey aims at reviewing the medicinal properties of Echinacea species, their cultivation, chemical composition, and the potential uses of these plants as antioxidant and antibacterial agents in foods and in a clinical context. Moreover, the factors affecting the chemical composition of Echinacea spp. are also covered. Copyright © 2018 John Wiley & Sons, Ltd.

Synthetic Approaches toward Monocyclic 3‐Amino‐β‐lactams

PubMed Central

Deketelaere, Sari; Van Nguyen, Tuyen; Stevens, Christian V.

2017-01-01

Abstract Due to the emerging resistance against classical β‐lactam‐based antibiotics, a growing number of bacterial infections has become harder to treat. This alarming tendency necessitates continued research on novel antibacterial agents. Many classes of β‐lactam antibiotics are characterized by the presence of the 3‐aminoazetidin‐2‐one core, which resembles the natural substrate of the target penicillin‐binding proteins. In that respect, this Review summarizes the different synthetic pathways toward this key structure for the development of new antibacterial agents. The most extensively applied methods for 3‐amino‐β‐lactam ring formation are discussed, in addition to a few less common strategies. Moreover, approaches to introduce the 3‐amino substituent after ring formation are also covered. PMID:28638759

Anti-Bacterial and Anti-Fungal Activity of Xanthones Obtained via Semi-Synthetic Modification of α-Mangostin from Garcinia mangostana.

PubMed

Narasimhan, Srinivasan; Maheshwaran, Shanmugam; Abu-Yousef, Imad A; Majdalawieh, Amin F; Rethavathi, Janarthanam; Das, Prince Edwin; Poltronieri, Palmiro

2017-02-12

The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry.

Efficient Recovery of Fluoroquinolone-Susceptible and Fluoroquinolone-Resistant Escherichia coli Strains From Frozen Samples

PubMed Central

Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N.; Harris, Anthony D.; Smith, Catherine A.; Maslow, Joel

2010-01-01

We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples. PMID:18279070

Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

PubMed

Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N; Harris, Anthony D; Smith, Catherine A; Maslow, Joel

2008-04-01

We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.

[Infections in orthopedics and traumatology. Pathogenesis and therapy].

PubMed

Scheffer, D; Hofmann, S; Pietsch, M; Wenisch, C

2008-07-01

Infections in orthopedics and traumatology are particularly challenging for the treating physician due to changing epidemiology and bacteriology, in particular immunosenescent patients and antimicrobial resistance. Numerous exogenous and endogenous factors contribute to the onset of bone/joint infection. Known clinical entities include osteitis/osteomyelitis, arthritis, prosthesis-associated infection and spondylitis/spondylodiscitis. Knowledge of epidemiology, bacteriology, and clinic and healing processes in infections leads to a better understanding of the various treatment strategies. Cephalosporin, fosfomycin, glycopeptide, lincosamide, oxazolidinones, ansamycins und fusidic acids represent the standard therapeutic agents in orthopedics and traumatology. Fluoroquinolones, glycylcyclines and lipopeptides are new and possibly promising alternatives. The most important indices of antibiotic agents used in everyday practice are discussed. In complicated cases, collaboration with a specialist for infectious diseases results in improved therapeutic results.

Antimicrobial and Antifouling Polymeric Agents for Surface Functionalization of Medical Implants.

PubMed

Zeng, Qiang; Zhu, Yiwen; Yu, Bingran; Sun, Yujie; Ding, Xiaokang; Xu, Chen; Wu, Yu-Wei; Tang, Zhihui; Xu, Fu-Jian

2018-05-09

Combating implant-associated infections is an urgent demand due to the increasing numbers in surgical operations such as joint replacements and dental implantations. Surface functionalization of implantable medical devices with polymeric antimicrobial and antifouling agents is an efficient strategy to prevent bacterial fouling and associated infections. In this work, antimicrobial and antifouling branched polymeric agents (GPEG and GEG) were synthesized via ring-opening reaction involving gentamicin and ethylene glycol species. Due to their rich primary amine groups, they can be readily coated on the polydopamine-modified implant (such as titanium) surfaces. The resultant surface coatings of Ti-GPEG and Ti-GEG produce excellent in vitro antibacterial efficacy toward both Staphylococcus aureus and Escherichia coli, while Ti-GPEG exhibit better antifouling ability. Moreover, the infection model with S. aureus shows that implanted Ti-GPEG possessed excellent antibacterial and antifouling ability in vivo. This study would provide a promising strategy for the surface functionalization of implantable medical devices to prevent implant-associated infections.

Novel quercetin glycosides as potent anti-MRSA and anti-VRE agents.

PubMed

Hossion, Abugafar M L; Sasaki, Kenji

2013-12-01

Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections (Threat report 2013). Vancomycin is an FDA approved antibiotic and is growing importance in the treatment of hospital infections, with particular emphasis on its value to fight against methicillin-resistant Staphylococcus aureus (MRSA). The increasing use of vancomycin to treat infections caused by the Gram-positive MRSA in the 1970s selected for drug-resistant enterococci, less potent than staphylococci but opportunistic in the space vacated by other bacteria and in patients with compromised immune systems. The dramatic rise of antibiotic-resistant bacteria over the past two decades has stressed the need for completely novel classes of antibacterial agents. This paper reports the recent patent review on the strategy for finding novel quercetinglycoside type antibacterial agents against vancomycin-resistant bacterial strains.

Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America.

PubMed

Boucher, Helen W; Talbot, George H; Bradley, John S; Edwards, John E; Gilbert, David; Rice, Louis B; Scheld, Michael; Spellberg, Brad; Bartlett, John

2009-01-01

The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.