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Sample records for multidrug-resistant bacteria interest

  1. Multidrug Resistance in Bacteria

    PubMed Central

    Nikaido, Hiroshi

    2010-01-01

    Large amounts of antibiotics used for human therapy, as well as for farm animals and even for fish in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. Multidrug resistance in bacteria may be generated by one of two mechanisms. First, these bacteria may accumulate multiple genes, each coding for resistance to a single drug, within a single cell. This accumulation occurs typically on resistance (R) plasmids. Second, multidrug resistance may also occur by the increased expression of genes that code for multidrug efflux pumps, extruding a wide range of drugs. This review discusses our current knowledge on the molecular mechanisms involved in both types of resistance. PMID:19231985

  2. [Innovative treatments for multidrug-resistant bacteria].

    PubMed

    Pierre, Tattevin; Aurélien, Lorleac'h; Matthieu, Revest

    2014-03-01

    The spread of multidrug-resistant bacteria has accelerated sharply in the last decade. According to the World Health Organization they are responsible for an estimated 25 000 deaths in Europe each year. In addition, few new antibiotics are under development, raising the spectrum of a return to the "pre-antibiotic era". Non antibiotic antibacterial agents have recently attracted renewed interest. The most promising candidates are: i) phages (bacteria-infecting viruses) have been widely used in Eastern European countries since the 1930s but come up against logistic and regulatory obstacles due to the evolutionary nature of these biologic agents, while convincing clinical data are lacking; ii) bacteriocines are smallantibacterialpeptidesproducedby numerous bacteria; some have a rapid bactericidal effect, good tolerability, and a limited impact on the commensal flora; however, clinical use of bacteriocines is complicated by their fragility, poor penetration, and substantial risk of resistance selection ; iii) antisense oligonucleo tides act by inactivating genes through specific interaction with a complementary DNA or RNA fragment, potentially allowing specific inhibition of selected bacterial virulence factors. However, this therapeutic class may be more suitable for viral or genetic diseases than for multidrug-resistant bacterial infections, owing to the difficulty of delivering them inside bacteria. PMID:26427289

  3. Combination Approaches to Combat Multi-Drug Resistant Bacteria

    PubMed Central

    Worthington, Roberta J.; Melander, Christian

    2013-01-01

    The increasing prevalence of infections caused by multi-drug resistant bacteria is a global health problem that is exacerbated by the dearth of novel classes of antibiotics entering the clinic over the past 40 years. Herein we describe recent developments toward combination therapies for the treatment of multi-drug resistant bacterial infections. These efforts include antibiotic-antibiotic combinations, and the development of adjuvants that either directly target resistance mechanisms such as the inhibition of β-lactamase enzymes, or indirectly target resistance by interfering with bacterial signaling pathways such as two-component systems. We also discuss screening of libraries of previously approved drugs to identify non-obvious antimicrobial adjuvants. PMID:23333434

  4. Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria.

    PubMed

    Abd-El-Aziz, Alaa S; Agatemor, Christian; Etkin, Nola; Overy, David P; Lanteigne, Martin; McQuillan, Katherine; Kerr, Russell G

    2015-11-01

    Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications. PMID:26452022

  5. Multidrug-resistant bacteria in hematology patients: emerging threats.

    PubMed

    Tatarelli, Paola; Mikulska, Malgorzata

    2016-06-01

    Multidrug-resistant (MDR) bacteria, particularly Gram negatives, such as Enterobacteriaceae resistant to third-generation cephalosporins or carbapenems and MDR Pseudomonas aeruginosa, are increasingly frequent in hematology patients. The prevalence of different resistant species varies significantly between centers. Thus, the knowledge of local epidemiology is mandatory for deciding the most appr-opriate management protocols. In the era of increasing antibiotic resistance, empirical therapy of febrile neutropenia should be individualized. A de-escalation approach is recommended in case of severe clinical presentation in patients who are at high risk for infection with a resistant strain. Targeted therapy of an MDR Gram negative usually calls for a combination treatment, although no large randomized trials exist in this setting. Infection control measures are the cornerstone of limiting the spread of MDR pathogens in hematology units. PMID:27196948

  6. Cationic compounds with activity against multidrug-resistant bacteria: interest of a new compound compared with two older antiseptics, hexamidine and chlorhexidine.

    PubMed

    Grare, M; Dibama, H Massimba; Lafosse, S; Ribon, A; Mourer, M; Regnouf-de-Vains, J-B; Finance, C; Duval, R E

    2010-05-01

    Use of antiseptics and disinfectants is essential in infection control practices in hospital and other healthcare settings. In this study, the in vitro activity of a new promising compound, para-guanidinoethylcalix[4]arene (Cx1), has been evaluated in comparison with hexamidine (HX) and chlorhexidine (CHX), two older cationic antiseptics. The MICs for 69 clinical isolates comprising methicillin-resistant Staphylococcus aureus, methicillin-sensitive S. aureus, coagulase-negative staphylococci (CoNS) (with or without mecA), vancomycin-resistant enterococci, Enterobacteriaceae producing various beta-lactamases and non-fermenting bacilli (Pseudomonas aeruginosa, Acinetobacter baumanii, Stenotrophomonas maltophilia) were determined. Cx1 showed similar activity against S. aureus, CoNS and Enterococcus spp., irrespective of the presence of mecA or van genes, or associated resistance genes, with very good activity against CoNS (MIC <1 mg/L). Variable activities were observed against Enterobacteriaceae; the MICs determined seemed to be dependent both on the genus (MICs of 2, 8 and 64 mg/L for Escherichia coli, Klebsiella pneumoniae and Yersinia enterocolitica, respectively) and on the resistance phenotype production of [Extended Spectrum beta-Lactase (ESBLs) or other beta-lactamases; overproduction of AmpC]. Poor activity was found against non-fermenting bacilli, irrespective of the resistance phenotype. CHX appeared to be the most active compound against all strains, with broad-spectrum and conserved activity against multidrug-resistant strains. HX showed a lower activity, essentially against Gram-positive strains. Consequently, the differences observed with respect to Cx1 suggest that they are certainly not the consequence of antibiotic resistance phenotypes, but rather the result of membrane composition modifications (e.g. of lipopolysaccharide), or of the presence of (activated) efflux-pumps. These results raise the possibility that Cx1 may be a potent new antibacterial

  7. ‘Old’ antibiotics for emerging multidrug-resistant bacteria

    PubMed Central

    Bergen, Phillip J.; Landersdorfer, Cornelia B.; Lee, Hee Ji; Li, Jian; Nation, Roger L.

    2014-01-01

    Purpose of review Increased emergence of bacterial resistance and the decline in newly developed antibiotics have necessitated the reintroduction of previously abandoned antimicrobial agents active against multidrug-resistant bacteria. Having never been subjected to contemporary drug development procedures, these ‘old’ antibiotics require redevelopment in order to optimize therapy. This review focuses on colistin as an exemplar of a successful redevelopment process and briefly discusses two other old antibiotics, fusidic acid and fosfomycin. Recent findings Redevelopment of colistin led to an improved understanding of its chemistry, pharmacokinetics and pharmacodynamics, enabling important steps towards optimizing its clinical use in different patient populations. A scientifically based dosing algorithm was developed for critically ill patients, including those with renal impairment. As nephrotoxicity is a dose-limiting adverse event of colistin, rational combination therapy with other antibiotics needs to be investigated. Summary The example of colistin demonstrated that state-of-the-art analytical, microbiological and pharmacokinetic/pharmacodynamic methods can facilitate optimized use of ‘old’ antibiotics in the clinic. Similar methods are now being applied to fosfomycin and fusidic acid in order to optimize therapy. To improve and preserve the usefulness of these antibiotics rational approaches for redevelopment need to be followed. PMID:23041772

  8. Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study

    PubMed Central

    Basak, Silpi; Singh, Priyanka; Rajurkar, Monali

    2016-01-01

    Background and Objective. Antimicrobial resistance is now a major challenge to clinicians for treating patients. Hence, this short term study was undertaken to detect the incidence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacterial isolates in a tertiary care hospital. Material and Methods. The clinical samples were cultured and bacterial strains were identified in the department of microbiology. The antibiotic susceptibility profile of different bacterial isolates was studied to detect MDR, XDR, and PDR bacteria. Results. The antibiotic susceptibility profile of 1060 bacterial strains was studied. 393 (37.1%) bacterial strains were MDR, 146 (13.8%) strains were XDR, and no PDR was isolated. All (100%) Gram negative bacterial strains were sensitive to colistin whereas all (100%) Gram positive bacterial strains were sensitive to vancomycin. Conclusion. Close monitoring of MDR, XDR, or even PDR must be done by all clinical microbiology laboratories to implement effective measures to reduce the menace of antimicrobial resistance. PMID:26942013

  9. [Significance of efflux pumps in multidrug resistance of Gram-negative bacteria].

    PubMed

    Wiercińska, Olga; Chojecka, Agnieszka; Kanclerski, Krzysztof; Rőhm-Rodowald, Ewa; Jakimiak, Bożenna

    2015-01-01

    The phenomenon of multidrug. resistance of bacteria is a serious problem of modern medicine. This resistance largely is a consequence of abuse and improper use of antibacterial substances, especially antibiotics and chemotherapeutics in hospital settings. Multidrug resistance is caused by a number of interacting mechanisms of resistance. Recent studies have indicated that efflux pumps and systems of efflux pumps are an important determinant of this phenomenon. Contribute to this particular RND efflux systems of Gram-negative bacteria, which possess a wide range of substrates such as antibiotics, dyes, detergents, toxins and active substances of disinfectants and antiseptics. These transporters are usually encoded on bacterial chromosomes. Genes encoding efflux pumps' proteins may also be carried on plasmids and other mobile genetic elements. Such pumps are usually specific to a small group of substrates, but as an additional mechanism of resistance may contribute to the multidrug resistance. PMID:26084076

  10. Photoexcited quantum dots for killing multidrug-resistant bacteria

    NASA Astrophysics Data System (ADS)

    Courtney, Colleen M.; Goodman, Samuel M.; McDaniel, Jessica A.; Madinger, Nancy E.; Chatterjee, Anushree; Nagpal, Prashant

    2016-05-01

    Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

  11. Preparation of silver nanoparticles fabrics against multidrug-resistant bacteria

    NASA Astrophysics Data System (ADS)

    Hanh, Truong Thi; Thu, Nguyen Thi; Hien, Nguyen Quoc; An, Pham Ngoc; Loan, Truong Thi Kieu; Hoa, Phan Thi

    2016-04-01

    The silver nanoparticles (AgNPs)/peco fabrics were prepared by immobilization of AgNPs on fabrics in which AgNPs were synthesized by γ-irradiation of the 10 mM AgNO3 chitosan solution at the dose of 17.6 kGy. The AgNPs size has been estimated to be about 11 nm from TEM image. The AgNPs content onto peco fabrics was of 143±6 mg/kg at the initial AgNPs concentration of 100 ppm. The AgNPs colloidal solution was characterized by UV-vis spectroscopy and TEM image. The antibacterial activity of AgNPs/peco fabrics after 60 washings against Staphylococcus aureus and Klebsiella pneumoniae was found to be over 99%. Effects of AgNPs fabics on multidrug-resistant pathogens from the clinical specimens were also tested.

  12. Recycling antibiotics into GUMBOS: A new combination strategy to combat multi-drug resistant bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence of multi-drug resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded ß-lactam antibiotics (amp...

  13. Multidrug-Resistant Bacteria in the Community: Trends and Lessons Learned.

    PubMed

    van Duin, David; Paterson, David L

    2016-06-01

    Multidrug resistant (MDR) bacteria are one of the most important threats to public health. Typically, MDR bacteria are associated with nosocomial infections. However, some MDR bacteria have become prevalent causes of community-acquired infections. The spread of MDR bacteria into the community is a crucial development, and is associated with increased morbidity, mortality, health care costs, and antibiotic use. Factors associated with community dissemination of MDR bacteria overlap but are distinct from those associated with nosocomial spread. Prevention of further community spread of MDR bacteria is of the utmost importance, and requires a multidisciplinary approach involving all stakeholders. PMID:27208764

  14. High isolation rates of multidrug-resistant bacteria from water and carpets of mosques

    PubMed Central

    Mohamed Ali, Mostafa Mohamed; Alemary, Fuoad; Alrtail, Amna; Rzeg, Moftah M.; Albakush, Abdulla M.; Ghenghesh, Khalifa Sifaw

    2014-01-01

    Objective There is little information regarding the isolation of antimicrobial-resistant potentially pathogenic bacteria from water and carpets of mosques worldwide. The objective of the present investigation is to determine the bacteriological quality of water and carpets of mosques in Elkhomes city in Libya. Methods Potentially pathogenic bacteria were isolated from water samples (n=44) and dust samples from carpets (n=50) of 50 mosques in Elkhomes city, Libya, using standard bacteriological procedures. Susceptibility of isolated bacteria to antimicrobial agents was determined by the disc-diffusion method. Results Of the water samples examined, 12 (27.3%) were positive for Escherichia coli, 10 (22.7%) for Klebsiella spp., and 15 (34.1%) for other enteric bacteria. Of the dust samples of carpets examined, 6 (12%) were positive for E. coli, 33 (66%) for Klebsiella spp., and 30 (60%) for Staphylococcus spp. Multidrug resistance (MDR, resistance to three or more antimicrobial groups) was found among 48.7% (19/37) and 46.9% (30/64) of the examined enterobacteria from water and carpets, respectively, and among 66.7% (20/30) of Staphylococcus spp. from carpets. In addition, methicillin-resistant Staphylococcus aureus (MRSA) was isolated from a carpet of one mosque. Conclusion Presence of multidrug-resistant potentially pathogenic bacteria in examined water and carpets indicate that mosques as communal environments may play a role in the spread of multidrug-resistant bacteria in the community and pose a serious health risk to worshipers. PMID:25128691

  15. [Antimicrobial therapy in severe infections with multidrug-resistant Gram-negative bacterias].

    PubMed

    Duszyńska, Wiesława

    2010-01-01

    Multidrug-resistant Gram-negative bacteria pose a serious and rapidly emerging threat to patients in healthcare settings, and are especially prevalent and problematic in intensive therapy units. Recently, the emergence of pandrug-resistance in Gram-negative bacteria poses additional concerns. This review examines the clinical impact and epidemiology of multidrug-resistant Gram-negative bacteria as a cause of increased morbidity and mortality among ITU patients. Beta-lactamases, cephalosporinases and carbapenemases play the most important role in resistance to antibiotics. Despite the tendency to increased resistance, carbapenems administered by continuous infusion remain the most effective drugs in severe sepsis. Drug concentration monitoring, albeit rarely used in practice, is necessary to ensure an effective therapeutic effect. PMID:21413423

  16. In vitro Antibacterial Activity of Aqueous and Ethanol Extracts of Aristolochia indica and Toddalia asiatica Against Multidrug-Resistant Bacteria.

    PubMed

    Venkatadri, B; Arunagirinathan, N; Rameshkumar, M R; Ramesh, Latha; Dhanasezhian, A; Agastian, P

    2015-01-01

    Bacteria have developed multidrug resistance against available antimicrobial agents. Infectious diseases caused by these multidrug-resistant bacteria are major causes of morbidity and mortality in human beings. Synthetic drugs are expensive and inadequate for the treatment of diseases, causing side effects and ineffective against multidrug-resistant bacteria. The medicinal plants are promising to have effective antimicrobial property due to presence of phytochemical compounds like alkaloids, flavanoids, tannins and phenolic compounds. The present study aimed to find the antimicrobial activity of medicinal plants against multidrug-resistant bacteria. Multidrug-resistant bacteria were identified by Kirby-Bauer disc diffusion method. Production of β-lactamases (extended spectrum β-lactamases, metallo β-lactamase and AmpC β-lactamase) were identified by combination disc method. Antibacterial activity of aqueous and ethanol extract of Aristolochia indica and Toddalia asiatica were detected by agar well diffusion assay and minimum inhibitory concentration. All bacteria used in this study showed antibiotic resistance to ≥3 antibiotics. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Vibrio cholerae were found to be positive for β-lactamase production. Ethanol extract of Aristolochia indica showed more significant antibacterial activity against multidrug-resistant bacteria than Toddalia asiatica. Ethanol extracts of Aristolochia indica and Toddalia asiatica showed minimum inhibitory concentration values of 50-100 μg/ml and 100-200 μg/ml, respectively against multidrug-resistant bacteria. From this study, it was concluded that Aristolochia indica has more potential to treat multidrug-resistant bacteria than Toddalia asiatica. PMID:26997710

  17. [Should we screen for colonization to control the spread of multidrug resistant bacteria?].

    PubMed

    Lepelletier, D; Perron, S; Huguenin, H; Picard, M; Bemer, P; Caillon, J; Juvin, M-E; Drugeon, H

    2003-10-01

    Should we screen for colonization to control the spread of multidrug-resistant bacteria? A multidrug-resistant bacteria surveillance program was performed in 1999 at Laënnec Hospital (Nantes, France). After a 3-year period, the results permit us to determine the strategy to strengthen their spread. In 2001, Staphylococcus aureus resistant to methicillin represented 45% of the 202 multidrug-resistant bacteria isolated. The global incidence rate per 100 admissions remained stable between 1999 and 2001 (0.42%), but those of infections acquired in our institution decreased significantly from 0.27% in 1999 to 0.18% in 2001 (P < 0.05), particularly in medical care units (P < 0.04). In spite of this surveillance program and hygiene trainings, the global incidence remained stable during the study period, even if our action contributed to decrease the incidence of S. aureus resistant to methicillin acquired in our institution. Isolation precautions and screening for colonization policy in intensive care units are not sufficient to control the spread of MRB at hospital level. They should be strengthened by procedures for the transfer of infected or colonized patients and by antibiotic use control. PMID:14568591

  18. Multidrug-resistant Gram-negative bacteria in solid organ transplant recipients with bacteremias.

    PubMed

    Wan, Q Q; Ye, Q F; Yuan, H

    2015-03-01

    Bloodstream infections (BSIs) remain as life-threatening complications and are associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Multidrug-resistant (MDR) Gram-negative bacteria can cause serious bacteremias in these recipients. Reviews have aimed to investigate MDR Gram-negative bacteremias; however, they were lacking in SOT recipients in the past. To better understand the characteristics of bacteremias due to MDR Gram-negative bacteria, optimize preventive and therapeutic strategies, and improve the outcomes of SOT recipients, this review summarize the epidemiology, clinical and laboratory characteristics, and explores the mechanisms, prevention, and treatment of MDR Gram-negative bacteria. PMID:25388855

  19. Thermotolerance and multidrug resistance in bacteria isolated from equids and their environment.

    PubMed

    Singh, B R

    2009-06-13

    Sixty-nine vaginal swabs and 138 rectal swabs collected from 195 equids were analysed for the presence of thermotolerant bacteria, that is, bacteria surviving at 60+/-0.1 degrees C for one hour. Thermotolerant Escherichia coli, Enterobacter species, Klebsiella pneumoniae, Proteus species and Pseudomonas species were isolated from 41, 16, nine, three and three of the 138 rectal swabs, respectively; seven of the E coli and two of the Enterobacter species isolates survived pasteurisation at 63.8+/-0.1 degrees C for 30 minutes. All except three E coli, two Enterobacter species and one Proteus species isolate were resistant to three or more antimicrobial drugs, that is, they were multidrug resistant. Thermotolerant E coli, Enterobacter species and Proteus species were isolated from 11, two and two of the 69 vaginal swabs, respectively, but only one isolate of E coli survived pasteurisation at 63.8+/-0.1 degrees C for 30 minutes. All except two of the E coli isolates were multidrug resistant. None of the four thermotolerant isolates from nine soil samples collected on four of the farms where the equids were kept was pasteurisation resistant, but they were all multidrug resistant. Of the 10 pasteurisation-resistant isolates, nine were multidrug resistant but none was resistant to chloramphenicol, ciprofloxacin, cotrimazine, cotrimoxazole or streptomycin. All the isolates grew at 42+/-0.1 degrees C but none grew at 46+/-0.1 degrees C or above. The Enterobacter isolates were more tolerant to pasteurisation than the E coli isolates, particularly during the first few minutes of exposure. PMID:19525523

  20. Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

    PubMed Central

    Piddock, Laura J. V.

    2006-01-01

    Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed. PMID:16614254

  1. [Monotherapy vs. combined therapy in the treatment of multi-drug resistance gramnegative bacteria].

    PubMed

    Martínez-Sagasti, F; González-Gallego, M A; Moneo-González, A

    2016-09-01

    The increasing number of multidrug resistant gram negative bacteria, particularly in patients with risk factors, but in those who suffer community infections as well, is doing more and more difficult to choose the appropriate treatment. The most challenging cases are due to the production of extended-spectrum-β-lactamases (ESBL) and carbapenemases. This mini-review will discuss the adequacy of administering carbapenems when suspecting infections due to ESBL that could be modified after knowing the MIC of the isolated bacteria and the combined therapy in cases of carbapenemases, being particularly important to include a carbapenem and/or colistine at high dosages in this combination. PMID:27608313

  2. Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria.

    PubMed

    Ni, Wentao; Li, Yanjun; Guan, Jie; Zhao, Jin; Cui, Junchang; Wang, Rui; Liu, Youning

    2016-05-01

    We tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially in Acinetobacter baumannii and Stenotrophomonas maltophilia These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP. PMID:26953203

  3. Presence of multidrug-resistant enteric bacteria in dairy farm topsoil.

    PubMed

    Burgos, J M; Ellington, B A; Varela, M F

    2005-04-01

    In addition to human and veterinary medicine, antibiotics are extensively used in agricultural settings, such as for treatment of infections, growth enhancement, and prophylaxis in food animals, leading to selection of drug and multidrug-resistant bacteria. To help circumvent the problem of bacterial antibiotic resistance, it is first necessary to understand the scope of the problem. However, it is not fully understood how widespread antibiotic-resistant bacteria are in agricultural settings. The lack of such surveillance data is especially evident in dairy farm environments, such as soil. It is also unknown to what extent various physiological modulators, such as salicylate, a component of aspirin and known model modulator of multiple antibiotic resistance (mar) genes, influence bacterial multi-drug resistance. We isolated and identified enteric soil bacteria from local dairy farms within Roosevelt County, NM, determined the resistance profiles to antibiotics associated with mar, such as chloramphenicol, nalidixic acid, penicillin G, and tetracycline. We then purified and characterized plasmid DNA and detected mar phenotypic activity. The minimal inhibitory concentrations (MIC) of antibiotics for the isolates ranged from 6 to >50 microg/mL for chloramphenicol, 2 to 8 microg/mL for nalidixic acid, 25 to >300 microg/mL for penicillin G, and 1 to >80 microg/mL for tetracycline. On the other hand, many of the isolates had significantly enhanced MIC for the same antibiotics in the presence of 5 mM salicylate. Plasmid DNA extracted from 12 randomly chosen isolates ranged in size from 6 to 12.5 kb and, in several cases, conferred resistance to chloramphenicol and penicillin G. It is concluded that enteric bacteria from dairy farm topsoil are multidrug resistant and harbor antibiotic-resistance plasmids. A role for dairy topsoil in zoonoses is suggested, implicating this environment as a reservoir for development of bacterial resistance against clinically relevant

  4. Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria.

    PubMed

    Ji, Yinduo; Lei, Ting

    2013-01-01

    Despite the availability of antibiotics and vaccines, infectious diseases remain one of most dangerous threats to humans and animals. The overuse and misuse of antibacterial agents have led to the emergence of multidrug resistant bacterial pathogens. Bacterial cells are often resilient enough to survive in even the most extreme environments. To do so, the organisms have evolved different mechanisms, including a variety of two-component signal transduction systems, which allow the bacteria to sense the surrounding environment and regulate gene expression in order to adapt and respond to environmental stimuli. In addition, some bacteria evolve resistance to antibacterial agents while many bacterial cells are able to acquire resistance genes from other bacterial species to enable them to survive in the presence of toxic antimicrobial agents. The crisis of antimicrobial resistance is an unremitting menace to human health and a burden on public health. The rapid increase in antimicrobial resistant organisms and limited options for development of new classes of antibiotics heighten the urgent need to develop novel potent antibacterial therapeutics in order to combat multidrug resistant infections. In this review, we introduce the regulatory mechanisms of antisense RNA and significant applications of regulated antisense RNA interference technology in early drug discovery. This includes the identification and evaluation of drug targets in vitro and in vivo, the determination of mode of action for antibiotics and new antibacterial agents, as well as the development of peptide-nucleic acid conjugates as novel antibacterials. PMID:23738437

  5. Multidrug-resistant Gram-negative bacteria: a product of globalization.

    PubMed

    Hawkey, P M

    2015-04-01

    Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of carbapenem antibiotics, resulting in the emergence of plasmid-mediated resistance to carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular carbapenemases--imipenem carbapenemases, Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase--and highlights the importance of control of antibiotic use. PMID:25737092

  6. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria

    PubMed Central

    2014-01-01

    Combination antibiotic therapy for Gram-negative sepsis is controversial. The present review provides a brief summary of the existing knowledge on combination therapy for severe infections with multidrug-resistant Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae. Empirical combination antibiotic therapy is recommended for severe sepsis and septic shock to reduce mortality related to inappropriate antibiotic treatment. Because definitive combination therapy has not been proven superior to monotherapy in meta-analyses, it is generally advised to de-escalate antibiotic therapy when the antibiotic susceptibility profile is known, although it cannot be excluded that some subgroups of patients might still benefit from continued combination therapy. Definitive combination therapy is recommended for carbapenemase-producing Enterobacteriaceae and should also be considered for severe infections with Pseudomonas and Acinetobacter spp. when beta-lactams cannot be used. Because resistance to broad-spectrum beta-lactams is increasing in Gram-negative bacteria and because no new antibiotics are expected to become available in the near future, the antibacterial potential of combination therapy should be further explored. In vitro data suggest that combinations can be effective even if the bacteria are resistant to the individual antibiotics, although existing evidence is insufficient to support the choice of combinations and explain the synergistic effects observed. In vitro models can be used to screen for effective combinations that can later be validated in animal or clinical studies. Further, in the absence of clinical evidence, in vitro data might be useful in supporting therapeutic decisions for severe infections with multidrug-resistant Gram-negative bacteria. PMID:24666223

  7. Multidrug-Resistance and Toxic Metal Tolerance of Medically Important Bacteria Isolated from an Aquaculture System

    PubMed Central

    Resende, Juliana Alves; Silva, Vânia L.; Fontes, Cláudia Oliveira; Souza-Filho, Job Alves; de Oliveira, Tamara Lopes Rocha; Coelho, Cíntia Marques; César, Dionéia Evangelista; Diniz, Cláudio Galuppo

    2012-01-01

    The use of antimicrobials and toxic metals should be considered carefully in aquaculture and surrounding environments. We aimed to evaluate medically relevant bacteria in an aquaculture system and their susceptibility to antimicrobials and toxic metals. Selective cultures for enterobacteria (ENT), non-fermenting Gram-negative rods (NFR) and Gram-positive cocci (GPC) were obtained from water samples collected in two different year seasons. The isolated bacteria were biochemically identified and antimicrobial and toxic metal susceptibility patterns were determined. Overall, 407 representative strains were recovered. In general, bacteria isolated from fish ponds showed higher multiple antibiotic resistance indices when compared to those isolated from a water-fed canal. Resistance to penicillin and azithromycin was observed more frequently in the GPC group, whereas resistance to ampicillin and ampicillin/sulbactam or gentamicin was observed more frequently in the ENT and NFR groups, respectively. All the isolated bacteria were tolerant to nickel, zinc, chromium and copper at high levels (≥1,024 μg mL−1), whereas tolerance to cadmium and mercury varied among the isolated bacteria (2–1,024 μg mL−1). Multidrug-resistant bacteria were more frequent and diverse in fish ponds than in the water-fed canal. A positive correlation was observed between antimicrobial resistance and metal tolerance. The data point out the need for water treatment associated with the aquaculture system. PMID:22972388

  8. Multidrug resistant bacteria isolated from cockroaches in long-term care facilities and nursing homes.

    PubMed

    Pai, Hsiu-Hua

    2013-01-01

    Residents in long-term care facilities and nursing homes have a relative higher risk for infections. The nocturnal and filthy habits of cockroaches may be ideal disseminators of pathogenic microorganisms in these institutions. This study was designed to determine the infestation and vector potential of cockroaches under this institutional environment. Cockroaches were collected from 69 long-term care facilities and nursing homes in Kaohsiung City. Risk factors related to cockroach infestation were determined by questionnaire survey. In addition, bacteria were isolated and identified from the alimentary tract and external surface of these insects. Antibiotic resistances of these microorganisms were then determined. Cockroach infestation was found in 45 (65.2%) institutions and 558 cockroaches (119 Periplaneta americana and 439 Blattella germanica) were collected. A significant association was found between cockroach infestation and indoor environmental sanitation. From 250 adult cockroaches, 38 species of gram-negative bacteria, 20 species of glucose non-fermenter bacilli and 6 species of gram-positive bacteria were isolated. Moreover, antibiotic resistances were found among the bacteria isolated. These findings indicate that cockroaches have the potential in transmitting pathogenic bacteria with multidrug resistances in long-term care facilities and nursing homes. PMID:22960645

  9. Incidence and Diversity of Antimicrobial Multidrug Resistance Profiles of Uropathogenic Bacteria

    PubMed Central

    Linhares, Inês; Raposo, Teresa; Rodrigues, António

    2015-01-01

    The aim of this study was to assess the most frequent multidrug resistant (MDR) profiles of the main bacteria implicated in community-acquired urinary tract infections (UTI). Only the MDR profiles observed in, at least, 5% of the MDR isolates were considered. A quarter of the bacteria were MDR and the most common MDR profile, including resistance to penicillins, quinolones, and sulfonamides (antibiotics with different mechanisms of action, all mainly recommended by the European Association of Urology for empirical therapy of uncomplicated UTI), was observed, alone or in association with resistance to other antimicrobial classes, in the main bacteria implicated in UTI. The penicillin class was included in all the frequent MDR profiles observed in the ten main bacteria and was the antibiotic with the highest prescription during the study period. The sulfonamides class, included in five of the six more frequent MDR profiles, was avoided between 2000 and 2009. The results suggest that the high MDR percentage and the high diversity of MDR profiles result from a high prescription of antibiotics but also from antibiotic-resistant genes transmitted with other resistance determinants on mobile genetic elements and that the UTI standard treatment guidelines must be adjusted for the community of Aveiro District. PMID:25834814

  10. Incidence and diversity of antimicrobial multidrug resistance profiles of uropathogenic bacteria.

    PubMed

    Linhares, Inês; Raposo, Teresa; Rodrigues, António; Almeida, Adelaide

    2015-01-01

    The aim of this study was to assess the most frequent multidrug resistant (MDR) profiles of the main bacteria implicated in community-acquired urinary tract infections (UTI). Only the MDR profiles observed in, at least, 5% of the MDR isolates were considered. A quarter of the bacteria were MDR and the most common MDR profile, including resistance to penicillins, quinolones, and sulfonamides (antibiotics with different mechanisms of action, all mainly recommended by the European Association of Urology for empirical therapy of uncomplicated UTI), was observed, alone or in association with resistance to other antimicrobial classes, in the main bacteria implicated in UTI. The penicillin class was included in all the frequent MDR profiles observed in the ten main bacteria and was the antibiotic with the highest prescription during the study period. The sulfonamides class, included in five of the six more frequent MDR profiles, was avoided between 2000 and 2009. The results suggest that the high MDR percentage and the high diversity of MDR profiles result from a high prescription of antibiotics but also from antibiotic-resistant genes transmitted with other resistance determinants on mobile genetic elements and that the UTI standard treatment guidelines must be adjusted for the community of Aveiro District. PMID:25834814

  11. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers.

    PubMed

    Lam, Shu J; O'Brien-Simpson, Neil M; Pantarat, Namfon; Sulistio, Adrian; Wong, Edgar H H; Chen, Yu-Yen; Lenzo, Jason C; Holden, James A; Blencowe, Anton; Reynolds, Eric C; Qiao, Greg G

    2016-01-01

    With the recent emergence of reports on resistant Gram-negative 'superbugs', infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs. Here, we show that a class of antimicrobial agents, termed 'structurally nanoengineered antimicrobial peptide polymers' (SNAPPs) exhibit sub-μM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity. SNAPPs are highly effective in combating CMDR Acinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy. Furthermore, we did not observe any resistance acquisition by A. baumannii (including the CMDR strain) to SNAPPs. Comprehensive analyses using a range of microscopy and (bio)assay techniques revealed that the antimicrobial activity of SNAPPs proceeds via a multimodal mechanism of bacterial cell death by outer membrane destabilization, unregulated ion movement across the cytoplasmic membrane and induction of the apoptotic-like death pathway, possibly accounting for why we did not observe resistance to SNAPPs in CMDR bacteria. Overall, SNAPPs show great promise as low-cost and effective antimicrobial agents and may represent a weapon in combating the growing threat of MDR Gram-negative bacteria. PMID:27617798

  12. Antibacterial activities of selected edible plants extracts against multidrug-resistant Gram-negative bacteria

    PubMed Central

    2013-01-01

    Background In response to the propagation of bacteria resistant to many antibiotics also called multi-drug resistant (MDR) bacteria, the discovery of new and more efficient antibacterial agents is primordial. The present study was aimed at evaluating the antibacterial activities of seven Cameroonian dietary plants (Adansonia digitata, Aframomum alboviolaceum, Aframomum polyanthum, Anonidium. mannii, Hibiscus sabdarifa, Ocimum gratissimum and Tamarindus indica). Methods The phytochemical screening of the studied extracts was performed using described methods whilst the liquid broth micro dilution was used for all antimicrobial assays against 27 Gram-negative bacteria. Results The results of the phytochemical tests indicate that all tested extracts contained phenols and triterpenes, other classes of chemicals being selectively present. The studied extracts displayed various degrees of antibacterial activities. The extracts of A. digitata, H. sabdarifa, A. polyanthum, A. alboviolaceum and O. gratissimum showed the best spectra of activity, their inhibitory effects being recorded against 81.48%, 66.66%, 62.96%, 55.55%, and 55.55% of the 27 tested bacteria respectively. The extract of A. polyanthum was very active against E. aerogenes EA294 with the lowest recorded minimal inhibitory concentration (MIC) of 32 μg/ml. Conclusion The results of the present work provide useful baseline information for the potential use of the studied edible plants in the fight against both sensitive and MDR phenotypes. PMID:23837916

  13. Synergistic Antimicrobial Activity of Camellia sinensis and Juglans regia against Multidrug-Resistant Bacteria

    PubMed Central

    Farooqui, Amber; Khan, Adnan; Borghetto, Ilaria; Kazmi, Shahana U.; Rubino, Salvatore; Paglietti, Bianca

    2015-01-01

    Synergistic combinations of antimicrobial agents with different mechanisms of action have been introduced as more successful strategies to combat infections involving multidrug resistant (MDR) bacteria. In this study, we investigated synergistic antimicrobial activity of Camellia sinensis and Juglans regia which are commonly used plants with different antimicrobial agents. Antimicrobial susceptibility of 350 Gram-positive and Gram-negative strains belonging to 10 different bacterial species, was tested against Camellia sinensis and Juglans regia extracts. Minimum inhibitory concentrations (MICs) were determined by agar dilution and microbroth dilution assays. Plant extracts were tested for synergistic antimicrobial activity with different antimicrobial agents by checkerboard titration, Etest/agar incorporation assays, and time kill kinetics. Extract treated and untreated bacteria were subjected to transmission electron microscopy to see the effect on bacterial cell morphology. Camellia sinensis extract showed higher antibacterial activity against MDR S. Typhi, alone and in combination with nalidixic acid, than to susceptible isolates.” We further explore anti-staphylococcal activity of Juglans regia that lead to the changes in bacterial cell morphology indicating the cell wall of Gram-positive bacteria as possible target of action. The synergistic combination of Juglans regia and oxacillin reverted oxacillin resistance of methicillin resistant Staphylococcus aureus (MRSA) strains in vitro. This study provides novel information about antimicrobial and synergistic activity of Camellia sinensis and Juglans regia against MDR pathogens PMID:25719410

  14. Use of Shotgun Metagenome Sequencing To Detect Fecal Colonization with Multidrug-Resistant Bacteria in Children.

    PubMed

    Andersen, Heidi; Connolly, Natalia; Bangar, Hansraj; Staat, Mary; Mortensen, Joel; Deburger, Barbara; Haslam, David B

    2016-07-01

    Prevention of multidrug-resistant (MDR) bacterial infections relies on accurate detection of these organisms. We investigated shotgun metagenome sequencing for the detection of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and MDR Enterobacteriaceae Fecal metagenomes were analyzed from high-risk inpatients and compared to those of low-risk outpatients and controls with minimal risk for a MDR bacterial infection. Principal-component analysis clustered patient samples into distinct cohorts, confirming that the microbiome composition was significantly different between cohorts (P = 0.006). Microbial diversity and relative anaerobe abundance were preserved in outpatients compared to those in controls. Relative anaerobe abundance was significantly reduced in inpatients compared to that in outpatients (P = 0.006). Although the potential for MDR bacteria was increased in inpatients and outpatients compared to that in controls (P < 0.001), there was no difference between inpatients and outpatients. However, 9 (53%) inpatients had colonization with a MDR bacterium that was not identified by culture. Unlike culture, shotgun sequencing quantitatively characterizes the burdens of multiple MDR bacteria relative to all of the microbiota within the intestinal community. We propose consideration of key microbiome features, such as diversity and relative anaerobe abundance, in addition to the detection of MDR bacteria by shotgun metagenome sequencing as a novel method that might better identify patients who are at increased risk of a MDR infection. PMID:27122381

  15. In vitro antibacterial potency of Butea monosperma Lam. against 12 clinically isolated multidrug resistant bacteria

    PubMed Central

    Sahu, Mahesh Chandra; Padhy, Rabindra Nath

    2013-01-01

    Objective To investigate the antibacterial activity, using cold and hot extraction procedures with five solvents, petroleum ether, acetone, ethanol, methanol and water to validate medicinal uses of Butea monosperma Lam (B. monosperma) in controlling infections; and to qualitatively estimate phytochemical constituents of leaf-extracts of the plant. Methods The antibacterial activity of leaf-extracts was evaluated by the agar-well diffusion method against clinically isolated 12 Gram-positive and -negative multidrug resistant (MDR) pathogenic bacteria in vitro. Values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of leaf-extracts against each bacterium were obtained in a 96-well micro-titre plate, by broth dilution micro-titre plate technique. Results The presence of tannins, flavonoids, starch, glycosides and carbohydrates in different leaf extracts was established. Pathogenic bacteria used were, Acinetobacter sp., Chromobacterium violaceum, Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella sp., Enterococcus sp., Staphylococcus aureus (S. aureus), methicillin resistant S. aureus and vancomycin resistant S. aureus, along with standard bacterial strains. These MDR bacteria had been recorded to have significant inhibitions by leaf extracts, obtained by cold and hot extraction procedures with five solvents. In addition, the hot aqueous extract against Enterococcus sp. had the highest inhibition zone-size (21 mm). Ciprofloxacin 30 µg/disc was the positive/reference control and the diluting solvent, 10% dimethyl sulphoxide was the negative control. Recorded MIC values of different extracts ranged between 0.23 and 13.30 mg/mL, and MBC values were 0.52 to 30.00 mg/mL, for these bacteria. Conclusions Leaf-extracts with hot water and ethanol had shown significant antibacterial activity against all bacteria. B. monosperma leaf-extract could be used in treating infectious

  16. Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

    PubMed Central

    Lubelski, Jacek; Konings, Wil N.; Driessen, Arnold J. M.

    2007-01-01

    Summary: Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria. PMID:17804667

  17. The role of nanotechnology in combating multi-drug resistant bacteria.

    PubMed

    Singh, Rajni; Smitha, M S; Singh, Surinder P

    2014-07-01

    The development of antibiotics has played a significant role in combating the dreaded infectious disease such as tuberculosis, pneumonia, typhoid fever and meningitis in 20th century. However, the improper use of antibiotics led to the development of multidrug resistance (MDR) in microbial flora raising a global public health concern of 21st century. This unforeseen threat demands the development of new drugs and strategies for combating antibiotic resistance shown by many microbial species. Recent developments in nanotechnology to engineer nanoparticles with desired physicochemical properties have been projected as a new line of defense against MDR micro-organism. In this review, we summarized and discussed the recent development demonstrating the potential of nanomaterials to evade the MDR. Nanoparticles have shown effective antimicrobial activity against MDR bacteria, such as Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Mycobacterium tuberculosis, vancomycin resistant enterococci, methicillin-resistant Staphylococcus aureus and others. Furthermore, new strategies like combination of radiation and drugs with nanoparticle that are being explored to potentiate the effectiveness against MDR bacteria have also been summarized. PMID:24757944

  18. Enhancement of neutrophil autophagy by an IVIG preparation against multidrug-resistant bacteria as well as drug-sensitive strains

    PubMed Central

    Itoh, Hiroshi; Matsuo, Hidemasa; Kitamura, Naoko; Yamamoto, Sho; Higuchi, Takeshi; Takematsu, Hiromu; Kamikubo, Yasuhiko; Kondo, Tadakazu; Yamashita, Kouhei; Sasada, Masataka; Takaori-Kondo, Akifumi; Adachi, Souichi

    2015-01-01

    Autophagy occurs in human neutrophils after the phagocytosis of multidrug-resistant bacteria and drug-sensitive strains, including Escherichia coli and Pseudomonas aeruginosa. The present study detected autophagy by immunoblot analysis of LC3B conversion, by confocal scanning microscopic examination of LC3B aggregate formation and by transmission electron microscopic examination of bacteria-containing autophagosomes. Patients with severe bacterial infections are often treated with IVIG alongside antimicrobial agents. Here, we showed that IVIG induced neutrophil-mediated phagocytosis of multidrug-resistant strains. Compared with untreated neutrophils, neutrophils exposed to IVIG showed increased levels of bacterial cell killing, phagocytosis, O2− release, MPO release, and NET formation. IVIG also increased autophagy in these cells. Inhibiting the late phase of autophagy (fusion of lysosomes with autophagosomes) with bafilomycin A1-reduced, neutrophil-mediated bactericidal activity. These findings indicate that autophagy plays a critical role in the bactericidal activity mediated by human neutrophils. Furthermore, the autophagosomes within the neutrophils contained bacteria only and their organelles only, or both bacteria and their organelles, a previously undocumented observation. Taken together, these results suggest that the contents of neutrophil autophagosomes may be derived from specific autophagic systems, which provide the neutrophil with an advantage. Thus, IVIG promotes the neutrophil-mediated killing of multidrug-resistant bacteria as well as drug-sensitive strains. PMID:25908735

  19. Isolation and molecular characterization of multidrug-resistant halophilic bacteria from shrimp farm effluents of Parangipettai coastal waters.

    PubMed

    Sundaramanickam, Arumugam; Kumar, Poominathan Suresh; Kumaresan, Saravanan; Balasubramanian, Thangavel

    2015-08-01

    Multidrug resistance of heterotrophic bacteria isolated from an aquaculture farm effluent in Parangipettai, at the southeastern coast of India, was investigated. In the initial screening, 27 antibiotic-resistant strains were isolated. All the strains were tested for antibiotic susceptibility against chloramphenicol with varying concentrations. From these, two highly resistant strains, i.e. S1 and S5, were isolated. The selected strains were identified by 16S ribosomal RNA (rRNA) sequencing techniques and confirmed as Bacillus pumilus and Bacillus flexus. Both the antibiotic-resistant strains were further utilized for multidrug susceptibility test by using various antibiotics. These two strains showed antibiotic resistance to 14 of 17 antibiotics tested. Both microdilution assay and well assay methods were used to determine the minimal inhibitory concentration (MIC) for the sensitive strains. Both the tests were shown to be almost similar. Our study highlights the occurrence of multidrug-resistant bacteria in the shrimp farm effluents. PMID:25850744

  20. Eradication of Multi-drug Resistant Bacteria by Ni Doped ZnO Nanorods: Structural, Raman and optical characteristics

    NASA Astrophysics Data System (ADS)

    Jan, Tariq; Iqbal, Javed; Ismail, Muhammad; Mansoor, Qaisar; Mahmood, Arshad; Ahmad, Amaar

    2014-07-01

    In this paper, ZnO nanorods doped with varying amounts of Ni have been prepared by chemical co-precipitation technique. Structural investigations provide the evidence that Ni is successfully doped into ZnO host matrix without having any secondary phases. Scanning electron microscopy (SEM) images reveal the formation of rodlike structure of undoped ZnO with average length and diameter of 1 μm and 80 nm, respectively. Raman spectroscopy results show that the E1LO phonons mode band shifts to the higher values with Ni doping, which is attributed to large amount of crystal defects. Ni doping is also found to greatly influence the optical properties of ZnO nanorods. The influence of Ni doping on antibacterial characteristics of ZnO nanorods have been studied by measuring the growth curves of Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) bacteria in the presence of prepared nanorods. ZnO nanorods antibacterial potency is found to increase remarkably with Ni doping against S. aureus and P. aeruginosa microbials, which might possibly be due to the increase in reactive oxygen species (ROS) generation. Interestingly, it is observed that Ni doped ZnO nanorods completely eradicates these multi-drug resistant bacteria.

  1. Targeted nanoparticles for enhanced X-ray radiation killing of multidrug-resistant bacteria

    NASA Astrophysics Data System (ADS)

    Luo, Yang; Hossain, Mainul; Wang, Chaoming; Qiao, Yong; An, Jincui; Ma, Liyuan; Su, Ming

    2012-12-01

    This paper describes a nanoparticle enhanced X-ray irradiation based strategy that can be used to kill multidrug resistant (MDR) bacteria. In the proof-of-concept experiment using MDR Pseudomonas aeruginosa (P. aeruginosa) as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of MDR P. aeruginosa are killed in the presence of 200 μg ml-1 bismuth nanoparticles, whereas only ~6% are killed in the absence of bismuth nanoparticles when exposed to 40 kVp X-rays for 10 min. The 200 μg ml-1 bismuth nanoparticles enhance localized X-ray dose by 35 times higher than the control with no nanoparticles. In addition, no significant harmful effects on human cells (HeLa and MG-63 cells) have been observed with 200 μg ml-1 bismuth nanoparticles and 10 min 40 kVp X-ray irradiation exposures, rendering the potential for future clinical use. Since X-rays can easily penetrate human tissues, this bactericidal strategy has the potential to be used in effectively killing deeply buried MDR bacteria in vivo.This paper describes a nanoparticle enhanced X-ray irradiation based strategy that can be used to kill multidrug resistant (MDR) bacteria. In the proof-of-concept experiment using MDR Pseudomonas aeruginosa (P. aeruginosa) as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of MDR P. aeruginosa are killed in the presence of 200 μg ml-1 bismuth nanoparticles, whereas only ~6% are killed in the absence of bismuth nanoparticles when exposed to 40 kVp X

  2. Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.

    PubMed

    Yap, Polly Soo Xi; Lim, Swee Hua Erin; Hu, Cai Ping; Yiap, Beow Chin

    2013-06-15

    In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC≤0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance. PMID:23537749

  3. In vitro antibacterial activity of Quercus infectoria gall extracts against multidrug resistant bacteria.

    PubMed

    Wan Nor Amilah, W A W; Masrah, M; Hasmah, A; Noor Izani, N J

    2014-12-01

    Antimicrobial activities of plants have long been evaluated for their promising use as antimicrobial agent and in minimizing the unwanted resistance effects of microorganisms. The study was conducted to evaluate the antibacterial activity of Quercus infectoria gall crude extracts against multidrug resistant (MDR) bacteria in vitro. The screening test was determined by disc diffusion technique using sterile filter paper discs impregnated with 1 mg/ disc (50 mg/ml) aqueous and ethanol extracts of Q. infectoria galls tested on five selected MDR bacterial strains. The minimum inhibitory concentration (MIC) was determined using the twofold serial micro dilution technique at concentration ranging from 5.00 mg/ml to 0.01 mg/ml. The minimum bactericidal concentration (MBC) was determined by sub culturing the microtitre wells showing no turbidity on the agar plate to obtain the MBC value. Both extracts showed substantial inhibitory effects against methicillin resistant coagulase negative Staphylococcus (MRCoNS) and methicillin resistant Staphylococcus aureus (MRSA). A slightly reduced inhibitory zone diameter was observed with MDR Acinetobacter sp. while no inhibitory effect was displayed among the extended spectrum beta lactamases (ESBL) K. pneumoniae and ESBL E. coli isolates. A significant difference in the zone sizes between both extracts was only observed in MRSA (p < 0.05). The MIC values ranged from 0.08 mg/ml to 0.63 mg/ml for aqueous and ethanol extracts against MRSA, MRCoNS and MDR Acinetobacter sp. while their MBC to MIC ratio values were 2 and less. The Q. infectoria gall extracts have shown very promising in vitro antibacterial activities and may be considered as a potentially good source of antimicrobial agent especially against MDR Gram positive bacteria. PMID:25776593

  4. Effective Targeted Photothermal Ablation of Multidrug Resistant Bacteria and Their Biofilms with NIR-Absorbing Gold Nanocrosses.

    PubMed

    Teng, Choon Peng; Zhou, Tielin; Ye, Enyi; Liu, Shuhua; Koh, Leng Duei; Low, Michelle; Loh, Xian Jun; Win, Khin Yin; Zhang, Lianhui; Han, Ming-Yong

    2016-08-01

    With the rapid evolution of antibiotic resistance in bacteria, antibiotic-resistant bacteria (in particular, multidrug-resistant bacteria) and their biofilms have been becoming more and more difficult to be effectively treated with conventional antibiotics. As such, there is a great demand to develop a nonantibiotic approach in efficiently eliminating such bacteria. Here, multibranched gold nanocrosses with strong near-infrared absorption falling in the biological window, which heat up quickly under near-infrared-light irradiation are presented. The gold nanocrosses are conjugated to secondary and primary antibodies for targeting PcrV, a type III secretion protein, which is uniquely expressed on the bacteria superbug, Pseudomonas aeruginosa. The conjugated gold nanocrosses are capable of completely destroying P. aeruginosa and its biofilms upon near-infrared-light irradiation for 5 min with an 800 nm laser at a low power density of ≈3.0 W cm(-2) . No bacterial activity is detected after 48 h postirradiation, which indicates that the heat generated from the irradiated plasmonic gold nanocrosses attached to bacteria is effective in eliminating and preventing the re-growth of the bacteria. Overall, the conjugated gold nanocrosses allow targeted and effective photothermal ablation of multidrug-resistant bacteria and their biofilms in the localized region with reduced nonspecific damage to normal tissue. PMID:27336752

  5. Prevalence of Multidrug-Resistant Bacteria on Fresh Vegetables Collected from Farmers' Markets in Connecticut.

    PubMed

    Karumathil, Deepti Prasad; Yin, Hsin-Bai; Kollanoor-Johny, Anup; Venkitanarayanan, Kumar

    2016-08-01

    This study determined the prevalence of multidrug-resistant (MDR) Acinetobacter baumannii on fresh vegetables collected from farmers' markets in Connecticut. One hundred samples each of fresh carrots, potatoes, and lettuce were sampled and streaked on selective media, namely Leeds Acinetobacter and MDR Acinetobacter agars. All morphologically different colonies from MDR Acinetobacter agar were identified by using Gram staining, biochemical tests, and PCR. In addition, susceptibility of the isolates to 10 antibiotics commonly used in humans, namely imipenem, ceftriaxone, cefepime, minocycline, erythromycin, colistin-sulfate, streptomycin, neomycin, doxycycline, and rifampin was determined by using an antibiotic disk diffusion assay. The results revealed that only two samples of potato and one sample of lettuce yielded A. baumannii. In addition, all carrot samples were found to be negative for the organism. However, several other opportunistic, MDR human pathogens, such as Burkholderia cepacia (1% potatoes, 5% carrots, and none in lettuce), Stenotrophomonas maltophilia (6% potatoes, 2% lettuce, and none in carrots), and Pseudomonas luteola (9% potatoes, 3% carrots, and none in lettuce) were recovered from the vegetables. Antibiotic susceptibility screening of the isolates revealed high resistance rates for the following: ceftriaxone (6 of 6), colistin-sulfate (5 of 6), erythromycin (5 of 6), and streptomycin (4 of 6) in B. cepacia; colistin-sulfate (11 of 11) and imipenem (10 of 11) in P. luteola; colistin-sulfate (8 of 8), ceftriaxone (8 of 8), cefepime (7 of 8), erythromycin (5 of 8), and imipenem (4 of 8) in S. maltophilia; and imipenem (3 of 3), ceftriaxone (3 of 3), erythromycin (3 of 3), and streptomycin (3 of 3) in A. baumannii. The results revealed the presence of MDR bacteria, including human pathogens on fresh produce, thereby highlighting the potential health risk in consumers, especially those with a compromised immune system. PMID:27497135

  6. Isolation and Genetic Analysis of Multidrug Resistant Bacteria from Diabetic Foot Ulcers

    PubMed Central

    Shahi, Shailesh K.; Kumar, Ashok

    2016-01-01

    Severe diabetic foot ulcers (DFUs) patients visiting Sir Sunderlal Hospital, Banaras Hindu University, Varanasi, were selected for this study. Bacteria were isolated from swab and deep tissue of 42 patients, for examining their prevalence and antibiotic sensitivity. DFUs of majority of the patients were found infected with Enterococcus spp. (47.61%), Escherichia coli (35.71%), Staphylococcus spp. (33.33%), Alcaligenes spp. (30.95%), Pseudomonas spp. (30.95%), and Stenotrophomonas spp. (30.95%). Antibiotic susceptibility assay of 142 bacteria with 16 antibiotics belonging to eight classes showed the presence of 38 (26.76%) isolates with multidrug resistance (MDR) phenotypes. MDR character appeared to be governed by integrons as class 1 integrons were detected in 26 (68.42%) isolates. Altogether six different arrays of genes (aadA1, aadB, aadAV, dhfrV, dhfrXII, and dhfrXVII) were found within class 1 integron. Gene cassette dhfrAXVII-aadAV (1.6 kb) was present in 12 (3 Gram positive and 9 Gram negative) isolates and was conserved across all the isolates as evident from RFLP analysis. In addition to the presence of class 1 integron, six β-lactamase resistance encoding genes namely blaTEM, blaSHV, blaOXA, blaCTX−M−gp1, blaCTX−M−gp2, and blaCTX−M−gp9 and two methicillin resistance genes namely mecA and femA and vancomycin resistance encoding genes (vanA and vanB) were identified in different isolates. Majority of the MDR isolates were positive for blaTEM (89.47%), blaOXA (52.63%), and blaCTX−M−gp1 (34.21%). To our knowledge, this is the first report of molecular characterization of antibiotic resistance in bacteria isolated from DFUs from North India. In conclusion, findings of this study suggest that class-1 integrons and β-lactamase genes contributed to the MDR in above bacteria. PMID:26779134

  7. Isolation and Genetic Analysis of Multidrug Resistant Bacteria from Diabetic Foot Ulcers.

    PubMed

    Shahi, Shailesh K; Kumar, Ashok

    2015-01-01

    Severe diabetic foot ulcers (DFUs) patients visiting Sir Sunderlal Hospital, Banaras Hindu University, Varanasi, were selected for this study. Bacteria were isolated from swab and deep tissue of 42 patients, for examining their prevalence and antibiotic sensitivity. DFUs of majority of the patients were found infected with Enterococcus spp. (47.61%), Escherichia coli (35.71%), Staphylococcus spp. (33.33%), Alcaligenes spp. (30.95%), Pseudomonas spp. (30.95%), and Stenotrophomonas spp. (30.95%). Antibiotic susceptibility assay of 142 bacteria with 16 antibiotics belonging to eight classes showed the presence of 38 (26.76%) isolates with multidrug resistance (MDR) phenotypes. MDR character appeared to be governed by integrons as class 1 integrons were detected in 26 (68.42%) isolates. Altogether six different arrays of genes (aadA1, aadB, aadAV, dhfrV, dhfrXII, and dhfrXVII) were found within class 1 integron. Gene cassette dhfrAXVII-aadAV (1.6 kb) was present in 12 (3 Gram positive and 9 Gram negative) isolates and was conserved across all the isolates as evident from RFLP analysis. In addition to the presence of class 1 integron, six β-lactamase resistance encoding genes namely bla TEM, bla SHV, bla OXA, bla CTX-M-gp1, bla CTX-M-gp2, and bla CTX-M-gp9 and two methicillin resistance genes namely mecA and femA and vancomycin resistance encoding genes (vanA and vanB) were identified in different isolates. Majority of the MDR isolates were positive for bla TEM (89.47%), bla OXA (52.63%), and bla CTX-M-gp1 (34.21%). To our knowledge, this is the first report of molecular characterization of antibiotic resistance in bacteria isolated from DFUs from North India. In conclusion, findings of this study suggest that class-1 integrons and β-lactamase genes contributed to the MDR in above bacteria. PMID:26779134

  8. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria

    PubMed Central

    2014-01-01

    Introduction The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses. Methods We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated. Results Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure. Conclusions TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria. PMID:24887101

  9. Phytochemical Screening and Antimicrobial Activity of Some Medicinal Plants Against Multi-drug Resistant Bacteria from Clinical Isolates

    PubMed Central

    Dahiya, Praveen; Purkayastha, Sharmishtha

    2012-01-01

    The in vitro antibacterial activity of various solvents and water extracts of aloe vera, neem, bryophyllum, lemongrass, tulsi, oregano, rosemary and thyme was assessed on 10 multi-drug resistant clinical isolates from both Gram-positive and Gram-negative bacteria and two standard strains including Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. The zone of inhibition as determined by agar well diffusion method varied with the plant extract, the solvent used for extraction, and the organism tested. Klebsiella pneumoniae 2, Escherichia coli 3 and Staphylococcus aureus 3 were resistant to the plant extracts tested. Moreover, water extracts did not restrain the growth of any tested bacteria. Ethanol and methanol extracts were found to be more potent being capable of exerting significant inhibitory activities against majority of the bacteria investigated. Staphylococcus aureus 1 was the most inhibited bacterial isolate with 24 extracts (60%) inhibiting its growth whereas Escherichia coli 2 exhibited strong resistance being inhibited by only 11 extracts (28%). The results obtained in the agar diffusion plates were in fair correlation with that obtained in the minimum inhibitory concentration tests. The minimum inhibitory concentration of tulsi, oregano, rosemary and aloe vera extracts was found in the range of 1.56-6.25 mg/ml for the multi-drug resistant Staphylococcus aureus isolates tested whereas higher values (6.25-25 mg/ml) were obtained against the multi-drug resistant isolates Klebsiella pneumoniae 1 and Escherichia coli 1 and 2. Qualitative phytochemical analysis demonstrated the presence of tannins and saponins in all plants tested. Thin layer chromatography and bioautography agar overlay assay of ethanol extracts of neem, tulsi and aloe vera indicated flavonoids and tannins as major active compounds against methicillin-resistant Staphylococcus aureus. PMID:23716873

  10. Phytochemical Screening and Antimicrobial Activity of Some Medicinal Plants Against Multi-drug Resistant Bacteria from Clinical Isolates.

    PubMed

    Dahiya, Praveen; Dahiya, P; Purkayastha, Sharmishtha

    2012-09-01

    The in vitro antibacterial activity of various solvents and water extracts of aloe vera, neem, bryophyllum, lemongrass, tulsi, oregano, rosemary and thyme was assessed on 10 multi-drug resistant clinical isolates from both Gram-positive and Gram-negative bacteria and two standard strains including Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. The zone of inhibition as determined by agar well diffusion method varied with the plant extract, the solvent used for extraction, and the organism tested. Klebsiella pneumoniae 2, Escherichia coli 3 and Staphylococcus aureus 3 were resistant to the plant extracts tested. Moreover, water extracts did not restrain the growth of any tested bacteria. Ethanol and methanol extracts were found to be more potent being capable of exerting significant inhibitory activities against majority of the bacteria investigated. Staphylococcus aureus 1 was the most inhibited bacterial isolate with 24 extracts (60%) inhibiting its growth whereas Escherichia coli 2 exhibited strong resistance being inhibited by only 11 extracts (28%). The results obtained in the agar diffusion plates were in fair correlation with that obtained in the minimum inhibitory concentration tests. The minimum inhibitory concentration of tulsi, oregano, rosemary and aloe vera extracts was found in the range of 1.56-6.25 mg/ml for the multi-drug resistant Staphylococcus aureus isolates tested whereas higher values (6.25-25 mg/ml) were obtained against the multi-drug resistant isolates Klebsiella pneumoniae 1 and Escherichia coli 1 and 2. Qualitative phytochemical analysis demonstrated the presence of tannins and saponins in all plants tested. Thin layer chromatography and bioautography agar overlay assay of ethanol extracts of neem, tulsi and aloe vera indicated flavonoids and tannins as major active compounds against methicillin-resistant Staphylococcus aureus. PMID:23716873

  11. A comparative study for the inactivation of multidrug resistance bacteria using dielectric barrier discharge and nano-second pulsed plasma

    PubMed Central

    Hoon Park, Ji; Kumar, Naresh; Hoon Park, Dae; Yusupov, Maksudbek; Neyts, Erik C.; Verlackt, Christof C. W.; Bogaerts, Annemie; Ho Kang, Min; Sup Uhm, Han; Ha Choi, Eun; Attri, Pankaj

    2015-01-01

    Bacteria can be inactivated through various physical and chemical means, and these have always been the focus of extensive research. To further improve the methodology for these ends, two types of plasma systems were investigated: nano-second pulsed plasma (NPP) as liquid discharge plasma and an Argon gas-feeding dielectric barrier discharge (Ar-DBD) as a form of surface plasma. To understand the sterilizing action of these two different plasma sources, we performed experiments with Staphylococcus aureus (S. aureus) bacteria (wild type) and multidrug resistant bacteria (Penicillum-resistant, Methicillin-resistant and Gentamicin-resistant). We observed that both plasma sources can inactivate both the wild type and multidrug-resistant bacteria to a good extent. Moreover, we observed a change in the surface morphology, gene expression and β-lactamase activity. Furthermore, we used X-ray photoelectron spectroscopy to investigate the variation in functional groups (C-H/C-C, C-OH and C=O) of the peptidoglycan (PG) resulting from exposure to plasma species. To obtain atomic scale insight in the plasma-cell interactions and support our experimental observations, we have performed molecular dynamics simulations to study the effects of plasma species, such as OH, H2O2, O, O3, as well as O2 and H2O, on the dissociation/formation of above mentioned functional groups in PG. PMID:26351132

  12. In Vitro Antibacterial Activity of Curcumin-Polymyxin B Combinations against Multidrug-Resistant Bacteria Associated with Traumatic Wound Infections.

    PubMed

    Betts, Jonathan W; Sharili, Amir S; La Ragione, Roberto M; Wareham, David W

    2016-06-24

    Bacterial infections resulting from nonsurgical traumatic wounds can be life threatening, especially those caused by multidrug-resistant (MDR) bacteria with limited therapeutic options. The antimicrobial activity of polymyxin B (1) and curcumin (2) alone and in combination was determined versus MDR bacterial isolates associated with traumatic wound infections. Cytotoxicity assays for 1 and 2 were undertaken in keratinocyte cell lines. Minimum inhibitory concentrations of 1 were significantly reduced in the presence of 2 (3- to 10-fold reduction), with synergy observed. Time-kill assays showed the combinations produced bactericidal activity. Cytotoxicity assays indicate the toxicity of 2 was reduced in the presence of 1. PMID:27295561

  13. Inactivation and regrowth of multidrug resistant bacteria in urban wastewater after disinfection by solar-driven and chlorination processes.

    PubMed

    Fiorentino, Antonino; Ferro, Giovanna; Alferez, María Castro; Polo-López, Maria Inmaculada; Fernández-Ibañez, Pilar; Rizzo, Luigi

    2015-07-01

    Solar disinfection and solar-driven advanced oxidation processes (AOPs) (namely H2O2/sunlight, TiO2/sunlight, H2O2/TiO2/sunlight, solar photo-Fenton) were evaluated in the inactivation of indigenous antibiotic-resistant bacteria (ARB) in real urban wastewater. A multidrug resistant (MDR) Escherichia coli strain isolated from the effluent of the biological process of an urban wastewater treatment plant was the target ARB. The higher inactivation rates (residual density under detection limit, 2 CFUm L(-1)) were achieved with H2O2/TiO2/sunlight (cumulative energy per unit of volume (QUV) in the range 3-5 kJ L(-1), depending on H2O2/TiO2 ratio) and H2O2/sunlight (QUV of 8 kJ L(-1)) processes. All investigated processes did not affect antibiotic resistance of survived colonies. Moreover, H2O2/sunlight was compared with conventional chlorination process to evaluate bacterial regrowth potential and particularly the proportion of indigenous MDR E. coli with respect to total indigenous E. coli population. Chlorination (1.0 mg Cl2 L(-1)) was more effective than H2O2/sunlight (50 mg H2O2 L(-1)) to achieve total inactivation of MDR E. coli (15 min Vs 90 min) but less effective in controlling their regrowth (24 h Vs 48 h). Interestingly, the percentage of MDR E. coli in H2O2/sunlight treated samples decreased as incubation time increased; the opposite was observed for chlorinated samples. PMID:25874661

  14. Liposomal nanoformulations of rhodamine for targeted photodynamic inactivation of multidrug resistant gram negative bacteria in sewage treatment plant.

    PubMed

    Vimaladevi, Mohan; Divya, Kurunchi Chellapathi; Girigoswami, Agnishwar

    2016-09-01

    The antimicrobial photodynamic therapy is an alternative method for killing bacterial cells in view of the rising problem of antibiotic resistance microorganisms. The present study examined the effect of a water soluble photosensitizer, Rhodamine 6G (R6G) in stealth liposomes on multidrug resistant Pseudomonas aeruginosa in the presence of visible light. Liposomes were prepared with cholesterol and phospholipids that extracted from hen eggs in a cost effective way and characterized by light microscopy, particle size analyzer, electron microscopy, steady state spectrophotometry and spectrofluorometry. The photoefficacies of R6G in polymer encapsulated liposomes and positively charged liposomes are much higher compared to the free R6G (R6G in water) in terms of singlet oxygen quantum yield. This high potential of producing more reactive oxygen species (ROS) by liposomal nanoformulated R6G leads to efficient photodynamic inactivation of multidrug resistant gram negative bacteria in waste water. Though the singlet oxygen quantum yield of polymer coated liposomal R6G was higher than the cationic liposomal formulation, a faster decrease in bacterial survival was observed for positively charged liposomal R6G treated bacteria due to electrostatic charge interactions. Therefore, it can be concluded that the positively charged liposomal nanoformulations of laser dyes are efficient for photodynamic inactivation of multiple drug resistant gram negative microorganisms. PMID:27371913

  15. Economic burden of multidrug-resistant bacteria in nursing homes in Germany: a cost analysis based on empirical data

    PubMed Central

    Huebner, Claudia; Roggelin, Marcus; Flessa, Steffen

    2016-01-01

    Objectives Infections and colonisations with multidrug-resistant organisms (MDROs) increasingly affect different types of healthcare facilities worldwide. So far, little is known about additional costs attributable to MDROs outside hospitals. The aim of this study was to analysis the economic burden of multidrug-resistant bacteria in nursing homes in Germany. Setting The cost analysis is performed from a microeconomic perspective of the healthcare facilities. Study took place in six long-term care facilities in north-eastern Germany. Participants Data of 71 residents with a positive MDRO status were included. Primary and secondary outcome measures The study analysed MDRO surveillance data from 2011 to 2013. It was supplemented by an empirical analysis to determine the burden on staff capacity and materials consumption. Results 11 793 days with a positive multidrug-resistant pathogen diagnosis could be included in the analysis. On average, 11.8 (SD±6.3) MDRO cases occurred per nursing home. Mean duration per case was 163.3 days (SD±97.1). The annual MDRO-related costs varied in nursing homes between €2449.72 and €153 263.74 on an average €12 682.23 per case. Main cost drivers were staff capacity (€43.95 per day and €7177.04 per case) and isolation materials (€24.70 per day and €4033.51 per case). Conclusions The importance of MDROs in nursing homes could be confirmed. MDRO-related cost data in this specific healthcare sector were collected for the first time. Knowledge about the burden of MDROs will enable to assess the efficiency of hygiene intervention measures in nursing homes in the future. PMID:26908511

  16. Hierarchal clustering yields insight into multidrug-resistant bacteria isolated from a cattle feedlot wastewater treatment system.

    PubMed

    Jahne, Michael A; Rogers, Shane W; Ramler, Ivan P; Holder, Edith; Hayes, Gina

    2015-01-01

    Forty-two percent of Escherichia coli and 58% of Enterococcus spp. isolated from cattle feedlot runoff and associated infiltration basin and constructed wetland treatment system were resistant to at least one antibiotic of clinical importance; a high level of multidrug resistance (22% of E. coli and 37% of Enterococcus spp.) was observed. Hierarchical clustering revealed a closely associated resistance cluster among drug-resistant E. coli isolates that included cephalosporins (ceftiofur, cefoxitin, and ceftriaxone), aminoglycosides (gentamycin, kanamycin, and amikacin), and quinolone nalidixic acid; antibiotics from these classes were used at the study site, and cross-resistance may be associated with transferrable multiple-resistance elements. For Enterococcus spp., co-resistance among vancomycin, linezolid, and daptomycin was common; these antibiotics are reserved for complicated clinical infections and have not been approved for animal use. Vancomycin resistance (n = 49) only occurred when isolates were resistant to linezolid, daptomycin, and all four of the MLSB (macrolide-lincosamide-streptogramin B) antibiotics tested (tylosin, erythromycin, lincomycin, and quinipristin/dalfopristin). This suggests that developing co-resistance to MLSB antibiotics along with cyclic lipopeptides and oxazolidinones may result in resistance to vancomycin as well. Effects of the treatment system on antibiotic resistance were pronounced during periods of no rainfall and low flow (long residence time). Increased hydraulic loading (short residence time) under the influence of rain caused antibiotic-resistant bacteria to be flushed through the treatment system. This presents concern for environmental discharge of multidrug-resistant organisms relevant to public health. PMID:25504186

  17. Transfer of Multidrug-Resistant Bacteria between Intermingled Ecological Niches: The Interface between Humans, Animals and the Environment

    PubMed Central

    da Costa, Paulo Martins; Loureiro, Luís; Matos, Augusto J. F.

    2013-01-01

    The use of antimicrobial agents has been claimed to be the driving force for the emergence and spread of microbial resistance. However, several studies have reported the presence of multidrug-resistant bacteria in populations exposed to low levels of antimicrobial drugs or even never exposed. For many pathogens, especially those organisms for which asymptomatic colonization typically precedes infection (e.g., Enterococcus spp. and Escherichia coli), the selective effects of antimicrobial use can only be understood if we considerer all biological and environmental pathways which enable these bacteria, and the genes they carry, to spread between different biomes. This ecological framework provides an essential perspective for formulating antimicrobial use policies, precisely because it encompasses the root causes of these problems rather than merely their consequences. PMID:23343983

  18. Control of multidrug resistant bacteria in a tertiary care hospital in India

    PubMed Central

    2012-01-01

    Background The objective of this study was to assess the impact of antimicrobial stewardship programs on the multidrug resistance patterns of bacterial isolates. The study comprised an initial retrospective analysis of multidrug resistance in bacterial isolates for one year (July 2007-June 2008) followed by prospective evaluation of the impact of Antimicrobial Stewardship programs on resistance for two years and nine months (July 2008-March 2011). Setting A 300-bed tertiary care private hospital in Gurgaon, Haryana (India) Findings Methods Study Design • July 2007 to June 2008: Resistance patterns of bacterial isolates were studied. • July 2008: Phase I intervention programme Implementation of an antibiotic policy in the hospital. • July 2008 to June 2010: Assessment of the impact of the Phase I intervention programme. • July 2010 to March 2011: Phase II intervention programme: Formation and effective functioning of the antimicrobial stewardship committee. Statistical correlation of the Defined daily dose (DDD) for prescribed drugs with the antimicrobial resistance of Gram negatives. Results Phase I intervention programme (July 2008) resulted in a decrease of 4.47% in ESBLs (E.coli and Klebsiella) and a significant decrease of 40.8% in carbapenem-resistant Pseudomonas. Phase II intervention (July 2010) brought a significant reduction (24.7%) in carbapenem-resistant Pseudomonas. However, the resistance in the other Gram negatives (E.coli, Klebsiella, and Acinetobacter) rose and then stabilized. A positive correlation was observed in Pseudomonas and Acinetobacter with carbapenems and cefoperazone-sulbactam. Piperacillin-tazobactam showed a positive correlation with Acinetobacter only. E.coli and Klebsiella showed positive correlation with cefoparazone-sulbactam and piperacillin-tazobactam. Conclusion An antimicrobial stewardship programme with sustained and multifaceted efforts is essential to promote the judicious use of antibiotics. PMID:22958481

  19. Which strategies follow from the surveillance of multidrug-resistant bacteria to strengthen the control of their spread? A French experience.

    PubMed

    Lepelletier, Didier; Perron, Stéphanie; Huguenin, Hélène; Picard, Monique; Bemer, Pascale; Caillon, Jocelyne; Juvin, Marie-Emmanuelle; Drugeon, Henri Bernard

    2004-02-01

    Efforts to enhance standard precautions and to isolate patients with positive routine clinical cultures during 3 years were insufficient to decrease multidrug-resistant bacteria infection rates. Routine screening for carriage in high-risk patients may be necessary to halt transmission and control the hospital reservoir. PMID:14994943

  20. Insertion Sequence IS26 Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition

    PubMed Central

    He, Susu; Hickman, Alison Burgess; Varani, Alessandro M.; Siguier, Patricia; Chandler, Michael; Dekker, John P.

    2015-01-01

    ABSTRACT Carbapenemase-producing Enterobacteriaceae (CPE), which are resistant to most or all known antibiotics, constitute a global threat to public health. Transposable elements are often associated with antibiotic resistance determinants, suggesting a role in the emergence of resistance. One insertion sequence, IS26, is frequently associated with resistance determinants, but its role remains unclear. We have analyzed the genomic contexts of 70 IS26 copies in several clinical and surveillance CPE isolates from the National Institutes of Health Clinical Center. We used target site duplications and their patterns as guides and found that a large fraction of plasmid reorganizations result from IS26 replicative transpositions, including replicon fusions, DNA inversions, and deletions. Replicative transposition could also be inferred for transposon Tn4401, which harbors the carbapenemase blaKPC gene. Thus, replicative transposition is important in the ongoing reorganization of plasmids carrying multidrug-resistant determinants, an observation that carries substantial clinical and epidemiological implications for understanding how such extreme drug resistance phenotypes evolve. PMID:26060276

  1. Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria

    PubMed Central

    Naqvi, Syed Zeeshan Haider; Kiran, Urooj; Ali, Muhammad Ishtiaq; Jamal, Asif; Hameed, Abdul; Ahmed, Safia; Ali, Naeem

    2013-01-01

    Biological synthesis of nanoparticles is a growing innovative approach that is relatively cheaper and more environmentally friendly than current physicochemical processes. Among various microorganisms, fungi have been found to be comparatively more efficient in the synthesis of nanomaterials. In this research work, extracellular mycosynthesis of silver nanoparticles (AgNPs) was probed by reacting the precursor salt of silver nitrate (AgNO3) with culture filtrate of Aspergillus flavus. Initially, the mycosynthesis was regularly monitored by ultraviolet-visible spectroscopy, which showed AgNP peaks of around 400–470 nm. X-ray diffraction spectra revealed peaks of different intensities with respect to angle of diffractions (2θ) corresponding to varying configurations of AgNPs. Transmission electron micrographs further confirmed the formation of AgNPs in size ranging from 5–30 nm. Combined and individual antibacterial activities of the five conventional antibiotics and AgNPs were investigated against eight different multidrug-resistant bacterial species using the Kirby–Bauer disk-diffusion method. The decreasing order of antibacterial activity (zone of inhibition in mm) of antibiotics, AgNPs, and their conjugates against bacterial group (average) was; ciprofloxacin + AgNPs (23) . imipenem + AgNPs (21) > gentamycin + AgNPs (19) > vancomycin + AgNPs (16) > AgNPs (15) . imipenem (14) > trimethoprim + AgNPs (14) > ciprofloxacin (13) > gentamycin (11) > vancomycin (4) > trimethoprim (0). Overall, the synergistic effect of antibiotics and nanoparticles resulted in a 0.2–7.0 (average, 2.8) fold-area increase in antibacterial activity, which clearly revealed that nanoparticles can be effectively used in combination with antibiotics in order to improve their efficacy against various pathogenic microbes. PMID:23986635

  2. Multidrug-Resistant Bacteria Isolated from Surface Water in Bassaseachic Falls National Park, Mexico

    PubMed Central

    Delgado-Gardea, Ma. Carmen E.; Tamez-Guerra, Patricia; Gomez-Flores, Ricardo; Zavala-Díaz de la Serna, Francisco Javier; Eroza-de la Vega, Gilberto; Nevárez-Moorillón, Guadalupe Virginia; Pérez-Recoder, María Concepción; Sánchez-Ramírez, Blanca; González-Horta, María del Carmen; Infante-Ramírez, Rocío

    2016-01-01

    Bacterial pathogens are a leading cause of waterborne disease, and may result in gastrointestinal outbreaks worldwide. Inhabitants of the Bassaseachic Falls National Park in Chihuahua, Mexico show seasonal gastroenteritis problems. This aim of this study was to detect enteropathogenic microorganisms responsible for diarrheal outbreaks in this area. In 2013, 49 surface water samples from 13 selected sampling sites along the Basaseachi waterfall and its main rivers, were collected during the spring, summer, autumn, and winter seasons. Fecal and total coliform counts were determined using standard methods; the AutoScan-4 system was used for identification of isolates and the antibiotic resistance profile by challenging each organism using 21 antibiotics. Significant differences among seasons were detected, where autumn samples resulted in the highest total (p < 0.05) and fecal (p < 0.001) coliform counts, whereas the lowest total coliform counts were recorded in spring. Significant differences between sampling sites were observed, where samples from sites 6, 8, and 11 had the highest total coliform counts (p < 0.009), whereas samples from site 9 exhibited the lowest one. From the microbiological analysis, 33 bacterial isolates from 13 different sites and four sampling seasons were selected; 53% of isolates were resistant to at least one antibiotic, and 15% exhibited a multidrug resistance (MDB) phenotype. MDB were identified as Klebsiella oxytoca (two out of four identified isolates), Escherichia coli (2/7), and Enterobacter cloacae (1/3). In addition, some water-borne microorganisms exhibited resistance to cefazoline, cefuroxime, ampicillin, and ampicillin-sulbactam. The presence of these microorganisms near rural settlements suggests that wastewater is the contamination source, providing one possible transmission mechanism for diarrheal outbreaks. PMID:27322297

  3. Multidrug-Resistant Bacteria Isolated from Surface Water in Bassaseachic Falls National Park, Mexico.

    PubMed

    Delgado-Gardea, Ma Carmen E; Tamez-Guerra, Patricia; Gomez-Flores, Ricardo; Zavala-Díaz de la Serna, Francisco Javier; Eroza-de la Vega, Gilberto; Nevárez-Moorillón, Guadalupe Virginia; Pérez-Recoder, María Concepción; Sánchez-Ramírez, Blanca; González-Horta, María Del Carmen; Infante-Ramírez, Rocío

    2016-01-01

    Bacterial pathogens are a leading cause of waterborne disease, and may result in gastrointestinal outbreaks worldwide. Inhabitants of the Bassaseachic Falls National Park in Chihuahua, Mexico show seasonal gastroenteritis problems. This aim of this study was to detect enteropathogenic microorganisms responsible for diarrheal outbreaks in this area. In 2013, 49 surface water samples from 13 selected sampling sites along the Basaseachi waterfall and its main rivers, were collected during the spring, summer, autumn, and winter seasons. Fecal and total coliform counts were determined using standard methods; the AutoScan-4 system was used for identification of isolates and the antibiotic resistance profile by challenging each organism using 21 antibiotics. Significant differences among seasons were detected, where autumn samples resulted in the highest total (p < 0.05) and fecal (p < 0.001) coliform counts, whereas the lowest total coliform counts were recorded in spring. Significant differences between sampling sites were observed, where samples from sites 6, 8, and 11 had the highest total coliform counts (p < 0.009), whereas samples from site 9 exhibited the lowest one. From the microbiological analysis, 33 bacterial isolates from 13 different sites and four sampling seasons were selected; 53% of isolates were resistant to at least one antibiotic, and 15% exhibited a multidrug resistance (MDB) phenotype. MDB were identified as Klebsiella oxytoca (two out of four identified isolates), Escherichia coli (2/7), and Enterobacter cloacae (1/3). In addition, some water-borne microorganisms exhibited resistance to cefazoline, cefuroxime, ampicillin, and ampicillin-sulbactam. The presence of these microorganisms near rural settlements suggests that wastewater is the contamination source, providing one possible transmission mechanism for diarrheal outbreaks. PMID:27322297

  4. Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

    PubMed Central

    Paramythiotou, Elisabeth; Routsi, Christina

    2016-01-01

    The incidence of gram-negative multidrug-resistant (MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit (ICU) setting. The clinical consequences of infections caused by MDR pathogens remain controversial. The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients. Twenty-four studies, conducted exclusively in ICU patients, were identified through PubMed search over the years 2000-2015. Bloodstream infection was the only infection examined in eight studies, respiratory infections in four and variable infections in others. Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies. In ten studies the presence of antimicrobial resistance was not associated with increased mortality; on the contrary, in other studies a significant impact of antibiotic resistance on mortality was found, though, sometimes, mediated by inappropriate antimicrobial treatment. Therefore, a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed. Sample size, presence of multiple confounders and other methodological issues may influence the results. These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients. PMID:27152254

  5. Recovery of multidrug-resistant bacteria from combat personnel evacuated from Iraq and Afghanistan at a single military treatment facility.

    PubMed

    Murray, Clinton K; Yun, Heather C; Griffith, Matthew E; Thompson, Bernadette; Crouch, Helen K; Monson, Linda S; Aldous, Wade K; Mende, Katrin; Hospenthal, Duane R

    2009-06-01

    U.S. combat casualties from Iraq and Afghanistan continue to develop infections with multidrug-resistant (MDR) bacteria. This study assesses the infection control database and clinical microbiology antibiograms at a single site from 2005 to 2007, a period when all Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) casualties admitted to the facility underwent initial isolation and screening for MDR pathogens. During this 3-year period, there were 2,242 OIF/OEF admissions: 560 in 2005, 724 in 2006, and 958 in 2007. The most commonly recovered pathogens from OIF/OEF admission screening cultures were methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Acinetobacter. The yearly nosocomial infection rate of these three pathogens among OIF/OEF admissions ranged between 2 and 4%. There were remarkable changes in resistance profiles for Acinetobacter, K. pneumoniae, and S. aureus over time. Despite aggressive infection control procedures, there is continued nosocomial transmission within the facility and increasing antimicrobial resistance in some pathogens. Novel techniques are needed to control the impact of MDR bacteria in medical facilities. PMID:19585772

  6. Antibiotic-potentiation activities of four Cameroonian dietary plants against multidrug-resistant Gram-negative bacteria expressing efflux pumps

    PubMed Central

    2014-01-01

    Background The continuous spread of multidrug-resistant (MDR) bacteria, partially due to efflux pumps drastically reduced the efficacy of the antibiotic armory, increasing the frequency of therapeutic failure. The search for new compounds to potentiate the efficacy of commonly used antibiotics is therefore important. The present study was designed to evaluate the ability of the methanol extracts of four Cameroonian dietary plants (Capsicum frutescens L. var. facilulatum, Brassica oleacera L. var. italica, Brassica oleacera L. var. butyris and Basilicum polystachyon (L.) Moench.) to improve the activity of commonly used antibiotics against MDR Gram-negative bacteria expressing active efflux pumps. Methods The qualitative phytochemical screening of the plant extracts was performed using standard methods whilst the antibacterial activity was performed by broth micro-dilution method. Results All the studied plant extracts revealed the presence of alkaloids, phenols, flavonoids, triterpenes and sterols. The minimal inhibitory concentrations (MIC) of the studied extracts ranged from 256-1024 μg/mL. Capsicum frutescens var. facilulatum extract displayed the largest spectrum of activity (73%) against the tested bacterial strains whilst the lower MIC value (256 μg/mL) was recorded with Basilicum polystachyon against E. aerogenes ATCC 13048 and P. stuartii ATCC 29916. In the presence of PAβN, the spectrum of activity of Brassica oleacera var. italica extract against bacteria strains increased (75%). The extracts from Brassica oleacera var. butyris, Brassica oleacera var. italica, Capsicum frutescens var. facilulatum and Basilicum polystachyon showed synergistic effects (FIC ≤ 0.5) against the studied bacteria, with an average of 75.3% of the tested antibiotics. Conclusion These results provide promising information for the potential use of the tested plants alone or in combination with some commonly used antibiotics in the fight against MDR Gram-negative bacteria

  7. Carriage of Multidrug Resistant Bacteria on Frequently Contacted Surfaces and Hands of Health Care Workers

    PubMed Central

    Visalachy, Sowndarya; Kopula, Sridharan Sathyamoorthy; Sekar, Uma

    2016-01-01

    Introduction Maximal contact between the patients and Health Care Workers (HCWs) happens in the Intensive Care Units (ICU). Control of nosocomial infections requires compliance with hand hygiene and contamination free surfaces. Aim To determine the colonization of potential pathogens in the hands of HCWs and frequent contacted environmental surfaces. Materials and Methods A cross sectional study was conducted between September 2012 and May 2013 at Sri Ramachandra Medical College and Hospital. A total of 327 samples were collected using Glove juice technique from hands and swabs from frequently contacted surfaces. A sum of 157 samples were collected by glove juice technique from the hands of HCWs which included Consultants (20), Internees (3), Residents (10), Staff nurse (102) and support staff (22). A total of 170 samples were collected through swabbing which included frequently touched surfaces of apron and dress (140 which included 10 consultants, 3 internees, 9 Residents, 101 Staff nurse and 17 support staff), 9 door handle, 4 key board, 12 tap handles and 5 monitors. The samples were inoculated into Blood agar, Chocolate agar and Mac-Conkey agar plates and incubated at 370C aerobically. The plates showing growth were further processed to identify the organisms by Gram staining and biochemical reactions. Antibiotic susceptibility testing was done for the isolates by Kirby-baur disc diffusion method as per CLSI guidelines. Results Out of the 157 hand sampling done by glove juice method 67(42.7%) of them showed growth and 90(57.3%) showed no growth. The potential pathogens grown were 13 (8.3%), consisting of Methicillin Sensitive Staphylococcus aureus (MSSA) 6(3.8%), Methicillin Resistant Staphylococcus aureus (MRSA) 2(1.3%), Pseudomonas spp 4(2.6%) and Acenitobacter spp 1 (0.6%). The MRSA was seen in Consultant 1(5%; n=20) and Staff nurse 1(0.9%; n= 102). Among the 140 sampling from the dress of HCWs growth was observed in 69(49.3%) and growth was absent in 71(50.7%). The potential pathogens observed were 14(10%) and they are MSSA 5(3.6%), MRSA 1 (0.7%), Pseudomonas spp 2(1.4%), Acenitobacter spp 3(2.1%) Enterobacter spp 1(0.7%), Klebseilla pneumoniae 1(0.7%) and Candida spp 1(0.7%). One MRSA was isolated from staff nurse (0.9%; n=101). Similarly multi-drug resistant Klebsiella pneumoniae 1(0.9%; n=102). Out of the 30 environmental samples 16(53.3%) showed growth and in 14(56.7%) growth was absent. The potential pathogens isolated were 3(10%) which included MSSA 2(6.6%) and MRSA 1(3.4%) and were isolated from the monitor. Conclusion Adherence to infection control practices among all categories of HCWs is must for control of HAI. Glove juice method is a simple, easy and practical technique for determination of colonization of hands of HCWs and can be adapted as a methodology for screening the hands of HCWs. PMID:27437214

  8. Rifaximin combined with polymyxins: A potential regimen for selective decontamination of multidrug-resistant bacteria in the digestive tract?

    PubMed

    Betts, J W; Phee, L M; Wareham, D W

    2016-03-01

    Selective decontamination of the digestive tract (SDD) using combinations of oral non-absorbable antibiotics has been proposed as a means of preventing multidrug-resistant (MDR) infections. The minimum inhibitory concentrations (MICs) of rifaximin (RIFAX) were determined against 262 Gram-negative and Gram-positive bacterial isolates by broth microtitre assay. Rifampicin (RIF) was used as a comparator in the analysis. Synergistic interactions between RIFAX and polymyxin B (PMB) were assessed by using the chequerboard method and calculating the fractional inhibitory concentration index (FICI). The antimicrobial activities of both RIFAX and RIF were similar with little variation in the overall MIC distributions for Gram-negative non-fermenters and Gram-positive bacteria. However, against Enterobacteriaceae higher MICs (>16mg/L) were observed for RIFAX than for RIF (50% vs 27%). Amongst the 262 isolates tested, 100 could be considered resistant to RIFAX. Overall, the combination of RIFAX and PMB was more active against all of the isolates tested compared with either drug alone, with reductions of 2-11 doubling dilutions in individual MICs. Potent synergy was observed with the RIFAX+PMB combination using FICI criteria (FICI range 0.02-0.5). The data presented here suggest that combination therapy may be significantly more effective against isolates with RIFAX and/or PMB resistance and could be considered as part of a SDD regimen aimed at reducing enteric carriage of MDR pathogens in colonised and infected patients. PMID:27436386

  9. Multidrug-resistant gram-negative bacteria colonization of healthy US military personnel in the US and Afghanistan

    PubMed Central

    2013-01-01

    Background The US military has seen steady increases in multidrug-resistant (MDR) gram-negative bacteria (GNB) infections in casualties from Iraq and Afghanistan. This study evaluates the prevalence of MDR GNB colonization in US military personnel. Methods GNB colonization surveillance of healthy, asymptomatic military personnel (101 in the US and 100 in Afghanistan) was performed by swabbing 7 anatomical sites. US-based personnel had received no antibiotics within 30 days of specimen collection, and Afghanistan-based personnel were receiving doxycycline for malaria chemoprophylaxis at time of specimen collection. Isolates underwent genotypic and phenotypic characterization. Results The only colonizing MDR GNB recovered in both populations was Escherichia coli (p=0.01), which was seen in 2% of US-based personnel (all perirectal) and 11% of Afghanistan-based personnel (10 perirectal, 1 foot+groin). Individuals with higher off-base exposures in Afghanistan did not show a difference in overall GNB colonization or MDR E. coli colonization, compared with those with limited off-base exposures. Conclusion Healthy US- and Afghanistan-based military personnel have community onset-MDR E. coli colonization, with Afghanistan-based personnel showing a 5.5-fold higher prevalence. The association of doxycycline prophylaxis or other exposures with antimicrobial resistance and increased rates of MDR E. coli colonization needs further evaluation. PMID:23384348

  10. Construction of Zinc Oxide into Different Morphological Structures to Be Utilized as Antimicrobial Agent against Multidrug Resistant Bacteria

    PubMed Central

    Elkady, M. F.; Shokry Hassan, H.; Hafez, Elsayed E.; Fouad, Ahmed

    2015-01-01

    Nano-ZnO has been successfully implemented in particles, rods, and tubes nanostructures via sol-gel and hydrothermal techniques. The variation of the different preparation parameters such as reaction temperature, time, and stabilizer agents was optimized to attain different morphological structures. The influence of the microwave annealing process on ZnO crystallinity, surface area, and morphological structure was monitored using XRD, BET, and SEM techniques, respectively. The antimicrobial activity of zinc oxide produced in nanotubes structure was examined against four different multidrug resistant bacteria: Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) strains. The activity of produced nano-ZnO was determined by disc diffusion technique and the results revealed that ZnO nanotubes recorded high activity against the studied strains due to their high surface area equivalent to 17.8 m2/g. The minimum inhibitory concentration (MIC) of ZnO nanotubes showed that the low concentrations of ZnO nanotubes could be a substitution for the commercial antibiotics when approached in suitable formula. Although the annealing process of ZnO improves the degree of material crystallinity, however, it declines its surface area and consequently its antimicrobial activity. PMID:26451136

  11. An Antimicrobial Metabolite from Bacillus sp.: Significant Activity Against Pathogenic Bacteria Including Multidrug-Resistant Clinical Strains

    PubMed Central

    Chalasani, Ajay G.; Dhanarajan, Gunaseelan; Nema, Sushma; Sen, Ramkrishna; Roy, Utpal

    2015-01-01

    In this study, the cell free modified tryptone soya broth (pH 7.4 ± 0.2) of Bacillus subtilis URID 12.1 showed significant antimicrobial activity against multidrug-resistant strains of Staphylococcus aureus, S. epidermidis, Streptococcus pyogenes and Enterococcus faecalis. The partially purified antimicrobial molecule was found to be resistant to extremes of pH and temperatures and also to higher concentrations of trypsin and proteinase K. The antimicrobial molecule was purified by a three-step method that included reversed-phase high performance liquid chromatography (RP-HPLC). The minimum inhibitory concentration (MIC) values were determined for 14 species of bacteria using a microbroth dilution technique. The HPLC-purified fraction showed the MICs ranging from 0.5 to 16 μg/ml for methicillin and vancomycin-resistant Staphylococcus aureus (MVRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) strains. The molecular mass of the antimicrobial compound was determined to be 842.37 Da. The same antimicrobial fraction showed negligible haemolytic activity against human red blood cells even at a concentration as high as 100 μg/ml. Because of its significant antimicrobial activity at low MIC values coupled with its non-haemolytic property, it may prove to be a novel antimicrobial lead molecule. PMID:26696963

  12. Multidrug Resistance in Quinolone-Resistant Gram-Negative Bacteria Isolated from Hospital Effluent and the Municipal Wastewater Treatment Plant.

    PubMed

    Vaz-Moreira, Ivone; Varela, Ana Rita; Pereira, Thamiris V; Fochat, Romário C; Manaia, Célia M

    2016-03-01

    This study is aimed to assess if hospital effluents represent an important supplier of multidrug-resistant (MDR) Gram-negative bacteria that, being discharged in the municipal collector, may be disseminated in the environment and bypassed in water quality control systems. From a set of 101 non-Escherichia coli Gram-negative bacteria with reduced susceptibility to quinolones, was selected a group of isolates comprised by those with the highest indices of MDR (defined as nonsusceptibility to at least one agent in six or more antimicrobial categories, MDR ≥6) or resistance to meropenem or ceftazidime (n = 25). The isolates were identified and characterized for antibiotic resistance phenotype, plasmid-mediated quinolone resistance (PMQR) genes, and other genetic elements and conjugative capacity. The isolates with highest MDR indices were mainly from hospital effluent and comprised ubiquitous bacterial groups of the class Gammaproteobacteria, of the genera Aeromonas, Acinetobacter, Citrobacter, Enterobacter, Klebsiella, and Pseudomonas, and of the class Flavobacteriia, of the genera Chryseobacterium and Myroides. In this group of 25 strains, 19 identified as Gammaproteobacteria harbored at least one PMQR gene (aac(6')-Ib-cr, qnrB, qnrS, or oqxAB) or a class 1 integron gene cassette encoding aminoglycoside, sulfonamide, or carbapenem resistance. Most of the E. coli J53 transconjugants with acquired antibiotic resistance resulted from conjugation with Enterobacteriaceae. These transconjugants demonstrated acquired resistance to a maximum of five classes of antibiotics, one or more PMQR genes and/or a class 1 integron gene cassette. This study shows that ubiquitous bacteria, other than those monitored in water quality controls, are important vectors of antibiotic resistance and can be disseminated from hospital effluent to aquatic environments. This information is relevant to support management options aiming at the control of this public health problem. PMID

  13. Surveillance of multidrug resistant uropathogenic bacteria in hospitalized patients in Indian

    PubMed Central

    Mishra, Monali Priyadarsini; Debata, Nagen Kumar; Padhy, Rabindra Nath

    2013-01-01

    Objective To record surveillance, antibiotic resistance of uropathogens of hospitalized patients over a period of 18 months. Methods Urine samples from wards and cabins were used for isolating urinary tract infection (UTI)-causing bacteria that were cultured on suitable selective media and identified by biochemical tests; and their antibiograms were ascertained by Kirby-Bauer's disc diffusion method, in each 6-month interval of the study period, using 18 antibiotics of five different classes. Results From wards and cabins, 1 245 samples were collected, from which 996 strains of bacteria belonging to 11 species were isolated, during April 2011 to September 2012. Two Gram-positive, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and nine Gram-negative bacteria, Acinetobacter baumannii, Citrobacter sp., Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were isolated. Both S. aureus and E. faecalis were vancomycin resistant, and resistant-strains of all pathogens increased in each 6-month period of study. Particularly, all Gram-negatives were resistant to nitrofurantoin and co-trimoxazole, the most preferred antibiotics of empiric therapy for UTI. Conclusions Antibiograms of 11 UTI-causing bacteria recorded in this study indicated moderately higher numbers of strains resistant to each antibiotic studied, generating the fear of precipitating fervent episodes in public health particularly with bacteria, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and S. aureus. Moreover, vancomycin resistance in strains of S. aureus and E. faecalis is a matter of concern. PMID:23620859

  14. Broad Specificity Efflux pumps and Their Role in Multidrug Resistance of Gram Negative Bacteria

    PubMed Central

    Nikaido, Hiroshi; Pagès, Jean-Marie

    2013-01-01

    Antibiotic resistance mechanisms reported in Gram-negative bacteria are producing a worldwide health problem. The continuous dissemination of «multi-drug resistant» (MDR) bacteria drastically reduces the efficacy of our antibiotic “arsenal” and consequently increases the frequency of therapeutic failure. In MDR bacteria, the over-expression of efflux pumps that expel structurally-unrelated drugs contributes to the reduced susceptibility by decreasing the intracellular concentration of antibiotics. During the last decade, several clinical data indicate an increasing involvement of efflux pumps in the emergence and dissemination of resistant Gram-negative bacteria. It is necessary to clearly define the molecular, functional and genetic bases of the efflux pump in order to understand the translocation of antibiotic molecules through the efflux transporter. The recent investigation on the efflux pump AcrB at its structural and physiological level, including the identification of drug affinity sites and kinetic parameters for various antibiotics, may open the way to rationally develop an improved new generation of antibacterial agents as well as efflux inhibitors in order to efficiently combat efflux-based resistance mechanisms. PMID:21707670

  15. Multidrug-resistant bacteria in unaccompanied refugee minors arriving in Frankfurt am Main, Germany, October to November 2015.

    PubMed

    Heudorf, Ursel; Krackhardt, Bernhard; Karathana, Maria; Kleinkauf, Niels; Zinn, Christian

    2016-01-01

    Many refugees arriving in Germany originate or have travelled through countries with high prevalence of multidrug-resistant Gram-negative organisms. Therefore, all unaccompanied refugee minors (<18 years-old) arriving in Frankfurt am Main between 12 October and 6 November 2015, were screened for multidrug-resistant Enterobacteriaceae in stool samples. Enterobacteriaceae with extended spectrum beta-lactamases (ESBL) were detected in 42 of 119 (35%) individuals, including nine with additional resistance to fluoroquinolones (8% of total screened), thus exceeding the prevalences in the German population by far. PMID:26838714

  16. Antibacterial activities of the methanol extracts of ten Cameroonian vegetables against Gram-negative multidrug-resistant bacteria

    PubMed Central

    2013-01-01

    Background Many edible plants are used in Cameroon since ancient time to control microbial infections. This study was designed at evaluating the antibacterial activities of the methanol extracts of ten Cameroonian vegetables against a panel of twenty nine Gram negative bacteria including multi-drug resistant (MDR) strains. Methods The broth microdilution method was used to determine the Minimal Inhibitory Concentrations (MIC) and the Minimal Bactericidal Concentrations (MBC) of the studied extracts. When chloramphenicol was used as a reference antibiotic, the MICs were also determined in the presence of Phenylalanine-Arginine β-Naphtylamide (PAβN), an efflux pumps inhibitor (EPI). The phytochemical screening of the extracts was performed using standard methods. Results All tested extracts exhibited antibacterial activities, with the MIC values varying from 128 to 1024 mg/L. The studied extracts showed large spectra of action, those from L. sativa, S. edule, C. pepo and S. nigrum being active on all the 29 bacterial strains tested meanwhile those from Amaranthus hybridus, Vernonia hymenolepsis, Lactuca.carpensis and Manihot esculenta were active on 96.55% of the strains used. The plant extracts were assessed for the presence of large classes of secondary metabolites: alkaloids, anthocyanins, anthraquinones, flavonoids, phenols, saponins, steroids, tannins and triterpenes. Each studied plant extract was found to contain compounds belonging to at least two of the above mentioned classes. Conclusion These results confirm the traditional claims and provide promising baseline information for the potential use of the tested vegetables in the fight against bacterial infections involving MDR phenotypes. PMID:23368430

  17. Prevalence of plasmid-mediated multidrug resistance determinants in fluoroquinolone-resistant bacteria isolated from sewage and surface water.

    PubMed

    Osińska, Adriana; Harnisz, Monika; Korzeniewska, Ewa

    2016-06-01

    % of FQRB. The highest prevalence of multidrug-resistant (MDR) microorganisms was detected in TWW and DRW samples. It indicates that discharged TWW harbors multiresistant bacterial strains and that mobile PMQR and ARGs elements may have a selective pressure for species affiliated to bacteria in the river water. PMID:26893181

  18. Active surveillance for multidrug-resistant Gram-negative bacteria in the intensive care unit.

    PubMed

    Abbott, Iain J; Jenney, Adam W J; Spelman, Denis W; Pilcher, David V; Sidjabat, Hanna E; Richardson, Leisha J; Paterson, David L; Peleg, Anton Y

    2015-10-01

    A short-term program of performing serial active screening cultures (ASC) in the intensive care unit was instituted to establish a method for the detection of antibiotic-resistant Gram-negative bacteria (GNB) and the local rates of colonisation. Of all submitted ASC, 25.9% (30/116 collected swabs) isolated an antibiotic-resistant GNB. ChromID ESBL agar (bioMérieux, France) identified the majority of these organisms, with the additional antibiotic-impregnated media [MacConkey agar (MCA) with ciprofloxacin, MCA with gentamicin and MCA with ceftazidime] adding limited benefit. Compared to swabs performed on admission, 37.8% (14/37) of patients cultured a new antibiotic-resistant isolate on discharge. Serial screening in intensive care has the ability to identify patients with unrecognised colonisation with antibiotic-resistant GNB; however, the increase in the laboratory workload and logistical challenges in the collection of the surveillance swabs may limit this program's expansion. PMID:26308128

  19. The global spread of healthcare-associated multidrug-resistant bacteria: a perspective from Asia.

    PubMed

    Molton, James S; Tambyah, Paul A; Ang, Brenda S P; Ling, Moi Lin; Fisher, Dale A

    2013-05-01

    Since antibiotics were first used, each new introduced class has been followed by a global wave of emergent resistance, largely originating in Europe and North America where they were first used. Methicillin-resistant Staphylococcus aureus spread from the United Kingdom and North America across Europe and then Asia over more than a decade. Vancomycin-resistant enterococci and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae followed a similar path some 20 years later. Recently however, metallo-β-lactamases have originated in Asia. New Delhi metallo-β-lactamase-1 was found in almost every continent within a year of its emergence in India. Metallo-β-lactamase enzymes are encoded on highly transmissible plasmids that spread rapidly between bacteria, rather than relying on clonal proliferation. Global air travel may have helped facilitate rapid dissemination. As the antibiotic pipeline offers little in the short term, our most important tools against the spread of antibiotic resistant organisms are intensified infection control, surveillance, and antimicrobial stewardship. PMID:23334810

  20. Detection of genes encoding multidrug resistance and biofilm virulence factor in uterine pathogenic bacteria in postpartum dairy cows.

    PubMed

    Kasimanickam, V R; Owen, K; Kasimanickam, R K

    2016-01-15

    Reckless use of antibiotics and/or development of biofilm are the rationale for the development of multidrug resistance (MDR) of pathogenic bacteria. The objective of the present study was to detect MDR genes in Trueperella pyogenes and to detect biofilm virulence factor (VF) genes in Escherichia coli isolated from the uterus of postpartum dairy cows. Uterine secretions from different parity postpartum Holstein cows (n = 40) were collected using cytobrush technique after a sterile procedure from cows with varying degree of uterine inflammatory conditions. The cytobrush was stored in a specimen collector, placed in a cooler with ice, and transported to the laboratory within 2 hours. The pathogens were isolated and were identified initially by their colony morphology and biochemical characteristics. To further identify and classify the single species, and to determine the presence of MDR and VF genes, the genes fragments were amplified using the respective primers by either singleplex or multiplex polymerase chain reaction protocol, and amplicons were detected by electrophoresis method. T pyogenes was isolated in 17 of 40 (42.5%) cows in the study population as recognized by the 16S rRNA gene. Of the positive T pyogenes samples, 8 of 17 (42.1%) were positive for integron type 1 (intI I), and none were positive for integron type 2 (intI II). Of those 8 positive for intI I, six of eight (66.7%) were positive for amplicons aadA5 and aadA24-ORF1 at 1048 and 1608 bp, respectively, associated with specific drug resistance. Presence of addA5 indicated resistance to sulfadiazine, bacitracin, florfenicol, and ceftiofur. Presence of addA24-ORF1 indicated resistant to sulfadiazine, bacitracin, penicillin, clindamycin, and erythromycin. E coli was isolated in 18 of 40 (45.0%) cows in the study population. The genes for VF, Agn43a, and Agn43 b, associated with biofilm production, were found in 6 of 18 (33.3%) of the positive isolates. Both T pyogenes MDR gene and E coli

  1. Multidrug Resistant Acinetobacter

    PubMed Central

    Manchanda, Vikas; Sanchaita, Sinha; Singh, NP

    2010-01-01

    Emergence and spread of Acinetobacter species, resistant to most of the available antimicrobial agents, is an area of great concern. It is now being frequently associated with healthcare associated infections. Literature was searched at PUBMED, Google Scholar, and Cochrane Library, using the terms ‘Acinetobacter Resistance, multidrug resistant (MDR), Antimicrobial Therapy, Outbreak, Colistin, Tigecycline, AmpC enzymes, and carbapenemases in various combinations. The terms such as MDR, Extensively Drug Resistant (XDR), and Pan Drug Resistant (PDR) have been used in published literature with varied definitions, leading to confusion in the correlation of data from various studies. In this review various mechanisms of resistance in the Acinetobacter species have been discussed. The review also probes upon the current therapeutic options, including combination therapies available to treat infections due to resistant Acinetobacter species in adults as well as children. There is an urgent need to enforce infection control measures and antimicrobial stewardship programs to prevent the further spread of these resistant Acinetobacter species and to delay the emergence of increased resistance in the bacteria. PMID:20927292

  2. The involvement of sphingolipids in multidrug resistance.

    PubMed

    Sietsma, H; Veldman, R J; Kok, J W

    2001-06-01

    Administration of most chemotherapeutic agents eventually results in the onset of apoptosis, despite the agents' variety in structure and molecular targets. Ceramide, the central molecule in cellular glycosphingolipid metabolism, has recently been identified as an important mediator of this process. Indeed, one of the events elicited by application of many cytotoxic drugs is an accumulation of this lipid. Treatment failure in cancer chemotherapy is largely attributable to multidrug resistance, in which tumor cells are typically cross-resistant to multiple chemotherapeutic agents. Different cellular mechanisms underlying this phenomenon have been described. Of these the drug efflux pump activity of P-glycoprotein and the multidrug resistance-associated proteins are the most extensively studied examples. Recently, an increased cellular capacity for ceramide glycosylation has been recognized as a novel multidrug resistance mechanism. Indeed, virtually all multidrug-resistant cells exhibit a deviating sphingolipid composition, most typically, increased levels of glucosylceramide. On the other hand, several direct molecular interactions between sphingolipids and drug efflux proteins have been described. Therefore, in addition to a role in the multidrug resistance phenotype by which ceramide accumulation and, thus, the onset of apoptosis are prevented, an indirect role for sphingolipids might be envisaged, by which the activity of these efflux proteins is modulated. In this review, we present an overview of the current understanding of the interesting relations that exist between sphingolipid metabolism and multidrug resistance. PMID:11420602

  3. Use of maggot therapy for treating a diabetic foot ulcer colonized by multidrug resistant bacteria in Brazil.

    PubMed

    Pinheiro, Marilia A R Q; Ferraz, Julianny B; Junior, Miguel A A; Moura, Andrew D; da Costa, Maria E S M; Costa, Fagner J M D; Neto, Valter F A; Neto, Renato M; Gama, Renata A

    2015-03-01

    This study reports the efficacy of maggot therapy in the treatment of diabetic foot ulcer infected with multidrug resistant microorganisms. A 74 year old female patient with diabetes for over 30 years, was treated with maggot therapy using larvae of Chrysomya megacephala. The microbiological samples were collected to evaluate aetiology of the infection. The therapy done for 43 days resulted in a reduction of necrosis and the ulcer's retraction of 0.7 cm [2] in area. Analysis of the bacteriological swabs revealed the presence of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Further studies need to be done to confirm the role of maggot therapy in wound healing using a large sample and a proper study design. PMID:25963495

  4. Use of maggot therapy for treating a diabetic foot ulcer colonized by multidrug resistant bacteria in Brazil

    PubMed Central

    Pinheiro, Marilia A.R.Q.; Ferraz, Julianny B.; Junior, Miguel A.A.; Moura, Andrew D.; da Costa, Maria E.S.M.; Costa, Fagner J.M.D.; Neto, Valter F.A.; Neto, Renato M.; Gama, Renata A.

    2015-01-01

    This study reports the efficacy of maggot therapy in the treatment of diabetic foot ulcer infected with multidrug resistant microorganisms. A 74 year old female patient with diabetes for over 30 years, was treated with maggot therapy using larvae of Chrysomya megacephala. The microbiological samples were collected to evaluate aetiology of the infection. The therapy done for 43 days resulted in a reduction of necrosis and the ulcer's retraction of 0.7 cm2 in area. Analysis of the bacteriological swabs revealed the presence of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Further studies need to be done to confirm the role of maggot therapy in wound healing using a large sample and a proper study design. PMID:25963495

  5. Enhancement of the antibiotic activity of aminoglycosides by extracts from Anadenanthera colubrine (Vell.) Brenan var. cebil against multi-drug resistant bacteria.

    PubMed

    Barreto, Humberto M; Coelho, Kivia M R N; Ferreira, Josie H L; Dos Santos, Bernadete H C; de Abreu, Aislan P L; Coutinho, Henrique D M; da Silva, Romezio A C; de Sousa, Taciana O; Citó, Antonia M das G L; Lopes, José A D

    2016-06-01

    The aim of this work was to evaluate the antimicrobial activity of ethanol (EEAC) and hexane (HFAC) extracts from the stem bark of Anadenanthera colubrina (Vell.) Brenan var. cebil alone or in combination with aminoglycosides against multi-drug resistant (MDR) bacteria. Minimal inhibitory concentrations (MICs) of the extracts were determined by using microdilution assay. For the evaluation of extracts as modulators of antibiotic resistance, MICs of neomycin and amikacin were determined in presence or absence of each compound at sub-inhibitory concentrations. Both EEAC and HFAC did not show antimicrobial activity against MDR strains tested. However, the addition of EEAC and HFAC enhanced the activity of neomycin and amikacin against Staphylococcus aureus SA10 strain. When the natural products were replaced by chlorpromazine, the same effect was observed. Anadenanthera colubrine var. cebil may be a source of phytochemicals able to potentiate the aminoglycoside activity against MDR S. aureus by the inhibition of efflux pump. PMID:26158209

  6. Antibiotic resistance and multidrug-resistant efflux pumps expression in lactic acid bacteria isolated from pozol, a nonalcoholic Mayan maize fermented beverage.

    PubMed

    Wacher-Rodarte, Maria Del Carmen; Trejo-Muñúzuri, Tanya Paulina; Montiel-Aguirre, Jesús Fernando; Drago-Serrano, Maria Elisa; Gutiérrez-Lucas, Raúl L; Castañeda-Sánchez, Jorge Ismael; Sainz-Espuñes, Teresita

    2016-05-01

    Pozol is a handcrafted nonalcoholic Mayan beverage produced by the spontaneous fermentation of maize dough by lactic acid bacteria. Lactic acid bacteria (LAB) are carriers of chromosomal encoded multidrug-resistant efflux pumps genes that can be transferred to pathogens and/or confer resistance to compounds released during the fermentation process causing food spoiling. The aim of this study was to evaluate the antibiotic sensibility and the transcriptional expression of ABC-type efflux pumps in LAB isolated from pozol that contributes to multidrug resistance. Analysis of LAB and Staphylococcus (S.) aureus ATCC 29213 and ATCC 6538 control strains to antibiotic susceptibility, minimal inhibitory concentration (MIC), and minimal bactericidal concentration (MBC) to ethidium bromide were based in "standard methods" whereas the ethidium bromide efflux assay was done by fluorometric assay. Transcriptional expression of efflux pumps was analyzed by RT-PCR. LAB showed antibiotic multiresistance profiles, moreover, Lactococcus (L.) lactis and Lactobacillus (L.) plantarum displayed higher ethidium bromide efflux phenotype than S. aureus control strains. Ethidium bromide resistance and ethidium bromide efflux phenotypes were unrelated with the overexpression of lmrD in L. lactics, or the underexpression of lmrA in L. plantarum and norA in S. aureus. These findings suggest that, moreover, the analyzed efflux pumps genes, other unknown redundant mechanisms may underlie the antibiotic resistance and the ethidium bromide efflux phenotype in L. lactis and L. plantarum. Phenotypic and molecular drug multiresistance assessment in LAB may improve a better selection of the fermentation starter cultures used in pozol, and to control the antibiotic resistance widespread and food spoiling for health safety. PMID:27247772

  7. Antibacterial activities of the methanol extracts of Canarium schweinfurthii and four other Cameroonian dietary plants against multi-drug resistant Gram-negative bacteria.

    PubMed

    Dzotam, Joachim K; Touani, Francesco K; Kuete, Victor

    2016-09-01

    Bacterial infections are among the major cause of morbidity and mortality worldwide. The present study was designed to evaluate the in vitro antibacterial activities of the methanol extracts of five Cameroonian edible plants namely Colocasia esculenta, Triumfetta pentandra, Hibiscus esculentus, Canarium schweinfurthii and Annona muricata against a panel of 19 multidrug resistant Gram-negative bacterial strains. The liquid broth microdilution was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts. The preliminary phytochemical screening of the extracts was conducted according to the standard phytochemical methods. Results showed that all extracts contained compounds belonging to the classes of polyphenols, triterpenes and steroids, other classes of chemicals being selectively distributed. Canarium schweinfurthii extract showed the best activity with MIC values ranging from 64 to 1024 μg/mL against 89.5% of the 19 tested bacteria strains. MIC values below or equal to 1024 μg/mL were also recorded with Triumfetta pentandra, Annona muricata, Colocasia esculenta and Hibiscus esculentus extracts respectively against 15/19 (78.9%), 11/19 (57.9%), 10/19 (52.6%) and 10/19 (52.6%) tested bacteria. Extract from C. schweinfurthii displayed the lowest MIC value (64 μg/mL) against Escherichia coli AG100ATet. Finally, the results of this work provide baseline information for the use of C. esculenta, T. pentandra, H. esculentus, C. schweinfurthii and A. muricata in the treatment of bacterial infections including multidrug resistant phenotypes. PMID:27579004

  8. Green synthesis of protein capped silver nanoparticles from phytopathogenic fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against multidrug-resistant bacteria

    NASA Astrophysics Data System (ADS)

    Chowdhury, Supriyo; Basu, Arpita; Kundu, Surekha

    2014-07-01

    In recent years, green synthesis of nanoparticles, i.e., synthesizing nanoparticles using biological sources like bacteria, algae, fungus, or plant extracts have attracted much attention due to its environment-friendly and economic aspects. The present study demonstrates an eco-friendly and low-cost method of biosynthesis of silver nanoparticles using cell-free filtrate of phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) revealed the presence of spherical silver nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2 θ values corresponding to silver nanoparticles. These nanoparticles were found to be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa protein band responsible for capping and stabilization of the silver nanoparticles. Antimicrobial activities of the silver nanoparticles against human as well as plant pathogenic multidrug-resistant bacteria were assayed. The particles showed inhibitory effect on the growth kinetics of human and plant bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with increasing concentrations was evaluated by DNA fragmentation studies using plasmid DNA.

  9. A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: design, synthesis, activity against multidrug-resistant bacteria and Candida.

    PubMed

    Mishra, Biswajit; Leishangthem, Geeta Devi; Gill, Kamaldeep; Singh, Abhay K; Das, Swagata; Singh, Kusum; Xess, Immaculata; Dinda, Amit; Kapil, Arti; Patro, Ishan K; Dey, Sharmistha

    2013-02-01

    Lactoferrin (LF) is believed to contribute to the host's defense against microbial infections. This work focuses on the antibacterial and antifungal activities of a designed peptide, L10 (WFRKQLKW) by modifying the first eight N-terminal residues of bovine LF by selective homologous substitution of amino acids on the basis of hydrophobicity, L10 has shown potent antibacterial and antifungal properties against clinically isolated extended spectrum beta lactamases (ESBL), producing gram-negative bacteria as well as Candida strains with minimal inhibitory concentrations (MIC) ranging from 1 to 8 μg/mL and 6.5 μg/mL, respectively. The peptide was found to be least hemolytic at a concentration of 800 μg/mL. Interaction with lipopolysaccharide (LPS) and lipid A (LA) suggests that the peptide targets the membrane of gram-negative bacteria. The membrane interactive nature of the peptide, both antibacterial and antifungal, was further confirmed by visual observations employing electron microscopy. Further analyses, by means of propidium iodide based flow cytometry, also supported the membrane permeabilization of Candida cells. The peptide was also found to possess anti-inflammatory properties, by virtue of its ability to inhibit cyclooxygenase-2 (COX-2). L10 therefore emerges as a potential therapeutic remedial solution for infections caused by ESBL positive, gram-negative bacteria and multidrug-resistant (MDR) fungal strains, on account of its multifunctional activities. This study may open up new approach to develop and design novel antimicrobials. PMID:23026014

  10. Green synthesis of protein capped silver nanoparticles from phytopathogenic fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against multidrug-resistant bacteria.

    PubMed

    Chowdhury, Supriyo; Basu, Arpita; Kundu, Surekha

    2014-01-01

    In recent years, green synthesis of nanoparticles, i.e., synthesizing nanoparticles using biological sources like bacteria, algae, fungus, or plant extracts have attracted much attention due to its environment-friendly and economic aspects. The present study demonstrates an eco-friendly and low-cost method of biosynthesis of silver nanoparticles using cell-free filtrate of phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) revealed the presence of spherical silver nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2θ values corresponding to silver nanoparticles. These nanoparticles were found to be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa protein band responsible for capping and stabilization of the silver nanoparticles. Antimicrobial activities of the silver nanoparticles against human as well as plant pathogenic multidrug-resistant bacteria were assayed. The particles showed inhibitory effect on the growth kinetics of human and plant bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with increasing concentrations was evaluated by DNA fragmentation studies using plasmid DNA. PMID:25114655

  11. Green synthesis of protein capped silver nanoparticles from phytopathogenic fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against multidrug-resistant bacteria

    PubMed Central

    2014-01-01

    In recent years, green synthesis of nanoparticles, i.e., synthesizing nanoparticles using biological sources like bacteria, algae, fungus, or plant extracts have attracted much attention due to its environment-friendly and economic aspects. The present study demonstrates an eco-friendly and low-cost method of biosynthesis of silver nanoparticles using cell-free filtrate of phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) revealed the presence of spherical silver nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2θ values corresponding to silver nanoparticles. These nanoparticles were found to be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa protein band responsible for capping and stabilization of the silver nanoparticles. Antimicrobial activities of the silver nanoparticles against human as well as plant pathogenic multidrug-resistant bacteria were assayed. The particles showed inhibitory effect on the growth kinetics of human and plant bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with increasing concentrations was evaluated by DNA fragmentation studies using plasmid DNA. PMID:25114655

  12. Antimicrobial activity of the bioactive components of essential oils from Pakistani spices against Salmonella and other multi-drug resistant bacteria

    PubMed Central

    2013-01-01

    activities against selected multi drug resistant clinical and soil bacterial strains. Cinnamaldehyde was identified as the most active antimicrobial component present in the cinnamon essential oil which acted as a strong inhibitory agent in MIC assay against the tested bacteria. The results indicate that essential oils from Pakistani spices can be pursued against multidrug resistant bacteria. PMID:24119438

  13. A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria.

    PubMed

    Marathe, Nachiket P; Regina, Viduthalai R; Walujkar, Sandeep A; Charan, Shakti Singh; Moore, Edward R B; Larsson, D G Joakim; Shouche, Yogesh S

    2013-01-01

    The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs) serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range). In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86%) of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE), Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1) was resistant to 36 antibiotics, while P. rettgeri (OSR3) was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80%) strains each, and 88/93 (95%) strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides insight into

  14. A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria

    PubMed Central

    Walujkar, Sandeep A.; Charan, Shakti Singh; Moore, Edward R. B.; Larsson, D. G. Joakim; Shouche, Yogesh S.

    2013-01-01

    The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs) serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range). In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86%) of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE), Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1) was resistant to 36 antibiotics, while P. rettgeri (OSR3) was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80%) strains each, and 88/93 (95%) strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides insight into

  15. Unexpected Challenges in Treating Multidrug-Resistant Gram-Negative Bacteria: Resistance to Ceftazidime-Avibactam in Archived Isolates of Pseudomonas aeruginosa

    PubMed Central

    Winkler, Marisa L.; Papp-Wallace, Krisztina M.; Hujer, Andrea M.; Domitrovic, T. Nicholas; Hujer, Kristine M.; Hurless, Kelly N.; Tuohy, Marion; Hall, Geraldine

    2014-01-01

    Pseudomonas aeruginosa is a notoriously difficult-to-treat pathogen that is a common cause of severe nosocomial infections. Investigating a collection of β-lactam-resistant P. aeruginosa clinical isolates from a decade ago, we uncovered resistance to ceftazidime-avibactam, a novel β-lactam/β-lactamase inhibitor combination. The isolates were systematically analyzed through a variety of genetic, biochemical, genomic, and microbiological methods to understand how resistance manifests to a unique drug combination that is not yet clinically released. We discovered that avibactam was able to inactivate different AmpC β-lactamase enzymes and that blaPDC regulatory elements and penicillin-binding protein differences did not contribute in a major way to resistance. By using carefully selected combinations of antimicrobial agents, we deduced that the greatest barrier to ceftazidime-avibactam is membrane permeability and drug efflux. To overcome the constellation of resistance determinants, we show that a combination of antimicrobial agents (ceftazidime/avibactam/fosfomycin) targeting multiple cell wall synthetic pathways can restore susceptibility. In P. aeruginosa, efflux, as a general mechanism of resistance, may pose the greatest challenge to future antibiotic development. Our unexpected findings create concern that even the development of antimicrobial agents targeted for the treatment of multidrug-resistant bacteria may encounter clinically important resistance. Antibiotic therapy in the future must consider these factors. PMID:25451057

  16. Multidrug resistance and transferability of blaCTX-M among extended-spectrum β-lactamase-producing enteric bacteria in biofilm.

    PubMed

    Maheshwari, Meenu; Ahmad, Iqbal; Althubiani, Abdullah Safar

    2016-09-01

    This study aimed to investigate the occurrence of biofilm-forming extended-spectrum β-lactamase (ESBL)-producing enteric bacteria in hospital wastewater and to evaluate their antibiotic resistance behaviour and transferability of the plasmid-encoded blaCTX-M gene in biofilm. ESBL production was confirmed using the combined disc test and Etest. Amplification of blaCTX-M was performed by PCR. Antibiotic susceptibility was evaluated using the disc diffusion assay and broth dilution method. Transfer of blaCTX-M in planktonic and biofilm state was performed by broth mating and filter mating experiments, respectively. Among 110 enteric bacteria, 24 (21.8%) isolates belonging to Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae were found to produce ESBL and formed varying levels of biofilm in vitro. Presence of blaCTX-M was detected in 18 (75%) ESBL-producing isolates. A many fold increase in resistance to antibiotics was observed in biofilm. Among ESBL-producers, seven isolates could transfer the blaCTX-M gene by conjugation, with transfer frequencies ranging from 2.22×10(-4) to 7.14×10(-2) transconjugants/recipient cell in the planktonic state and from 3.04×10(-3) to 9.15×10(-1) in biofilm. The transfer frequency of blaCTX-M was significantly higher in biofilm compared with the planktonic state, and co-transfer of ciprofloxacin resistance was also detected in five isolates. This study demonstrates that biofilm-forming ESBL-producing enteric bacteria with a greater transfer frequency of resistance genes will lead to frequent dissemination of β-lactam and fluoroquinolone resistance genes in environmental settings. The emergence and spread of such multidrug resistance is a serious threat to animal and public health. PMID:27530857

  17. Prevalence of multidrug resistant uropathogenic bacteria in pediatric patients of a tertiary care hospital in eastern India.

    PubMed

    Mishra, Monali P; Sarangi, Rachita; Padhy, Rabindra N

    2016-01-01

    Today, because systemic infections such as urinary tract infection (UTI) affect even pediatric patients, antibiotic resistant bacteria have become a constant clinical challenge. In the present study, a total of 1054 urine samples were collected from pediatric patients over 18 months. From these samples, 510 isolates of pathogenic bacteria were collected using HiCrome UTI agar. Antibiotic sensitivity tests of isolates were performed using the Kirby-Bauer method. Two Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and 7 Gram-negative bacteria (Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella oxytoca, K. pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa) were isolated. Antibiograms of isolated bacteria were ascertained using antibiotics of 4 classes: aminoglycosides, β-lactams, fluoroquinolones and 2 stand-alones (co-trimoxazole and nitrofurantoin). Based on percent values of antibiotic resistance, isolated bacteria were (in decreasing order of number of isolated isolates): E. coli (109)>S. aureus (65)>E. faecalis (82)>E. aerogenes (64)>C. freundii (41)>P. aeruginosa (32)>K. pneumoniae (45)>K. oxytoca (50)>P. vulgaris (22). Surveillance results show that MDR isolates of 9 pathogenic bacteria were prevalent in the environment around the hospital. Thus, revisions to the antimicrobial stewardship program in this area of the country are required to increase clinician confidence in empiric therapy, which is often used for UTI cases. PMID:26617250

  18. Occurrence of Multidrug Resistant Extended Spectrum Beta-Lactamase-Producing Bacteria on Iceberg Lettuce Retailed for Human Consumption

    PubMed Central

    Talreja, Deepa; Rana, Sonia Walia; Walia, Sandeep; Walia, Satish K.

    2015-01-01

    Antibiotic resistance in bacteria is a global problem exacerbated by the dissemination of resistant bacteria via uncooked food, such as green leafy vegetables. New strains of bacteria are emerging on a daily basis with novel expanded antibiotic resistance profiles. In this pilot study, we examined the occurrence of antibiotic resistant bacteria against five classes of antibiotics on iceberg lettuce retailed in local convenience stores in Rochester, Michigan. In this study, 138 morphologically distinct bacterial colonies from 9 iceberg lettuce samples were randomly picked and tested for antibiotic resistance. Among these isolates, the vast majority (86%) demonstrated resistance to cefotaxime, and among the resistant bacteria, the majority showed multiple drug resistance, particularly against cefotaxime, chloramphenicol, and tetracycline. Three bacterial isolates (2.17%) out of 138 were extended spectrum beta-lactamase (ESBL) producers. Two ESBL producers (T1 and T5) were identified as Klebsiella pneumoniae, an opportunistic pathogen with transferable sulfhydryl variable- (SHV-) and TEM-type ESBLs, respectively. The DNA sequence analysis of the blaSHV detected in K. pneumoniae isolate T1 revealed 99% relatedness to blaSHV genes found in clinical isolates. This implies that iceberg lettuce is a potential reservoir of newly emerging and evolving antibiotic resistant bacteria and its consumption poses serious threat to human health. PMID:26064922

  19. Thin Layer Chromatography-Bioautography and Gas Chromatography-Mass Spectrometry of Antimicrobial Leaf Extracts from Philippine Piper betle L. against Multidrug-Resistant Bacteria

    PubMed Central

    Valle, Demetrio L.; Puzon, Juliana Janet M.; Cabrera, Esperanza C.

    2016-01-01

    This study isolated and identified the antimicrobial compounds of Philippine Piper betle L. leaf ethanol extracts by thin layer chromatography- (TLC-) bioautography and gas chromatography-mass spectrometry (GC-MS). Initially, TLC separation of the leaf ethanol extracts provided a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV 366 nm. Agar-overlay bioautography of the isolated compounds demonstrated two spots with Rf values of 0.86 and 0.13 showing inhibitory activities against two Gram-positive multidrug-resistant (MDR) bacteria, namely, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. The compound with an Rf value of 0.86 also possessed inhibitory activity against Gram-negative MDR bacteria, namely, carbapenem-resistant Enterobacteriaceae-Klebsiella pneumoniae and metallo-β-lactamase-producing Acinetobacter baumannii. GC-MS was performed to identify the semivolatile and volatile compounds present in the leaf ethanol extracts. Six compounds were identified, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, 3-fluoro-2-propynenitrite, 4-(2-propenyl)phenol, and eugenol. The results of this study could lead to the development of novel therapeutic agents capable of dealing with specific diseases that either have weakened reaction or are currently not responsive to existing drugs. PMID:27478476

  20. Mechanisms of β-lactam antimicrobial resistance and epidemiology of major community- and healthcare-associated multidrug-resistant bacteria.

    PubMed

    Tang, Sarah S; Apisarnthanarak, Anucha; Hsu, Li Yang

    2014-11-30

    Alexander Fleming's discovery of penicillin heralded an age of antibiotic development and healthcare advances that are premised on the ability to prevent and treat bacterial infections both safely and effectively. The resultant evolution of antimicrobial resistant mechanisms and spread of bacteria bearing these genetic determinants of resistance are acknowledged to be one of the major public health challenges globally, and threatens to unravel the gains of the past decades. We describe the major mechanisms of resistance to β-lactam antibiotics - the most widely used and effective antibiotics currently - in both Gram-positive and Gram-negative bacteria, and also briefly detail the existing and emergent pharmacological strategies to overcome such resistance. The global epidemiology of the four major types of bacteria that are responsible for the bulk of antimicrobial-resistant infections in the healthcare setting - methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Enterobactericeae, and Acinetobacter baumannii - are also briefly described. PMID:25134490

  1. Emerging clinical role of pivmecillinam in the treatment of urinary tract infection in the context of multidrug-resistant bacteria.

    PubMed

    Dewar, Simon; Reed, Lee C; Koerner, Roland J

    2014-02-01

    The continuing spread of resistant Gram-negative bacteria is a therapeutic challenge and prudent use of antimicrobials is therefore essential. Urinary tract infections (UTIs), usually due to Gram-negative bacteria, are among the most common infections seen in the community. Moreover, bacterial strains producing extended-spectrum β-lactamases (ESBLs) that are resistant not only to cephalosporins and penicillins, but also to fluoroquinolones and trimethoprim, are becoming more prevalent in the community. This means that oral antibiotic options to treat these infections are limited. The discovery of new drugs to tackle these problems has been difficult and slow paced; it is therefore timely to 'rediscover' the current antibiotics we have available in our clinical formulary, to determine how best they can be used. Pivmecillinam is an oral antibiotic with excellent clinical efficacy in the treatment of uncomplicated UTIs. It has been used extensively in Nordic countries with few problems, but, despite this, it is not widely used in other countries. There is emerging in vitro and in vivo evidence of its activity against ESBL-producing organisms and its synergistic potential with β-lactamase inhibitors. Pivmecillinam is well tolerated with a low side-effect profile. Pivmecillinam also has a minimal effect on the intestinal and vaginal flora of the host; thus, there is a lower rate of selection of resistant bacteria, vaginal candidiasis and, of note, Clostridium difficile. PMID:24068280

  2. Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria.

    PubMed

    Sanabria-Ríos, David J; Rivera-Torres, Yaritza; Rosario, Joshua; Gutierrez, Ricardo; Torres-García, Yeireliz; Montano, Nashbly; Ortíz-Soto, Gabriela; Ríos-Olivares, Eddy; Rodríguez, José W; Carballeira, Néstor M

    2015-11-15

    The first total synthesis of a C5-curcumin-2-hexadecynoic acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13% overall yield and tested for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Our results revealed that 6 was active against eight MRSA strains at MICs that range between 31.3 and 62.5 μg/mL. It was found that the presence of 2-hexadecynoic acid (2-HDA, 4) in conjugate 6 increased 4-8-fold its antibacterial activity against MRSA strains supporting our hypothesis that the chemical connection of 4 to C5-curcumin (2) increases the antibacterial activity of 2 against Gram-positive bacteria. Combinational index (CIn) values that range between 1.6 and 2.3 were obtained when eight MRSA strains were treated with an equimolar mixture of 2 and 4. These results demonstrated that an antagonistic effect is taking place. Finally, it was investigated whether conjugate 6 can affect the replication process of S. aureus, since this compound inhibited the supercoiling activity of the S. aureus DNA gyrase at minimum inhibitory concentrations (MIC) of 250 μg/mL (IC50=100.2±13.9 μg/mL). Moreover, it was observed that the presence of 4 in conjugate 6 improves the anti-topoisomerase activity of 2 towards S. aureus DNA gyrase, which is in agreement with results obtained from antibacterial susceptibility tests involving MRSA strains. PMID:26483137

  3. In Vitro Antibacterial Efficacy of 21 Indian Timber-Yielding Plants Against Multidrug-Resistant Bacteria Causing Urinary Tract Infection

    PubMed Central

    Mishra, Monali P.; Padhy, Rabindra N.

    2013-01-01

    Objectives To screen methanolic leaf extracts of 21 timber-yielding plants for antibacterial activity against nine species of uropathogenic bacteria isolated from clinical samples of a hospital (Enterococcus faecalis, Staphylococcus aureus, Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa). Methods Bacterial strains were subjected to antibiotic sensitivity tests by the Kirby–Bauer's disc diffusion method. The antibacterial potentiality of leaf extracts was monitored by the agar-well diffusion method with multidrug-resistant (MDR) strains of nine uropathogens. Results Two Gram-positive isolates, E. faecalis and S. aureus, were resistant to 14 of the 18 antibiotics used. Gram-negative isolates A. baumannii, C. freundii, E. aerogenes, E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa were resistant to 10, 12, 9, 11, 11, 10, and 11 antibiotics, respectively, of the 14 antibiotics used. Methanolic leaf extracts of Anogeissus acuminata had the maximum zone of inhibition size—29 mm against S. aureus and 28 mm against E. faecalis and P. aeruginosa. Cassia tora had 29 mm as the zone of inhibition size for E. faecalis, E. aerogenes, and P. aeruginosa. Based on the minimum inhibitory concentration and minimum bactericidal concentration values, the most effective 10 plants against uropathogens could be arranged in decreasing order as follows: C. tora > A. acuminata > Schleichera oleosa > Pterocarpus santalinus > Eugenia jambolana > Bridelia retusa > Mimusops elengi > Stereospermum kunthianum > Tectona grandis > Anthocephalus cadamba. The following eight plants had moderate control capacity: Artocarpus heterophyllus, Azadirachta indica, Dalbergia latifolia, Eucalyptus citriodora, Gmelina arborea, Pongamia pinnata, Pterocarpus marsupium, and Shorea robusta. E. coli, followed by A. baumannii, C. freundii, E. aerogenes, P. mirabilis, and P

  4. Complete genome sequence of Acinetobacter baumannii XH386 (ST208), a multi-drug resistant bacteria isolated from pediatric hospital in China

    PubMed Central

    Fang, Youhong; Quan, Jingjing; Hua, Xiaoting; Feng, Ye; Li, Xi; Wang, Jianfeng; Ruan, Zhi; Shang, Shiqiang; Yu, Yunsong

    2015-01-01

    Acinetobacter baumannii is an important bacterium that emerged as a significant nosocomial pathogen worldwide. The rise of A. baumannii was due to its multi-drug resistance (MDR), while it was difficult to treat multi-drug resistant A. baumannii with antibiotics, especially in pediatric patients for the therapeutic options with antibiotics were quite limited in pediatric patients. A. baumannii ST208 was identified as predominant sequence type of carbapenem resistant A. baumannii in the United States and China. As we knew, there was no complete genome sequence reproted for A. baumannii ST208, although several whole genome shotgun sequences had been reported. Here, we sequenced the 4087-kilobase (kb) chromosome and 112-kb plasmid of A. baumannii XH386 (ST208), which was isolated from a pediatric hospital in China. The genome of A. baumannii XH386 contained 3968 protein-coding genes and 94 RNA-only encoding genes. Genomic analysis and Minimum inhibitory concentration assay showed that A. baumannii XH386 was multi-drug resistant strain, which showed resistance to most of antibiotics, except for tigecycline. The data may be accessed via the GenBank accession number CP010779 and CP010780. PMID:26981403

  5. Modulation of Bacterial Multidrug Resistance Efflux Pumps of the Major Facilitator Superfamily

    PubMed Central

    Kumar, Sanath; Mukherjee, Mun Mun; Varela, Manuel F.

    2013-01-01

    Bacterial infections pose a serious public health concern, especially when an infectious disease has a multidrug resistant causative agent. Such multidrug resistant bacteria can compromise the clinical utility of major chemotherapeutic antimicrobial agents. Drug and multidrug resistant bacteria harbor several distinct molecular mechanisms for resistance. Bacterial antimicrobial agent efflux pumps represent a major mechanism of clinical resistance. The major facilitator superfamily (MFS) is one of the largest groups of solute transporters to date and includes a significant number of bacterial drug and multidrug efflux pumps. We review recent work on the modulation of multidrug efflux pumps, paying special attention to those transporters belonging primarily to the MFS. PMID:25750934

  6. A randomized, controlled trial of enhanced cleaning to reduce contamination of healthcare worker gowns and gloves with multidrug-resistant bacteria

    PubMed Central

    Hess, Aaron S.; Shardell, Michelle; Johnson, J.Kristie; Thom, Kerri A.; Roghmann, Mary-Claire; Netzer, Giora; Amr, Sania; Morgan, Daniel J.; Harris, Anthony D.

    2013-01-01

    Objective To determine whether enhanced daily cleaning would reduce contamination of healthcare worker (HCW) gowns and gloves with methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Acinetobacter baumannii (MDRAB). Design A cluster-randomized controlled trial. Setting Four intensive care units (ICUs) in an urban tertiary care hospital. Participants ICU rooms occupied by patients colonized with MRSA or MDRAB. Intervention Extra enhanced daily cleaning of ICU room surfaces frequently touched by HCWs. Results A total of 4,444 cultures were collected from 132 rooms over 10 months. Using fluorescent dot markers at 2,199 surfaces, we found that 26% of surfaces in control rooms were cleaned and 100% of surfaces in experimental rooms were cleaned (p < 0.001). The mean proportion of contaminated HCW gowns and gloves following routine care provision and before leaving the rooms of patients with MDRAB was 16% among control rooms and 12% among experimental rooms (RR: 0.77, 95% CI: 0.28 – 2.11, p = 0.230). For MRSA, the mean proportions were 22% and 19%, respectively (RR: 0.89, 95%: 0.5 – 1.53, p = 0.158). Discussion Intense enhanced daily cleaning of ICU rooms occupied by patients colonized with MRSA or MDRAB was associated with a nonsignificant reduction in contamination of HCW gowns and gloves after routine patient care activities. Further research is needed to determine whether intense environmental cleaning will lead to significant reductions and fewer infections. PMID:23571365

  7. Breaking the Spell: Combating Multidrug Resistant 'Superbugs'.

    PubMed

    Khan, Shahper N; Khan, Asad U

    2016-01-01

    Multidrug-resistant (MDR) bacteria have become a severe threat to community wellbeing. Conventional antibiotics are getting progressively more ineffective as a consequence of resistance, making it imperative to realize improved antimicrobial options. In this review we emphasized the microorganisms primarily reported of being resistance, referred as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacteriaceae) accentuating their capacity to "escape" from routine antimicrobial regimes. The upcoming antimicrobial agents showing great potential and can serve as alternative therapeutic options are discussed. We also provided succinct overview of two evolving technologies; specifically network pharmacology and functional genomics profiling. Furthermore, In vivo imaging techniques can provide novel targets and a real time tool for potential lead molecule assessment. The employment of such approaches at prelude of a drug development process, will enables more informed decisions on candidate drug selection and will maximize or predict therapeutic potential before clinical testing. PMID:26925046

  8. [Multidrug resistance (MDR) in oncology].

    PubMed

    Souvirón Rodríguez, A; Ruiz Gómez, M J; Morales Moreno, J A; Martínez Morillo, M

    1997-03-01

    Multidrug resistance or mdr is a frequent phenomenon for which tumor cells can develop, in only one step, cross-resistance to a different anticancer drugs such as antibiotics, vinca alkaloids and podophylotoxins. This is due to an extrusion of drugs out of the cells, since it is interrelated with the decrease of the intracellular concentration of the drug, compared to sensitive cells. This phenomeno of multidrug resistance (mdr) is considered one of the principal causes of failure in quimiotherapic treatment of cancer, and is associated in many cases to an hyperexpression of mdr-I gene, that codifies for a high molecular weight glycoprotein (p-170) (170-180 Kdaltons), also called p-glycoprotein (pgp). Locadet it in the cellular membrane extracts, like a pump, the quimiotherapic drugs with consumption of ATP. In humans, there are two principal genes that codify for pgp: mdr-I and mdr2/3; being the most important the mdr-I gene. The structure of p-glycoprotein consists in two symmetrical halves anchored in the cellular membrane that includes three extracellular dominances each one, and on intracellular portion with the ATP binding site. Also, has got an for extracellular carbohydrates chain. It is specially important to find drugs that reverse the multidrug resistance. Chemicals such as verapamil, nifedine, quinidine and calmodulin inhibitors are joined to pgp inhibiting it. A Cyclosporine and its non-immunosuppressors derivateds such as SDZ 280-125 and SDZ PSC 833 reverse mdr. At present it is being advancing in clinical trials, but the results are not satisfactory. Most useful chemicals are verapamil, better R-verapamil and A-cyclosporine or its non-immunosuppressors derivates. Futures possibilities are grateful. From diagnostic point of view the mains are: 1. Detection of mdr-I gene. 2. Recognition of the presence of mRNA for pgp. 3. Detection of pgp by flow cytometry or western blot. 4. Immunohistochemistry with monoclonal antibodies to pgp. 5. Rhodamine 123 to

  9. A randomized controlled trial of enhanced cleaning to reduce contamination of healthcare worker gowns and gloves with multidrug-resistant bacteria.

    PubMed

    Hess, Aaron S; Shardell, Michelle; Johnson, J Kristie; Thom, Kerri A; Roghmann, Mary-Claire; Netzer, Giora; Amr, Sania; Morgan, Daniel J; Harris, Anthony D

    2013-05-01

    OBJECTIVE. To determine whether enhanced daily cleaning would reduce contamination of healthcare worker (HCW) gowns and gloves with methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Acinetobacter baumannii (MDRAB). DESIGN. A cluster-randomized controlled trial. SETTING. Four intensive care units (ICUs) in an urban tertiary care hospital. PARTICIPANTs. ICU rooms occupied by patients colonized with MRSA or MDRAB. INTERVENTION. Extra enhanced daily cleaning of ICU room surfaces frequently touched by HCWs. RESULTS. A total of 4,444 cultures were collected from 132 rooms over 10 months. Using fluorescent dot markers at 2,199 surfaces, we found that 26% of surfaces in control rooms were cleaned and that 100% of surfaces in experimental rooms were cleaned (P < .001). The mean proportion of contaminated HCW gowns and gloves following routine care provision and before leaving the rooms of patients with MDRAB was 16% among control rooms and 12% among experimental rooms (relative risk, 0.77 [95% confidence interval, 0.28-2.11]; P = .23). For MRSA, the mean proportions were 22% and 19%, respectively (relative risk, 0.89 [95% confidence interval, 0.50-1.53]; P = .16). DISCUSSION. Intense enhanced daily cleaning of ICU rooms occupied by patients colonized with MRSA or MDRAB was associated with a nonsignificant reduction in contamination of HCW gowns and gloves after routine patient care activities. Further research is needed to determine whether intense environmental cleaning will lead to significant reductions and fewer infections. PMID:23571365

  10. Chloramphenicol – A Potent Armament Against Multi-Drug Resistant (MDR) Gram Negative Bacilli?

    PubMed Central

    2016-01-01

    Introduction Multidrug-resistant gram-negative bacteria cause infections which are hard to treat and cause high morbidity and mortality. Due to limited therapeutic options there is a renewed interest upon older antimicrobials which had fallen into disuse as a result of toxic side effects. One such antibiotic is chloramphenicol which was sidelined due to reports linking its use with the development of aplastic anaemia. Aim A study was conducted to evaluate the susceptibility of chloramphenicol in light of the emerging problem of multi-drug resistant gram negative bacteria (MDR GNB). Materials and Methods A total of 483 MDR GNB of the 650 consecutive Gram Negative Bacteria isolated from various clinical samples of patients admitted at a tertiary care hospital in Jaipur between January-June 2014 were screened for chloramphenicol susceptibility by the disc diffusion method as per CLSI guidelines. Results The MDR GNB isolates were obtained from 217 (45%) urine, 163 (34%) from respiratory samples, 52(11%) from pus, 42 (9%) from blood and 9 (2%) from body fluids. A 68% of the MDR GNB isolates were found to be sensitive to chloramphenicol. Conclusion Clinicians should always check for the local susceptibility of Gram-negative bacteria to chloramphenicol. This antibiotic has a potential to play a role in the therapeutic management of infections due to MDR GNB pathogens. PMID:27042458

  11. [Proteins in cancer multidrug resistance].

    PubMed

    Popęda, Marta; Płuciennik, Elżbieta; Bednarek, Andrzej K

    2014-01-01

    Multidrug Resistance (MDR) is defined as insensitivity to administered medicines that are structurally unrelated and have different molecular targets. Cancers possess numerous mechanisms of drug resistance, involving various aspects of cell biology. A pivotal role in this phenomenon is played by proteins--enzymatic or structural parts of the cell. Membrane transporters, including the main members of ABC protein family--P-gp, MRP1 and BCRP, as well as LRP, which builds structure of vaults, determine the multidrug-resistant phenotype by decreasing drug concentration within the cell or modifying its distribution to intracellular compartments. The π isoform of protein enzyme--glutathione S-transferase (GSTP-1), is responsible for excessive intensity of detoxification of cytostatics. A common example of altered drug target site that does not respond to chemotherapy is topoisomerase II α (TopoIIa). Alterations of programmed cell death result from expression of metallothionein (MT)--inhibitor of the process, and cytokeratin 18 (CK18), which, if in high concentration, also prevents apoptosis of cells. Several methods of decreasing activity of these proteins have been developed, aiming to overcome MDR in cancer cells. However, for a variety of reasons, their clinical suitability is still very low, leading to continuous increase in death rate among patients. This paper presents current state of knowledge on the most important examples of proteins responsible for MDR of cancer cells and molecular mechanisms of their action. PMID:24864112

  12. Role of multidrug resistance in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Diddens, Heyke C.

    1992-06-01

    Multidrug resistance in cancer chemotherapy is a well established phenomenon. One of the most common phenotypical changes in acquired or intrinsic multidrug resistance in human tumor cells is the overexpression of the mdrl gene product P-glycoprotein, which acts as an active efflux pump. Increased levels of P-glycoprotein are associated with resistance to a variety of anticancer drugs commonly used in tumor chemotherapy like anthracyclins, vinca- alcaloids, epipodophyllotoxins or actinomycin D. We investigated the efficacy or photodynamic therapy in the treatment of tumor cells expressing the multidrug resistance phenotype. Our data show that multidrug resistant cells are highly cross resistant to the phototoxic stain rhodamine 123 but exhibit only low degrees of cross resistance (2 - 3 -folds) to the photosensitizers Photosan-3, Clorin-2, methylene blue and meso-tetra (4- sulfonatophenyl) porphine (TPPS4). Resistance is associated with a decrease in intracellular accumulation of the photosensitizer. Verapamil, a membrane active compound known to enhance drug sensitivity in multidrug resistant cells by inhibition of P-glycoprotein, also increases phototoxicity in multidrug resistant cells. Our results imply that tumors expressing the multidrug resistance phenotype might fail to respond to photochemotherapy with rhodamine 123. On the other hand, multidrug resistance may not play an important role in photodynamic therapy with Photosan-3, Chlorin-2, methylene blue or TPPS4.

  13. Pharmacotherapy for multidrug resistant tuberculosis

    PubMed Central

    Chhabra, Naveen; Aseri, M. L.; Dixit, Ramakant; Gaur, S.

    2012-01-01

    The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs namely, isoniazid and rifampicin. Emergence of multidrug resistance tuberculosis (MDR-TB) is now a health problem faced by most of the developing countries as well as developed countries across the globe. MDR-TB is a man-made disease that is caused by improper treatment, inadequate drug supplies, and poor patient supervision. HIV infection and AIDS have been implicated as important cause for this. The review of a published literature suggests that the most powerful predictor of treatment of MDR-TB is a history of treatment of TB. Although the treatment is efficacious, there are also a number of adverse effects caused by drugs used in the treatment of MDR-TB. PMID:22629081

  14. Popcorn-shaped magnetic core-plasmonic shell multifunctional nanoparticles for the targeted magnetic separation and enrichment, label-free SERS imaging, and photothermal destruction of multidrug-resistant bacteria.

    PubMed

    Fan, Zhen; Senapati, Dulal; Khan, Sadia Afrin; Singh, Anant Kumar; Hamme, Ashton; Yust, Brian; Sardar, Dhiraj; Ray, Paresh Chandra

    2013-02-18

    Over the last few years, one of the most important and complex problems facing our society is treating infectious diseases caused by multidrug-resistant bacteria (MDRB), by using current market-existing antibiotics. Driven by this need, we report for the first time the development of the multifunctional popcorn-shaped iron magnetic core-gold plasmonic shell nanotechnology-driven approach for targeted magnetic separation and enrichment, label-free surface-enhanced Raman spectroscopy (SERS) detection, and the selective photothermal destruction of MDR Salmonella DT104. Due to the presence of the "lightning-rod effect", the core-shell popcorn-shaped gold-nanoparticle tips provided a huge field of SERS enhancement. The experimental data show that the M3038 antibody-conjugated nanoparticles can be used for targeted separation and SERS imaging of MDR Salmonella DT104. A targeted photothermal-lysis experiment, by using 670 nm light at 1.5 W cm(-2) for 10 min, results in selective and irreparable cellular-damage to MDR Salmonella. We discuss the possible mechanism and operating principle for the targeted separation, label-free SERS imaging, and photothermal destruction of MDRB by using the popcorn-shaped magnetic/plasmonic nanotechnology. PMID:23296491

  15. Essential Oils and Non-volatile Compounds Derived from Chamaecyparis obtusa: Broad Spectrum Antimicrobial Activity against Infectious Bacteria and MDR(multidrug resistant) Strains.

    PubMed

    Bae, Min-Suk; Park, Dae-Hun; Choi, Chul-Yung; Kim, Gye-Yeop; Yoo, Jin-Cheol; Cho, Seung-Sik

    2016-05-01

    The aim of this study was to evaluate the antibacterial activity of essential oil from Chamaecyparis obtusa against general infectious microbes and drug resistant strains of clinical origin. The results indicate that both essential oil and non-volatile residue have broad inhibitory activity against test strains. Essential oil and non-volatile residues showed antimicrobial activity not only against general infectious bacteria, but also against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. PMID:27319153

  16. Retrospective observational study to assess the clinical management and outcomes of hospitalised patients with complicated urinary tract infection in countries with high prevalence of multidrug resistant Gram-negative bacteria (RESCUING)

    PubMed Central

    Shaw, Evelyn; Addy, Ibironke; Stoddart, Margaret; Vank, Christiane; Grier, Sally; Wiegand, Irith; Leibovici, Leonard; Eliakim-Raz, Noa; Vallejo-Torres, Laura; Morris, Stephen; MacGowan, Alasdair; Carratalà, Jordi; Pujol, Miquel

    2016-01-01

    Introduction The emergence of multidrug resistant (MDR) Gram-negative bacteria (GNB), including carbapenemase-producing strains, has become a major therapeutic challenge. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. The study has been designed to gain insight into the epidemiology, clinical management, outcome and healthcare cost of patients with cUTI, especially in countries with high prevalence of MDR GNB. Methods and analysis This multinational and multicentre observational, retrospective study will identify cases from 1 January 2013 to 31 December 2014 in order to collect data on patients with cUTI as a cause of hospital admission, and patients who develop cUTI during their hospital stay. The primary end point will be treatment failure defined as the presence of any of the following criteria: (1) signs or symptoms of cUTI present at diagnosis that have not improved by days 5–7 with appropriate antibiotic therapy, (2) new cUTI-related symptoms that have developed within 30 days of diagnosis, (3) urine culture taken within 30 days of diagnosis, either during or after completion of therapy, that grows ≥104 colony-forming unit/mL of the original pathogen and (4) death irrespective of cause within 30 days of the cUTI diagnosis. Sample size 1000 patients afford a power of 0.83 (α=0.05) to detect an absolute difference of 10% in the treatment failure rate between MDR bacteria and other pathogens. This should allow for the introduction of about 20 independent risk factors (or their interaction) in a logistic regression model looking at risk factors for failure. Ethics and dissemination Approval will be sought from all relevant Research Ethics Committees. Publication of this study will be considered as a joint publication by the participating investigator leads, and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). Trial

  17. Multidrug resistance phenotypes are widespread over different bacterial taxonomic groups thriving in surface water.

    PubMed

    Narciso-da-Rocha, Carlos; Manaia, Célia M

    2016-09-01

    The environment is the original and most ancient source of the antibiotic resistance determinants that threat the human health nowadays. In the environment, water is a privileged habitat and mode of dissemination of bacteria of different origins. Freshwater bodies that cross urban areas are supposed to hold a complex mixture of both human/animal origin and strictly environmental bacteria. In this study, we were interested in unveiling the bacterial diversity in urban river transects and, simultaneously, investigate the occurrence of antibiotic resistant bacteria, in particular the multidrug resistant (MDR). With this aim, water and sediments of two rivers were sampled from an urban transect and the bacterial diversity was assessed based on 16S rRNA gene-based community analysis and, simultaneously, total heterotrophic bacteria were isolated in the presence and in the absence of antibiotics. The three predominant phyla were Proteobacteria, Bacteroidetes and Actinobacteria, in water, or Acidobacteria, in sediments. MDR bacteria were observed to belong to the predominant phyla observed in water, mostly of the classes Gamma- and Betaproteobacteria (Proteobacteria) and Sphingobacteriia and Flavobacteriia (Bacteroidetes) and belonged to genera of ubiquitous (Pseudomonas, Acinetobacter, Stenotrophomonas) or mainly environmental (Chitinophaga, Chryseobacterium) bacteria. The observation that MDR bacteria are widespread in the environment and over distinct phylogenetic lineages has two relevant implications: i) the potential of environmental bacteria as source or facilitators for antibiotic resistance acquisition; ii) the need to complement culture-independent methods with culture-based approaches in order to identify major sources of MDR profiles. PMID:27131885

  18. Fecal Microbiota Transplantation Inhibits Multidrug-Resistant Gut Pathogens: Preliminary Report Performed in an Immunocompromised Host.

    PubMed

    Biliński, Jarosław; Grzesiowski, Paweł; Muszyński, Jacek; Wróblewska, Marta; Mądry, Krzysztof; Robak, Katarzyna; Dzieciątkowski, Tomasz; Wiktor-Jedrzejczak, Wiesław; Basak, Grzegorz W

    2016-06-01

    Colonization of the gastrointestinal tract with multidrug-resistant (MDR) bacteria is a consequence of gut dysbiosis. We describe the successful utilization of fecal microbiota transplantation to inhibit Klebsiella pneumoniae MBL(+) and Escherichia coli ESBL(+) gut colonization in the immunocompromised host as a novel tool in the battle against MDR microorganisms. ClinicalTrials.gov identifier NCT02461199. PMID:26960790

  19. LL-37-Derived Peptides Eradicate Multidrug-Resistant Staphylococcus aureus from Thermally Wounded Human Skin Equivalents

    PubMed Central

    de Breij, Anna; Chan, Heelam; van Dissel, Jaap T.; Drijfhout, Jan W.; Hiemstra, Pieter S.; El Ghalbzouri, Abdoelwaheb; Nibbering, Peter H.

    2014-01-01

    Burn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistant Staphylococcus aureus (MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains of S. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria. PMID:24841266

  20. LL-37-derived peptides eradicate multidrug-resistant Staphylococcus aureus from thermally wounded human skin equivalents.

    PubMed

    Haisma, Elisabeth M; de Breij, Anna; Chan, Heelam; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; El Ghalbzouri, Abdoelwaheb; Nibbering, Peter H

    2014-08-01

    Burn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistant Staphylococcus aureus (MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains of S. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria. PMID:24841266

  1. Multidrug Resistance Proteins (MRPs) and Cancer Therapy.

    PubMed

    Zhang, Yun-Kai; Wang, Yi-Jun; Gupta, Pranav; Chen, Zhe-Sheng

    2015-07-01

    The ATP-binding cassette (ABC) transporters are members of a protein superfamily that are known to translocate various substrates across membranes, including metabolic products, lipids and sterols, and xenobiotic drugs. Multidrug resistance proteins (MRPs) belong to the subfamily C in the ABC transporter superfamily. MRPs have been implicated in mediating multidrug resistance by actively extruding chemotherapeutic substrates. Moreover, some MRPs are known to be essential in physiological excretory or regulatory pathways. The importance of MRPs in cancer therapy is also implied by their clinical insights. Modulating the function of MRPs to re-sensitize chemotherapeutic agents in cancer therapy shows great promise in cancer therapy; thus, multiple MRP inhibitors have been developed recently. This review article summarizes the structure, distribution, and physiological as well as pharmacological function of MRP1-MRP9 in cancer chemotherapy. Several novel modulators targeting MRPs in cancer therapy are also discussed. PMID:25840885

  2. Facing multi-drug resistant tuberculosis.

    PubMed

    Sotgiu, Giovanni; Migliori, Giovanni Battista

    2015-06-01

    Multi-drug resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis strains resistant to at least two of the most effective anti-tuberculosis drugs (i.e., isoniazid and rifampicin). Therapeutic regimens based on second- and third-line anti-tuberculosis medicines showed poor efficacy, safety, and tolerability profiles. It was estimated that in 2012 the multi-drug resistant tuberculosis incidence ranged from 300,000 to 600,000 cases, mainly diagnosed in the Eastern European and Central Asian countries. The highest proportion of cases is among individuals previously exposed to anti-tuberculosis drugs. Three main conditions can favour the emergence and spread of multi-drug resistant tuberculosis: the poor implementation of the DOTS strategy, the shortage or the poor quality of the anti-tuberculosis drugs, and the poor therapeutic adherence of the patients to the prescribed regimens. Consultation with tuberculosis experts (e.g., consilium) is crucial to tailor the best anti-tuberculosis therapy. New therapeutic options are necessary: bedaquiline and delamanid seem promising drugs; in particular, during the development phase they demonstrated a protective effect against the emergence of further resistances towards the backbone drugs. In the recent past, other antibiotics have been administered off-label: the most relevant efficacy, safety, and tolerability profile was proved in linezolid-, meropenem/clavulanate-, cotrimoxazole-containing regimens. New research and development activities are needed in the diagnostic, therapeutic, preventive fields. PMID:24792579

  3. Colonization of multidrug resistant pathogens in a hybrid pediatric cardiac surgery center

    PubMed Central

    Haponiuk, Ireneusz; Steffens, Mariusz; Arlukowicz, Elzbieta; Irga-Jaworska, Ninela; Chojnicki, Maciej; Kwasniak, Ewelina; Zielinski, Jacek

    2016-01-01

    Introduction The incidence of multidrug resistant microorganisms worldwide is increasing. The aim of the study was to present institutional experience with the multidrug resistant microorganism colonization patterns observed in children with congenital heart diseases hospitalized in a hybrid pediatric cardiac surgery center. Material and methods Microbiological samples were routinely collected in all children admitted to our department. All microbiological samples were analyzed with regard to multidrug resistant microorganisms: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Gram-negative rods producing extended-spectrum beta-lactamases (ESBL), multidrug resistant Gram-negative rods (MDR-GNRs), carbapenemase-producing Klebsiella pneumoniae (KPC), carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA). Results In 30 (9%) swabs ‘alert’ pathogens from the above group of listed microorganisms were found. All positive swabs were isolated in 19 (16.1%) children. Multidrug resistant pathogen colonization was statistically significantly more often observed in children admitted from other medical facilities than in children admitted from home (38% vs. 10%, p = 0.0089). In the group of children younger than 6 months ‘alert’ pathogen were more often observed than in older children (34.1% vs. 5.4%, p < 0.001). Conclusions Preoperative multidrug resistant pathogen screening in children admitted and referred for congenital heart disease procedures may be of great importance since many of these patients are colonized with resistant bacteria. Knowledge of the patient's microbiome is important in local epidemiological control along with tailoring the most effective preoperative prophylactic antibiotic for each patient. The impact of preoperative screening on postoperative infections and other complications requires further analysis. PMID:27279859

  4. Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients

    PubMed Central

    Göhring, Katharina; Hamprecht, Klaus; Jahn, Gerhard

    2015-01-01

    In pediatric and adult patients after stem cell transplantation (SCT) disseminated infections caused by human cytomegalovirus (HCMV) can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV), foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97) and the polymerase-gene (UL54). Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation could be detected in specific compartments exclusively and not in blood. PMID:25750703

  5. Inhibition of bacterial multidrug resistance by celecoxib, a cyclooxygenase-2 inhibitor.

    PubMed

    Kalle, Arunasree M; Rizvi, Arshad

    2011-01-01

    Multidrug resistance (MDR) is a major problem in the treatment of infectious diseases and cancer. Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)-specific inhibitor celecoxib would not only inhibit COX-2 but also help in the reversal of drug resistance in cancers by inhibiting the MDR1 efflux pump. Here, we demonstrate that celecoxib increases the sensitivity of bacteria to the antibiotics ampicillin, kanamycin, chloramphenicol, and ciprofloxacin by accumulating the drugs inside the cell, thus reversing MDR in bacteria. PMID:20937780

  6. Breaking the Spell: Combating Multidrug Resistant ‘Superbugs’

    PubMed Central

    Khan, Shahper N.; Khan, Asad U.

    2016-01-01

    Multidrug-resistant (MDR) bacteria have become a severe threat to community wellbeing. Conventional antibiotics are getting progressively more ineffective as a consequence of resistance, making it imperative to realize improved antimicrobial options. In this review we emphasized the microorganisms primarily reported of being resistance, referred as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacteriaceae) accentuating their capacity to “escape” from routine antimicrobial regimes. The upcoming antimicrobial agents showing great potential and can serve as alternative therapeutic options are discussed. We also provided succinct overview of two evolving technologies; specifically network pharmacology and functional genomics profiling. Furthermore, In vivo imaging techniques can provide novel targets and a real time tool for potential lead molecule assessment. The employment of such approaches at prelude of a drug development process, will enables more informed decisions on candidate drug selection and will maximize or predict therapeutic potential before clinical testing. PMID:26925046

  7. Multidrug resistance in pediatric urinary tract infections.

    PubMed

    Gaspari, Romolo J; Dickson, Eric; Karlowsky, James; Doern, Gary

    2006-01-01

    Urinary tract infections (UTIs) represent a common infection in the pediatric population. Escherichia coli is the most common uropathogen in children, and antimicrobial resistance in this species complicates the treatment of pediatric UTIs. Despite the impact of resistance on empiric antibiotic choice, there is little data on multidrug resistance in pediatric patients. In this paper, we describe characteristics of multidrug-resistant E. coli in pediatric patients using a large national database of uropathogens antimicrobial sensitivities. Antimicrobial susceptibility patterns to commonly prescribed antibiotics were performed on uropathogens isolated from children presenting to participating hospitals between 1999 and 2001. Data were analyzed separately for four pediatric age groups. Single and multidrug resistance to ampicillin, amoxicillin-clavulanate, cefazolin, ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole (TMP-SMX) were performed on all specimens. There were a total of 11,341 E. coli urine cultures from 343 infants (0-4 weeks), 1,801 toddlers (5 weeks-24 months), 6,742 preteens (2-12 years), and 2,455 teens (13-17 years). E. coli resistance to ampicillin peaked in toddlers (52.8%) but was high in preteens (52.1%), infants (50.4%), and teens (40.6%). Resistance to two or more antibiotics varied across age groups, with toddlers (27%) leading preteens (23.1%), infants (21%), and teens (15.9%). Resistance to three or more antibiotics was low in all age groups (range 3.1-5.2%). The most common co-resistance in all age groups was ampicillin/TMP-SMZ. In conclusion, less than half of all pediatric UTIs are susceptible to all commonly used antibiotics. In some age groups, there is a significant percentage of co-resistance between the two most commonly used antibiotics (ampicillin and TMP-SMZ). PMID:16922629

  8. Emerging therapies for multidrug resistant Acinetobacter baumannii.

    PubMed

    García-Quintanilla, Meritxell; Pulido, Marina R; López-Rojas, Rafael; Pachón, Jerónimo; McConnell, Michael J

    2013-03-01

    The global emergence of multidrug resistant Acinetobacter baumannii has reduced the number of clinically available antibiotics that retain activity against this pathogen. For this reason, the development of novel prevention and treatment strategies for infections caused by A. baumannii is necessary. Several studies have begun to characterize nonantibiotic approaches that utilize novel mechanisms of action to achieve antibacterial activity. Recent advances in phage therapy, iron chelation therapy, antimicrobial peptides, prophylactic vaccination, photodynamic therapy, and nitric oxide (NO)-based therapies have all been shown to have activity against A. baumannii. However, before these approaches can be used clinically there are still limitations and remaining questions that must be addressed. PMID:23317680

  9. Congenital Transmission of Multidrug-Resistant Tuberculosis

    PubMed Central

    Espiritu, Nora; Aguirre, Lino; Jave, Oswaldo; Sanchez, Luis; Kirwan, Daniela E.; Gilman, Robert H.

    2014-01-01

    This article presents a case of multidrug-resistant tuberculosis (TB) in a Peruvian infant. His mother was diagnosed with disseminated TB, and treatment commenced 11 days postpartum. The infant was diagnosed with TB after 40 days and died at 2 months and 2 days of age. Congenital transmission of TB to the infant was suspected, because direct postpartum transmission was considered unlikely; also, thorough screening of contacts for TB was negative. Spoligotyping confirmed that both mother and baby were infected with identical strains of the Beijing family (SIT1). PMID:24821847

  10. Multidrug resistance and ESBL-producing Salmonella spp. isolated from broiler processing plants

    PubMed Central

    Ziech, Rosangela Estel; Lampugnani, Camila; Perin, Ana Paula; Sereno, Mallu Jagnow; Sfaciotte, Ricardo Antônio Pilegi; Viana, Cibeli; Soares, Vanessa Mendonça; de Almeida Nogueira Pinto, José Paes; dos Santos Bersot, Luciano

    2016-01-01

    The aim of this study was to investigate the occurrence of multidrug-resistant, extended spectrum beta-lactamase (ESBL) producing Salmonella spp. isolated from conveyor belts of broiler cutting rooms in Brazilian broiler processing plants. Ninety-eight strains of Salmonella spp. were analyzed. Multidrug resistance was determined by the disk diffusion test and the susceptibility of the isolated bacteria was evaluated against 18 antimicrobials from seven different classes. The double disk diffusion test was used to evaluate ESBL production. Of the 98 strains tested, 84 were multidrug resistant. The highest rates of resistance were against nalidixic acid (95%), tetracycline (91%), and the beta-lactams: ampicillin and cefachlor (45%), followed by streptomycin and gentamicin with 19% and 15% of strain resistance, respectively. By contrast, 97% of the strains were sensitive to chloramphenicol. 45% of the strains were positive for the presence of ESBL activity. In this study, high rates of multidrug resistance and ESBL production were observed in Salmonella spp. PMID:26887244

  11. Multidrug resistance and ESBL-producing Salmonella spp. isolated from broiler processing plants.

    PubMed

    Ziech, Rosangela Estel; Lampugnani, Camila; Perin, Ana Paula; Sereno, Mallu Jagnow; Sfaciotte, Ricardo Antônio Pilegi; Viana, Cibeli; Soares, Vanessa Mendonça; Pinto, José Paes de Almeida Nogueira; Bersot, Luciano dos Santos

    2016-01-01

    The aim of this study was to investigate the occurrence of multidrug-resistant, extended spectrum beta-lactamase (ESBL) producing Salmonella spp. isolated from conveyor belts of broiler cutting rooms in Brazilian broiler processing plants. Ninety-eight strains of Salmonella spp. were analyzed. Multidrug resistance was determined by the disk diffusion test and the susceptibility of the isolated bacteria was evaluated against 18 antimicrobials from seven different classes. The double disk diffusion test was used to evaluate ESBL production. Of the 98 strains tested, 84 were multidrug resistant. The highest rates of resistance were against nalidixic acid (95%), tetracycline (91%), and the beta-lactams: ampicillin and cefachlor (45%), followed by streptomycin and gentamicin with 19% and 15% of strain resistance, respectively. By contrast, 97% of the strains were sensitive to chloramphenicol. 45% of the strains were positive for the presence of ESBL activity. In this study, high rates of multidrug resistance and ESBL production were observed in Salmonella spp. PMID:26887244

  12. [Prevalence of multidrug-resistant Proteus spp. strains in clinical specimens and their susceptibility to antibiotics].

    PubMed

    Reśliński, Adrian; Gospodarek, Eugenia; Mikucka, Agnieszka

    2005-01-01

    Proteus sp. are opportunistic microorganisms which cause urinary tract and wounds infections, bacteriaemia and sepsis. The aim of this study was analysis of prevalence of multidrug-resistant Proteus sp. strains in clinical specimens and evaluation of their susceptibility to selected antibiotics. The study was carried out of 1499 Proteus sp. strains were isolated in 2000-2003 from patients of departments and dispensaries of the University Hospital CM in Bydgoszcz UMK in Torun. The strains were identified on the basis of appearance of bacterial colonies on bloody and McConkey's agars, movement ability, indole and urease production and in questionable cases biochemical profile in ID GN or ID E (bio-Mérieux) tests was also included. Antibiotic susceptibility was tested by disk diffusion method. Isolated strains were regarded as multidrug-resistant when they were resistant to three kinds of antibiotics at least. Received Proteus sp. the most frequently belonged to P. mirabilis species (92.3%). Most of these bacteria were isolated from urine from patients of Rehabilitation Clinic. All of multidrug-resistant strains were resistant to penicillins and cephalosporins, 98.9% to co-trimoxazole, 77.7% to quinolones, 63.8% to tetracyclines, 38.5% to aminoglycosides, 19.3% to monobactams and 3.4% to carbapenems. Almost 25% multidrug-resistant Proteus sp. produced ESBL. PMID:16134389

  13. NANOPREPARATIONS TO OVERCOME MULTIDRUG RESISTANCE IN CANCER

    PubMed Central

    Patel, Niravkumar R.; Pattni, Bhushan S.; Abouzeid, Abraham H.; Torchilin, Vladimir P.

    2013-01-01

    Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing micro tumor tissues in vitro are discussed in detail. PMID:23973912

  14. Management of multidrug-resistant enterococcal infections

    PubMed Central

    Arias, C. A.; Contreras, G. A.; Murray, B. E.

    2013-01-01

    Enterococci are organisms with a remarkable ability to adapt to the environment and acquire antibiotic resistance determinants. The evolution of antimicrobial resistance in these organisms poses enormous challenges for clinicians when faced with patients affected with severe infections. The increased prevalence and dissemination of multidrug-resistant Enterococcus faecium worldwide has resulted in a major decrease in therapeutic options because the majority of E. faecium isolates are now resistant to ampicillin and vancomycin, and exhibit high-level resistance to aminoglycosides, which are three of the traditionally most useful anti-enterococcal antibiotics. Newer antibiotics such as linezolid, daptomycin and tigecycline have good in vitro activity against enterococcal isolates, although their clinical use may be limited in certain clinical scenarios as a result of reduced rates of success, possible underdosing for enterococci and low serum levels, respectively, and also by the emergence of resistance. The experimental agent oritavancin may offer some hope for the treatment of vancomycin-resistant enterococci but clinical data are still lacking. Thus, optimal therapies for the treatment of multidrug-resistant enterococcal infections continue to be based on empirical observations and extrapolations from in vitro and animal data. Clinical studies evaluating new strategies, including combination therapies, to treat severe vancomycin-resistant E. faecium infections are urgently needed. PMID:20569266

  15. Phosphorylation of the multidrug resistance associated glycoprotein

    SciTech Connect

    Mellado, W.; Horwitz, S.B.

    1987-11-03

    Drug-resistant cell lines derived from the mouse macrophage-like cell line J774.2 express the multidrug resistant phenotype which includes the overexpression of a membrane glycoprotein (130-140 kilodaltons). Phosphorylation of this resistant-specific glycoprotein (P-glycoprotein) in intact cells and in cell-free membrane fractions has been studied. The phosphorylated glycoprotein can be immunoprecipitated by a rabbit polyclonal antibody specific for the glycoprotein. Phosphorylation studies done with partially purified membrane fractions derived from colchicine-resistant cells indicated that (a) phosphorylation of the glycoprotein in 1 mM MgCl/sub 2/ was enhanced a minimum of 2-fold by 10 ..mu..M cAMP and (b) the purified catalytic subunit of the cAMP-dependent protein kinase (protein kinase A) phosphorylated partially purified glycoprotein that was not phosphorylated by (..gamma..-/sup 32/P)ATP alone, suggesting that autophosphorylation was not involved. These results indicate that the glycoprotein is a phosphoprotein and that at least one of the kinases responsible for its phosphorylation is a membrane-associated protein kinase A. The state of phosphorylation of the glycoprotein, which is a major component of the multidrug resistance phenotype, may be related to the role of the glycoprotein in maintaining drug resistance.

  16. Phosphorylation of the multidrug resistance associated glycoprotein.

    PubMed

    Mellado, W; Horwitz, S B

    1987-11-01

    Drug-resistant cell lines derived from the mouse macrophage-like cell line J774.2 express the multidrug resistance phenotype which includes the overexpression of a membrane glycoprotein (130-140 kilodaltons). Phosphorylation of this resistant-specific glycoprotein (P-glycoprotein) in intact cells and in cell-free membrane fractions has been studied. The phosphorylated glycoprotein can be immunoprecipitated by a rabbit polyclonal antibody specific for the glycoprotein. Phosphorylation studies done with partially purified membrane fractions derived from colchicine-resistant cells indicated that (a) phosphorylation of the glycoprotein in 1 mM MgCl2 was enhanced a minimum of 2-fold by 10 microM cAMP and (b) the purified catalytic subunit of the cAMP-dependent protein kinase (protein kinase A) phosphorylated partially purified glycoprotein that was not phosphorylated by [gamma-32P]ATP alone, suggesting that autophosphorylation was not involved. These results indicate that the glycoprotein is a phosphoprotein and that at least one of the kinases responsible for its phosphorylation is a membrane-associated protein kinase A. The state of phosphorylation of the glycoprotein, which is a major component of the multidrug resistance phenotype, may be related to the role of the glycoprotein in maintaining drug resistance. PMID:3427052

  17. Viper metalloproteinase (Agkistrodon halys pallas) with antimicrobial activity against multi-drug resistant human pathogens.

    PubMed

    Samy, Ramar Perumal; Gopalakrishnakone, Ponnampalam; Chow, Vincent T K; Ho, Bow

    2008-07-01

    Metalloproteinases are abundant enzymes in crotalidae and viperidae snake venoms. Snake venom metalloproteinases (SVMPs) comprise a family of zinc-dependent enzymes, which display many different biological activities. A 23.1 kDa protein was isolated from Agkistrodon halys (pallas, Chinese viper) snake venom. The toxin is a single chain polypeptide with a molecular weight of 23146.61 and an N-terminal sequence (MIQVLLVTICLAVFPYQGSSIILES) relatively similar to that of other metalloprotein-like proteases isolated from the snake venoms of the Viperidae family. The antibacterial effect of Agkistrodon halys metalloproteinase (AHM) on Burkholderia pseudomallei (strains TES and KHW), Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacterium) was studied at a concentration 120 microM. Interestingly, we found that the metalloproteinase exhibited antibacterial properties and was more active against S. aureus, P. vulgaris, P. mirabilis and multi-drug resistant B. pseudomallei (strain KHW) bacteria. AHM variants with high bacteriostatic activity (MIC 1.875-60 microM) also tended to be less cytotoxic against U-937 human monocytic cells up to 1 mM concentrations. These results suggest that this metalloprotein exerts its antimicrobial effect by altering membrane packing and inhibiting mechanosensitive targets. PMID:18297685

  18. Yeast ABC proteins involved in multidrug resistance.

    PubMed

    Piecuch, Agata; Obłąk, Ewa

    2014-03-01

    Pleiotropic drug resistance is a complex phenomenon that involves many proteins that together create a network. One of the common mechanisms of multidrug resistance in eukaryotic cells is the active efflux of a broad range of xenobiotics through ATP-binding cassette (ABC) transporters. Saccharomyces cerevisiae is often used as a model to study such activity because of the functional and structural similarities of its ABC transporters to mammalian ones. Numerous ABC transporters are found in humans and some are associated with the resistance of tumors to chemotherapeutics. Efflux pump modulators that change the activity of ABC proteins are the most promising candidate drugs to overcome such resistance. These modulators can be chemically synthesized or isolated from natural sources (e.g., plant alkaloids) and might also be used in the treatment of fungal infections. There are several generations of synthetic modulators that differ in specificity, toxicity and effectiveness, and are often used for other clinical effects. PMID:24297686

  19. Epidemiology and Treatment of Multidrug Resistant Tuberculosis

    PubMed Central

    Mitnick, Carole D.; Appleton, Sasha C.; Shin, Sonya S.

    2010-01-01

    Multidrug resistant tuberculosis is now thought to afflict between 1 and 2 million patients annually. Although significant regional variability in the distribution of disease has been recorded, surveillance data are limited by several factors. The true burden of disease is likely underestimated. Nevertheless, the estimated burden is substantial enough to warrant concerted action. A range of approaches is possible, but all appropriate interventions require scale-up of laboratories and early treatment with regimens containing a sufficient number of second-line drugs. Ambulatory treatment for most patients, and improved infection control, can facilitate scale-up with decreased risk of nosocomial transmission. Several obstacles have been considered to preclude worldwide scale-up of treatment, mostly attributable to inadequate human, drug, and financial resources. Further delays in scale-up, however, risk continued generation and transmission of resistant tuberculosis, as well as associated morbidity and mortality. PMID:18810684

  20. Nanomedicine to overcome cancer multidrug resistance.

    PubMed

    Yang, Xi; Yi, Cheng; Luo, Na; Gong, Changyang

    2014-01-01

    Cancer is still considered to be one of the most severe diseases so far. Multidrug resistance (MDR) is a major obstacle against curative cancer chemotherapy. The over-expression of drug efflux pumps in cellular membrane plays a critical role in preventing cancer cells from conventional chemotherapy. Nanotechnology is emerging as a class of therapeutics for MDR. This review mainly focuses on some pivotal strategies to combat MDR, including the enhanced permeability and retention (EPR) effect, stealth nanoparticles to prolong circulation time, endosomal escape, active drug delivery, stimuli sensitive drug release, and targeted co-delivery of different compounds. While convinced challenges need combatting, large numbers of preclinical studies strongly suggest that nanomedicine formations have potential application for improving the treatment of MDR. PMID:25255871

  1. Role of old antibiotics in multidrug resistant bacterial infections.

    PubMed

    Maviglia, R; Nestorini, R; Pennisi, M

    2009-09-01

    Multidrug resistant bacteria infections are associated with an increase in attributable mortality and morbidity in ICU patients. Unfortunately, an emerging resistance to novel antibiotics used in the therapy of gram negative and gram positive bacteria infections is often reported in literature. Old antibiotics have been reintroduced in clinical practice. In this review we report the efficacy and safety use of older antimicrobial agents in critically ill patients. Polymyxins are used for nosocomial infection caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant strains. Patients with polymyxin-only susceptible gram-negative nosocomial pneumonia are reported to be successfully treated with inhaled colistin. Isepamicin can probably be used in intensive care units that harbor Gram-negative bacteria resistant to other aminoglycosides. Fosfomycin may be a useful alternative to linezolid and quinupristin-dalfopristin in the treatment of Vancomycin Resistant Enterococci (VRE) infections in certain clinical situations, e.g. uncomplicated urinary tract infections. Chloramphenicol has a wide antimicrobial spectrum and excellent tissue penetration; though it is sometimes used empirically in the hospital setting for the treatment of patients with unknown source of fever, its role is still a matter of controversy. The colistin/rifampicin combination might have a synergistic effect in Acinetobacter baumannii and Pseudomonas aeruginosa infections. Fusidic acid is active against staphylococcal strains. PMID:19799544

  2. Differences in the motility phenotype of multidrug-resistant Salmonella enterica serovar Typhimurium exposed to various antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the most prevalent foodborne-associated bacteria in humans and livestock, and over 35 per cent of these isolates are resistant to three or more antibiotics. This is a concern as multidrug-resistant (MDR) Salmonella has been associat...

  3. Tetracycline can induce the expression of invasion factors in multidrug-resistant Salmonella during early-log phase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The prevalence of multidrug-resistant (MDR) Salmonella continues to be an important health and safety concern in both humans and animals worldwide. Because the response of drug resistant bacteria exposed to antibiotics can affect a variety of cellular processes, such as motility, attachment, and in...

  4. Place of Colistin-Rifampicin Association in the Treatment of Multidrug-Resistant Acinetobacter Baumannii Meningitis: A Case Study

    PubMed Central

    Souhail, Dahraoui; Bouchra, Belefquih; Belarj, Badia; Laila, Rar; Mohammed, Frikh; Nassirou, Oumarou Mamane; Azeddine, Ibrahimi; Haimeur, Charki; Lemnouer, Abdelhay; Elouennass, Mostafa

    2016-01-01

    Treatment of Acinetobacter baumannii meningitis is an important challenge due to the accumulation of resistance of this bacteria and low meningeal diffusion of several antimicrobial requiring use of an antimicrobial effective combination to eradicate these species. We report a case of Acinetobacter baumannii multidrug-resistant nosocomial meningitis which was successfully treated with intravenous and intrathecal colistin associated with rifampicin. PMID:27064923

  5. BRCA2-deficient sarcomatoid mammary tumors exhibit multidrug resistance.

    PubMed

    Jaspers, Janneke E; Sol, Wendy; Kersbergen, Ariena; Schlicker, Andreas; Guyader, Charlotte; Xu, Guotai; Wessels, Lodewyk; Borst, Piet; Jonkers, Jos; Rottenberg, Sven

    2015-02-15

    Pan- or multidrug resistance is a central problem in clinical oncology. Here, we use a genetically engineered mouse model of BRCA2-associated hereditary breast cancer to study drug resistance to several types of chemotherapy and PARP inhibition. We found that multidrug resistance was strongly associated with an EMT-like sarcomatoid phenotype and high expression of the Abcb1b gene, which encodes the drug efflux transporter P-glycoprotein. Inhibition of P-glycoprotein could partly resensitize sarcomatoid tumors to the PARP inhibitor olaparib, docetaxel, and doxorubicin. We propose that multidrug resistance is a multifactorial process and that mouse models are useful to unravel this. PMID:25511378

  6. Community-acquired multidrug-resistant Gram-negative bacterial infective endocarditis

    PubMed Central

    Naha, Sowjanya; Naha, Kushal; Acharya, Vasudev; Hande, H Manjunath; Vivek, G

    2014-01-01

    We describe two cases of bacterial endocarditis secondary to multidrug-resistant Gram-negative organisms. In both cases, the diagnosis was made in accordance with the modified Duke's criteria and confirmed by histopathological analysis. Furthermore, in both instances there were no identifiable sources of bacteraemia and no history of contact with hospital or other medical services prior to the onset of symptoms. The patients were managed in similar fashion with prolonged broad-spectrum antibiotic therapy and surgical intervention and made complete recoveries. These cases highlight Gram-negative organisms as potential agents for endocarditis, as well as expose the dissemination of such multidrug-resistant bacteria into the community. The application of an integrated medical and surgical approach and therapeutic dilemmas encountered in managing these cases are described. PMID:25096655

  7. Multidrug-resistant Vibrio associated with an estuary affected by shrimp farming in Northeastern Brazil.

    PubMed

    Rocha, Rafael Dos Santos; Sousa, Oscarina Viana de; Vieira, Regine Helena Silva Dos Fernandes

    2016-04-15

    Bacteria of genus Vibrio with multidrug resistance in shrimp farm environment were recurrent. Thus, the aim of this study was to evaluate the antimicrobial resistance profile of 70 strains of Vibrio isolated from water and sediment of Acaraú estuary, Ceará, Brazil. In order to achieve this goal, disk diffusion technique was used with the following antimicrobial agents: ampicillin (Amp), aztreonam (Atm), cephalothin (Cef), cefotaxime (Ctx), ceftriaxone (Cro), ciprofloxacin (Cip), chloramphenicol (Clo), florfenicol (Flo), nitrofurantoin (Nit), gentamicin (Gen), oxytetracycline (Otc), tetracycline (Tet), streptomycin (Str), nalidixic acid (Nal), and sulfazotrim (Sut). All Vibrio strains were resistant to at least one antimicrobial agent, being verified as 17 multidrug-resistant profiles. All strains resistant to Otc and Tet were characterized to exhibit plasmidial resistance. Therefore, Vibrio strains from Acaraú estuary pose a risk to public health and aquatic culture. PMID:26876560

  8. Multidrug-Resistant Acinetobacter spp.: Increasingly Problematic Nosocomial Pathogens

    PubMed Central

    Lee, Kyungwon; Yong, Dongeun; Jeong, Seok Hoon

    2011-01-01

    Pathogenic bacteria have increasingly been resisting to antimicrobial therapy. Recently, resistance problem has been relatively much worsened in Gram-negative bacilli. Acinetobacter spp. are typical nosocomial pathogens causing infections and high mortality, almost exclusively in compromised hospital patients. Acinetobacter spp. are intrinsically less susceptible to antibiotics than Enterobacteriaceae, and have propensity to acquire resistance. A surveillance study in Korea in 2009 showed that resistance rates of Acinetobacter spp. were very high: to fluoroquinolone 67%, to amikacin 48%, to ceftazidime 66% and to imipenem 51%. Carbapenem resistance was mostly due to OXA type carbapenemase production in A. baumannii isolates, whereas it was due to metallo-β-lactamase production in non-baumannii Acinetobacter isolates. Colistin-resistant isolates were rare but started to be isolated in Korea. Currently, the infection caused by multidrug-resistant A. baumannii is among the most difficult ones to treat. Analysis at tertiary care hospital in 2010 showed that among the 1,085 isolates of Acinetobacter spp., 14.9% and 41.8% were resistant to seven, and to all eight antimicrobial agents tested, respectively. It is known to be difficult to prevent Acinetobacter spp. infection in hospitalized patients, because the organisms are ubiquitous in hospital environment. Efforts to control resistant bacteria in Korea by hospitals, relevant scientific societies and government agencies have only partially been successful. We need concerted multidisciplinary efforts to preserve the efficacy of currently available antimicrobial agents, by following the principles of antimicrobial stewardship. PMID:22028150

  9. Identification of compounds selectively killing multidrug resistant cancer cells

    PubMed Central

    Türk, Dóra; Hall, Matthew D.; Chu, Benjamin F.; Ludwig, Joseph A.; Fales, Henry M.; Gottesman, Michael M.; Szakács, Gergely

    2009-01-01

    There is a great need for the development of novel chemotherapeutic agents that overcome the emergence of multidrug resistance in cancer. We catalogued the National Cancer Institute’s Developmental Therapeutics Program (DTP) drug repository in search of compounds showing increased toxicity in multidrug resistant (MDR) cells. By comparing the sensitivity of parental cell lines with multidrug resistant derivatives, we identified 22 compounds possessing MDR-selective activity. Analysis of structural congeners led to the identification of 15 additional drugs showing increased toxicity in Pgp-expressing cells. Analysis of MDR-selective compounds led to the formulation of structure activity relationships (SAR) and pharmacophore models. This data mining coupled with experimental data points to a possible mechanism of action linked to metal chelation. Taken together, the discovery of the MDR-selective compound set demonstrates the robustness of the developing field of MDR-targeting therapy as a new strategy for resolving Pgp-mediated multidrug resistance. PMID:19843850

  10. Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library.

    PubMed

    Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

    2016-07-01

    With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim-sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim-sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim-sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

  11. Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library

    PubMed Central

    Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

    2016-01-01

    With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim–sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim–sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim–sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

  12. [Multidrug resistance in Klebsiella pneumoniae: multicenter study].

    PubMed

    Boutiba-Ben Boubaker, Ilhem; Ben Salah, Dorra; Besbes, Makram; Mahjoubi, Faouzia; Ghozzi, Rafiaa; Ben Redjeb, Saida; Ben Hassen, Assia; Hammami, Adnène

    2002-01-01

    The extensive use of broad spectrum antibiotics, especially the third generation cephalosporins (C3G), was followed by the emergence of newer plasmid mediated betalactamases called extended spectrum betalactamases (ESBLs). To assess the impact of K. pneumoniae resistant to 3GC in Tunisia, this study was conducted in 3 teaching hospitals. A total of 1110 strains of K pneumoniae was collected. The antibiotics susceptibilities were tested by diffusion method using Mueller-Hinton agar. The quality control was regularly performed. I ESBLs producing solates were detected using the double-disc synergy test. Data analysis was done using the Whonet 4 software. 23.6% K. pneumoniae isolates showed phenotype pattern of ESBLs producers. The double-disc synergy test was positive in 75% of the cases. These isolates were recovered from hospitalized patients in different wards but mainly from pediatrics (23.6%), medicine (23.2%), surgery (22.9%), intensive care units (11%) and neonatology (11%). 54% were isolated from urines, 22% from blood cultures. These isolates remained susceptible to imipenem (100%) and most of them to cefoxitin (96.4%) but all had associated resistance to aminoglycosides, quinolones and trimethoprim-sulfamethoxazole. The prevalence of multidrug resistant K. pneumoniae is high. This resistance can be minimized by the implementation of infection control measures including handwashing and isolation procedures. PMID:12071040

  13. Resin glycosides from Ipomoea wolcottiana as modulators of the multidrug resistance phenotype in vitro.

    PubMed

    Corona-Castañeda, Berenice; Rosas-Ramírez, Daniel; Castañeda-Gómez, Jhon; Aparicio-Cuevas, Manuel Alejandro; Fragoso-Serrano, Mabel; Figueroa-González, Gabriela; Pereda-Miranda, Rogelio

    2016-03-01

    Recycling liquid chromatography was used for the isolation and purification of resin glycosides from the CHCl3-soluble extracts prepared using flowers of Ipomoea wolcottiana Rose var. wolcottiana. Bioassay-guided fractionation, using modulation of both antibiotic activity against multidrug-resistant strains of Gram-negative bacteria and vinblastine susceptibility in breast carcinoma cells, was used to isolate the active glycolipids as modulators of the multidrug resistance phenotype. An ester-type dimer, wolcottine I, one tetra- and three pentasaccharides, wolcottinosides I-IV, in addition to the known intrapilosin VII, were characterized by NMR spectroscopy and mass spectrometry. In vitro assays established that none of these metabolites displayed antibacterial activity (MIC>512 μg/mL) against multidrug-resistant strains of Escherichia coli, and two nosocomial pathogens: Salmonella enterica serovar Typhi and Shigella flexneri; however, when tested (25 μg/mL) in combination with tetracycline, kanamycin or chloramphenicol, they exerted a potentiation effect of the antibiotic susceptibility up to eightfold (64 μg/mL from 512 μg/mL). It was also determined that these non-cytotoxic (CI50>8.68 μM) agents modulated vinblastine susceptibility at 25 μg/mL in MFC-7/Vin(+) cells with a reversal factor (RFMCF-7/Vin(+)) of 2-130 fold. PMID:26774597

  14. Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

    PubMed Central

    Delgado-Valverde, Mercedes; Sojo-Dorado, Jesús; Pascual, Álvaro

    2013-01-01

    Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to low-level resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem. PMID:25165544

  15. Centromere anatomy in the multidrug-resistant pathogen Enterococcus faecium

    PubMed Central

    Derome, Andrew; Hoischen, Christian; Bussiek, Malte; Grady, Ruth; Adamczyk, Malgorzata; Kędzierska, Barbara; Diekmann, Stephan; Barillà, Daniela; Hayes, Finbarr

    2008-01-01

    Multidrug-resistant variants of the opportunistic human pathogen Enterococcus have recently emerged as leading agents of nosocomial infection. The acquisition of plasmid-borne resistance genes is a driving force in antibiotic-resistance evolution in enterococci. The segregation locus of a high-level gentamicin-resistance plasmid, pGENT, in Enterococcus faecium was identified and dissected. This locus includes overlapping genes encoding PrgP, a member of the ParA superfamily of segregation proteins, and PrgO, a site-specific DNA binding homodimer that recognizes the cenE centromere upstream of prgPO. The centromere has a distinctive organization comprising three subsites, CESII separates CESI and CESIII, each of which harbors seven TATA boxes spaced by half-helical turns. PrgO independently binds both CESI and CESIII, but with different affinities. The topography of the complex was probed by atomic force microscopy, revealing discrete PrgO foci positioned asymmetrically at the CESI and CESIII subsites. Bending analysis demonstrated that cenE is intrinsically curved. The organization of the cenE site and of certain other plasmid centromeres mirrors that of yeast centromeres, which may reflect a common architectural requirement during assembly of the mitotic apparatus in yeast and bacteria. Moreover, segregation modules homologous to that of pGENT are widely disseminated on vancomycin and other resistance plasmids in enterococci. An improved understanding of segrosome assembly may highlight new interventions geared toward combating antibiotic resistance in these insidious pathogens. PMID:18245388

  16. Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae

    PubMed Central

    Al-Marzooq, Farah; Mohd Yusof, Mohd Yasim; Tay, Sun Tee

    2015-01-01

    Infections caused by multidrug resistant Klebsiella pneumoniae have been increasingly reported in many parts of the world. A total of 93 Malaysian multidrug resistant K. pneumoniae isolated from patients attending to University of Malaya Medical Center, Kuala Lumpur, Malaysia from 2010-2012 were investigated for antibiotic resistance determinants including extended-spectrum beta-lactamases (ESBLs), aminoglycoside and trimethoprim/sulfamethoxazole resistance genes and plasmid replicons. CTX-M-15 (91.3%) was the predominant ESBL gene detected in this study. aacC2 gene (67.7%) was the most common gene detected in aminoglycoside-resistant isolates. Trimethoprim/sulfamethoxazole resistance (90.3%) was attributed to the presence of sul1 (53.8%) and dfrA (59.1%) genes in the isolates. Multiple plasmid replicons (1-4) were detected in 95.7% of the isolates. FIIK was the dominant replicon detected together with 13 other types of plasmid replicons. Conjugative plasmids (1-3 plasmids of ~3-100 kb) were obtained from 27 of 43 K. pneumoniae isolates. An ESBL gene (either CTX-M-15, CTX-M-3 or SHV-12) was detected from each transconjugant. Co-detection with at least one of other antibiotic resistance determinants [sul1, dfrA, aacC2, aac(6ˊ)-Ib, aac(6ˊ)-Ib-cr and qnrB] was noted in most conjugative plasmids. The transconjugants were resistant to multiple antibiotics including β-lactams, gentamicin and cotrimoxazole, but not ciprofloxacin. This is the first study describing the characterization of plasmids circulating in Malaysian multidrug resistant K. pneumoniae isolates. The results of this study suggest the diffusion of highly diverse plasmids with multiple antibiotic resistance determinants among the Malaysian isolates. Effective infection control measures and antibiotic stewardship programs should be adopted to limit the spread of the multidrug resistant bacteria in healthcare settings. PMID:26203651

  17. Salvage therapy for multidrug-resistant tuberculosis.

    PubMed

    Seung, K J; Becerra, M C; Atwood, S S; Alcántara, F; Bonilla, C A; Mitnick, C D

    2014-05-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin, is challenging under the best of circumstances, and particularly in resource-limited settings. For patients who remain persistently sputum-culture-positive despite therapy with second-line TB drugs, treatment options are limited, especially if disease is too advanced for resective surgery. Salvage therapy refers to the design of a regimen combining new and previously used drugs in a final effort to attain sputum conversion before declaring treatment to have failed. We retrospectively evaluated the outcomes of salvage therapy in 213 Peruvian patients. Salvage regimens included a median of two new drugs (range 1-6) and nine (range 5-13) total (new plus previously used) drugs. The most frequently used new drug was moxifloxacin, followed by capreomycin, amoxicillin-clavulanate, kanamycin and clarithromycin. Culture conversion occurred in 65 (30.5%) patients. Salvage regimens that included moxifloxacin were significantly more likely to be followed by culture conversion (OR 2.2; p 0.02). Later-generation fluoroquinolones such as moxifloxacin should be used in salvage therapy but also in the initial treatment of MDR-TB, if the best clinical strategy is to use the most effective drugs when the patient has the best chance for cure. New TB drugs are most likely to be initially used in salvage patients, in conditions similar to those described here. Close bacteriological monitoring of these patients will be essential, as useful information about the best way to use these new drugs can be gained from analysis of salvage therapy cohorts. PMID:23991934

  18. Mammalian multidrug-resistance proteins (MRPs).

    PubMed

    Slot, Andrew J; Molinski, Steven V; Cole, Susan P C

    2011-09-01

    Subfamily C of the human ABC (ATP-binding cassette) superfamily contains nine proteins that are often referred to as the MRPs (multidrug-resistance proteins). The 'short' MRP/ABCC transporters (MRP4, MRP5, MRP8 and ABCC12) have a typical ABC structure with four domains comprising two membrane-spanning domains (MSD1 and MSD2) each followed by a nucleotide-binding domain (NBD1 and NBD2). The 'long' MRP/ABCCs (MRP1, MRP2, MRP3, ABCC6 and MRP7) have five domains with the extra domain, MSD0, at the N-terminus. The proteins encoded by the ABCC6 and ABCC12 genes are not known to transport drugs and are therefore referred to as ABCC6 and ABCC12 (rather than MRP6 and MRP9) respectively. A large number of molecules are transported across the plasma membrane by the MRPs. Many are organic anions derived from exogenous sources such as conjugated drug metabolites. Others are endogenous metabolites such as the cysteinyl leukotrienes and prostaglandins which have important signalling functions in the cell. Some MRPs share a degree of overlap in substrate specificity (at least in vitro), but differences in transport kinetics are often substantial. In some cases, the in vivo substrates for some MRPs have been discovered aided by studies in gene-knockout mice. However, the molecules that are transported in vivo by others, including MRP5, MRP7, ABCC6 and ABCC12, still remain unknown. Important differences in the tissue distribution of the MRPs and their membrane localization (apical in contrast with basolateral) in polarized cells also exist. Together, these differences are responsible for the unique pharmacological and physiological functions of each of the nine ABCC transporters known as the MRPs. PMID:21967058

  19. Multidrug-resistant Gram-negative bacterial infections: the emerging threat and potential novel treatment options.

    PubMed

    Vergidis, Paschalis I; Falagas, Matthew E

    2008-02-01

    Gram-negative bacterial infections constitute an emerging threat because of the development of multidrug-resistant organisms. There is a relative shortage of new drugs in the antimicrobial development pipeline that have been tested in vitro and evaluated in clinical studies. Antibiotics that are in the pipeline for the treatment of serious Gram-negative bacterial infections include the cephalosporins, ceftobiprole, ceftarolin and FR-264205. Tigecycline is the first drug approved from a new class of antibiotics called glycylcyclines, and there has been renewed interest in this drug for the treatment of some multidrug-resistant Gram-negative organisms. Carbapenems in the pipeline include tomopenem, with the approved drugs doripenem and faropenem, an oral agent, under evaluation for activity against multidrug-resistant Gram-negative bacterial infections. Polymyxins are old antibiotics traditionally considered to be toxic, but which are being used because of their activity against resistant Gram-negative organisms. New pharmacokinetic and pharmacodynamic data are available regarding the use of these agents. Finally, antimicrobial peptides and efflux pump inhibitors are two new classes of agents under development. This review of investigational antibiotics shows that several new agents will become available in the coming years, even though the pace of antimicrobial research is far from ideal. PMID:18246520

  20. Comparative Genomics of Multidrug Resistance in Acinetobacter baumannii

    PubMed Central

    2006-01-01

    Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. It has now become a major cause of hospital-acquired infections worldwide due to its remarkable propensity to rapidly acquire resistance determinants to a wide range of antibacterial agents. Here we use a comparative genomic approach to identify the complete repertoire of resistance genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is epidemic in France, as well as to investigate the mechanisms of their acquisition by comparison with the fully susceptible A. baumannii strain SDF, which is associated with human body lice. The assembly of the whole shotgun genome sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb, respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a resistance island—the largest identified to date—in which 45 resistance genes are clustered. At the homologous location, the SDF strain exhibits a 20 kb-genomic island flanked by transposases but devoid of resistance markers. Such a switching genomic structure might be a hotspot that could explain the rapid acquisition of resistance markers under antimicrobial pressure. Sequence similarity and phylogenetic analyses confirm that most of the resistance genes found in the A. baumannii strain AYE have been recently acquired from bacteria of the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in the discovery of 19 new putative resistance genes. Whole-genome sequencing appears to be a fast and efficient approach to the exhaustive identification of resistance genes in epidemic infectious agents of clinical significance. PMID:16415984

  1. Biosynthesis of heterogeneous forms of multidrug resistance-associated glycoproteins.

    PubMed

    Greenberger, L M; Williams, S S; Horwitz, S B

    1987-10-01

    Multidrug-resistant J774.2 mouse macrophage-like cells, selected for resistance to colchicine, vinblastine, or taxol, overexpress antigenically related glycoproteins with distinct electrophoretic mobilities. These plasma membrane glycoproteins are likely to play a pivotal role in the expression of the multidrug resistance phenotype. To determine how these multidrug resistance-associated glycoproteins differ, the biosynthesis and N-linked carbohydrate composition of these proteins were examined and compared. Vinblastineor colchicine-selected cells made a 125-kDa precursor that was rapidly processed (t1/2 approximately equal to 20 min) to mature forms of 135 and 140 kDa, respectively. Heterogeneity between the 135- and 140-kDa forms of the molecule can be attributed to N-linked carbohydrate. In contrast, taxol-selected cells made two precursors, 125 and 120 kDa, which appeared within 5 and 15 min after the onset of pulse labeling, respectively. They were processed to mature forms of 140 and 130 kDa. Since a single deglycosylated precursor or mature form was not observed after enzymatic removal of N-linked oligosaccharides, other differences, besides N-linked glycosylation, which occur in early processing compartments, are likely to account for the two multidrug resistance-associated glycoproteins in taxol-selected cells. These results demonstrate that a family of multidrug resistance-associated glycoproteins can be differentially expressed. PMID:2888763

  2. Phorbol esters induce multidrug resistance in human breast cancer cells

    SciTech Connect

    Fine, R.L.; Patel, J.; Chabner, B.A.

    1988-01-01

    Mechanisms responsible for broad-based resistance to antitumor drugs derived from natural products (multidrug resistance) are incompletely understood. Agents known to reverse the multidrug-resistant phenotype (verapamil and trifluoperazine) can also inhibit the activity of protein kinase C. When the authors assayed human breast cancer cell lines for protein kinase C activity, they found that enzyme activity was 7-fold higher in the multidrug-resistance cancer cells compared with the control, sensitive parent cells. Exposure of drug-sensitive cells to the phorbol ester phorbol 12,13-dibutyate (P(BtO)/sub 2/) led to an increase in protein kinase C activity and induced a drug-resistance phenotype, whereas exposure of drug-resistant cells to P(BtO)/sub 2/ further increased drug resistance. In sensitive cells, this increased resistance was accomplished by a 3.5-fold increased phosphorylation of a 20-kDa particulate protein and a 35-40% decreased intracellular accumulation of doxorubicin and vincristine. P(BtO)/sub 2/ induced resistance to agents involved in the multidrug-resistant phenotype (doxorubicin and vincristine) but did not affect sensitivity to an unrelated alkylating agent (melphalan). The increased resistance was partially or fully reversible by the calcium channel blocker verapamil and by the calmodulin-antagonist trifluoperazine. These data suggest that stimulation of protein kinase C playus a role in the drug-transport changes in multidrug-resistant cells. This may occur through modulation of an efflux pump by protein phosphorylation.

  3. The Widespread Presence of a Multidrug-Resistant Escherichia coli ST131 Clade among Community-Associated and Hospitalized Patients

    PubMed Central

    den Reijer, P. Martijn; van Burgh, Sebastian; Burggraaf, Arjan; Ossewaarde, Jacobus M.; van der Zee, Anneke

    2016-01-01

    Background & Aims The extent of entry of multidrug-resistant Escherichia coli from the community into the hospital and subsequent clonal spread amongst patients is unclear. To investigate the extent and direction of clonal spread of these bacteria within a large teaching hospital, we prospectively genotyped multidrug-resistant E. coli obtained from community- and hospital associated patient groups and compared the distribution of diverse genetic markers. Methods A total of 222 E. coli, classified as multi-drug resistant according to national guidelines, were retrieved from both screening (n = 184) and non-screening clinical cultures (n = 38) from outpatients and patients hospitalized for various periods. All isolates were routinely genotyped using an amplified fragment length polymorphism (AFLP) assay and real-time PCR for CTX-M genes. Multi-locus sequence typing was additionally performed to confirm clusters. Based on demographics, patients were categorized into two groups: patients that were not hospitalized or less than 72 hours at time of strain isolation (group I) and patients that were hospitalized for at least 72 hours (group II). Results Genotyping showed that most multi-drug resistant E. coli either had unique AFLP profiles or grouped in small clusters of maximally 8 isolates. We identified one large ST131 clade comprising 31% of all isolates, containing several AFLP clusters with similar profiles. Although different AFLP clusters were found in the two patient groups, overall genetic heterogeneity was similar (35% vs 28% of isolates containing unique AFLP profiles, respectively). In addition, similar distributions of CTX-M groups, including CTX-M 15 (40% and 44% of isolates in group I and II, respectively) and ST131 (32% and 30% of isolates, respectively) were found. Conclusion We conclude that multi-drug resistant E. coli from the CTX-M 15 associated lineage ST131 are widespread amongst both community- and hospital associated patient groups, with similar

  4. Multidrug-resistant organisms detected in refugee patients admitted to a University Hospital, Germany June‒December 2015.

    PubMed

    Reinheimer, Claudia; Kempf, Volkhard A J; Göttig, Stephan; Hogardt, Michael; Wichelhaus, Thomas A; O'Rourke, Fiona; Brandt, Christian

    2016-01-01

    Multidrug-resistant Gram-negative bacteria (MDR GNB) were found to colonise 60.8% (95% confidence interval: 52.3-68.9) of 143 refugee patients mainly from Syria (47), Afghanistan (29), and Somalia (14) admitted to the University Hospital Frankfurt, Germany, between June and December 2015. This percentage exceeds the prevalence of MDR GNB in resident patients four-fold. Healthcare personnel should be aware of this and the need to implement or adapt adequate infection control measures. PMID:26794850

  5. Characterization of a Multidrug-Resistant, Novel Bacteroides Genomospecies

    PubMed Central

    Salipante, Stephen J.; Kalapila, Aley; Pottinger, Paul S.; Hoogestraat, Daniel R.; Cummings, Lisa; Duchin, Jeffrey S.; Sengupta, Dhruba J.; Pergam, Steven A.; Cookson, Brad T.

    2015-01-01

    Metronidazole- and carbapenem-resistant Bacteroides fragilis are rare in the United States. We isolated a multidrug-resistant anaerobe from the bloodstream and intraabdominal abscesses of a patient who had traveled to India. Whole-genome sequencing identified the organism as a novel Bacteroides genomospecies. Physicians should be aware of the possibility for concomitant carbapenem- and metronidazole-resistant Bacteroides infections. PMID:25529016

  6. Epidemiology of Primary Multidrug-Resistant Tuberculosis, Vladimir Region, Russia.

    PubMed

    Ershova, Julia V; Volchenkov, Grigory V; Kaminski, Dorothy A; Somova, Tatiana R; Kuznetsova, Tatiana A; Kaunetis, Natalia V; Cegielski, J Peter; Kurbatova, Ekaterina V

    2015-11-01

    We studied the epidemiology of drug-resistant tuberculosis (TB) in Vladimir Region, Russia, in 2012. Most cases of multidrug-resistant TB (MDR TB) were caused by transmission of drug-resistant strains, and >33% were in patients referred for testing after mass radiographic screening. Early diagnosis of drug resistance is essential for preventing transmission of MDR TB. PMID:26488585

  7. Aquariums as Reservoirs for Multidrug-resistant Salmonella Paratyphi B

    PubMed Central

    Levings, Renee S.; Lightfoot, Diane; Hall, Ruth M.

    2006-01-01

    Multidrug-resistant Salmonella enterica serovar Paratyphi B dT+ isolates from patients with gastroenteritis were identical with isolates from their home aquariums. Matched isolates had identical phage types, XbaI and IS200 profiles, and Salmonella genomic island 1 (SGI1). Ornamental fish tanks are reservoirs for SGI1-containing S. Paratyphi B dT+. PMID:16704796

  8. Multidrug-Resistant Acinetobacter baumannii in Veterinary Clinics, Germany

    PubMed Central

    Prenger-Berninghoff, Ellen; Weiss, Reinhard; van der Reijden, Tanny; van den Broek, Peterhans; Baljer, Georg; Dijkshoorn, Lenie

    2011-01-01

    An increase in prevalence of multidrug-resistant Acinetobacter spp. in hospitalized animals was observed at the Justus-Liebig-University (Germany). Genotypic analysis of 56 isolates during 2000–2008 showed 3 clusters that corresponded to European clones I–III. Results indicate spread of genotypically related strains within and among veterinary clinics in Germany. PMID:21888812

  9. Human multidrug-resistant Mycobacterium bovis infection in Mexico.

    PubMed

    Vazquez-Chacon, Carlos A; Martínez-Guarneros, Armando; Couvin, David; González-Y-Merchand, Jorge A; Rivera-Gutierrez, Sandra; Escobar-Gutierrez, Alejandro; De-la-Cruz López, Juan J; Gomez-Bustamante, Adriana; Gonzalez-Macal, Gabriela A; Gonçalves Rossi, Livia Maria; Muñiz-Salazar, Raquel; Rastogi, Nalin; Vaughan, Gilberto

    2015-12-01

    Here, we describe the molecular characterization of six human Mycobacterium bovis clinical isolates, including three multidrug resistant (MDR) strains, collected in Mexico through the National Survey on Tuberculosis Drug Resistance (ENTB-2008), a nationally representative survey conducted during 2008-2009 in nine states with a stratified cluster sampling design. The genetic background of bovine M. bovis strains identified in three different states of Mexico was studied in parallel to assess molecular relatedness of bovine and human strains. Additionally, resistance to first and second line anti-tuberculosis (TB) drugs and molecular identification of mutations conferring drug resistance was also performed. All strains were characterized by spoligotyping and 24-loci MIRU-VNTRs, and analyzed using the SITVIT2 (n = 112,000 strains) and SITVITBovis (n = 25,000 strains) proprietary databases of Institut Pasteur de la Guadeloupe. Furthermore, data from this study (n = 55 isolates), were also compared with genotypes recorded for M. bovis from USA (n = 203), Argentina (n = 726), as well as other isolates from Mexico (independent from the present study; n = 147), to determine any evidence for genetic relatedness between circulating M. bovis strains. The results showed that all human M. bovis cases were not genetically related between them or to any bovine strain. Interestingly, a high degree of genetic variability was observed among bovine strains. Several autochthonous and presumably imported strains were identified. The emergence of drug-resistant M. bovis is an important public health problem that jeopardizes the success of TB control programs in the region. PMID:26299906

  10. Reversal of multidrug resistance by 7-O-benzoylpyripyropene A in multidrug-resistant tumor cells.

    PubMed

    Rho, M C; Hayashi, M; Fukami, A; Obata, R; Sunazuka, T; Tomoda, H; Komiyama, K; Omura, S

    2000-10-01

    7-O-Benzoylpyripyropene A (7-O-BzP), a semi-synthetic analog of pyripyropene, was investigated for its reversing effect on multidrug-resistant (MDR) tumor cells. 7-O-BzP (6.25 microg/ml) completely reversed resistance against vincristine and adriamycin in vincristine-resistant KB cells (VJ-300) and adriamycin-resistant P388 cells (P388/ADR), respectively. 7-O-BzP alone had no effect on the growth of drug sensitive and drug-resistant cells. 7-O-BzP (6.25 microg/ml) significantly enhanced accumulation of [3H]vincristine in VJ-300 cells and completely inhibited the binding of [3H]azidopine to the P-glycoprotein in VJ-300 cells and P388/ADR cells. The result suggests that 7-O-BzP effectively reverses P-glycoprotein-related MDR by interacting directly with P-glycoprotein in drug resistant VJ-300 and P388/ADR cells. PMID:11132967

  11. Engineered Endolysin-Based “Artilysins” To Combat Multidrug-Resistant Gram-Negative Pathogens

    PubMed Central

    Briers, Yves; Walmagh, Maarten; Van Puyenbroeck, Victor; Cornelissen, Anneleen; Cenens, William; Aertsen, Abram; Oliveira, Hugo; Azeredo, Joana; Verween, Gunther; Pirnay, Jean-Paul; Miller, Stefan; Volckaert, Guido

    2014-01-01

    ABSTRACT The global threat to public health posed by emerging multidrug-resistant bacteria in the past few years necessitates the development of novel approaches to combat bacterial infections. Endolysins encoded by bacterial viruses (or phages) represent one promising avenue of investigation. These enzyme-based antibacterials efficiently kill Gram-positive bacteria upon contact by specific cell wall hydrolysis. However, a major hurdle in their exploitation as antibacterials against Gram-negative pathogens is the impermeable lipopolysaccharide layer surrounding their cell wall. Therefore, we developed and optimized an approach to engineer these enzymes as outer membrane-penetrating endolysins (Artilysins), rendering them highly bactericidal against Gram-negative pathogens, including Pseudomonas aeruginosa and Acinetobacter baumannii. Artilysins combining a polycationic nonapeptide and a modular endolysin are able to kill these (multidrug-resistant) strains in vitro with a 4 to 5 log reduction within 30 min. We show that the activity of Artilysins can be further enhanced by the presence of a linker of increasing length between the peptide and endolysin or by a combination of both polycationic and hydrophobic/amphipathic peptides. Time-lapse microscopy confirmed the mode of action of polycationic Artilysins, showing that they pass the outer membrane to degrade the peptidoglycan with subsequent cell lysis. Artilysins are effective in vitro (human keratinocytes) and in vivo (Caenorhabditis elegans). PMID:24987094

  12. Genome Sequence of a Multidrug-Resistant Strain of Stenotrophomonas maltophilia with Carbapenem Resistance, Isolated from King Abdullah Medical City, Makkah, Saudi Arabia

    PubMed Central

    Abdel-Haleem, Alyaa M.; Rchiad, Zineb; Khan, Babar K.; Abdallah, Abdallah M.; Naeem, Raeece; Nikhat Sheerin, Shalam; Solovyev, Victor; Ahmed, Abdalla

    2015-01-01

    The emergence and spread of multidrug-resistant (MDR) bacteria have been regarded as major challenges among health care-associated infections worldwide. Here, we report the draft genome sequence of an MDR Stenotrophomonas maltophilia strain isolated in 2014 from King Abdulla Medical City, Makkah, Saudi Arabia. PMID:26472828

  13. Genome Sequence of a Multidrug-Resistant Strain of Stenotrophomonas maltophilia with Carbapenem Resistance, Isolated from King Abdullah Medical City, Makkah, Saudi Arabia.

    PubMed

    Abdel-Haleem, Alyaa M; Rchiad, Zineb; Khan, Babar K; Abdallah, Abdallah M; Naeem, Raeece; Nikhat Sheerin, Shalam; Solovyev, Victor; Ahmed, Abdalla; Pain, Arnab

    2015-01-01

    The emergence and spread of multidrug-resistant (MDR) bacteria have been regarded as major challenges among health care-associated infections worldwide. Here, we report the draft genome sequence of an MDR Stenotrophomonas maltophilia strain isolated in 2014 from King Abdulla Medical City, Makkah, Saudi Arabia. PMID:26472828

  14. Multidrug Resistance in Escherichia coli Strains Isolated from Infections in Dogs and Cats in Poland (2007–2013)

    PubMed Central

    Rzewuska, Magdalena; Czopowicz, Michał; Kizerwetter-Świda, Magdalena; Chrobak, Dorota; Błaszczak, Borys; Binek, Marian

    2015-01-01

    The antimicrobial susceptibility of Escherichia coli isolates associated with various types of infections in dogs and cats was determined. The studied isolates were most frequently susceptible to fluoroquinolones and the extended-spectrum cephalosporins (ESCs), antimicrobials commonly used in treatment of infections in companion animals. However, an increase in the percentage of strains resistant to β-lactam antibiotics including ESCs was noted between January 2007 and December 2013. The frequency of multidrug-resistant (MDR) E. coli isolation (66.8% of isolates) is alarming. Moreover, the statistically significant increase of the percentage of MDR isolates was observed during the study period. No difference in the prevalence of multidrug resistance was found between bacteria causing intestinal and extraintestinal infections and between canine and feline isolates. Nonhemolytic E. coli isolates were MDR more often than hemolytic ones. Our study showed the companion animals in Poland as an important reservoir of MDR bacteria. These results indicate that continuous monitoring of canine and feline E. coli antimicrobial susceptibility is required. Furthermore, introduction and application of recommendations for appropriate use of antimicrobials in small animal practice should be essential to minimize the emergence of multidrug resistance among E. coli in companion animals. PMID:25667937

  15. Molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates.

    PubMed

    Hou, Xiang-hua; Song, Xiu-yu; Ma, Xiao-bo; Zhang, Shi-yang; Zhang, Jia-qin

    2015-01-01

    Klebsiella pneumoniae is an important cause of healthcare-associated infections worldwide. Selective pressure, the extensive use of antibiotics, and the conjugational transmission of antibiotic resistance genes across bacterial species and genera facilitate the emergence of multidrug-resistant (MDR) K. pneumoniae. Here, we examined the occurrence, phenotypes and genetic features of MDR K. pneumoniae isolated from patients in intensive care units (ICUs) at the First Affiliated Hospital of Xiamen University in Xiamen, China, from January to December 2011. Thirty-eight MDR K. pneumoniae strains were collected. These MDR K. pneumoniae isolates possessed at least seven antibiotic resistance determinants, which contribute to the high-level resistance of these bacteria to aminoglycosides, macrolides, quinolones and β-lactams. Among these isolates, 24 strains were extended-spectrum β-lactamase (ESBL) producers, 2 strains were AmpC producers, and 12 strains were both ESBL and AmpC producers. The 38 MDR isolates also contained class I (28/38) and class II integrons (10/38). All 28 class I-positive isolates contained aacC1, aacC4, orfX, orfX' and aadA1 genes. β-lactam resistance was conferred through bla SHV (22/38), bla TEM (10/38), and bla CTX-M (7/38). The highly conserved bla KPC-2 (37/38) and bla OXA-23(1/38) alleles were responsible for carbapenem resistance, and a gyrAsite mutation (27/38) and the plasmid-mediated qnrB gene (13/38) were responsible for quinolone resistance. Repetitive-sequence-based PCR (REP-PCR) fingerprinting of these MDR strains revealed the presence of five groups and sixteen patterns. The MDR strains from unrelated groups showed different drug resistance patterns; however, some homologous strains also showed different drug resistance profiles. Therefore, REP-PCR-based analyses can provide information to evaluate the epidemic status of nosocomial infection caused by MDR K. pneumoniae; however, this test lacks the power to discriminate some

  16. Molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates

    PubMed Central

    Hou, Xiang-hua; Song, Xiu-yu; Ma, Xiao-bo; Zhang, Shi-yang; Zhang, Jia-qin

    2015-01-01

    Klebsiella pneumoniae is an important cause of healthcare-associated infections worldwide. Selective pressure, the extensive use of antibiotics, and the conjugational transmission of antibiotic resistance genes across bacterial species and genera facilitate the emergence of multidrug-resistant (MDR) K. pneumoniae. Here, we examined the occurrence, phenotypes and genetic features of MDR K. pneumoniae isolated from patients in intensive care units (ICUs) at the First Affiliated Hospital of Xiamen University in Xiamen, China, from January to December 2011. Thirty-eight MDR K. pneumoniae strains were collected. These MDR K. pneumoniae isolates possessed at least seven antibiotic resistance determinants, which contribute to the high-level resistance of these bacteria to aminoglycosides, macrolides, quinolones and β-lactams. Among these isolates, 24 strains were extended-spectrum β-lactamase (ESBL) producers, 2 strains were AmpC producers, and 12 strains were both ESBL and AmpC producers. The 38 MDR isolates also contained class I (28/38) and class II integrons (10/38). All 28 class I-positive isolates contained aacC1, aacC4, orfX, orfX’ and aadA1 genes. β-lactam resistance was conferred through bla SHV (22/38), bla TEM (10/38), and bla CTX-M (7/38). The highly conserved bla KPC-2 (37/38) and bla OXA-23(1/38) alleles were responsible for carbapenem resistance, and a gyrAsite mutation (27/38) and the plasmid-mediated qnrB gene (13/38) were responsible for quinolone resistance. Repetitive-sequence-based PCR (REP-PCR) fingerprinting of these MDR strains revealed the presence of five groups and sixteen patterns. The MDR strains from unrelated groups showed different drug resistance patterns; however, some homologous strains also showed different drug resistance profiles. Therefore, REP-PCR-based analyses can provide information to evaluate the epidemic status of nosocomial infection caused by MDR K. pneumoniae; however, this test lacks the power to discriminate some

  17. In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates

    PubMed Central

    Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy

    2016-01-01

    Aim/Background: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Materials and Methods: Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. Results: The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. Conclusions: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants’ potential for developing new antimicrobials. PMID:27366345

  18. Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system

    PubMed Central

    Habazettl, Judith; Allan, Martin; Jensen, Pernille Rose; Sass, Hans-Jürgen; Thompson, Charles J.; Grzesiek, Stephan

    2014-01-01

    TipA is a transcriptional regulator found in diverse bacteria. It constitutes a minimal autoregulated multidrug resistance system against numerous thiopeptide antibiotics. Here we report the structures of its drug-binding domain TipAS in complexes with promothiocin A and nosiheptide, and a model of the thiostrepton complex. Drug binding induces a large transition from a partially unfolded to a globin-like structure. The structures rationalize the mechanism of promiscuous, yet specific, drug recognition: (i) a four-ring motif present in all known TipA-inducing antibiotics is recognized specifically by conserved TipAS amino acids; and (ii) the variable part of the antibiotic is accommodated within a flexible cleft that rigidifies upon drug binding. Remarkably, the identified four-ring motif is also the major interacting part of the antibiotic with the ribosome. Hence the TipA multidrug resistance mechanism is directed against the same chemical motif that inhibits protein synthesis. The observed identity of chemical motifs responsible for antibiotic function and resistance may be a general principle and could help to better define new leads for antibiotics. PMID:25489067

  19. Multidrug-Resistant Salmonella Isolates from Swine in the Eastern Cape Province, South Africa.

    PubMed

    Iwu, Chinwe Juliana; Iweriebor, Benson Chuks; Obi, Larry Chikwelu; Basson, Albertus Kotze; Okoh, Anthony Ifeanyi

    2016-07-01

    The exposure of farm animals to antimicrobials for treatment, prophylaxis, or growth promotion can select for resistant bacteria that can be transmitted to humans, and Salmonella as an important zoonotic pathogen can act as a potential reservoir of antimicrobial resistance determinants. We assessed the antibiogram profiles of Salmonella species isolated from pig herds in two commercial farms in South Africa. Two hundred fifty-eight presumptive Salmonella isolates were recovered from the fecal samples of 500 adult pigs. Specific primers targeting Salmonella serogroups A, B, C1, C2, and D were used to determine the prevalence of different serogroups. Only serogroup A (n = 48) was detected, while others were not. Antimicrobial susceptibility of the confirmed Salmonella serogroup A isolates was performed by using the disk diffusion method against a panel of 18 antibiotics. All the 48 isolates were resistant to tetracycline and oxytetracycline, while 75% were resistant to ampicillin, sulphamethoxazole-trimethoprim, nalidixic acid, and streptomycin. All the isolates exhibited multidrug resistance, with the predominant phenotype being against 11 antibiotics, and multiple antibiotic resistance index ranged between 0.3 and 0.6. The incidence of genes encoding resistance against ampicillin (ampC), tetracycline (tetA), and streptomycin (strA) were 54, 61, and 44%, respectively. We conclude that healthy pigs are potential reservoirs of multidrug-resistant Salmonella that could be transmitted to humans through the food chain and, hence, a significant public health threat. PMID:27357044

  20. Multidrug-resistant Salmonella Typhimurium in Four Animal Facilities

    PubMed Central

    Wright, Jennifer G.; Tengelsen, Leslie A.; Smith, Kirk E.; Bender, Jeff B.; Frank, Rodney K.; Grendon, John H.; Rice, Daniel H.; Thiessen, Ann Marie B.; Gilbertson, Catherine Jo; Sivapalasingam, Sumathi; Barrett, Timothy J.; Besser, Thomas E.; Hancock, Dale D.

    2005-01-01

    In 1999 and 2000, 3 state health departments reported 4 outbreaks of gastrointestinal illness due to Salmonella enterica serotype Typhimurium in employees, clients, and client animals from 3 companion animal veterinary clinics and 1 animal shelter. More than 45 persons and companion animals became ill. Four independent investigations resulted in the testing of 19 human samples and >200 animal samples; 18 persons and 36 animals were culture-positive for S. Typhimurium. One outbreak was due to multidrug-resistant S. Typhimurium R-type ACKSSuT, while the other 3 were due to multidrug-resistant S. Typhimurium R-type ACSSuT DT104. This report documents nosocomial transmission of S. Typhimurium and demonstrates that companion animal facilities may serve as foci of transmission for salmonellae between animals and humans if adequate precautions are not followed. PMID:16102313

  1. Pregnane glycoside multidrug-resistance modulators from Cynanchum wilfordii.

    PubMed

    Hwang, B Y; Kim, S E; Kim, Y H; Kim, H S; Hong, Y S; Ro, J S; Lee, K S; Lee, J J

    1999-04-01

    The methanol-soluble extracts of the roots of Cynanchum wilfordii showed a significant multidrug-resistance-reversing activity, and four known pregnane glycosides were isolated by bioassay-directed fractionation and separation. Their structures were identified as gagaminin 3-O-beta-D-cymaropyranosyl-(1-->4)-beta-D-oleandropyranosyl- (1-->4)-b eta-D-cymaropyranosyl-(1-->4)-beta-D-cymaropyranoside (1), wilfoside K1N (2), wilfoside C1N (3), and cynauricuoside A (4). In particular, compound 1, at a concentration level of 1 microM, was found to completely reverse the multidrug-resistance of KB-V1 and MCF7/ADR cells to adriamycin, vinblastine, and colchicine. PMID:10217732

  2. Multidrug-resistant Fusarium keratitis: diagnosis and treatment considerations.

    PubMed

    Sara, Sergio; Sharpe, Kendall; Morris, Sharon

    2016-01-01

    Mycotic keratitis is an ocular infective process derived from any fungal species capable of corneal invasion. Despite its rarity in developed countries, its challenging and elusive diagnosis may result in keratoplasty or enucleation following failed medical management. Filamentous fungi such as Fusarium are often implicated in mycotic keratitis. Bearing greater morbidity than its bacterial counterpart, mycotic keratitis requires early clinical suspicion and initiation of antifungal therapy to prevent devastating consequences. We describe a case of multidrug-resistant mycotic keratitis in a 46-year-old man who continued to decline despite maximal therapy and therapeutic keratoplasty. Finally, enucleation was performed as a means of source control preventing dissemination of a likely untreatable fungal infection into the orbit. Multidrug-resistant Fusarium is rare, and may progress to endophthalmitis. We discuss potential management options which may enhance diagnosis and outcome in this condition. PMID:27489066

  3. Isolation of multidrug-resistant Salmonella in Singapore

    PubMed Central

    Phoon, Yee Wei; Chan, Yuen Yue Candice; Koh, Tze Hsien

    2015-01-01

    Multidrug-resistant Salmonella is a well-recognised problem worldwide, especially in developing countries such as India, where non-typhoidal Salmonella infections and enteric fever are endemic. Antimicrobial resistance, particularly to fluoroquinolones, is common and leads to the frequent use of alternative agents, such as azithromycin. We herein describe the first reported case of azithromycin-resistant Salmonella gastroenteritis in a Singaporean patient. PMID:26311915

  4. Chromosome-Mediated Multidrug Resistance in Salmonella enterica Serovar Typhi

    PubMed Central

    Alam, Munirul; Kuo, Jung-Che; Liu, Yen-Yi; Wang, Pei-Jen

    2014-01-01

    A salmonella genomic island, designated SGI11, was found in 18 of 26 multidrug-resistant Salmonella enterica serovar Typhi isolates from Bangladesh. SGI11 was an IS1 composite transposon and carried 7 resistance genes that conferred resistance to 5 first-line antimicrobials. Eleven of the 18 SGI11-carrying S. Typhi isolates had developed resistance to high levels of ciprofloxacin. PMID:25367917

  5. Multidrug-resistant tuberculosis treatment with linezolid-containing regimen

    PubMed Central

    Farshidpour, Maham; Ebrahimi, Golnaz; Mirsaeidi, Mehdi

    2014-01-01

    The following is a case of multidrug-resistant pulmonary tuberculosis (MDR-TB) that was treated successfully with a linezolid-containing regimen. It was found that linezolid is an efficient medicine for MDR-TB treatment with an acceptable side effect profile. Treatment was maintained for 18 months, and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite our expectation, thrombocytopenia was seen after 2 years follow-up. PMID:25110635

  6. Multidrug Resistant Shigella flexneri Infection Simulating Intestinal Intussusception.

    PubMed

    Sreenivasan, Srirangaraj; Kali, Arunava; Pradeep, Jothimani

    2016-01-01

    Shigella enteritis remains an important cause of mortality and morbidity in all age groups, in developing as well as developed countries. Owing to the emerging resistance to multiple antibiotics among Shigella spp., it has been recognized as a major global public health concern and warrants constant monitoring of its resistance pattern. We report a case of segmental ileitis caused by non.-ESBL producing multidrug resistant Shigella flexneri in an infant clinically mimicking intussusception, which was effectively treated by ceftriaxone. PMID:27013815

  7. Multidrug Resistant Shigella flexneri Infection Simulating Intestinal Intussusception

    PubMed Central

    Sreenivasan, Srirangaraj; Kali, Arunava; Pradeep, Jothimani

    2016-01-01

    Shigella enteritis remains an important cause of mortality and morbidity in all age groups, in developing as well as developed countries. Owing to the emerging resistance to multiple antibiotics among Shigella spp., it has been recognized as a major global public health concern and warrants constant monitoring of its resistance pattern. We report a case of segmental ileitis caused by non.-ESBL producing multidrug resistant Shigella flexneri in an infant clinically mimicking intussusception, which was effectively treated by ceftriaxone. PMID:27013815

  8. Multidrug-Resistant Bacterial Donor-Derived Infections in Solid Organ Transplantation.

    PubMed

    Lewis, Jessica D; Sifri, Costi D

    2016-06-01

    Although rare, donor-derived infections (DDIs) caused by multidrug-resistant (MDR) bacteria can have devastating consequences for organ transplant recipients. Recognition of MDR bacterial DDIs can be challenging, as MDR bacteria are prevalent in most hospitals and distinguishing their transmission through transplantation from other, more typical routes of acquisition are difficult. New technologies such as whole genome sequencing have recently proven to be a powerful advance in the investigation of MDR bacterial DDIs. Once recognized, the optimal treatment of MDR bacterial DDIs is not clear. Herein, we review the clinical manifestations, outcomes, and management of MDR bacterial DDIs, and identify areas of uncertainty toward which the transplant community should direct further research efforts. PMID:27115701

  9. Selection of a Multidrug Resistance Plasmid by Sublethal Levels of Antibiotics and Heavy Metals

    PubMed Central

    Gullberg, Erik; Albrecht, Lisa M.; Karlsson, Christoffer; Sandegren, Linus

    2014-01-01

    ABSTRACT How sublethal levels of antibiotics and heavy metals select for clinically important multidrug resistance plasmids is largely unknown. Carriage of plasmids generally confers substantial fitness costs, implying that for the plasmid-carrying bacteria to be maintained in the population, the plasmid cost needs to be balanced by a selective pressure conferred by, for example, antibiotics or heavy metals. We studied the effects of low levels of antibiotics and heavy metals on the selective maintenance of a 220-kbp extended-spectrum β-lactamase (ESBL) plasmid identified in a hospital outbreak of Klebsiella pneumoniae and Escherichia coli. The concentrations of antibiotics and heavy metals required to maintain plasmid-carrying bacteria, the minimal selective concentrations (MSCs), were in all cases below (almost up to 140-fold) the MIC of the plasmid-free susceptible bacteria. This finding indicates that the very low antibiotic and heavy metal levels found in polluted environments and in treated humans and animals might be sufficiently high to maintain multiresistance plasmids. When resistance genes were moved from the plasmid to the chromosome, the MSC decreased, showing that MSC for a specific resistance conditionally depends on genetic context. This finding suggests that a cost-free resistance could be maintained in a population by an infinitesimally low concentration of antibiotic. By studying the effect of combinations of several compounds, it was observed that for certain combinations of drugs each new compound added lowered the minimal selective concentration of the others. This combination effect could be a significant factor in the selection of multidrug resistance plasmids/bacterial clones in complex multidrug environments. PMID:25293762

  10. Involvement of EGFR in the promotion of malignant properties in multidrug resistant breast cancer cells.

    PubMed

    Xu, Jia-Wen; Li, Qing-Quan; Tao, Li-Li; Cheng, Yuan-Yuan; Yu, Juan; Chen, Qi; Liu, Xiu-Ping; Xu, Zu-De

    2011-12-01

    Multidrug resistance is the most predominant phenomenon leading to chemotherapy treatment failure in breast cancer patients. Despite many studies having suggested that overexpression of epidermal growth factor receptor (EGFR) is a potent predictor of malignancy in cancers, systematic research of EGFR in multidrug resistant (MDR) breast cancer cells is lacking. In order to clarify the role of EGFR in MDR breast cancer cells, MCF7/Adr expressing relatively higher EGFR, and its parental cell line MCF7 expressing relatively lower EGFR, were chosen for this study. Knockdown of EGFR by siRNA in MCF7/Adr cells showed that EGFR siRNA inhibits cell migration, invasion and proliferation in vitro; converse effects were observed in MCF7 cells transfected with pcDNA3.0-EGFR plasmid. Moreover, we found that EGFR upregulated migration and invasion via EMMPRIN, MMP2 and MMP9 in addition to promoting cell cycle passage via elevation of cyclin D1 and CDK4 in MDR breast cancer cells. Interestingly, MCF7/Adr cells not expressing EGFR showed significant decrease of P-glycoprotein (P-gp) and ABCG2 expression levels, and became more sensitive to treatment of adriamycin (ADR) and paclitaxel (Taxol); the above results indicated that MDR of cancer cells is related to S-phase arrest. In conclusion, EGFR is an important factor enhancing the malignancy of MDR breast cancer cells, partially, inducing MDR. Anti-EGFR therapy may improve outcome in chemorefractory breast cancer patients. PMID:21805028

  11. Probable Levofloxacin-associated Secondary Intracranial Hypertension in a Child With Multidrug-resistant Tuberculosis.

    PubMed

    van der Laan, Louvina E; Schaaf, H Simon; Solomons, Regan; Willemse, Marianne; Mohamed, Nabil; Baboolal, Sandika O; Hesseling, Anneke C; van Toorn, Ronald; Garcia-Prats, Anthony J

    2016-06-01

    Fluoroquinolones are a key component of multidrug-resistant tuberculosis treatment. We describe the first reported case of probable levofloxacin-associated intracranial hypertension in a 6-year-old girl with pulmonary multidrug-resistant tuberculosis. The case highlights the potential risk of secondary intracranial hypertension in multidrug-resistant tuberculosis patients who require prolonged fluoroquinolone therapy and the need for ophthalmologic screening in children with suggestive signs and symptoms. PMID:26974890

  12. Supramolecular Cationic Assemblies against Multidrug-Resistant Microorganisms: Activity and Mechanism of Action

    PubMed Central

    de Melo Carrasco, Letícia Dias; Sampaio, Jorge Luiz Mello; Carmona-Ribeiro, Ana Maria

    2015-01-01

    The growing challenge of antimicrobial resistance to antibiotics requires novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes are tested against four multidrug-resistant (MDR) strains of clinical importance. The non-hemolytic poly(diallyldimethylammonium) chloride (PDDA) polymer as the outer NP layer shows a remarkable activity against these organisms. The mechanism of cell death involves bacterial membrane lysis as determined from the leakage of inner phosphorylated compounds and possibly disassembly of the NP with the appearance of multilayered fibers made of the NP components and the biopolymers withdrawn from the cell wall. The NPs display broad-spectrum activity against MDR microorganisms, including Gram-negative and Gram-positive bacteria and yeast. PMID:25809608

  13. Persistence of Multi-Drug Resistance Plasmids in Sterile Water under Very Low Concentrations of Tetracycline

    PubMed Central

    Bien, Thi Lan Thanh; Sato-Takabe, Yuki; Ogo, Mitsuko; Usui, Masaru; Suzuki, Satoru

    2015-01-01

    The persistence of the multi-drug resistance plasmids pAQU1 and IncFIB was examined in bacterial populations under very low selective pressure. We herein demonstrated that these plasmids stably remained not only in the original host, but also in a transconjugant, even after being in a non-culturable state. In seawater microcosms containing Photobacterium damselae 04Ya311 possessing pAQU1, no significant loss of pAQU1 was observed during a 30-d starvation period. The copy numbers of pAQU1 and IncFIB in E. coli were constant. The results of the present study suggest that these plasmids have the ability to remain among various bacteria under oligotrophic conditions with low antibiotic selection pressure. PMID:26639579

  14. Antimicrobial resistance determinant microarray for analysis of multi-drug resistant isolates

    NASA Astrophysics Data System (ADS)

    Taitt, Chris Rowe; Leski, Tomasz; Stenger, David; Vora, Gary J.; House, Brent; Nicklasson, Matilda; Pimentel, Guillermo; Zurawski, Daniel V.; Kirkup, Benjamin C.; Craft, David; Waterman, Paige E.; Lesho, Emil P.; Bangurae, Umaru; Ansumana, Rashid

    2012-06-01

    The prevalence of multidrug-resistant infections in personnel wounded in Iraq and Afghanistan has made it challenging for physicians to choose effective therapeutics in a timely fashion. To address the challenge of identifying the potential for drug resistance, we have developed the Antimicrobial Resistance Determinant Microarray (ARDM) to provide DNAbased analysis for over 250 resistance genes covering 12 classes of antibiotics. Over 70 drug-resistant bacteria from different geographic regions have been analyzed on ARDM, with significant differences in patterns of resistance identified: genes for resistance to sulfonamides, trimethoprim, chloramphenicol, rifampin, and macrolide-lincosamidesulfonamide drugs were more frequently identified in isolates from sources in Iraq/Afghanistan. Of particular concern was the presence of genes responsible for resistance to many of the last-resort antibiotics used to treat war traumaassociated infections.

  15. Successful Management of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia after Kidney Transplantation in a Dog

    PubMed Central

    PARK, Kyung-Mee; NAM, Hyun-Suk; WOO, Heung-Myong

    2013-01-01

    ABSTRACT An 8-year-old male mongrel dog that had undergone renal transplantation was presented 25 days later with an acute cough, anorexia and exercise intolerance. During the investigation, neutrophilic leukocytosis was noted, and thoracic radiographs revealed caudal lung lobe infiltration. While being treated with two broad-spectrum antibiotics, clinical signs worsened. Pneumonia due to infection with multidrug-resistant (MDR) Pseudomonas (P.) aeruginosa, sensitive only to imipenem and amikacin, was confirmed by bacteria isolation. After treatment with imipenem-cilastatin without reducing the immunosuppressant dose, clinical signs completely resolved. During the 2-year follow-up period, no recurrence was observed. To the best of authors’ knowledge, this is the first report of pneumonia caused by MDR P. aeruginosa in a renal recipient dog and successful management of this disease. PMID:23842146

  16. Antimicrobial activity of some essential oils against oral multidrug-resistant Enterococcus faecalis in both planktonic and biofilm state

    PubMed Central

    Benbelaïd, Fethi; Khadir, Abdelmounaïm; Abdoune, Mohamed Amine; Bendahou, Mourad; Muselli, Alain; Costa, Jean

    2014-01-01

    Objective To evaluate some essential oils in treatment of intractable oral infections, principally caused by biofilm of multidrug-resistant Enterococcus faecalis (E. faecalis), such as persistent endodontic infections in which their treatment exhibits a real challenge for dentists. Methods Ten chemically analyzed essential oils by gas chromatography-mass spectrometry were evaluated for antimicrobial activity against sensitive and resistant clinical strains of E. faecalis in both planktonic and biofilm state using two methods, disk diffusion and broth micro-dilution. Results Studied essential oils showed a good antimicrobial activity and high ability in E. faecalis biofilm eradication, whether for sensitive or multidrug-resistant strains, especially those of Origanum glandulosum and Thymbra capitata with interesting minimum inhibitory concentration, biofilm inhibitory concentration, and biofilm eradication concentration values which doesn't exceed 0.063%, 0.75%, and 1.5%, respectively. Conclusions Findings of this study indicate that essential oils extracted from aromatic plants can be used in treatment of intractable oral infections, especially caused by biofilm of multidrug-resistant E. faecalis. PMID:25182948

  17. Vaccine Approaches for Multidrug Resistant Gram negative infections

    PubMed Central

    Campfield, Brian; Chen, Kong; Kolls, Jay K.

    2014-01-01

    Multidrug resistant (MDR) Gram negative bacterial infections are increasing in frequency and are associated with significant financial costs, morbidity and mortality. Current antibiotic therapies are associated with unacceptably poor clinical outcomes and toxicity. Unfortunately, the development of novel antimicrobials is stagnant leaving a significant clinical need for alternative treatments of MDR Gram negative rod infections. Recent preclinical studies have identified Th17 cells as critical mediators of broadly protective adaptive immunity, including protection against MDR infections. Studies of Th17 eliciting antigens, adjuvants and routes of immunization have identified potential vaccine strategies that may confer long-lived adaptive immunity against MDR Gram negative bacterial infections. PMID:24637162

  18. Multidrug-resistant tuberculosis in prison inmates, Azerbaijan.

    PubMed Central

    Pfyffer, G. E.; Strässle, A.; van Gorkum, T.; Portaels, F.; Rigouts, L.; Mathieu, C.; Mirzoyev, F.; Traore, H.; van Embden, J. D.

    2001-01-01

    In a tuberculosis (TB) program in the Central Penitentiary Hospital of Azerbaijan, we analyzed 65 isolates of Mycobacterium tuberculosis by IS6110-based restriction fragment-length polymorphism (RFLP) and spoligotyping. From 11 clusters associated with 33 patients, 31 isolates had an IS6110-based banding pattern characteristic of the Beijing genotype of M. tuberculosis. In addition, 15 M. tuberculosis isolates with similar RFLP patterns constituted a single group by spoligotyping, matching the Beijing genotype. Multidrug resistance, always involving isoniazid and rifampin, was seen in 34 (52.3%) of 65 isolates, with 28 belonging to the Beijing genotype. PMID:11747699

  19. Multidrug-resistant tuberculosis that required 2 years for diagnosis.

    PubMed

    Yano, Shuichi; Kobayashi, Kanako; Ikeda, Toshikazu

    2012-01-01

    Isoniazid (H) or rifampicin (R) mono-resistant disease can be treated easily and effectively with first-line drugs, while combined H and R resistance (ie, multidrug-resistant tuberculosis (MDRTB)) requires treatment with at least four agents, including a quinolone and an injectable agent. Drug-resistant Mycobacterium tuberculosis strains are reported to be extremely difficult to cultivate invitro. The authors report a case of MDRTB that required 2 years for diagnosis, and was detected only in sputum culture on solid medium. Physicians should consider MDRTB if TB is suspected but pathogens are not detected. PMID:22605803

  20. Environmental contamination by multidrug-resistant microorganisms after daily cleaning.

    PubMed

    Gavaldà, Laura; Pequeño, Sandra; Soriano, Ana; Dominguez, M Angeles

    2015-07-01

    We analyzed 91 samples of high-touch surfaces obtained within the first hour after daily cleaning in intensive care unit rooms occupied with patients with multidrug-resistant organisms (MDROs). We determined that 22% of high-touch surfaces in rooms with methicillin-resistant Staphylococcus aureus patients and 5% of high-touch surfaces in rooms with multiresistant Pseudomonas aeruginosa patients were colonized with the same strain as the patient. We postulated that textile cleaning wipes could be contaminated with MDROs and may contribute to its spreading within the room. PMID:25907783

  1. Chlorine Dioxide is a Better Disinfectant than Sodium Hypochlorite against Multi-Drug Resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii.

    PubMed

    Hinenoya, Atsushi; Awasthi, Sharda Prasad; Yasuda, Noritomo; Shima, Ayaka; Morino, Hirofumi; Koizumi, Tomoko; Fukuda, Toshiaki; Miura, Takanori; Shibata, Takashi; Yamasaki, Shinji

    2015-01-01

    In this study, we evaluated and compared the antibacterial activity of chlorine dioxide (ClO2) and sodium hypochlorite (NaClO) on various multidrug-resistant strains in the presence of bovine serum albumin and sheep erythrocytes to mimic the blood contamination that frequently occurs in the clinical setting. The 3 most important species that cause nosocomial infections, i.e., methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MDRP), and multidrug-resistant Acinetobacter baumannii (MDRA), were evaluated, with three representative strains of each. At a 10-ppm concentration, ClO2 drastically reduced the number of bacteria of all MDRP and MDRA strains, and 2 out of 3 MRSA strains. However, 10 ppm of NaClO did not significantly kill any of the 9 strains tested in 60 seconds (s). In addition, 100 ppm of ClO2 completely killed all MRSA strains, whereas 100 ppm of NaClO failed to significantly lower the number of 2 MRSA strains and 1 MDRA strain. A time-course experiment demonstrated that, within 15 s, 100 ppm of ClO2, but not 100 ppm of NaClO, completely killed all tested strains. Taken together, these data suggest that ClO2 is more effective than NaClO against MRSA, MDRP, and MDRA, and 100 ppm is an effective concentration against these multidrug-resistant strains, which cause fatal nosocomial infections. PMID:25672403

  2. Treatment for patients with multidrug resistant Acinetobacter baumannii pulmonary infection

    PubMed Central

    PAN, TAO; LIU, XIAOYUN; XIANG, SHOUGUI; JI, WENLI

    2016-01-01

    Bacterial infections are common but have become increasingly resistant to drugs. The aim of the present study was to examine the combined treatment of traditional Chinese and Western medicine in 30 cases of pulmonary infection with multidrug resistant Acinetobacter baumannii. Patients were divided into groups A and B according to drug treatments. Cefoperazone or sulbactam and tanreqing were administered in group A, and cefoperazone or sulbactam in group B. The curative effect and prognosis of the two groups were recorded and the remaining treatments were performed routinely in the clinic. For the combined therapy group, which was administered sulperazone and tanreqing, 8 patients were recovered, 6 patients had significant effects, 3 patients exhibited some improvement and 1 patient had no response. One of the patients did not survive after 28 days. By contrast, there were 4 patients that were successfully treated, 3 patients with significant effects, 2 patients with some improvement and 2 patients had no response in the sulperazone group, and 4 patients did not survive after 28 days. In conclusion, the combined therapy of cefoperazone or sulbactam supplemented with tanreqing was identified to be more effective than cefoperazone or sulbactam as monotherapy, for treating multidrug resistant Acinetobacter baumannii. PMID:27073447

  3. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections

    PubMed Central

    Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N.

    2015-01-01

    Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections. PMID:26111644

  4. Multidrug resistance ABC transporter structure predictions by homology modeling approaches.

    PubMed

    Honorat, Mylène; Falson, Pierre; Terreux, Raphael; Di Pietro, Attilio; Dumontet, Charles; Payen, Léa

    2011-03-01

    Human multidrug resistance ABC transporters are ubiquitous membrane proteins responsible for the efflux of multiple, endogenous or exogenous, compounds out of the cells, and therefore they are involved in multi-drug resistance phenotype (MDR). They thus deeply impact the pharmacokinetic parameters and toxicity properties of drugs. A great pressure to develop inhibitors of these pumps is carried out, by either ligand-based drug design or (more ideally) structure-based drug design. In that goal, many biochemical studies have been carried out to characterize their transport functions, and many efforts have been spent to get high-resolution structures. Currently, beside the 3D-structures of bacterial ABC transporters Sav1866 and MsbA, only the mouse ABCB1 complete structure has been published at high-resolution, illustrating the tremendous difficulty in getting such information, taking into account that the human genome accounts for 48 ABC transporters encoding genes. Homology modeling is consequently a reasonable approach to overcome this obstacle. The present review describes, in the first part, the different approaches which have been published to set up human ABC pump 3D-homology models allowing the localization of binding sites for drug candidates, and the identification of critical residues therein. In a second part, the review proposes a more accurate strategy and practical keys to use such biological tools for initiating structure-based drug design. PMID:21470105

  5. Emergence of Multidrug-resistant Salmonella Paratyphi B dT+, Canada

    PubMed Central

    Boyd, David; Cloeckaert, Axel; Ahmed, Rafiq; Ng, Lai-King

    2004-01-01

    We document an increase in the number of multidrug-resistant Salmonella enterica serovar Paratyphi B dT+ identified in Canada. Most of these strains harbor Salmonella genomic island 1 (SGI1). Further studies are needed to determine factors contributing to the observed emergence of this multidrug-resistant strain. PMID:15324556

  6. Human Multidrug-Resistant Salmonella Newport Infections, Wisconsin, 2003–2005

    PubMed Central

    Archer, John R.; Sotir, Mark J.; Monson, Timothy A.; Kazmierczak, James J.

    2007-01-01

    We conducted a retrospective study of Salmonella Newport infections among Wisconsin residents during 2003–2005. Multidrug resistance prevalence was substantially greater in Wisconsin than elsewhere in the United States. Persons with multidrug-resistant infections were more likely than persons with susceptible infections to report exposure to cattle, farms, and unpasteurized milk. PMID:18217570

  7. Multidrug-Resistant Shigella Infections in Patients with Diarrhea, Cambodia, 2014–2015

    PubMed Central

    Poramathikul, Kamonporn; Chiek, Sivhour; Oransathid, Wilawan; Ruekit, Sirigade; Nobthai, Panida; Lurchachaiwong, Woradee; Serichantalergs, Oralak; Lon, Chanthap; Swierczewski, Brett

    2016-01-01

    We observed multidrug resistance in 10 (91%) of 11 Shigella isolates from a diarrheal surveillance study in Cambodia. One isolate was resistant to fluoroquinolones and cephalosporins and showed decreased susceptibility to azithromycin. We found mutations in gyrA, parC, β-lactamase, and mphA genes. Multidrug resistance increases concern about shigellosis treatment options. PMID:27532684

  8. Draft Genome Sequence of Neisseria gonorrhoeae Sequence Type 1407, a Multidrug-Resistant Clinical Isolate.

    PubMed

    Anselmo, A; Ciammaruconi, A; Carannante, A; Neri, A; Fazio, C; Fortunato, A; Palozzi, A M; Vacca, P; Fillo, S; Lista, F; Stefanelli, P

    2015-01-01

    Gonorrhea may become untreatable due to the spread of resistant or multidrug-resistant strains. Cefixime-resistant gonococci belonging to sequence type 1407 have been described worldwide. We report the genome sequence of Neisseria gonorrhoeae strain G2891, a multidrug-resistant isolate of sequence type 1407, collected in Italy in 2013. PMID:26272575

  9. Multidrug-Resistant Shigella Infections in Patients with Diarrhea, Cambodia, 2014-2015.

    PubMed

    Poramathikul, Kamonporn; Bodhidatta, Ladaporn; Chiek, Sivhour; Oransathid, Wilawan; Ruekit, Sirigade; Nobthai, Panida; Lurchachaiwong, Woradee; Serichantalergs, Oralak; Lon, Chanthap; Swierczewski, Brett

    2016-09-01

    We observed multidrug resistance in 10 (91%) of 11 Shigella isolates from a diarrheal surveillance study in Cambodia. One isolate was resistant to fluoroquinolones and cephalosporins and showed decreased susceptibility to azithromycin. We found mutations in gyrA, parC, β-lactamase, and mphA genes. Multidrug resistance increases concern about shigellosis treatment options. PMID:27532684

  10. Identifying more epidemic clones during a hospital outbreak of multidrug-resistant Acinetobacter baumannii.

    PubMed

    Domenech de Cellès, Matthieu; Salomon, Jérôme; Marinier, Anne; Lawrence, Christine; Gaillard, Jean-Louis; Herrmann, Jean-Louis; Guillemot, Didier

    2012-01-01

    Infections caused by multidrug-resistant bacteria are a major concern in hospitals. Current infection-control practices legitimately focus on hygiene and appropriate use of antibiotics. However, little is known about the intrinsic abilities of some bacterial strains to cause outbreaks. They can be measured at a population level by the pathogen's transmission rate, i.e. the rate at which the pathogen is transmitted from colonized hosts to susceptible hosts, or its reproduction number, counting the number of secondary cases per infected/colonized host. We collected data covering a 20-month surveillance period for carriage of multidrug-resistant Acinetobacter baumannii (MDRAB) in a surgery ward. All isolates were subjected to molecular fingerprinting, and a cluster analysis of profiles was performed to identify clonal groups. We then applied stochastic transmission models to infer transmission rates of MDRAB and each MDRAB clone. Molecular fingerprinting indicated that 3 clonal complexes spread in the ward. A first model, not accounting for different clones, quantified the level of in-ward cross-transmission, with an estimated transmission rate of 0.03/day (95% credible interval [0.012-0.049]) and a single-admission reproduction number of 0.61 [0.30-1.02]. The second model, accounting for different clones, suggested an enhanced transmissibility of clone 3 (transmission rate 0.047/day [0.018-0.091], with a single-admission reproduction number of 0.81 [0.30-1.56]). Clones 1 and 2 had comparable transmission rates (respectively, 0.016 [0.001-0.045], 0.014 [0.001-0.045]). The method used is broadly applicable to other nosocomial pathogens, as long as surveillance data and genotyping information are available. Building on these results, more epidemic clones could be identified, and could lead to follow-up studies dissecting the functional basis for variation in transmissibility of MDRAB lineages. PMID:23029226

  11. Simple Method for Markerless Gene Deletion in Multidrug-Resistant Acinetobacter baumannii.

    PubMed

    Oh, Man Hwan; Lee, Je Chul; Kim, Jungmin; Choi, Chul Hee; Han, Kyudong

    2015-05-15

    The traditional markerless gene deletion technique based on overlap extension PCR has been used for generating gene deletions in multidrug-resistant Acinetobacter baumannii. However, the method is time-consuming because it requires restriction digestion of the PCR products in DNA cloning and the construction of new vectors containing a suitable antibiotic resistance cassette for the selection of A. baumannii merodiploids. Moreover, the availability of restriction sites and the selection of recombinant bacteria harboring the desired chimeric plasmid are limited, making the construction of a chimeric plasmid more difficult. We describe a rapid and easy cloning method for markerless gene deletion in A. baumannii, which has no limitation in the availability of restriction sites and allows for easy selection of the clones carrying the desired chimeric plasmid. Notably, it is not necessary to construct new vectors in our method. This method utilizes direct cloning of blunt-end DNA fragments, in which upstream and downstream regions of the target gene are fused with an antibiotic resistance cassette via overlap extension PCR and are inserted into a blunt-end suicide vector developed for blunt-end cloning. Importantly, the antibiotic resistance cassette is placed outside the downstream region in order to enable easy selection of the recombinants carrying the desired plasmid, to eliminate the antibiotic resistance cassette via homologous recombination, and to avoid the necessity of constructing new vectors. This strategy was successfully applied to functional analysis of the genes associated with iron acquisition by A. baumannii ATCC 19606 and to ompA gene deletion in other A. baumannii strains. Consequently, the proposed method is invaluable for markerless gene deletion in multidrug-resistant A. baumannii. PMID:25746991

  12. Immunization against Multidrug-Resistant Acinetobacter baumannii Effectively Protects Mice in both Pneumonia and Sepsis Models

    PubMed Central

    Huang, Weiwei; Yao, Yufeng; Long, Qiong; Yang, Xu; Sun, Wenjia; Liu, Cunbao; Jin, Xiaomei; li, Yang; Chu, Xiaojie; Chen, Bin; Ma, Yanbing

    2014-01-01

    Objective Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections. Methods Mice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay. Results Intramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates. Conclusions Utilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections. PMID:24956279

  13. A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps.

    PubMed

    Phillips, Joshua L; Gnanakaran, S

    2015-01-01

    Many bacterial pathogens are becoming increasingly resistant to antibiotic treatments, and a detailed understanding of the molecular basis of antibiotic resistance is critical for the development of next-generation approaches for combating bacterial infections. Studies focusing on pathogens have revealed the profile of resistance in these organisms to be due primarily to the presence of multidrug resistance efflux pumps: tripartite protein complexes which span the periplasm bridging the inner and outer membranes of Gram-negative bacteria. An atomic-level resolution tripartite structure remains imperative to advancing our understanding of the molecular mechanisms of pump function using both theoretical and experimental approaches. We develop a fast and consistent method for constructing tripartite structures which leverages existing data-driven models and provide molecular modeling approaches for constructing tripartite structures of multidrug resistance efflux pumps. Our modeling studies reveal that conformational changes in the inner membrane component responsible for drug translocation have limited impact on the conformations of the other pump components, and that two distinct models derived from conflicting experimental data are both consistent with all currently available measurements. Additionally, we investigate putative drug translocation pathways via geometric simulations based on the available crystal structures of the inner membrane pump component, AcrB, bound to two drugs which occupy distinct binding sites: doxorubicin and linezolid. These simulations suggest that smaller drugs may enter the pump through a channel from the cytoplasmic leaflet of the inner membrane, while both smaller and larger drug molecules may enter through a vestibule accessible from the periplasm. PMID:24957790

  14. Simple Method for Markerless Gene Deletion in Multidrug-Resistant Acinetobacter baumannii

    PubMed Central

    Oh, Man Hwan; Lee, Je Chul; Kim, Jungmin

    2015-01-01

    The traditional markerless gene deletion technique based on overlap extension PCR has been used for generating gene deletions in multidrug-resistant Acinetobacter baumannii. However, the method is time-consuming because it requires restriction digestion of the PCR products in DNA cloning and the construction of new vectors containing a suitable antibiotic resistance cassette for the selection of A. baumannii merodiploids. Moreover, the availability of restriction sites and the selection of recombinant bacteria harboring the desired chimeric plasmid are limited, making the construction of a chimeric plasmid more difficult. We describe a rapid and easy cloning method for markerless gene deletion in A. baumannii, which has no limitation in the availability of restriction sites and allows for easy selection of the clones carrying the desired chimeric plasmid. Notably, it is not necessary to construct new vectors in our method. This method utilizes direct cloning of blunt-end DNA fragments, in which upstream and downstream regions of the target gene are fused with an antibiotic resistance cassette via overlap extension PCR and are inserted into a blunt-end suicide vector developed for blunt-end cloning. Importantly, the antibiotic resistance cassette is placed outside the downstream region in order to enable easy selection of the recombinants carrying the desired plasmid, to eliminate the antibiotic resistance cassette via homologous recombination, and to avoid the necessity of constructing new vectors. This strategy was successfully applied to functional analysis of the genes associated with iron acquisition by A. baumannii ATCC 19606 and to ompA gene deletion in other A. baumannii strains. Consequently, the proposed method is invaluable for markerless gene deletion in multidrug-resistant A. baumannii. PMID:25746991

  15. Overcoming of multidrug resistance by introducing the apoptosis gene, bcl-Xs, into MRP-overexpressing drug resistant cells.

    PubMed

    Ohi, Y; Kim, R; Toge, T

    2000-05-01

    Multidrug resistance associated protein (MRP) is one of drug transport membranes that confer multidrug resistance in cancer cells. Multidrug resistance has been known to be associated with resistance to apoptosis. In this study, using MRP overexpressing multidrug resistant nasopharyngeal cancer cells, we examined the expression of apoptosis related genes including p53, p21WAF1, bax and bcl-Xs between drug sensitive KB and its resistant KB/7D cells. We also examined whether the introduction of apoptosis related gene could increase the sensitivity to anticancer drugs in association with apoptotic cell death. The relative resistances to anticancer drugs in KB/7D cells evaluated by IC50 values were 3.6, 61.3, 10.4 and 10.5 to adriamycin (ADM), etoposide (VP-16), vincristine (VCR) and vindesine (VDS), respectively. The resistance to anticancer drugs in KB/7D cells was associated with the attenuation of internucleosomal DNA ladder formation in apoptosis. Of important, the mRNA expression of bcl-Xs gene in KB/7D cells was decreased in one-fourth as compared to that of KB cells among the apoptosis genes. The mRNA expression of bcl-Xs gene in a bcl-Xs transfected clone (KB/7Dbcl-Xs) was increased about 2-fold compared to that of KB/7Dneo cells, while the mRNA expression of MRP gene was not significantly different in KB/7bcl-Xs and KB/7Dneo cells. The sensitivities to anticancer drugs including ADM, VCR and VDS except VP-16 were increased in KB/7Dbcl-Xs cells, in turn, the relative resistance in KB/7Dbcl-Xs cells was decreased to 1.4, 4.0, and 3.0 in ADM, VCR and VDS, respectively, as compared to those of KB/7Dneo cells. Of interest, the studies on the accumulation of [3H]VCR showed that the decrease of [3H]VCR accumulation in KB/7Dbcl-Xs was not significantly different from that of KB/7Dneo cells. Collectively, these results indicated that the mechanism(s) of drug resistance in KB/7D cells could be explained at least by two factors: a) reduced drug accumulation mediated by

  16. Feroniellin A-induced autophagy causes apoptosis in multidrug-resistant human A549 lung cancer cells.

    PubMed

    Kaewpiboon, Chutima; Surapinit, Serm; Malilas, Waraporn; Moon, Jeong; Phuwapraisirisan, Preecha; Tip-Pyang, Santi; Johnston, Randal N; Koh, Sang Seok; Assavalapsakul, Wanchai; Chung, Young-Hwa

    2014-04-01

    During the screening of natural chemicals that can reverse multidrug resistance in human A549 lung cancer cells resistant to etoposide (A549RT-eto), we discovered that Feroniellin A (FERO), a novel furanocoumarin, shows toxicity toward A549RT-eto cells in a dose- and time-dependent manner. FERO reduced the expression of NF-κB, leading to downregulation of P-glycoprotein (P-gp), encoded by MDR1, which eventually sensitized A549RT-eto cells to apoptosis. FERO specifically diminished transcription and promoter activity of MDR1 but did not inhibit the expression of other multidrug resistance genes MRP2 and BCRP. Moreover, co-administration of FERO with Bay11-7802, an inhibitor of NF-κB, accelerated apoptosis of A549RT-eto cells through decreased expression of P-gp, indicating that NF-κB is involved in multidrug resistance. Conversely, addition of Z-VAD, a pan-caspase inhibitor, blocked FERO-induced apoptosis in A549RT-eto cells but did not block downregulation of P-gp, indicating that a decrease in P-gp expression is necessary but not sufficient for FERO-induced apoptosis. Interestingly, we found that FERO also induces autophagy, which is characterized by the conversion of LC3 I to LC3 II, induction of GFP-LC3 puncta, enhanced expression of Beclin-1 and ATG5, and inactivation of mTOR. Furthermore, suppression of Beclin-1 by siRNA reduced FERO-induced apoptosis in A549RT-eto cells and activation of autophagy by rapamycin accelerated FERO-induced apoptosis, suggesting that autophagy plays an active role in FERO-induced apoptosis. Herein, we report that FERO reverses multidrug resistance in A549RT-eto cells and exerts its cytotoxic effect by induction of both autophagy and apoptosis, which suggests that FERO can be a useful anticancer drug for multidrug-resistant lung cancer. PMID:24535083

  17. Human ABCG2: structure, function, and its role in multidrug resistance

    PubMed Central

    Mo, Wei; Zhang, Jian-Ting

    2012-01-01

    Human ABCG2 is a member of the ATP-binding cassette (ABC) transporter superfamily and is known to contribute to multidrug resistance (MDR) in cancer chemotherapy. Among ABC transporters that are known to cause MDR, ABCG2 is particularly interesting for its potential role in protecting cancer stem cells and its complex oligomeric structure. Recent studies have also revealed that the biogenesis of ABCG2 could be modulated by small molecule compounds. These modulators, upon binding to ABCG2, accelerate the endocytosis and trafficking to lysosome for degradation and effectively reduce the half-life of ABCG2. Hence, targeting ABCG2 stability could be a new venue for therapeutic discovery to sensitize drug resistant human cancers. In this report, we review recent progress on understanding the structure, function, biogenesis, as well as physiological and pathophysiological functions of ABCG2. PMID:22509477

  18. Intracellular target delivery of 10-hydroxycamptothecin with solid lipid nanoparticles against multidrug resistance.

    PubMed

    Liu, Min; Chen, Didi; Wang, Chenxu; Chen, Xunhu; Wen, Zhili; Cao, Yu; He, Hongxuan

    2015-01-01

    The main objective of this study was to design a suitable drug delivery system for 10-hydroxycamptothecin (HCPT). In this study, HCPT-loaded solid lipid nanoparticle (HCPT-loaded SLN) was successfully prepared. The HCPT-loaded SLN was characterized by size, entrapment efficiency and drug release manner. The cytotoxicity of HCPT-loaded SLN was assessed in vitro using HepG2/HCPT cells and in vivo utilizing human tumor xenograft nude mouse model. HCPT-loaded SLN indicated the ability to target HepG2/HCPT cells and accumulated higher drug content in HepG2/HCPT cells. HCPT-loaded SLN enhanced the cytotoxicity of HCPT in a concentration-dependent manner. Based on these results, HCPT-loaded SLN suggested being a promising vehicle for liver-targeted drug delivery. Moreover, it can be of clinical interest to overcome multidrug resistance (MDR) effectively. PMID:25766079

  19. Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates

    PubMed Central

    Chang, David; Garcia, Rebecca A.; Akers, Kevin S.; Mende, Katrin; Murray, Clinton K.; Wenke, Joseph C.; Sanchez, Carlos J.

    2016-01-01

    Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO3)3 was moderately effective at reducing planktonic bacteria (64 to 128 µM) with little activity against biofilms (≥512 µM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. PMID:26999163

  20. Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii.

    PubMed

    Chung, Joon-Hui; Bhat, Abhayprasad; Kim, Chang-Jin; Yong, Dongeun; Ryu, Choong-Min

    2016-01-01

    Polymyxins are last-resort antibiotics for treating infections of Gram-negative bacteria. The recent emergence of polymyxin-resistant bacteria, however, urgently demands clinical optimisation of polymyxin use to minimise further evolution of resistance. In this study we developed a novel combination therapy using minimal concentrations of polymyxin B. After large-scale screening of Streptomyces secondary metabolites, we identified a reliable polymixin synergist and confirmed as netropsin using high-pressure liquid chromatography, nuclear magnetic resonance, and mass spectrometry followed by in vitro assays using various Gram-negative pathogenic bacteria. To evaluate the effectiveness of combining polymixin B and netropsin in vivo, we performed survival analysis on greater wax moth Galleria mellonella infected with colistin-resistant clinical Acinetobacter baumannii isolates as well as Escherichia coli, Shigella flexineri, Salmonella typhimuruim, and Pseudomonas aeruginosa. The survival of infected G. mellonella was significantly higher when treated with polymyxin B and netropsin in combination than when treated with polymyxin B or netropsin alone. We propose a netropsin combination therapy that minimises the use of polymyxin B when treating infections with multidrug resistant Gram-negative bacteria. PMID:27306928

  1. Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii

    PubMed Central

    Chung, Joon-hui; Bhat, Abhayprasad; Kim, Chang-Jin; Yong, Dongeun; Ryu, Choong-Min

    2016-01-01

    Polymyxins are last-resort antibiotics for treating infections of Gram-negative bacteria. The recent emergence of polymyxin-resistant bacteria, however, urgently demands clinical optimisation of polymyxin use to minimise further evolution of resistance. In this study we developed a novel combination therapy using minimal concentrations of polymyxin B. After large-scale screening of Streptomyces secondary metabolites, we identified a reliable polymixin synergist and confirmed as netropsin using high-pressure liquid chromatography, nuclear magnetic resonance, and mass spectrometry followed by in vitro assays using various Gram-negative pathogenic bacteria. To evaluate the effectiveness of combining polymixin B and netropsin in vivo, we performed survival analysis on greater wax moth Galleria mellonella infected with colistin-resistant clinical Acinetobacter baumannii isolates as well as Escherichia coli, Shigella flexineri, Salmonella typhimuruim, and Pseudomonas aeruginosa. The survival of infected G. mellonella was significantly higher when treated with polymyxin B and netropsin in combination than when treated with polymyxin B or netropsin alone. We propose a netropsin combination therapy that minimises the use of polymyxin B when treating infections with multidrug resistant Gram-negative bacteria. PMID:27306928

  2. Arbekacin: another novel agent for treating infections due to methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative pathogens

    PubMed Central

    Matsumoto, Tetsuya

    2014-01-01

    Arbekacin sulfate (ABK), an aminoglycoside antibiotic, was discovered in 1972 and was derived from dibekacin to stabilize many common aminoglycoside modifying enzymes. ABK shows broad antimicrobial activities against not only Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) but also Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. ABK has been approved as an injectable formulation in Japan since 1990, under the trade name Habekacin, for the treatment of patients with pneumonia and sepsis caused by MRSA. The drug has been used in more than 250,000 patients, and its clinical benefit and safety have been proven over two decades. ABK currently shows promise for the application for the treatment of multidrug-resistant Gram-negative bacterial infections such as multidrug-resistant strains of P. aeruginosa and Acinetobacter baumannii because of its synergistic effect in combination with beta-lactams. PMID:25298740

  3. Nanomedicinal strategies to treat multidrug-resistant tumors: current progress

    PubMed Central

    Dong, Xiaowei; Mumper, Russell J

    2010-01-01

    Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. P-glycoprotein is an important and the best-known membrane transporter involved in MDR. Several strategies have been used to address MDR, especially P-glycoprotein-mediated drug resistance in tumors. However, clinical success has been limited, largely due to issues regarding lack of efficacy and/or safety. Nanoparticles have shown the ability to target tumors based on their unique physical and biological properties. To date, nanoparticles have been investigated primarily to address P-glycoprotein and the observed improved anticancer efficacy suggests that nanomedicinal strategies provide a new opportunity to overcome MDR. This article focuses on nanotechnology-based formulations and current nanomedicine approaches to address MDR in tumors and discusses the proposed mechanisms of action. PMID:20528455

  4. Cell biological mechanisms of multidrug resistance in tumors.

    PubMed Central

    Simon, S M; Schindler, M

    1994-01-01

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleiotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs. PMID:7909602

  5. How to Measure Export via Bacterial Multidrug Resistance Efflux Pumps.

    PubMed

    Blair, Jessica M A; Piddock, Laura J V

    2016-01-01

    Bacterial multidrug resistance (MDR) efflux pumps are an important mechanism of antibiotic resistance and are required for many pathogens to cause infection. They are also being harnessed to improve microbial biotechnological processes, including biofuel production. Therefore, scientists of many specialties must be able to accurately measure efflux activity. However, myriad methodologies have been described and the most appropriate method is not always clear. Within the scientific literature, many methods are misused or data arising are misinterpreted. The methods for measuring efflux activity can be split into two groups, (i) those that directly measure efflux and (ii) those that measure the intracellular accumulation of a substrate, which is then used to infer efflux activity. Here, we review the methods for measuring efflux and explore the most recent advances in this field, including single-cell or cell-free technologies and mass spectrometry, that are being used to provide more detailed information about efflux pump activity. PMID:27381291

  6. Cell Biological Mechanisms of Multidrug Resistance in Tumors

    NASA Astrophysics Data System (ADS)

    Simon, Sanford M.; Schindler, Melvin

    1994-04-01

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs.

  7. An outbreak of multidrug-resistant tuberculosis among a family.

    PubMed

    Iliaz, Sinem; Caglar, Emel; Koksalan, Orhan Kaya; Chousein, Efsun Gonca Ugur

    2016-04-01

    Tuberculosis is a major public health problem and it may be complicated by multidrug-resistant tuberculosis (MDR-TB). Wide transmission among immunocompetent contacts of the index case is possible. If you detect tuberculosis in two contacts of the index case, it is called an outbreak. The aim of our paper is to evaluate the characteristics of a MDR-TB outbreak affecting 7 people in a family treated during 2012-2014 in Istanbul Yedikule Training and Research Hospital for Chest Disease and Thoracic Surgery, Turkey. The cultures, spoligotyping, and DNA fingerprinting revealed the same Mycobacterium tuberculosis species as T1 genotype and ST53 subtype. All patients were negative for human immunodeficiency virus and free of other underlying diseases. PMID:27451825

  8. How to Measure Export via Bacterial Multidrug Resistance Efflux Pumps

    PubMed Central

    Blair, Jessica M. A.

    2016-01-01

    ABSTRACT Bacterial multidrug resistance (MDR) efflux pumps are an important mechanism of antibiotic resistance and are required for many pathogens to cause infection. They are also being harnessed to improve microbial biotechnological processes, including biofuel production. Therefore, scientists of many specialties must be able to accurately measure efflux activity. However, myriad methodologies have been described and the most appropriate method is not always clear. Within the scientific literature, many methods are misused or data arising are misinterpreted. The methods for measuring efflux activity can be split into two groups, (i) those that directly measure efflux and (ii) those that measure the intracellular accumulation of a substrate, which is then used to infer efflux activity. Here, we review the methods for measuring efflux and explore the most recent advances in this field, including single-cell or cell-free technologies and mass spectrometry, that are being used to provide more detailed information about efflux pump activity. PMID:27381291

  9. Functional expression of murine multidrug resistance in Xenopus laevis oocytes

    SciTech Connect

    Castillo, G.; Vera, J.C.; Rosen, O.M. ); Yang, Chiaping Huang; Horwitz, S.B. )

    1990-06-01

    The development of multidrug resistance (MDR) is associated with the overproduction of a plasma membrane glycoprotein, P glycoprotein. Here the authors report the functional expression of a member of the murine MDR family of proteins and show that Xenopus oocytes injected with RNA encoding the mouse mdr1b P glycoprotein develop a MDR-like phenotype. Immunological analysis indicated that oocytes injected with the mdr1b RNA synthesized a protein with the size and immunological characteristics of the mouse mdr1b P glycoprotein. These oocytes exhibited a decreased accumulation of ({sup 3}H)vinblastine and showed an increased capacity to extrude the drug compared to control oocytes not expressing the P glycoprotein. In addition, competition experiments indicated that verapamil, vincristine, daunomycin, and quinidine, but not colchicine, can overcome the rapid drug efflux conferred by the expression of the mouse P glycoprotein.

  10. Is Resistance Useless? Multidrug Resistance and Collateral Sensitivity

    PubMed Central

    Hall, Matthew D.; Handley, Misty D.; Gottesman, Michael M.

    2009-01-01

    When cancer cells develop resistance to chemotherapeutics, it is frequently conferred by the ATP-dependent efflux pump P-glycoprotein (MDR1, P-gp, ABCB1). P-gp can efflux a wide range of cancer drugs; thus its expression confers cross-resistance, termed multidrug resistance (MDR), to a wide range of drugs. Strategies to overcome this resistance have been actively sought for over 30 years, yet no clinical solutions exist. A less understood aspect of MDR is the hypersensitivity of resistant cancer cells to other drugs, a phenomenon generally known as collateral sensitivity (CS). This review highlights the extent of this effect for the first time, discusses hypotheses such as ROS generation to account for the underlying generality of this phenomenon, and proposes the exploitation of CS as a strategy to improve response to chemotherapy. PMID:19762091

  11. Multidrug-resistant tuberculosis in the United Kingdom and Lithuania.

    PubMed

    Gonzalo, X; Hutchison, D C S; Drobniewski, F A; Pimkina, E; Davidaviciene, E

    2014-06-01

    Rates of resistance to first- and second-line drugs in multidrug-resistant tuberculosis (MDR-TB) cases in the United Kingdom were studied during 2010-2012. The highest rates for ethambutol, pyrazinamide and aminoglycosides occurred among patients originating in Eastern Europe, of whom 47% were Lithuanian. Rates of resistance to kanamycin were significantly lower (P < 0.0001) in the Lithuanian National TB Register than among Lithuanian patients resident in the United Kingdom (5% vs. 78%). In 2010, the majority of UK patients of Eastern European origin were located within the London region, whereas in 2011 the majority were located outside this region, a significant change (P = 0.01). PMID:24903935

  12. Chinese hamster pleiotropic multidrug-resistant cells are not radioresistant

    SciTech Connect

    Mitchell, J.B.; Gamson, J.; Russo, A.; Friedman, N.; DeGraff, W.; Carmichael, J.; Glatstein, E.

    1988-01-01

    The inherent cellular radiosensitivity of a Chinese hamster ovary pleiotropic cell line that is multidrug resistant (CHRC5) was compared to that of its parental cell line (AuxB1). Radiation survival curve parameters n and D0 were 4.5 and 1.1 Gy, respectively, for the CHRC5 line and 5.0 and 1.2 Gy, respectively, for the parental line. Thus, the inherent radiosensitivity of the two lines was similar even though key intracellular free radical scavenging and detoxifying systems employing glutathione, glutathione transferase, and catalase produced enzyme levels that were 2.0-, 1.9-, and 1.9-fold higher, respectively, in the drug-resistant cell line. Glutathione depletion by buthionine sulfoximine resulted in the same extent of aerobic radiosensitization in both lines (approximately 10%). Incorporation of iododeoxyuridine into cellular DNA sensitized both cell lines to radiation. These studies indicate that pleiotropic drug resistance does not necessarily confer radiation resistance.

  13. Biomimetic RNA Silencing Nanocomplexes Overcome Multidrug Resistance in Cancer Cells**

    PubMed Central

    Wang, Zhongliang; Wang, Zhe; Liu, Dingbin; Yan, Xuefeng; Wang, Fu; Niu, Gang

    2015-01-01

    RNA interference (RNAi) is an RNA-dependent gene silencing approach controlled by RNA-induced silencing complex (RISC). Here we represent a synthetic RISC-mimic nanocomplex, which can actively cleave its target RNA in a sequence-specific manner. With high enzymatic stability and efficient self-delivery to target cells, the designed nanocomplex can selectively and potently induce gene silencing without cytokine activation. The nanocomplexes targeting to multidrug resistance are able to not only bypass P-glycoprotein (Pgp) transporter due to their nano-size effect, but also effectively suppress the Pgp expression, thus resulting in successful restoration of drug sensitivity of OVCAR8/ADR cells to Pgp-transportable cytotoxic agents. This nanocomplex approach has the potential for both functional genomics and cancer therapy. PMID:24446433

  14. Prevalence of Multidrug Resistant Pulmonary Tuberculosis in North Bihar

    PubMed Central

    Kumar, Rajesh; Singh, Surya Deo

    2015-01-01

    Introduction Multidrug resistant tuberculosis (MDR-TB) is caused by Infection with Mycobacterium tuberculosis which is resistant to both isoniazid (INH) and rifampicin (RIF), with or without any other anti tubercular drug. It is caused by resistant mutant strains due to inadequate treatment and poor compliance. Due to time taking conventional diagnostic methods, drug resistant strains continue to spread. Therefore rapid diagnosis and treatment of MDR-TB strains are prerequisites for the worldwide fight against TB. Objective To determine the prevalence of MDR TB in North Bihar by molecular diagnostic method and to facilitate early diagnosis and treatment. Also, to find out the number of those diagnosed cases who were successfully initiated the treatment in MDR TB Centre of DMCH. Materials and Methods This six month observational study was carried out in IRL Darbhanga, Damien TB research Centre of the Darbhanga Medical College and Hospital, Bihar, India. During the period of February-July 2014, 256 sputum samples were collected from suspected cases of multidrug resistant tuberculosis, from 6 districts of North Bihar around Darbhanga. These samples were subjected to routine microscopy and culture to detect Mycobacterium tuberculosis. Positive cases were subjected to drug sensitivity test by a molecular diagnostic method, Using Genotype MTBDR plus kit. Result Out of 256 sputum samples from suspected cases of MDR TB, 122 cases were microscopy positive for tuberculosis. Among these 122 cases, tuberculosis was confirmed by PCR in 114 cases. Finally with the help of Line Probe Assay (LPA), 39(15%) samples were found to have resistance to both INH and Rifampicin. Male female ratio was 4:1. Conclusion The Prevalence of Multi drug resistant pulmonary tuberculosis in North Bihar is 15%. It needs early diagnosis by molecular diagnostic method and prompt treatment to reduce the spread of MDR TB cases. PMID:26674711

  15. Nanodrug delivery in reversing multidrug resistance in cancer cells.

    PubMed

    Kapse-Mistry, Sonali; Govender, Thirumala; Srivastava, Rohit; Yergeri, Mayur

    2014-01-01

    Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance (MDR) which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, overexpression of drug transporter such as P-glycoprotein(P-gp), multidrug resistance-associated proteins (MRP1, MRP2), and breast cancer resistance protein (BCRP). Currently nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles, quantum dots, dendrimers, liposomes, micelles has emerged as an innovative, effective, and promising platforms for treatment of drug resistant cancer cells. Nanocarriers have potential to improve drug therapeutic index, ability for multifunctionality, divert ABC-transporter mediated drug efflux mechanism and selective targeting to tumor cells, cancer stem cells, tumor initiating cells, or cancer microenvironment. Selective nanocarrier targeting to tumor overcomes dose-limiting side effects, lack of selectivity, tissue toxicity, limited drug access to tumor tissues, high drug doses, and emergence of multiple drug resistance with conventional or combination chemotherapy. Current review highlights various nanodrug delivery systems to overcome mechanism of MDR by neutralizing, evading, or exploiting the drug efflux pumps and those independent of drug efflux pump mechanism by silencing Bcl-2 and HIF1α gene expressions by siRNA and miRNA, modulating ceramide levels and targeting NF-κB. "Theragnostics" combining a cytotoxic agent, targeting moiety, chemosensitizing agent, and diagnostic imaging aid are highlighted as effective and innovative systems for tumor localization and overcoming MDR. Physical approaches such as combination of drug with thermal/ultrasound/photodynamic therapies to overcome MDR are focused. The review focuses on newer drug delivery systems developed to overcome MDR in

  16. Nanodrug delivery in reversing multidrug resistance in cancer cells

    PubMed Central

    Kapse-Mistry, Sonali; Govender, Thirumala; Srivastava, Rohit; Yergeri, Mayur

    2014-01-01

    Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance (MDR) which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, overexpression of drug transporter such as P-glycoprotein(P-gp), multidrug resistance-associated proteins (MRP1, MRP2), and breast cancer resistance protein (BCRP). Currently nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles, quantum dots, dendrimers, liposomes, micelles has emerged as an innovative, effective, and promising platforms for treatment of drug resistant cancer cells. Nanocarriers have potential to improve drug therapeutic index, ability for multifunctionality, divert ABC-transporter mediated drug efflux mechanism and selective targeting to tumor cells, cancer stem cells, tumor initiating cells, or cancer microenvironment. Selective nanocarrier targeting to tumor overcomes dose-limiting side effects, lack of selectivity, tissue toxicity, limited drug access to tumor tissues, high drug doses, and emergence of multiple drug resistance with conventional or combination chemotherapy. Current review highlights various nanodrug delivery systems to overcome mechanism of MDR by neutralizing, evading, or exploiting the drug efflux pumps and those independent of drug efflux pump mechanism by silencing Bcl-2 and HIF1α gene expressions by siRNA and miRNA, modulating ceramide levels and targeting NF-κB. “Theragnostics” combining a cytotoxic agent, targeting moiety, chemosensitizing agent, and diagnostic imaging aid are highlighted as effective and innovative systems for tumor localization and overcoming MDR. Physical approaches such as combination of drug with thermal/ultrasound/photodynamic therapies to overcome MDR are focused. The review focuses on newer drug delivery systems developed to overcome

  17. The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies.

    PubMed

    Baker, Thomas M; Satlin, Michael J

    2016-10-01

    Prolonged neutropenia and chemotherapy-induced mucositis render patients with hematologic malignancies highly vulnerable to Gram-negative bacteremia. Unfortunately, multidrug-resistant (MDR) Gram-negative bacteria are increasingly encountered globally, and current guidelines for empirical antibiotic coverage in these patients may not adequately treat these bacteria. This expansion of resistance, coupled with traditional culturing techniques requiring 2-4 days for bacterial identification and antimicrobial susceptibility results, have grave implications for these immunocompromised hosts. This review characterizes the epidemiology, risk factors, resistance mechanisms, recommended treatments, and outcomes of the MDR Gram-negative bacteria that commonly cause infections in patients with hematologic malignancies. We also examine the infection prevention strategies in hematology patients, such as infection control practices, antimicrobial stewardship, and targeted decolonization. Finally, we assess the strategies to improve outcomes of the infected patients, including gastrointestinal screening to guide empirical antibiotic therapy, new rapid diagnostic tools for expeditious identification of MDR pathogens, and use of two new antimicrobial agents, ceftolozane/tazobactam and ceftazidime/avibactam. PMID:27339405

  18. Evaluation of aromatic plants and compounds used to fight multidrug resistant infections.

    PubMed

    Perumal Samy, Ramar; Manikandan, Jayapal; Al Qahtani, Mohammed

    2013-01-01

    Traditional medicine plays a vital role for primary health care in India, where it is widely practiced to treat various ailments. Among those obtained from the healers, 78 medicinal plants were scientifically evaluated for antibacterial activity. Methanol extract of plants (100  μ g of residue) was tested against the multidrug resistant (MDR) Gram-negative and Gram-positive bacteria. Forty-seven plants showed strong activity against Burkholderia pseudomallei (strain TES and KHW) and Staphylococcus aureus, of which Tragia involucrata L., Citrus acida Roxb. Hook.f., and Aegle marmelos (L.) Correa ex Roxb. showed powerful inhibition of bacteria. Eighteen plants displayed only a moderate effect, while six plants failed to provide any evidence of inhibition against the tested bacteria. Purified compounds showed higher antimicrobial activity than crude extracts. The compounds showed less toxic effect to the human skin fibroblasts (HEPK) cells than their corresponding aromatic fractions. Phytochemical screening indicates that the presence of various secondary metabolites may be responsible for this activity. Most of the plant extracts contained high levels of phenolic or polyphenolic compounds and exhibited activity against MDR pathogens. In conclusion, plants are promising agents that deserve further exploration. Lead molecules available from such extracts may serve as potential antimicrobial agents for future drug development to combat diseases caused by the MDR bacterial strains as reported in this study. PMID:24223059

  19. Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates.

    PubMed Central

    Malléa, Monique; Mahamoud, Abdallah; Chevalier, Jacqueline; Alibert-Franco, Sandrine; Brouant, Pierre; Barbe, Jacques; Pagès, Jean-Marie

    2003-01-01

    Over the last decade, MDR (multidrug resistance) has increased worldwide in microbial pathogens by efflux mechanisms, leading to treatment failures in human infections. Several Gram-negative bacteria efflux pumps have been described. These proteinaceous channels are capable of expelling structurally different drugs across the envelope and conferring antibiotic resistance in various bacterial pathogens. Combating antibiotic resistance is an urgency and the blocking of efflux pumps is an attractive response to the emergence of MDR phenotypes in infectious bacteria. In the present study, various alkylaminoquinolines were tested as potential inhibitors of drug transporters. We showed that alkylaminoquinolines are capable of restoring susceptibilities to structurally unrelated antibiotics in clinical isolates of MDR Gram-negative bacteria. Antibiotic efflux studies indicated that 7-nitro-8-methyl-4-[2'-(piperidino)ethyl]aminoquinoline acts as an inhibitor of the AcrAB-TolC efflux pump and restores a high level of intracellular drug concentration. Inhibitory activity of this alkylaminoquinoline is observed on clinical isolates showing different resistance phenotypes. PMID:12959639

  20. Evaluation of Aromatic Plants and Compounds Used to Fight Multidrug Resistant Infections

    PubMed Central

    Perumal Samy, Ramar; Manikandan, Jayapal; Al Qahtani, Mohammed

    2013-01-01

    Traditional medicine plays a vital role for primary health care in India, where it is widely practiced to treat various ailments. Among those obtained from the healers, 78 medicinal plants were scientifically evaluated for antibacterial activity. Methanol extract of plants (100 μg of residue) was tested against the multidrug resistant (MDR) Gram-negative and Gram-positive bacteria. Forty-seven plants showed strong activity against Burkholderia pseudomallei (strain TES and KHW) and Staphylococcus aureus, of which Tragia involucrata L., Citrus acida Roxb. Hook.f., and Aegle marmelos (L.) Correa ex Roxb. showed powerful inhibition of bacteria. Eighteen plants displayed only a moderate effect, while six plants failed to provide any evidence of inhibition against the tested bacteria. Purified compounds showed higher antimicrobial activity than crude extracts. The compounds showed less toxic effect to the human skin fibroblasts (HEPK) cells than their corresponding aromatic fractions. Phytochemical screening indicates that the presence of various secondary metabolites may be responsible for this activity. Most of the plant extracts contained high levels of phenolic or polyphenolic compounds and exhibited activity against MDR pathogens. In conclusion, plants are promising agents that deserve further exploration. Lead molecules available from such extracts may serve as potential antimicrobial agents for future drug development to combat diseases caused by the MDR bacterial strains as reported in this study. PMID:24223059

  1. Multidrug-Resistant Bacterial Outbreaks in Burn Units: A Synthesis of the Literature According to the ORION Statement.

    PubMed

    Girerd-Genessay, Isabelle; Bénet, Thomas; Vanhems, Philippe

    2016-01-01

    The objective of this study is to review the literature on multidrug-resistant bacteria (MDRB) outbreaks in burn units according to the outbreak reports and intervention studies of nosocomial infection statement. A PubMed search engine was enlisted to identify reports, in English and French, on MDRB outbreaks in burn units, with no date restrictions, using the following key words: ("burn" OR "burns" OR "severe burn") AND ("unit" OR "critical care" OR "acute care" OR "intensive care" OR "center" OR "centre" OR "department") AND ("outbreak" OR "epidemic") AND ("resistant" OR "multidrug-resistant" OR "resistance" OR "MDR" OR "MDRO"). Twenty-nine articles on such outbreaks in burn units were analyzed. A wide variety of these outbreaks were studied in terms of the microbial agents involved, length of outbreak, and attack rate (1.9-66.7%). The most frequent bacteria were methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii. Screening of staff revealed carrier rates of 0 to 20% in 16 studies. Environmental samples were taken in 21 studies and were positive in 14 of them. The mortality rate among infected patients varied from 0 to 33%. Implementation of isolation precautions did not always suffice, with unit closure being necessary in five outbreaks. The lack of consensus on how to manage such outbreak was highlighted. MDRB infections or colonizations are responsible for increased morbidity and mortality in vulnerable burn patients. Their management is problematic because of multifactorial transmission and limited therapeutic possibilities. PMID:26056755

  2. Multidrug-resistant organisms in refugees: prevalences and impact on infection control in hospitals

    PubMed Central

    Heudorf, Ursel; Albert-Braun, Sabine; Hunfeld, Klaus-Peter; Birne, Franz-Ulrich; Schulze, Jörg; Strobel, Klaus; Petscheleit, Knut; Kempf, Volkhard A. J.; Brandt, Christian

    2016-01-01

    Introduction: The refugee crisis is a great challenge to the social and healthcare system in European countries, especially in Germany. An abundance of data has been published on the refugees’ health problems (infections as well as physical diseases and psychiatric problems) and their prevention (i.e., sanitary and vaccination programs). However, data on prevalences of multidrug-resistant organisms (MDRO) in refugees are scarce, although it is known that most refugees are from or travelled through countries with high prevalences of MDRO. This paper presents current data on MDRO colonization of refugees admitted to hospitals, and the impact of screening upon admission and infection control in hospitals is discussed. Methods: Anonymous data obtained by screening upon hospital admission were reported by hospitals in the Rhine-Main region of Germany to the local public health department. Screening and microbiological analyses were performed from December 2015 to March 2016 according to standardized and validated methods. Results: 9.8% of the refugees screened (32/325) exhibited colonization with methicillin-resistant Staphylococcus aureus (MRSA), and 23.3% of the refugees (67/290) were colonized with Gram-negative bacteria with extended spectrum beta-lactamases, and/or enterobacteria with resistance against 3 or 4 groups of antibacterials, so-called 3MRGN (multidrug-resistant Gram-negative bacteria with resistance against penicillins, cephalosporins and quinolones) and 4MRGN (with additional resistance against carbapenems). Carbapenem-resistant Gram-negative bacteria (CRGN) were detected in 2.1% (6/290) of the refugees. Conclusion: The data confirms the studies published between 2014 and 2016, encompassing refugees tested in Germany, the Netherlands and Israel, with prevalences of MRSA and CRGN up to 13.5% and 5.6%. The MDRO prevalences are higher than those of “risk groups” for MRSA, such as hemodialysis patients and patients depending on outpatient home

  3. BC4707 Is a Major Facilitator Superfamily Multidrug Resistance Transport Protein from Bacillus cereus Implicated in Fluoroquinolone Tolerance

    PubMed Central

    Simm, Roger; Vörös, Aniko; Ekman, Jaakko V.; Sødring, Marianne; Nes, Ingerid; Kroeger, Jasmin K.; Saidijam, Massoud; Bettaney, Kim E.; Henderson, Peter J. F.; Salkinoja-Salonen, Mirja; Kolstø, Anne-Brit

    2012-01-01

    Transcriptional profiling highlighted a subset of genes encoding putative multidrug transporters in the pathogen Bacillus cereus that were up-regulated during stress produced by bile salts. One of these multidrug transporters (BC4707) was selected for investigation. Functional characterization of the BC4707 protein in Escherichia coli revealed a role in the energized efflux of xenobiotics. Phenotypic analyses after inactivation of the gene bc4707 in Bacillus cereus ATCC14579 suggested a more specific, but modest role in the efflux of norfloxacin. In addition to this, transcriptional analyses showed that BC4707 is also expressed during growth of B. cereus under non-stressful conditions where it may have a role in the normal physiology of the bacteria. Altogether, the results indicate that bc4707, which is part of the core genome of the B. cereus group of bacteria, encodes a multidrug resistance efflux protein that is likely involved in maintaining intracellular homeostasis during growth of the bacteria. PMID:22615800

  4. Nanoscale analysis of the effects of antibiotics and CX1 on a Pseudomonas aeruginosa multidrug-resistant strain

    NASA Astrophysics Data System (ADS)

    Formosa, C.; Grare, M.; Jauvert, E.; Coutable, A.; Regnouf-de-Vains, J. B.; Mourer, M.; Duval, R. E.; Dague, E.

    2012-08-01

    Drug resistance is a challenge that can be addressed using nanotechnology. We focused on the resistance of the bacteria Pseudomonas aeruginosa and investigated, using Atomic Force Microscopy (AFM), the behavior of a reference strain and of a multidrug resistant clinical strain, submitted to two antibiotics and to an innovative antibacterial drug (CX1). We measured the morphology, surface roughness and elasticity of the bacteria under physiological conditions and exposed to the antibacterial molecules. To go further in the molecules action mechanism, we explored the bacterial cell wall nanoscale organization using functionalized AFM tips. We have demonstrated that affected cells have a molecularly disorganized cell wall; surprisingly long molecules being pulled off from the cell wall by a lectin probe. Finally, we have elucidated the mechanism of action of CX1: it destroys the outer membrane of the bacteria as demonstrated by the results on artificial phospholipidic membranes and on the resistant strain.

  5. Synergistic and Additive Effect of Oregano Essential Oil and Biological Silver Nanoparticles against Multidrug-Resistant Bacterial Strains.

    PubMed

    Scandorieiro, Sara; de Camargo, Larissa C; Lancheros, Cesar A C; Yamada-Ogatta, Sueli F; Nakamura, Celso V; de Oliveira, Admilton G; Andrade, Célia G T J; Duran, Nelson; Nakazato, Gerson; Kobayashi, Renata K T

    2016-01-01

    Bacterial resistance to conventional antibiotics has become a clinical and public health problem, making therapeutic decisions more challenging. Plant compounds and nanodrugs have been proposed as potential antimicrobial alternatives. Studies have shown that oregano (Origanum vulgare) essential oil (OEO) and silver nanoparticles have potent antibacterial activity, also against multidrug-resistant strains; however, the strong organoleptic characteristics of OEO and the development of resistance to these metal nanoparticles can limit their use. This study evaluated the antibacterial effect of a two-drug combination of biologically synthesized silver nanoparticles (bio-AgNP), produced by Fusarium oxysporum, and OEO against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. OEO and bio-AgNP showed bactericidal effects against all 17 strains tested, with minimal inhibitory concentrations (MIC) ranging from 0.298 to 1.193 mg/mL and 62.5 to 250 μM, respectively. Time-kill curves indicated that OEO acted rapidly (within 10 min), while the metallic nanoparticles took 4 h to kill Gram-negative bacteria and 24 h to kill Gram-positive bacteria. The combination of the two compounds resulted in a synergistic or additive effect, reducing their MIC values and reducing the time of action compared to bio-AgNP used alone, i.e., 20 min for Gram-negative bacteria and 7 h for Gram-positive bacteria. Scanning electron microscopy (SEM) revealed similar morphological alterations in Staphylococcus aureus (non-methicillin-resistant S. aureus, non-MRSA) cells exposed to three different treatments (OEO, bio-AgNP and combination of the two), which appeared cell surface blebbing. Individual and combined treatments showed reduction in cell density and decrease in exopolysaccharide matrix compared to untreated bacterial cells. It indicated that this composition have an antimicrobial activity against S. aureus by disrupting cells. Both compounds showed very low

  6. Synergistic and Additive Effect of Oregano Essential Oil and Biological Silver Nanoparticles against Multidrug-Resistant Bacterial Strains

    PubMed Central

    Scandorieiro, Sara; de Camargo, Larissa C.; Lancheros, Cesar A. C.; Yamada-Ogatta, Sueli F.; Nakamura, Celso V.; de Oliveira, Admilton G.; Andrade, Célia G. T. J.; Duran, Nelson; Nakazato, Gerson; Kobayashi, Renata K. T.

    2016-01-01

    Bacterial resistance to conventional antibiotics has become a clinical and public health problem, making therapeutic decisions more challenging. Plant compounds and nanodrugs have been proposed as potential antimicrobial alternatives. Studies have shown that oregano (Origanum vulgare) essential oil (OEO) and silver nanoparticles have potent antibacterial activity, also against multidrug-resistant strains; however, the strong organoleptic characteristics of OEO and the development of resistance to these metal nanoparticles can limit their use. This study evaluated the antibacterial effect of a two-drug combination of biologically synthesized silver nanoparticles (bio-AgNP), produced by Fusarium oxysporum, and OEO against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. OEO and bio-AgNP showed bactericidal effects against all 17 strains tested, with minimal inhibitory concentrations (MIC) ranging from 0.298 to 1.193 mg/mL and 62.5 to 250 μM, respectively. Time-kill curves indicated that OEO acted rapidly (within 10 min), while the metallic nanoparticles took 4 h to kill Gram-negative bacteria and 24 h to kill Gram-positive bacteria. The combination of the two compounds resulted in a synergistic or additive effect, reducing their MIC values and reducing the time of action compared to bio-AgNP used alone, i.e., 20 min for Gram-negative bacteria and 7 h for Gram-positive bacteria. Scanning electron microscopy (SEM) revealed similar morphological alterations in Staphylococcus aureus (non-methicillin-resistant S. aureus, non-MRSA) cells exposed to three different treatments (OEO, bio-AgNP and combination of the two), which appeared cell surface blebbing. Individual and combined treatments showed reduction in cell density and decrease in exopolysaccharide matrix compared to untreated bacterial cells. It indicated that this composition have an antimicrobial activity against S. aureus by disrupting cells. Both compounds showed very low

  7. Draft genome sequence of Acinetobacter baumannii strain NCTC 13423, a multidrug-resistant clinical isolate.

    PubMed

    Michiels, Joran E; Van den Bergh, Bram; Fauvart, Maarten; Michiels, Jan

    2016-01-01

    Acinetobacter baumannii is a pathogen that is becoming increasingly important and causes serious hospital-acquired infections. We sequenced the genome of A. baumannii NCTC 13423, a multidrug-resistant strain belonging to the international clone II group, isolated from a human infection in the United Kingdom in 2003. The 3,937,944 bp draft genome has a GC-content of 39.0 % and a total of 3672 predicted protein-coding sequences. The availability of genome sequences of multidrug-resistant A. baumannii isolates will fuel comparative genomic studies to help understand the worrying spread of multidrug resistance in this pathogen. PMID:27594976

  8. Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics.

    PubMed

    Hirsch, Elizabeth B; Zucchi, Paola C; Chen, Alice; Raux, Brian R; Kirby, James E; McCoy, Christopher; Eliopoulos, George M

    2016-05-01

    Increasing resistance among Gram-negative uropathogens limits treatment options, and susceptibility data for multidrug-resistant isolates are limited. We assessed the activity of five oral agents against 91 multidrug-resistant Gram-negative urine isolates that were collected from emergency department/hospitalized patients. Fosfomycin and nitrofurantoin were most active (>75% susceptibility). Susceptibilities to sulfamethoxazole-trimethoprim, ciprofloxacin, and ampicillin were ≤40%; empirical use of these agents likely provides inadequate coverage in areas with a high prevalence of multidrug-resistant uropathogens. PMID:26883704

  9. Role of wild birds as carriers of multi-drug resistant Escherichia coli and Escherichia vulneris.

    PubMed

    Shobrak, Mohammed Y; Abo-Amer, Aly E

    2014-01-01

    Emergence and distribution of multi-drug resistant (MDR) bacteria in environments pose a risk to human and animal health. A total of 82 isolates of Escherichia spp. were recovered from cloacal swabs of migrating and non-migrating wild birds. All bacterial isolates were identified and characterized morphologically and biochemically. 72% and 50% of isolates recovered from non-migrating and migrating birds, respectively, showed positive congo red dye binding (a virulence factor). Also, hemolysin production (a virulence factor) was showed in 8% of isolates recovered from non-migrating birds and 75% of isolates recovered from migrating birds. All isolates recovered from non-migrating birds were found resistant to Oxacillin while all isolates recovered from migrating birds demonstrated resistance to Oxacillin, Chloramphenicol, Oxytetracycline and Lincomycin. Some bacterial isolates recovered from non-migrating birds and migrating birds exhibited MDR phenotype. The MDR isolates were further characterized by API 20E and 16S rRNA as E. coli and E. vulneris. MDR Escherichia isolates contain ~1-5 plasmids of high-molecular weights. Accordingly, wild birds could create a potential threat to human and animal health by transmitting MDR bacteria to water streams and other environmental sources through their faecal residues, and to remote regions by migration. PMID:25763023

  10. Multidrug-resistant Enterobacteriaceae from indoor air of an urban wastewater treatment plant.

    PubMed

    Teixeira, Juliana V; Cecílio, Pedro; Gonçalves, Daniela; Vilar, Vítor J P; Pinto, Eugénia; Ferreira, Helena N

    2016-07-01

    Wastewater treatment plants (WWTPs) have been recognized as sources of bioaerosols that may act as vehicles for dissemination of pathogens and multidrug-resistant (MDR) bacteria. The occurrence of MDR Enterobacteriaceae in indoor air of an urban WWTP was investigated. A possible airborne contamination with extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae was also explored. Fourteen of 39 Enterobacteriaceae isolates were MDR. These isolates were found at all sampling sites, mainly at the secondary sedimentation settings. The highest levels of resistance were detected in three different species: Enterobacter cloacae, Escherichia coli, and Citrobacter freundii. Furthermore, one of the airborne E. coli isolates was phenotypically characterized as an ESBL producer. Additionally, five isolates showed non-susceptibility to at least one carbapenem tested. The presence of genes encoding relevant beta-lactamase types in these ESBL-producing and carbapenem-resistant Enterobacteriaceae isolates was investigated by PCR. Results showed amplification for bla CTX-M and bla OXA. These findings are relevant both in terms of occupational/public health and of environmental dissemination of MDR bacteria. PMID:27260528

  11. Cockroaches as a Source of High Bacterial Pathogens with Multidrug Resistant Strains in Gondar Town, Ethiopia

    PubMed Central

    Huruy, Kahsay; Muluye, Dagnachew; Feleke, Tigist; G/Silassie, Fisha; Ayalew, Getenet; Nagappan, Raja

    2016-01-01

    Background. Cockroaches are source of bacterial infections and this study was aimed to assess bacterial isolates and their antimicrobial profiles from cockroaches in Gondar town, Ethiopia. Methods. A total of 60 cockroaches were collected from March 1 to May 30, 2014, in Gondar town. Bacterial species were isolated from external and internal parts of cockroaches. Disk diffusion method was used to determine antibiotic susceptibility patterns. Data were entered and analyzed by using SPSS version 20; P values <0.005 were considered as statistically significant. Results. Of 181 identified bacteria species, 110 (60.8%) and 71 (39.2%) were identified from external and internal parts of cockroaches, respectively. Klebsiella pneumoniae 32 (17.7%), Escherichia coli 29 (16%), and Citrobacter spp. 27 (15%) were the predominant isolates. High resistance rate was observed to cotrimoxazole, 60 (33.1%), and least resistance rate was noted to ciprofloxacin, 2 (1.1%). Additionally, 116 (64.1%) of the isolates were MDR strains; Salmonella spp. were the leading MDR isolates (100%) followed by Enterobacter (90.5%) and Shigella spp. (76.9%). Conclusion. Cockroaches are the potential source of bacteria pathogens with multidrug resistant strains and hence effective preventive and control measures are required to minimize cockroach related infections. PMID:27340653

  12. Role of wild birds as carriers of multi-drug resistant Escherichia coli and Escherichia vulneris

    PubMed Central

    Shobrak, Mohammed Y.; Abo-Amer, Aly E.

    2014-01-01

    Emergence and distribution of multi-drug resistant (MDR) bacteria in environments pose a risk to human and animal health. A total of 82 isolates of Escherichia spp. were recovered from cloacal swabs of migrating and non-migrating wild birds. All bacterial isolates were identified and characterized morphologically and biochemically. 72% and 50% of isolates recovered from non-migrating and migrating birds, respectively, showed positive congo red dye binding (a virulence factor). Also, hemolysin production (a virulence factor) was showed in 8% of isolates recovered from non-migrating birds and 75% of isolates recovered from migrating birds. All isolates recovered from non-migrating birds were found resistant to Oxacillin while all isolates recovered from migrating birds demonstrated resistance to Oxacillin, Chloramphenicol, Oxytetracycline and Lincomycin. Some bacterial isolates recovered from non-migrating birds and migrating birds exhibited MDR phenotype. The MDR isolates were further characterized by API 20E and 16S rRNA as E. coli and E. vulneris. MDR Escherichia isolates contain ~1–5 plasmids of high-molecular weights. Accordingly, wild birds could create a potential threat to human and animal health by transmitting MDR bacteria to water streams and other environmental sources through their faecal residues, and to remote regions by migration. PMID:25763023

  13. Cockroaches as a Source of High Bacterial Pathogens with Multidrug Resistant Strains in Gondar Town, Ethiopia.

    PubMed

    Moges, Feleke; Eshetie, Setegn; Endris, Mengistu; Huruy, Kahsay; Muluye, Dagnachew; Feleke, Tigist; G/Silassie, Fisha; Ayalew, Getenet; Nagappan, Raja

    2016-01-01

    Background. Cockroaches are source of bacterial infections and this study was aimed to assess bacterial isolates and their antimicrobial profiles from cockroaches in Gondar town, Ethiopia. Methods. A total of 60 cockroaches were collected from March 1 to May 30, 2014, in Gondar town. Bacterial species were isolated from external and internal parts of cockroaches. Disk diffusion method was used to determine antibiotic susceptibility patterns. Data were entered and analyzed by using SPSS version 20; P values <0.005 were considered as statistically significant. Results. Of 181 identified bacteria species, 110 (60.8%) and 71 (39.2%) were identified from external and internal parts of cockroaches, respectively. Klebsiella pneumoniae 32 (17.7%), Escherichia coli 29 (16%), and Citrobacter spp. 27 (15%) were the predominant isolates. High resistance rate was observed to cotrimoxazole, 60 (33.1%), and least resistance rate was noted to ciprofloxacin, 2 (1.1%). Additionally, 116 (64.1%) of the isolates were MDR strains; Salmonella spp. were the leading MDR isolates (100%) followed by Enterobacter (90.5%) and Shigella spp. (76.9%). Conclusion. Cockroaches are the potential source of bacteria pathogens with multidrug resistant strains and hence effective preventive and control measures are required to minimize cockroach related infections. PMID:27340653

  14. Bactericidal activity of Musca domestica cecropin (Mdc) on multidrug-resistant clinical isolate of Escherichia coli.

    PubMed

    Lu, X; Shen, J; Jin, X; Ma, Y; Huang, Y; Mei, H; Chu, F; Zhu, J

    2012-08-01

    The housefly (Musca domestica) larvae have been used clinically to cure osteomyelitis, decubital necrosis, lip boil, ecthyma and malnutritional stagnation ever since the Ming/Qing Dynasty (1368 Anno Domini) till now, in China. In prior research, we have cloned and characterized a new gene of antimicrobial peptide cecropin from M. domestica larvae. This peptide was potently active against Gram-positive and Gram-negative bacteria standard strain. In the present study, we evaluated the possibility of Mdc to be a potential bactericidal agent against clinical isolates of multidrug-resistant (MDR) Escherichia coli and to elucidate the related antimicrobial mechanisms. Antimicrobial activity assays indicated a minimal inhibitory concentration (MIC) of 1.56 μM. Bactericidal kinetics at MIC showed that Mdc rapid killing of MDR E. coli. Lipopolysaccharide (LPS) dose-dependently suppressed Mdc antibacterial potency indicates that LPS is the initial binding site of Mdc in E. coli. Propidium iodide-based flow cytometry revealed that Mdc causes E. coli membrane permeabilization. Transmission electron micrographs further indicated that a remarkable damage in the bacteria's outer and inner membrane, even the leakage of cytoplasmic contents induced by Mdc. DNA binding experimental result implies that DNA is one of the possible intracellular targets of Mdc. Of note, Mdc did not show a perceptible cytotoxic effect on human red blood cells. Altogether, these results suggest that Mdc could be an excellent candidate for the development of more efficacious bactericidal agents. PMID:22202966

  15. Relationships between the Regulatory Systems of Quorum Sensing and Multidrug Resistance

    PubMed Central

    Xu, Gang-Ming

    2016-01-01

    Cell–cell communications, known as quorum sensing (QS) in bacteria, involve the signal molecules as chemical languages and the corresponding receptors as transcriptional regulators. In Gram-negative bacteria, orphan LuxR receptors recognize signals more than just acylhomoserine lactones, and modulate interspecies and interkingdom communications. Whereas, in the Gram-positive Streptomyces, pseudo gamma-butyrolactones (GBLs) receptors bind antibiotics other than GBL signals, and coordinate antibiotics biosynthesis. By interacting with structurally diverse molecules like antibiotics, the TetR family receptors regulate multidrug resistance (MDR) by controlling efflux pumps. Antibiotics at subinhibitory concentration may act as signal molecules; while QS signals also have antimicrobial activity at high concentration. Moreover, the QS and MDR systems may share the same exporters to transport molecules. Among these orphan LuxR, pseudo GBL receptors, and MDR regulators, although only with low sequence homology, they have some structure similarity and function correlation. Therefore, perhaps there might be evolutionary relationship and biological relevance between the regulatory systems of QS and MDR. Since the QS systems become new targets for antimicrobial strategy, it would expand our understanding about the evolutionary history of these regulatory systems. PMID:27379084

  16. Antibacterial activities of Beilschmiedia obscura and six other Cameroonian medicinal plants against multi-drug resistant Gram-negative phenotypes

    PubMed Central

    2014-01-01

    Background The rapid spread of bacteria expressing multi-drug resistance propels the search for new antibacterial agents. The present study was designed to evaluate the antibacterial activities of the methanol extracts from Beilschmiedia obscura and six other Cameroonian plants against a panel of twenty nine Gram-negative bacteria including Multi-drug resistant (MDR) phenotypes. Methods The phytochemical investigations of the extracts were carried out according to the standard methods and the liquid micro-dilution assay was used for all antibacterial assays. Results Phytochemical analysis showed the presence of alkaloids in all studied extracts. Other chemical classes of secondary metabolites such as anthocyanines, anthraquinones flavonoids, saponins, tannins, sterols and triterpenes were selectively detected in the extracts. The extract from the fruits of Beilschmiedia obscura, Pachypodanthium staudtii leaves and Peperomia fernandopoiana (whole plant) displayed the best spectrum of activity with MIC values ranging from 16 to 1024 μg/mL against at least 65% and above of the tested bacteria. The extract from Beilschmiedia obscura was the most active with MIC values below 100 μg/mL against ten of the tested bacteria. This extract also showed MBC values below 1024 μg/mL against 55.17% of the studied microorganisms. Phenylalanine arginine β-naphthylamide (PAβN) significantly modulated the activities of extracts from the leaves and fruits of Pachypodanthium staudtii and Beilschmiedia obscura respectively, by increasing their inhibitory activity against Klebsiella pneumoniae KP55 strain at least four fold. Conclusion The overall results of the present investigation provide information for the possible use of the methanol extracts of the studied plant species, especially B. obscura to fight infectious diseases caused by Gram-negative bacteria including MDR phenotypes. PMID:25023038

  17. [New Drugs for the Treatment of Multidrug-resistant Tuberculosis (MDR-TB)].

    PubMed

    Schaberg, T; Otto-Knapp, R; Bauer, T

    2015-05-01

    This article summarizes the state of development of new drugs for the treatment of multidrug-resistant tuberculosis. We focused on delamanid, bedaquiline, pretomanid, SQ 109 and sutezolid. PMID:25970122

  18. Incidence of Multidrug-Resistant Pseudomonas Spp. in ICU Patients with Special Reference to ESBL, AMPC, MBL and Biofilm Production

    PubMed Central

    Gupta, Richa; Malik, Abida; Rizvi, Meher; Ahmed, S. Moied

    2016-01-01

    Background: Multidrug-resistant (MDR) Pseudomonas spp. have been reported to be the important cause of ICU infections. The appearance of ESBL, AmpC and MBL genes and their spread among bacterial pathogens is a matter of great concern. Biofilm production also attributes to antimicrobial resistance due to close cell to cell contact that permits bacteria to more effectively transfer plasmids to one another. This study aimed at determining the incidence of ESBL, AmpC, MBL and biofilm producing Pseudomonas spp. in ICU patients. Material and Methods: The clinical specimens were collected aseptically from 150 ICU patients from February 2012 to October 2013. Identification and antimicrobial susceptibility was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. ESBLs and AmpC were detected phenotypically and genotypically. MBL was detected by modified Hodge and imipenem-EDTA double-disk synergy test. Results: Pseudomonas spp. 35(28%) were the most prevalent pathogen in ICU infections. Multidrug resistance and biofilm production was observed in 80.1% and 60.4% isolates, respectively. Prevalence of ESBL, AmpC and MBL was 22.9%, 42.8% and 14.4%, respectively. The average hospital stay was 25 days and was associated with 20% mortality. Conclusions: A regular surveillance is required to detect ESBL, AmpC and MBL producers especially in ICU patients. Carbapenems should be judiciously used to prevent their spread. The effective antibiotics, such as fluoroquinolones and piperacillin-tazobactum should be used after sensitivity testing. PMID:27013841

  19. Metal Accumulation and Vanadium-Induced Multidrug Resistance by Environmental Isolates of Escherichia hermannii and Enterobacter cloacae

    PubMed Central

    Hernández, Alicia; Mellado, Rafael P.; Martínez, José L.

    1998-01-01

    Contaminated soils from an oil refinery were screened for the presence of microorganisms capable of accumulating either nickel, vanadium, or both metals. Three strains of bacteria that belonged to the family Enterobacteriaceae were selected. Two of them were Escherichia hermannii strains, and outer membrane profile (OMP) analysis showed that they were similar to a strain of clinical origin; the other one was an Enterobacter cloacae strain that differed from clinical isolates. The selected bacteria accumulated both nickel and vanadium. Growth in the presence of vanadium induced multidrug resistance phenotypes in E. hermannii and E. cloacae. Incubation with this metal changed the OMP profile of E. hermannii but did not produce variations in the expression of the major OMPs of E. cloacae. PMID:9797283

  20. Causes, consequences, and perspectives in the variations of intestinal density of colonization of multidrug-resistant enterobacteria

    PubMed Central

    Ruppé, Etienne; Andremont, Antoine

    2013-01-01

    The intestinal microbiota is a complex environment that hosts 1013 to 1014 bacteria. Among these bacteria stand multidrug-resistant enterobacteria (MDRE), which intestinal densities can substantially vary, especially according to antibiotic exposure. The intestinal density of MDRE and their relative abundance (i.e., the proportion between the density of MDRE and the density of total enterobacteria) could play a major role in the infection process or patient-to-patient transmission. This review discusses the recent advances in understanding (i) what causes variations in the density or relative abundance of intestinal colonization, (ii) what are the clinical consequences of these variations, and (iii) what are the perspectives for maintaining these markers at low levels. PMID:23755045

  1. [Multidrug-resistant tuberculosis: challenges of a global emergence].

    PubMed

    Comolet, T

    2015-10-01

    Drug-resistant tuberculosis, in particular Multi-Drug Resistant (MDR-TB) is an increasing global concern and a major burden for some developing countries, especially the BRICS. It is assumed that every year roughly 350 000 new MDR-TB cases occur in the world, on average in 20.5% of TB patients that have been previously treated but also in 3.5% of persons that have never been on TB treatment before. The global distribution of cases is very heterogeneous and is now better understood thanks to a growing number of specific surveys and routine surveillance systems: incidence is much higher in southern Africa and in all countries formerly part of the USSR. Countries with weak health systems and previously inefficient TB control programs are highly vulnerable to MDR epidemics because program failures do help creating, maintaining and spreading resistances. Global response is slowly rolled out and diagnosis capacities are on the rise (mostly with genotypic methods) but adequate and successful treatment and care is still limited to a minority of global cases. From a public health perspective the MDR-TB growing epidemics will not be controlled merely by the introduction of few new antibiotics because it is also linked to patient's compliance and adequate case management supported by efficient TB program. In depth quality improvement will only be achieved after previous errors are thoroughly analyzed and boldly corrected. PMID:26289547

  2. Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages.

    PubMed

    Zarrilli, Raffaele; Pournaras, Spyros; Giannouli, Maria; Tsakris, Athanassios

    2013-01-01

    The rapid expansion of Acinetobacter baumannii clinical isolates exhibiting resistance to carbapenems and most or all available antibiotics during the last decade is a worrying evolution. The apparent predominance of a few successful multidrug-resistant lineages worldwide underlines the importance of elucidating the mode of spread and the epidemiology of A. baumannii isolates in single hospitals, at a country-wide level and on a global scale. The evolutionary advantage of the dominant clonal lineages relies on the capability of the A. baumannii pangenome to incorporate resistance determinants. In particular, the simultaneous presence of divergent strains of the international clone II and their increasing prevalence in international hospitals further support the ongoing adaptation of this lineage to the hospital environment. Indeed, genomic and genetic studies have elucidated the role of mobile genetic elements in the transfer of antibiotic resistance genes and substantiate the rate of genetic alterations associated with acquisition in A. baumannii of various resistance genes, including OXA- and metallo-β-lactamase-type carbapenemase genes. The significance of single nucleotide polymorphisms and transposon mutagenesis in the evolution of A. baumannii has been also documented. Establishment of a network of reference laboratories in different countries would generate a more complete picture and a fuller understanding of the importance of high-risk A. baumannii clones in the international dissemination of antibiotic resistance. PMID:23127486

  3. Trametinib modulates cancer multidrug resistance by targeting ABCB1 transporter

    PubMed Central

    Qiu, Jian-Ge; Zhang, Yao-Jun; Li, Yong; Zhao, Jin-Ming; Zhang, Wen-Ji; Jiang, Qi-Wei; Mei, Xiao-Long; Xue, You-Qiu; Qin, Wu-Ming; Yang, Yang; Zheng, Di-Wei; Chen, Yao; Wei, Meng-Ning; Shi, Zhi

    2015-01-01

    Overexpression of adenine triphosphate (ATP)-binding cassette (ABC) transporters is one of the main reasons of multidrug resistance (MDR) in cancer cells. Trametinib, a novel specific small-molecule mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, is currently used for the treatment of melanoma in clinic. In this study, we investigated the effect of trametinib on MDR mediated by ABC transporters. Trametinib significantly potentiated the effects of two ABCB1 substrates vincristine and doxorubicin on inhibition of growth, arrest of cell cycle and induction of apoptosis in cancer cells overexpressed ABCB1, but not ABCC1 and ABCG2. Furthermore, trametinib did not alter the sensitivity of non-ABCB1 substrate cisplatin. Mechanistically, trametinib potently blocked the drug-efflux activity of ABCB1 to increase the intracellular accumulation of rhodamine 123 and doxorubicin and stimulates the ATPase of ABCB1 without alteration of the expression of ABCB1. Importantly, trametinib remarkably enhanced the effect of vincristine against the xenografts of ABCB1-overexpressing cancer cells in nude mice. The predicted binding mode showed the hydrophobic interactions of trametinib within the large drug binding cavity of ABCB1. Consequently, our findings may have important implications for use of trametinib in combination therapy for cancer treatment. PMID:25915534

  4. Purification of a Multidrug Resistance Transporter for Crystallization Studies

    PubMed Central

    Alegre, Kamela O.; Law, Christopher J.

    2015-01-01

    Crystallization of integral membrane proteins is a challenging field and much effort has been invested in optimizing the overexpression and purification steps needed to obtain milligram amounts of pure, stable, monodisperse protein sample for crystallography studies. Our current work involves the structural and functional characterization of the Escherichia coli multidrug resistance transporter MdtM, a member of the major facilitator superfamily (MFS). Here we present a protocol for isolation of MdtM to increase yields of recombinant protein to the milligram quantities necessary for pursuit of structural studies using X-ray crystallography. Purification of MdtM was enhanced by introduction of an elongated His-tag, followed by identification and subsequent removal of chaperonin contamination. For crystallization trials of MdtM, detergent screening using size exclusion chromatography determined that decylmaltoside (DM) was the shortest-chain detergent that maintained the protein in a stable, monodispersed state. Crystallization trials of MdtM performed using the hanging-drop diffusion method with commercially available crystallization screens yielded 3D protein crystals under several different conditions. We contend that the purification protocol described here may be employed for production of high-quality protein of other multidrug efflux members of the MFS, a ubiquitous, physiologically and clinically important class of membrane transporters. PMID:27025617

  5. Multidrug resistant citrobacter: an unusual cause of liver abscess

    PubMed Central

    Kumar, Prabhat; Ghosh, Soumik; Rath, Deepak; Gadpayle, A K

    2013-01-01

    Liver abscesses are infectious, space occupying lesions in the liver, the two most common abscesses being pyogenic and amoebic. A pyogenic liver abscess (PLA) is a rare condition with a reported incidence of 20 per 100 000 hospital admissions in the western population. The right lobe of the liver is the most common site in both types of liver abscess. Clinical presentation is elusive with complaints of fever, right upper quadrant pain in the abdomen and hepatomegaly with or without jaundice. The aetiology of PLA has changed in the past few decades and may be of biliary, portal, arterial or traumatic origin, but many cases are still cryptogenic. The most common organisms causing PLA are Gram-negative aerobes, especially Escherichia coli and Klebsiella pneumoniae. Studies have shown a high degree of antimicrobial susceptibility of isolated organism resulting in an overall lower mortality in PLA. Here, we present a case of PLA caused by multidrug-resistant Citrobacter freundii, which is an unusual organism to be isolated. PMID:23608848

  6. Wallichinine reverses ABCB1-mediated cancer multidrug resistance.

    PubMed

    Lv, Min; Qiu, Jian-Ge; Zhang, Wen-Ji; Jiang, Qi-Wei; Qin, Wu-Ming; Yang, Yang; Zheng, Di-Wei; Chen, Yao; Huang, Jia-Rong; Wang, Kun; Wei, Meng-Ning; Cheng, Ke-Jun; Shi, Zhi

    2016-01-01

    Overexpression of ABCB1 in cancer cells is one of the main reasons of cancer multidrug resistance (MDR). Wallichinine is a compound isolated from piper wallichii and works as an antagonist of platelet activiating factor receptor to inhibit the gathering of blood platelet. In this study, we investigate the effect of wallichinine on cancer MDR mediated by ABCB1 transporter. Wallichinine significantly potentiates the effects of two ABCB1 substrates vincristine and doxorubicin on inhibition of growth, arrest of cell cycle and induction of apoptosis in ABCB1 overexpressing cancer cells. Furthermore, wallichinine do not alter the sensitivity of non-ABCB1 substrate cisplatin. Mechanistically, wallichinine blocks the drug-efflux activity of ABCB1 to increase the intracellular accumulation of rhodamine 123 and doxorubicin and stimulates the ATPase of ABCB1 without alteration of the expression of ABCB1. The predicted binding mode shows the hydrophobic interactions of wallichinine within the large drug binding cavity of ABCB1. At all, our study of the interaction of wallichinine with ABCB1 presented herein provides valuable clues for the development of novel MDR reversal reagents from natural products. PMID:27508017

  7. Multidrug-Resistant Tuberculosis in Europe, 2010–2011

    PubMed Central

    Günther, Gunar; van Leth, Frank; Alexandru, Sofia; Altet, Neus; Avsar, Korkut; Bang, Didi; Barbuta, Raisa; Bothamley, Graham; Ciobanu, Ana; Crudu, Valeriu; Davilovits, Manfred; Dedicoat, Martin; Duarte, Raquel; Gualano, Gina; Kunst, Heinke; de Lange, Wiel; Leimane, Vaira; Magis-Escurra, Cecile; McLaughlin, Anne-Marie; Muylle, Inge; Polcová, Veronika; Pontali, Emanuele; Popa, Christina; Rumetshofer, Rudolf; Skrahina, Alena; Solodovnikova, Varvara; Spinu, Victor; Tiberi, Simon; Viiklepp, Piret

    2015-01-01

    Drug-resistant Mycobacterium tuberculosis is challenging elimination of tuberculosis (TB). We evaluated risk factors for TB and levels of second-line drug resistance in M. tuberculosis in patients in Europe with multidrug-resistant (MDR) TB. A total of 380 patients with MDR TB and 376 patients with non–MDR TB were enrolled at 23 centers in 16 countries in Europe during 2010–2011. A total of 52.4% of MDR TB patients had never been treated for TB, which suggests primary transmission of MDR M. tuberculosis. At initiation of treatment for MDR TB, 59.7% of M. tuberculosis strains tested were resistant to pyrazinamide, 51.1% were resistant to ≥1 second-line drug, 26.6% were resistant to second-line injectable drugs, 17.6% were resistant to fluoroquinolones, and 6.8% were extensively drug resistant. Previous treatment for TB was the strongest risk factor for MDR TB. High levels of primary transmission and advanced resistance to second-line drugs characterize MDR TB cases in Europe. PMID:25693485

  8. Multidrug-resistant tuberculosis in an adult with cystic fibrosis.

    PubMed

    Manika, K; Giouleka, P; Zarogoulidis, K; Kioumis, I

    2013-01-01

    Mycobacterium tuberculosis infection in patients with cystic fibrosis (CF) is rare. We report a 22-year-old CF patient with high fever, dyspnea and weight loss that progressively worsened over 2 weeks before admission. The patient suffered from liver cirrhosis, was colonized with Pseudomonas aeruginosa and had been repeatedly hospitalized for pulmonary infections. The patient was treated initially as for an exacerbation of P. aeruginosa infection, but tuberculosis (TBC) was suspected due to lack of improvement. A CT of the chest revealed enlarged bilateral cavities in the upper and middle lobes. A tuberculin skin test was positive, and M. tuberculosis nucleic acid was isolated from sputum samples. After receiving first-line anti-TBC drugs for 1 month, the patient's condition continued to worsen so molecular drug susceptibility testing was performed. Multidrug-resistant TBC was discovered, leading to a change in regimen. The patient was treated with ethionamide, moxifloxacin, linezolid, amikacin, imipenem/cilastatin and rifabutin and showed a remarkable clinical improvement. Although nontuberculous mycobacteria are more common in CF, the possibility of TBC should not be ignored. In that setting, early suspicion of infection due to resistant M. tuberculosis can be life saving. PMID:22869452

  9. Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis

    PubMed Central

    van der Werf, Marieke J.; Langendam, Miranda W.; Huitric, Emma; Manissero, Davide

    2012-01-01

    We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0–141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles. PMID:22005918

  10. Intracellular pH and the Control of Multidrug Resistance

    NASA Astrophysics Data System (ADS)

    Simon, Sanford; Roy, Deborshi; Schindler, Melvin

    1994-02-01

    Many anticancer drugs are classified as either weak bases or molecules whose binding to cellular structures is pH dependent. Accumulation of these drugs within tumor cells should be affected by transmembrane pH gradients. Indeed, development of multidrug resistance (MDR) in tumor cells has been correlated with an alkaline shift of cytosolic pH. To examine the role of pH in drug partitioning, the distribution of two drugs, doxorubicin and daunomycin, was monitored in fibroblasts and myeloma cells. In both cell types the drugs rapidly accumulated within the cells. The highest concentrations were measured in the most acidic compartments-e.g., lysosomes. Modifying the cellular pH in drug-sensitive cells to mimic reported shifts in MDR caused an immediate change in the cellular drug concentration. Drug accumulation was enhanced by acidic shifts and reversed by alkaline shifts. All of these effects were rapid and reversible. These results demonstrate that the alkaline shift observed in MDR is sufficient to prevent the accumulation of chemotherapeutic drugs independent of active drug efflux.

  11. Multiwavelength videomicrofluorometry for multiparametric investigations of multidrug resistance

    NASA Astrophysics Data System (ADS)

    Rocchi, Emmanuelle; Salmon, Jean-Marie; Vigo, Jean; Viallet, Pierre M.

    1996-05-01

    A major problem in the cancer chemotherapy is the development of resistance to a whole range of drugs not only similar to the drugs used for resistance induction but also to some functionally and structurally unrelated. It's one of the multifactorial causes of failure of chemotherapy. Thus it appears essential to evaluate the multi-drug resistance (MDR) in living cells populations to: detect the MDR phenotype, to discriminate between resistant and sensitive cells, to identify mechanisms which are involved in the induction or the reversion of resistance and to study the cytotoxic process. Such a challenge implies the use of multiparametric approach that has been possible using a protocol involving microfluorometry connected to numerical image analysis on single living cells. This protocol relays on the correlation existing between the decreased intracellular accumulation of some fluorescent probes such as Hoechst 33342 (Ho342) and Rhodamine 123 (R123) in resistant cells. The simultaneous estimation of the fluorescence intensities of these probes has required the use of a third probe, the Nile Red, for cell contour delineation. The analysis of parameters related to Ho342 and R123 allows the discrimination of sensitive and resistant cells. So the multiparametric approach using multi-wavelength image analysis, which appears to be a powerful technique, has allowed us to show on human lymphoblastoid CCRF-CEM cells lines that the cytotoxic effects could be different depending on the cell resistance or on the cytotoxic drug used: Adriamycine, Vinblastine and the different cell behavior could be used for cell differentiation.

  12. Purification of a Multidrug Resistance Transporter for Crystallization Studies.

    PubMed

    Alegre, Kamela O; Law, Christopher J

    2015-01-01

    Crystallization of integral membrane proteins is a challenging field and much effort has been invested in optimizing the overexpression and purification steps needed to obtain milligram amounts of pure, stable, monodisperse protein sample for crystallography studies. Our current work involves the structural and functional characterization of the Escherichia coli multidrug resistance transporter MdtM, a member of the major facilitator superfamily (MFS). Here we present a protocol for isolation of MdtM to increase yields of recombinant protein to the milligram quantities necessary for pursuit of structural studies using X-ray crystallography. Purification of MdtM was enhanced by introduction of an elongated His-tag, followed by identification and subsequent removal of chaperonin contamination. For crystallization trials of MdtM, detergent screening using size exclusion chromatography determined that decylmaltoside (DM) was the shortest-chain detergent that maintained the protein in a stable, monodispersed state. Crystallization trials of MdtM performed using the hanging-drop diffusion method with commercially available crystallization screens yielded 3D protein crystals under several different conditions. We contend that the purification protocol described here may be employed for production of high-quality protein of other multidrug efflux members of the MFS, a ubiquitous, physiologically and clinically important class of membrane transporters. PMID:27025617

  13. Multidrug-resistant tuberculosis: Treatment and outcomes of 93 patients

    PubMed Central

    Brode, Sarah K; Varadi, Robert; McNamee, Jane; Malek, Nina; Stewart, Sharon; Jamieson, Frances B; Avendano, Monica

    2015-01-01

    BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide and the emergence of multidrug-resistant TB (MDR TB) poses a threat to its control. There is scanty evidence regarding optimal management of MDR TB. The majority of Canadian cases of MDR TB are diagnosed in Ontario; most are managed by the Tuberculosis Service at West Park Healthcare Centre in Toronto. The authors reviewed 93 cases of MDR TB admitted from January 1, 2000 to December 31, 2011. RESULTS: Eighty-nine patients were foreign born. Fifty-six percent had a previous diagnosis of TB and most (70%) had only pulmonary involvement. Symptoms included productive cough, weight loss, fever and malaise. The average length of inpatient stay was 126 days. All patients had a peripherally inserted central catheter for the intensive treatment phase because medications were given intravenously. Treatment lasted for 24 months after bacteriologic conversion, and included a mean (± SD) of 5±1 drugs. A successful outcome at the end of treatment was observed in 84% of patients. Bacteriological conversion was achieved in 98% of patients with initial positive sputum cultures; conversion occurred by four months in 91%. CONCLUSIONS: MDR TB can be controlled with the available anti-TB drugs. PMID:25493698

  14. Starvation, detoxification, and multidrug resistance in cancer therapy

    PubMed Central

    Lee, Changhan; Raffaghello, Lizzia; Longo, Valter D.

    2013-01-01

    The selection of chemotherapy drugs is based on the cytotoxicity to specific tumor cell types and the relatively low toxicity to normal cells and tissues. However, the toxicity to normal cells poses a major clinical challenge, particularly when malignant cells have acquired resistance to chemotherapy. This drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. Much progress in the understanding of tumor cell resistance has been made in the past 35 years, owing to milestone discoveries such as the identification and characterization of ABC transporters. Nonetheless, the complexity of the genetic and epigenetic rewiring of cancer cells makes drug resistance an equally complex phenomenon that is difficult to overcome. In this review, we discuss how the remarkable changes in the levels of glucose, IGF-I, IGFBP-1 and in other proteins caused by fasting have the potential to improve the efficacy of chemotherapy against tumors by protecting normal cells and tissues and possibly by diminishing multidrug resistance in malignant cells. PMID:22391012

  15. Wallichinine reverses ABCB1-mediated cancer multidrug resistance

    PubMed Central

    Lv, Min; Qiu, Jian-Ge; Zhang, Wen-Ji; Jiang, Qi-Wei; Qin, Wu-Ming; Yang, Yang; Zheng, Di-Wei; Chen, Yao; Huang, Jia-Rong; Wang, Kun; Wei, Meng-Ning; Cheng, Ke-Jun; Shi, Zhi

    2016-01-01

    Overexpression of ABCB1 in cancer cells is one of the main reasons of cancer multidrug resistance (MDR). Wallichinine is a compound isolated from piper wallichii and works as an antagonist of platelet activiating factor receptor to inhibit the gathering of blood platelet. In this study, we investigate the effect of wallichinine on cancer MDR mediated by ABCB1 transporter. Wallichinine significantly potentiates the effects of two ABCB1 substrates vincristine and doxorubicin on inhibition of growth, arrest of cell cycle and induction of apoptosis in ABCB1 overexpressing cancer cells. Furthermore, wallichinine do not alter the sensitivity of non-ABCB1 substrate cisplatin. Mechanistically, wallichinine blocks the drug-efflux activity of ABCB1 to increase the intracellular accumulation of rhodamine 123 and doxorubicin and stimulates the ATPase of ABCB1 without alteration of the expression of ABCB1. The predicted binding mode shows the hydrophobic interactions of wallichinine within the large drug binding cavity of ABCB1. At all, our study of the interaction of wallichinine with ABCB1 presented herein provides valuable clues for the development of novel MDR reversal reagents from natural products. PMID:27508017

  16. Emerging cephalosporin and multidrug-resistant gonorrhoea in Europe.

    PubMed

    Cole, M J; Spiteri, G; Chisholm, S A; Hoffmann, S; Ison, C A; Unemo, M; Van de Laar, M

    2014-01-01

    Neisseria gonorrhoeae has consistently developed resistance to antimicrobials used therapeutically for gonorrhoea and few antimicrobials remain for effective empiric first-line therapy. Since 2009 the European gonococcal antimicrobial surveillance programme (Euro-GASP) has been running as a sentinel surveillance system across Member States of the European Union (EU) and European Economic Area (EEA) to monitor antimicrobial susceptibility in N. gonorrhoeae. During 2011, N. gonorrhoeae isolates were collected from 21 participating countries, and 7.6% and 0.5% of the examined gonococcal isolates had in vitro resistance to cefixime and ceftriaxone, respectively. The rate of ciprofloxacin and azithromycin resistance was 48.7% and 5.3%, respectively. Two (0.1%) isolates displayed high-level resistance to azithromycin, i.e. a minimum inhibitory concentration (MIC) ≥256 mg/L. The current report further highlights the public health need to implement the European response plan, including further strengthening of Euro-GASP, to control and manage the threat of multidrug resistant N. gonorrhoeae. PMID:25411689

  17. Phenothiazinium antimicrobial photosensitizers are substrates of bacterial multidrug resistance pumps.

    PubMed

    Tegos, George P; Hamblin, Michael R

    2006-01-01

    Antimicrobial photodynamic therapy (PDT) combines a nontoxic photoactivatable dye, or photosensitizer (PS), with harmless visible light to generate singlet oxygen and free radicals that kill microbial cells. Although the light can be focused on the diseased area, the best selectivity is achieved by choosing a PS that binds and penetrates microbial cells. Cationic phenothiazinium dyes, such as methylene blue and toluidine blue O, have been studied for many years and are the only PSs used clinically for antimicrobial PDT. Multidrug resistance pumps (MDRs) are membrane-localized proteins that pump drugs out of cells and have been identified for a wide range of organisms. We asked whether phenothiazinium salts with structures that are amphipathic cations could potentially be substrates of MDRs. We used MDR-deficient mutants of Staphylococcus aureus (NorA), Escherichia coli (TolC), and Pseudomonas aeruginosa (MexAB) and found 2 to 4 logs more killing than seen with wild-type strains by use of three different phenothiazinium PSs and red light. Mutants that overexpress MDRs were protected from killing compared to the wild type. Effective antimicrobial PSs of different chemical structures showed no difference in light-mediated killing depending on MDR phenotype. Differences in uptake of phenothiazinium PS by the cells depending on level of MDR expression were found. We propose that specific MDR inhibitors could be used in combination with phenothiazinium salts to enhance their photodestructive efficiency. PMID:16377686

  18. Targeting protein kinases to reverse multidrug resistance in sarcoma.

    PubMed

    Chen, Hua; Shen, Jacson; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

    2016-02-01

    Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma. PMID:26827688

  19. Marine Natural Products as Models to Circumvent Multidrug Resistance.

    PubMed

    Long, Solida; Sousa, Emília; Kijjoa, Anake; Pinto, Madalena M M

    2016-01-01

    Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds. PMID:27399665

  20. Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray

    PubMed Central

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G.; Chandler, Darrell P.

    2014-01-01

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice. PMID:24796567

  1. Gatifloxacin for short, effective treatment of multidrug-resistant tuberculosis.

    PubMed

    Chiang, C-Y; Van Deun, A; Rieder, H L

    2016-09-01

    The 9-month regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) piloted in Bangladesh and used, with modifications, in Cameroon and Niger, has achieved treatment success in a very large proportion of patients; gatifloxacin (GFX) is likely to have played a critical role in this success. Two months after the publication of a study reporting that GFX and not moxifloxacin (MFX) was associated with dysglycaemia, the manufacturer announced the withdrawal of GFX from the market. The findings of that study may have less significance for the majority of MDR-TB patients living in high-incidence countries who are much younger, have a lower risk of dysglycaemia and suffer from a highly fatal condition. The problem of dysglycaemia is not limited to GFX use and may occur with other fluoroquinolones; furthermore, GFX-associated dysglycemia was manageable among those MDR-TB patients in Bangladesh and Niger in whom it occurred. GFX has now become unavailable in Bangladesh, Cameroon, Niger and other countries piloting the shorter MDR-TB regimens, depriving resource-poor countries of an efficacious, effective and inexpensive drug with a demonstrated good safety profile for the given indication. There is little reason not to make GFX available for MDR-TB treatment as long as the superiority of non-GFX-based MDR-TB regimens is not demonstrated. PMID:27510237

  2. Revisiting the ABCs of multidrug resistance in cancer chemotherapy.

    PubMed

    Tiwari, Amit K; Sodani, Kamlesh; Dai, Chun-Ling; Ashby, Charles R; Chen, Zhe-Sheng

    2011-04-01

    The adenosine tri-phosphate binding cassette (ABC) transporters are one of the largest transmembrane gene families in humans. The ABC transporters are present in a number of tissues, providing protection against xenobiotics and certain endogenous molecules. Unfortunately, their presence produces suboptimal chemotherapeutic outcomes in cancer patient tumor cells. It is well established that they actively efflux antineoplastic agents from cancer cells, producing the multidrug resistance (MDR) phenotype. The inadequate response to chemotherapy and subsequent poor prognosis in cancer patients can be in part the result of the clinical overexpression of ABC transporters. In fact, one of the targeted approaches for overcoming MDR in cancer cells is that directed towards blocking or inhibiting ABC transporters. Indeed, for almost three decades, research has been conducted to overcome MDR through pharmacological inhibition of ABC transporters with limited clinical success. Therefore, contemporary strategies to identify or to synthesize selective "resensitizers" of ABC transporters with limited nonspecific toxicity have been undertaken. Innovative approaches en route to understanding specific biochemical role of ABC transporters in MDR and tumorigenesis will prove essential to direct our knowledge towards more effective targeted therapies. This review briefly discusses the current knowledge regarding the clinical involvement of ABC transporters in MDR to antineoplastic drugs and highlights approaches undertaken so far to overcome ABC transporter-mediated MDR in cancer. PMID:21118094

  3. Effects of Mefloquine Use on Plasmodium vivax Multidrug Resistance

    PubMed Central

    Khim, Nimol; Andrianaranjaka, Voahangy; Popovici, Jean; Kim, Saorin; Ratsimbasoa, Arsene; Benedet, Christophe; Barnadas, Celine; Durand, Remy; Thellier, Marc; Legrand, Eric; Musset, Lise; Menegon, Michela; Severini, Carlo; Nour, Bakri Y.M.; Tichit, Magali; Bouchier, Christiane; Mercereau-Puijalon, Odile

    2014-01-01

    Numerous studies have indicated a strong association between amplification of the multidrug resistance-1 gene and in vivo and in vitro mefloquine resistance of Plasmodium falciparum. Although falciparum infection usually is not treated with mefloquine, incorrect diagnosis, high frequency of undetected mixed infections, or relapses of P. vivax infection triggered by P. falciparum infections expose non–P. falciparum parasites to mefloquine. To assess the consequences of such unintentional treatments on P. vivax, we studied variations in number of Pvmdr-1 (PlasmoDB accession no. PVX_080100, NCBI reference sequence NC_009915.1) copies worldwide in 607 samples collected in areas with different histories of mefloquine use from residents and from travelers returning to France. Number of Pvmdr-1 copies correlated with drug use history. Treatment against P. falciparum exerts substantial collateral pressure against sympatric P. vivax, jeopardizing future use of mefloquine against P. vivax. A drug policy is needed that takes into consideration all co-endemic species of malaria parasites. PMID:25272023

  4. Establishment and characterization of gemcitabine-resistant human cholangiocarcinoma cell lines with multidrug resistance and enhanced invasiveness.

    PubMed

    Wattanawongdon, Wareeporn; Hahnvajanawong, Chariya; Namwat, Nisana; Kanchanawat, Sirimas; Boonmars, Thidarut; Jearanaikoon, Patcharee; Leelayuwat, Chanwit; Techasen, Anchalee; Seubwai, Wunchana

    2015-07-01

    To establish and characterize the gemcitabine-resistant cholangiocarcinoma (CCA) cell lines, CCA KKU‑M139 and KKU‑M214 cell lines were exposed stepwisely to increasing gemcitabine (GEM). The resultant drug-resistant cell lines, KKU‑M139/GEM and KKU‑M214/GEM, retained the resistant phenotype in drug-free medium at least for 2 months. Sulforhodamine B assay demonstrated that KKU‑M139/GEM and KKU‑M214/GEM were 25.88- and 62.31-fold more resistant to gemcitabine than their parental cells. Both gemcitabine-resistant cell lines were cross-resistant to 5-fluorouracil (5-FU), doxorubicin and paclitaxel indicating their multidrug-resistant nature. Using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and western blot analyses, gemcitabine-resistant cells showed upregulation of RRM1 and downregulation of hENT1 and dCK. In relation to multidrug resistance, these cell lines showed upregulation of multidrug resistance protein 1 (MRP1) leading to an increase of drug efflux. Using cell adhesion and Boyden chamber transwell assays, these cell lines also showed higher cell adhesion, migration and invasion capabilities via the activations of protein kinase C (PKC), focal adhesion kinase (FAK), extracellular signal-regulated kinase-1/2 (ERK1/2) and nuclear factor-κB (NF-κB). Higher activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) was also observed by a gelatin zymography assay and a casein-plasminogen zymography assay. Flow cytometry analysis indicated the G2/M arrest regulated by downregulation of cyclin B1 and cyclin-dependent kinase 1 (Cdk1) resulted in an extended population doubling time. Using Annexin V/propidium iodide staining, evasion of apoptosis via an intrinsic pathway was observed in both cell lines in association with upregulation of Bcl-2 and downregulation of Bax. Interestingly, Fas was additionally downregulated in KKU‑M214/GEM supporting the view of its higher GEM resistant

  5. Multidrug-Resistant Organism Infections in Patients with Left Ventricular Assist Devices

    PubMed Central

    Donahey, Elisabeth E.; Polly, Derek M.; Vega, J. David; Lyon, Marshall; Butler, Javed; Nguyen, Duc; Pekarek, Ann; Wittersheim, Kristin; Kilgo, Patrick

    2015-01-01

    Left ventricular assist devices improve survival prospects in patients with end-stage heart failure; however, infection complicates up to 59% of implantation cases. How many of these infections are caused by multidrug-resistant organisms is unknown. We sought to identify the incidence, risk factors, and outcomes of multidrug-resistant organism infection in patients who have left ventricular assist devices. We retrospectively evaluated the incidence of multidrug-resistant organisms and the independent risk factors associated with them in 57 patients who had permanent left ventricular assist devices implanted at our institution from May 2007 through October 2011. Outcomes included death, transplantation, device explantation, number of subsequent hospital admissions, and number of subsequent admissions related to infection. Infections were categorized in accordance with criteria from the Infectious Diseases Council of the International Society for Heart and Lung Transplantation. Multidrug-resistant organism infections developed in 18 of 57 patients (31.6%)—a high incidence. We found 3 independent risk factors: therapeutic goal (destination therapy vs bridging), P=0.01; body mass index, P=0.04; and exposed velour at driveline exit sites, P=0.004. We found no significant differences in mortality, transplantation, or device explantation rates; however, there was a statistically significant increase in postimplantation hospital admissions in patients with multidrug-resistant organism infection. To our knowledge, this is the first report in the medical literature concerning multidrug-resistant organism infection in patients who have permanent left ventricular assist devices. PMID:26664303

  6. Reversal effect of vitamin D on different multidrug-resistant cells.

    PubMed

    Yan, M; Nuriding, H

    2014-01-01

    We investigated the reversal effect of vitamin D on the multidrug-resistant leukemic Jurkat/ADR and K562/ADR cell lines and conducted a preliminary investigation of its reversal mechanism. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the reversal effect of vitamin D on multidrug-resistant cells. Real-time polymerase chain reaction was used to determine the effect of vitamin D on intracellular expression of mRNA of the multidrug-resistant gene (MDRI) and the multidrug-resistance-related gene (MRP1). A protein quantitative analysis method was used to determine the effect of vitamin D on intracellular glutathione content. After treatment of Jurkat/ADR and K562/ADR cells with vitamin D, multidrug resistance was reversed in a dose-dependent manner, which may have reduced mRNA expression of the MDR1 and MRP1 genes, the P-glycoprotein content on the cell surface, and the intracellular glutathione level. Different concentrations of vitamin D showed varying reversal effects on different multidrug-resistant cells. The resistance mechanism may be related to the inhibition of the expression of MDR1 and MRP1 genes. PMID:25158250

  7. PEITC reverse multi-drug resistance of human gastric cancer SGC7901/DDP cell line.

    PubMed

    Tang, Tao; Song, Xin; Liu, Yu-Fen; Wang, Wen-Yue

    2014-04-01

    Gastric cancer is one of the leading causes of cancer death in the world and nearly all patients who respond initially to cisplatin later develop drug resistance, indicating multi-drug resistance is an essential aspect of the failure of treatment. Phenethyl isothiocyanate (PEITC) has been implicated in inhibiting metastasis of several types of human cancer. However, the effect and potential mechanism of PEITC reversed multi-drug resistance of human gastric cancer is not fully clear. We have identified the role of PEITC in multi-drug resistance reversal of human gastric cancer SGC7901/DDP cell line. PEITC inhibited cisplatin-resistant human SGC7901/DDP cell growth in a dose-dependent manner, causing increased apoptosis, ROS generation, glutathione depletion, accumulation of Rhodamine-123, decreased expression of P-glycoprotein and cell cycle arrest. mRNA and protein expression of the multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), survivin, and Mad2 was decreased, and phosphorylation of Akt and transcriptional activation of NF-κB were suppressed. PEITC may be useful as the therapeutic strategy for overcoming multi-drug resistance through suppressing the PI3K-Akt pathway in human gastric cancer. PMID:23956061

  8. Reversal effect of Dioscin on multidrug resistance in human hepatoma HepG2/adriamycin cells.

    PubMed

    Sun, Bu Tong; Zheng, Li Hua; Bao, Yong Li; Yu, Chun Lei; Wu, Yin; Meng, Xiang Ying; Li, Yu Xin

    2011-03-01

    Multidrug resistance is a serious obstacle encountered in cancer treatment. Since drug resistance in human cancer is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a target for multidrug resistance reversion drug screening. In the present study, HEK293T cells were transfected with pGL3 reporter plasmids containing the 2kb of MDR1 promoter, and the transfected cells were used as models to screen for candidate multidrug resistance inhibitors from over 300 purified naturally occurring compounds extracted from plants and animals. Dioscin was found to have an inhibiting effect on MDR1 promoter activity. The resistant HepG2 cell line (HepG2/adriamycin) was used to validate the activity of multidrug resistance reversal by Dioscin. Results showed that Dioscin could decrease the resistance degree of HepG2/adriamycin cells, and significantly inhibit P-glycoprotein expression, as well as increase the accumulation of adriamycin in HepG2/adriamycin cells as measured by Flow Cytometric analysis. These results suggest that Dioscin is a potent multidrug resistance reversal agent and may be a potential adjunctive agent for tumor chemotherapy. PMID:21195709

  9. Antimicrobial Blue Light Therapy for Multidrug-Resistant Acinetobacter baumannii Infection in a Mouse Burn Model: Implications for Prophylaxis and Treatment of Combat-related Wound Infections

    PubMed Central

    Zhang, Yunsong; Zhu, Yingbo; Gupta, Asheesh; Huang, Yingying; Murray, Clinton K.; Vrahas, Mark S.; Sherwood, Margaret E.; Baer, David G.; Hamblin, Michael R.; Dai, Tianhong

    2014-01-01

    In this study, we investigated the utility of antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model. A bioluminescent clinical isolate of multidrug-resistant A. baumannii was obtained. The susceptibility of A. baumannii to blue light (415 nm)–inactivation was compared in vitro to that of human keratinocytes. Repeated cycles of sublethal inactivation of bacterial by blue light were performed to investigate the potential resistance development of A. baumannii to blue light. A mouse model of third degree burn infected with A. baumannii was developed. A single exposure of blue light was initiated 30 minutes after bacterial inoculation to inactivate A. baumannii in mouse burns. It was found that the multidrug-resistant A. baumannii strain was significantly more susceptible than keratinocytes to blue light inactivation. Transmission electron microscopy revealed blue light–induced ultrastructural damage in A. baumannii cells. Fluorescence spectroscopy suggested that endogenous porphyrins exist in A. baumannii cells. Blue light at an exposure of 55.8 J/cm2 significantly reduced the bacterial burden in mouse burns. No resistance development to blue light inactivation was observed in A. baumannii after 10 cycles of sublethal inactivation of bacteria. No significant DNA damage was detected in mouse skin by means of a skin TUNEL assay after a blue light exposure of 195 J/cm2. PMID:24381206

  10. Carbapenemase Genes among Multidrug Resistant Gram Negative Clinical Isolates from a Tertiary Hospital in Mwanza, Tanzania

    PubMed Central

    Mushi, Martha F.; Mshana, Stephen E.; Imirzalioglu, Can; Bwanga, Freddie

    2014-01-01

    The burden of antimicrobial resistance (AMR) is rapidly growing across antibiotic classes, with increased detection of isolates resistant to carbapenems. Data on the prevalence of carbapenem resistance in developing countries is limited; therefore, in this study, we determined the prevalence of carbapenemase genes among multidrug resistant gram negative bacteria (MDR-GNB) isolated from clinical specimens in a tertiary hospital in Mwanza, Tanzania. A total of 227 MDR-GNB isolates were analyzed for carbapenem resistance genes. For each isolate, five different PCR assays were performed, allowing for the detection of the major carbapenemase genes, including those encoding the VIM-, IMP-, and NDM-type metallo-beta-lactamases, the class A KPC-type carbapenemases, and the class D OXA-48 enzyme. Of 227 isolates, 80 (35%) were positive for one or more carbapenemase gene. IMP-types were the most predominant gene followed by VIM, in 49 (21.59%) and 28 (12%) isolates, respectively. Carbapenemase genes were most detected in K. pneumoniae 24 (11%), followed by P. aeruginosa 23 (10%), and E. coli with 19 isolates (8%). We have demonstrated for the first time a high prevalence of MDR-GNB clinical isolates having carbapenem resistance genes in Tanzania. We recommend routine testing for carbapenem resistance among the MDR-GNB particularly in systemic infections. PMID:24707481

  11. PcrV antibody protects multi-drug resistant Pseudomonas aeruginosa induced acute lung injury.

    PubMed

    Wang, Qin; Li, Huayin; Zhou, Jian; Zhong, Ming; Zhu, Duming; Feng, Nana; Liu, Fanglei; Bai, Chunxue; Song, Yuanlin

    2014-03-01

    Blocking PcrV, an essential component of the Type III secretion system (TTSS), has demonstrated efficacy against Pseudomonas aeruginosa infections. However, most of the results came from laboratory strains. Whether it is applicable to clinically isolated multi-drug resistant (MDR) strains is unknown. In this study we investigated the expression level of TTSS in clinically isolated MDR P. aeruginosa strains and the effects of anti-PcrV antibody on MDR isolate induced acute lung injury (ALI). The expression level of TTSS was quantified in 53 isolates including 25 MDR strains and 28 susceptible strains. We investigated the effect of anti-PcrV antibody through a murine model induced by instillation of a MDR strain into the left lung through trachea. Our results showed that the expression level of TTSS in MDR strains is comparable to susceptible strains. Anti-PcrV ensured the survival of challenged mice, reduced the bacteria numbers and attenuated lung inflammation and injury. This study proved that anti-PcrV may be a potentially effective strategy against MDR P. aeruginosa induced ALI. PMID:24418353

  12. Multidrug resistant Shigella flexneri : a rare case of septicemia in an infant.

    PubMed

    Jain, Sanjay; Sharma, Mukesh; Gupta, Raju; Shree, Neetu; Kumar, Manoj

    2014-06-01

    Shigellosis is still an important public health problem in developing and under-developed countries. It may lead to rare but potentially fatal various extra intestinal complications like septicemia, involvement of CNS, urinary tract and liver especially in young malnourished children. The disease is difficult to prevent as only few bacteria are required for causing infection and there is increasing infection with multi drug resistant strains. A 6-month-old infant developed septicemia caused by multi drug resistant Shigella flexneri during an episode of gastrointestinal infection. The patient was managed in the emergency ward but unfortunately the infant expired. Considering septic shock, blood culture, stool culture and other relevant investigations were done. Stool as well as blood culture yielded Shigella flexneri. The isolates were multidrug resistant. Following is a rare case presentation of Shigella septicemia with severe shock, DIC and convulsions. The case report demonstrates how shigellosis can lead to a rare life threatening complication and hence should be considered as a possibility in septicemia associated with diarrhea and vomiting in infant and young children. PMID:25120984

  13. Genomic Plasticity of Multidrug-Resistant NDM-1 Positive Clinical Isolate of Providencia rettgeri.

    PubMed

    Olaitan, Abiola Olumuyiwa; Diene, Seydina M; Assous, Marc Victor; Rolain, Jean-Marc

    2016-03-01

    We performed a detailed whole-genome sequence analysis of Providencia rettgeri H1736, a multidrug-resistant clinical pathogen isolated in Israel in 2011. The objective was to describe the genomic flexibility of this bacterium that has greatly contributed to its pathogenicity. The genome has a chromosome size of 4,609,352 bp with 40.22% GC content. Five plasmids were predicted, as well as other mobile genetic elements (MGEs) including phages, genomic islands, and integrative and conjugative elements. The resistome consisted of a total of 27 different antibiotic resistance genes including blaNDM-1, mostly located on MGEs. Phenotypically, the bacteria displayed resistance to a total of ten different antimicrobial classes. Various features such as metabolic operons (including a novel carbapenem biosynthesis operon) and virulence genes were also borne on the MGEs, making P. rettgeri H1736 significantly different from other P. rettgeri isolates. A large quantity of the genetic diversity that exists in P. rettgeri H1736 was due to extensive horizontal gene transfer events, leading to an enormous presence of MGEs in its genome. Most of these changes contributed toward the pathogenic evolution of this bacterium. PMID:27386606

  14. Multidrug-resistant organisms in liver transplant: Mitigating risk and managing infections.

    PubMed

    Hand, Jonathan; Patel, Gopi

    2016-08-01

    Liver transplant (LT) recipients are vulnerable to infections with multidrug-resistant (MDR) pathogens. Risk factors for colonization and infection with resistant bacteria are ubiquitous and unavoidable in transplantation. During the past decade, progress in transplantation and infection prevention has contributed to the decreased incidence of infections with methicillin-resistant Staphylococcus aureus. However, even in the face of potentially effective antibiotics, vancomycin-resistant enterococci continue to plague LT. Gram-negative bacilli prove to be more problematic and are responsible for high rates of both morbidity and mortality. Despite the licensure of novel antibiotics, there is no universal agent available to safely and effectively treat infections with MDR gram-negative organisms. Currently, efforts dedicated toward prevention and treatment require involvement of multiple disciplines including transplant providers, specialists in infectious diseases and infection prevention, and researchers dedicated to the development of rapid diagnostics and safe and effective antibiotics with novel mechanisms of action. Liver Transplantation 22 1143-1153 2016 AASLD. PMID:27228555

  15. Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance

    PubMed Central

    Watkins, Richard R.; Papp-Wallace, Krisztina M.; Drawz, Sarah M.; Bonomo, Robert A.

    2013-01-01

    The increasing incidence and prevalence of multi-drug resistance (MDR) among contemporary Gram-negative bacteria represents a significant threat to human health. Since their discovery, β-lactam antibiotics have been a major component of the armamentarium against these serious pathogens. Unfortunately, a wide range of β-lactamase enzymes have emerged that are capable of inactivating these powerful drugs. In the past 30 years, a major advancement in the battle against microbes has been the development of β-lactamase inhibitors, which restore the efficacy of β-lactam antibiotics (e.g., ampicillin/sulbactam, amoxicillin/clavulanate, ticarcillin/clavulanate, and piperacillin/tazobactam). Unfortunately, many newly discovered β-lactamases are not inactivated by currently available inhibitors. Is there hope? For the first time in many years, we can anticipate the development and introduction into clinical practice of novel inhibitors. Although these inhibitors may still not be effective for all β-lactamases, their introduction is still welcome. This review focuses on the novel β-lactamase inhibitors that are closest to being introduced in the clinic. PMID:24399995

  16. Multidrug-resistant Gram-negative bacterial infections: are you ready for the challenge?

    PubMed

    Curcio, Daniel

    2014-02-01

    Paralleling the developments in Gram-positive bacteria, infections caused by multidrug-resistant (MDR) Gramnegative bacilli have become a growing challenge. The most important resistance problems are encountered in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp., 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 (ie. KPC, NDM and other metallo-β; -lactamases). This paper reviews the evidence in the published literature of the pharmacokinetic/pharmacodynamic profile, clinical efficacy of new antimicrobial agents, against MDR- Gram-negative pathogens, such us: i-new carbapenems (doripenem, biapenem, panipenem, tonopenem, FSI-1686); ii-new cephalosporins (ceftaroline, ceftobiprole); iii-tigecycline; and iv- β- lactamases inhibitors (BLI-489, Ro 48-1220, ME 1071, aviactam [NXL104]). PMID:23489027

  17. Simple avarone mimetics as selective agents against multidrug resistant cancer cells.

    PubMed

    Jeremić, Marko; Pešić, Milica; Dinić, Jelena; Banković, Jasna; Novaković, Irena; Šegan, Dejan; Sladić, Dušan

    2016-08-01

    In this work, synthesis of alkylamino and aralkylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone was described. For all obtained derivatives biological activity was studied. Cytotoxic activity of the synthesized derivatives towards multidrug resistant MDR human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) as well as detection of cell death superoxide anion generation were investigated. Antimicrobial activity towards Gram positive and Gram negative bacteria and fungal cultures was determined. The results showed that strong cytotoxic activity toward cancer cells was improved with simple avarone mimetics. Some derivatives were selective towards MDR cancer cells. The most active derivatives induced apoptosis in both cancer cell lines, but not in normal cells. Superoxide production was induced by 2,6-disubstituted compounds in MDR cancer cells and not by less active 2,5-disubstituted compounds and was accompanied by the collapse of the mitochondrial transmembrane potential. Two tert-butylquinone derivatives were particularly selective towards MDR cancer cells. Some tert-butylquinone derivatives exhibited a strong antimicrobial activity. PMID:27128177

  18. Genitourinary and pulmonary multidrug resistant Mycobacterium tuberculosis infection in an Asian elephant (Elephas maximus).

    PubMed

    Dumonceaux, Genevieve A; St Leger, Judy; Olsen, John H; Burton, Michael S; Ashkin, David; Maslow, Joel N

    2011-12-01

    A female Asian elephant (Elephas maximus) developed vaginal and trunk discharge. Cultures were positive for pan-susceptible Mycobacterium tuberculosis. Isoniazid and pyrazinamide were given rectally and monitored by serum levels. After being trained at 10 mo to accept oral dosing, treatment was changed and rifampin was added. Oral medications were administered for another 10 mo. A year after completion of therapy, the vaginal discharge increased and cultures yielded M. tuberculosis, resistant to isoniazid and rifampin. Treatment with oral ethambutol, pyrazinamide, and enrofloxacin and intramuscular amikacin was initiated. Although followup cultures became negative, adverse reactions to medications precluded treatment completion. Due to public health concerns related to multidrug resistant M. tuberculosis (MDR-TB), the elephant was euthanized. Postmortem smears from the lung, peribronchial, and abdominal lymph nodes yielded acid-fast bacteria, although cultures were negative. This case highlights important considerations in the treatment of M. tuberculosis in animals and the need for a consistent approach to diagnosis, treatment, and follow-up. PMID:22204067

  19. Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli.

    PubMed

    Iqbal, Junaid; Dufendach, Kevin R; Wellons, John C; Kuba, Maria G; Nickols, Hilary H; Gómez-Duarte, Oscar G; Wynn, James L

    2016-01-01

    Neonatal meningitis is a rare but devastating condition. Multi-drug resistant (MDR) bacteria represent a substantial global health risk. This study reports on an aggressive case of lethal neonatal meningitis due to a MDR Escherichia coli (serotype O75:H5:K1). Serotyping, MDR pattern and phylogenetic typing revealed that this strain is an emergent and highly virulent neonatal meningitis E. coli isolate. The isolate was resistant to both ampicillin and gentamicin; antibiotics currently used for empiric neonatal sepsis treatment. The strain was also positive for multiple virulence genes including K1 capsule, fimbrial adhesion fimH, siderophore receptors iroN, fyuA and iutA, secreted autotransporter toxin sat, membrane associated proteases ompA and ompT, type II polysaccharide synthesis genes (kpsMTII) and pathogenicity-associated island (PAI)-associated malX gene. The presence of highly-virulent MDR organisms isolated in neonates underscores the need to implement rapid drug resistance diagnostic methods and should prompt consideration of alternate empiric therapy in neonates with Gram negative meningitis. PMID:27030919

  20. Pathogens of Bovine Respiratory Disease in North American Feedlots Conferring Multidrug Resistance via Integrative Conjugative Elements

    PubMed Central

    Klima, Cassidy L.; Zaheer, Rahat; Cook, Shaun R.; Booker, Calvin W.; Hendrick, Steve

    2014-01-01

    In this study, we determined the prevalence of bovine respiratory disease (BRD)-associated viral and bacterial pathogens in cattle and characterized the genetic profiles, antimicrobial susceptibilities, and nature of antimicrobial resistance determinants in collected bacteria. Nasopharyngeal swab and lung tissue samples from 68 BRD mortalities in Alberta, Canada (n = 42), Texas (n = 6), and Nebraska (n = 20) were screened using PCR for bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza type 3 virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Excepting bovine herpesvirus 1, all agents were detected. M. haemolytica (91%) and BVDV (69%) were the most prevalent, with cooccurrence in 63% of the cattle. Isolates of M. haemolytica (n = 55), P. multocida (n = 8), and H. somni (n = 10) from lungs were also collected. Among M. haemolytica isolates, a clonal subpopulation (n = 8) was obtained from a Nebraskan feedlot. All three bacterial pathogens exhibited a high rate of antimicrobial resistance, with 45% exhibiting resistance to three or more antimicrobials. M. haemolytica (n = 18), P. multocida (n = 3), and H. somni (n = 3) from Texas and Nebraska possessed integrative conjugative elements (ICE) that conferred resistance for up to seven different antimicrobial classes. ICE were shown to be transferred via conjugation from P. multocida to Escherichia coli and from M. haemolytica and H. somni to P. multocida. ICE-mediated multidrug-resistant profiles of bacterial BRD pathogens could be a major detriment to many of the therapeutic antimicrobial strategies currently used to control BRD. PMID:24478472

  1. Genomic Plasticity of Multidrug-Resistant NDM-1 Positive Clinical Isolate of Providencia rettgeri

    PubMed Central

    Olaitan, Abiola Olumuyiwa; Diene, Seydina M.; Assous, Marc Victor; Rolain, Jean-Marc

    2016-01-01

    We performed a detailed whole-genome sequence analysis of Providencia rettgeri H1736, a multidrug-resistant clinical pathogen isolated in Israel in 2011. The objective was to describe the genomic flexibility of this bacterium that has greatly contributed to its pathogenicity. The genome has a chromosome size of 4,609,352 bp with 40.22% GC content. Five plasmids were predicted, as well as other mobile genetic elements (MGEs) including phages, genomic islands, and integrative and conjugative elements. The resistome consisted of a total of 27 different antibiotic resistance genes including blaNDM-1, mostly located on MGEs. Phenotypically, the bacteria displayed resistance to a total of ten different antimicrobial classes. Various features such as metabolic operons (including a novel carbapenem biosynthesis operon) and virulence genes were also borne on the MGEs, making P. rettgeri H1736 significantly different from other P. rettgeri isolates. A large quantity of the genetic diversity that exists in P. rettgeri H1736 was due to extensive horizontal gene transfer events, leading to an enormous presence of MGEs in its genome. Most of these changes contributed toward the pathogenic evolution of this bacterium. PMID:27386606

  2. Prediction of multi-drug resistance transporters using a novel sequence analysis method

    PubMed Central

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; Gosink, Luke; Lindemann, Stephen R.

    2015-01-01

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequence similarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir. PMID:26913187

  3. The impact of multidrug resistance in healthcare-associated and nosocomial Gram-negative bacteraemia on mortality and length of stay: cohort study.

    PubMed

    Lye, D C; Earnest, A; Ling, M L; Lee, T-E; Yong, H-C; Fisher, D A; Krishnan, P; Hsu, L-Y

    2012-05-01

    Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging public health threat. Accurate estimates of their clinical impact are vital for justifying interventions directed towards preventing or managing infections caused by these pathogens. A retrospective observational cohort study was conducted between 1 January 2007 and 31 July 2009, involving subjects with healthcare-associated and nosocomial Gram-negative bacteraemia at two large Singaporean hospitals. Outcomes studied were mortality and length of stay post-onset of bacteraemia in survivors (LOS). There were 675 subjects (301 with MDR-GNB) matching study inclusion criteria. On multivariate analysis, multidrug resistance was not associated with 30-day mortality, but it was independently associated with longer LOS in survivors (coefficient, 0.34; 95% CI, 0.21-0.48; p < 0.001). The excess LOS attributable to multidrug resistance after adjustment for confounders was 6.1 days. Other independent risk factors for higher mortality included male gender, higher APACHE II score, higher Charlson comorbidity index, intensive care unit stay and presence of concomitant pneumonia. Concomitant urinary tract infection and admission to a surgical discipline were associated with lower risk of mortality. Appropriate empirical antibiotic therapy was neither associated with 30-day mortality nor LOS, although the study was not powered to assess this covariate adequately. Our study adds to existing evidence that multidrug resistance per se is not associated with higher mortality when effective antibiotics are used for definitive therapy. However, its association with longer hospitalization justifies the use of control efforts. PMID:21851482

  4. The multidrug resistant modulator HZ08 reverses multidrug resistance via P-glycoprotein inhibition and apoptosis sensitization in human epidermoid carcinoma cell line KBV200.

    PubMed

    Zhu, Y-L; Cen, J; Zhang, Y-Y; Feng, Y-D; Yang, Y; Li, Y-M; Huang, W-L

    2012-05-01

    Previous studies have demonstrated that the multidrug resistance modulator HZ08 has a strong multidrug resistance reversal effect in vitro and in vivo by inhibiting P-glycoprotein and multidrug resistance-associated protein 1 in K562/A02 and MCF-7/ADM cells, respectively. However, there are many other mechanisms responsible for resistance. In this study, MTT assay was used to examine the cytotoxicity and multidrug resistance reversal of HZ08 in KBV200 cells. It was also used to detect Rh123 and adriamycin accumulation in the presence of HZ08 to assess the effect on P-glycoprotein. Caspase-3 activity was analyzed under the incubation of HZ08 per se and in combination with vincristine. Results showed that HZ08 could increase the activity of caspase-3 with P-glycoprotein inhibition. Further studies revealed that HZ08 increased vincristine-induced apoptosis, characterized as an intrinsic apoptosis pathway with enhanced G2/M phase arrest, since HZ08 had an effect on the intrinsic apoptotic regulator Bcl-2 and Bax. Therefore, the outstanding reversal effect of HZ08 occurs not only through suppressing the P-glycoprotein function but also through activating the intrinsic apoptosis pathway. PMID:22344570

  5. Antimicrobial Activity of Copper Alloys Against Invasive Multidrug-Resistant Nosocomial Pathogens.

    PubMed

    Eser, Ozgen Koseoglu; Ergin, Alper; Hascelik, Gulsen

    2015-08-01

    The emergence and spread of antibiotic resistance demanded novel approaches for the prevention of nosocomial infections, and metallic copper surfaces have been suggested as an alternative for the control of multidrug-resistant (MDR) bacteria in surfaces in the hospital environment. This study aimed to evaluate the antimicrobial activity of copper material for invasive MDR nosocomial pathogens isolated over time, in comparison to stainless steel. Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n:4), OXA-23 and OXA-58 positive, MDR Acinetobacter baumannii (n:6) and Pseudomonas aeruginosa (n:4) were evaluated. The antimicrobial activity of coupons containing 99 % copper and a brass alloy containing 63 % copper was assessed against stainless steel. All the materials demonstrated statistically significant differences within each other for the logarithmic reduction of microorganisms. Among the three materials, the highest reduction of microorganisms was seen in 99 % copper and the least in stainless steel. The result was statistically significant especially for 0, 2, and 4 h (P = 0.05). 99 % copper showed a bactericidal effect at less than 1 h for MRSA and at 2 h for P. aeruginosa. 63 % copper showed a bactericidal effect at 24 h for P. aeruginosa strains only. Stainless steel surfaces exhibited a bacteriostatic effect after 6 h for P. aeruginosa strains only. 99 % copper reduced the number of bacteria used significantly, produced a bactericidal effect and was more effective than 63 % copper. The use of metallic copper material could aid in reducing the concentration of bacteria, especially for invasive nosocomial pathogens on hard surfaces in the hospital environment. PMID:26044991

  6. 5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii

    PubMed Central

    Tseng, Sung-Pin; Hung, Wei-Chun; Huang, Chiung-Yao; Lin, Yin-Shiou; Chan, Min-Yu; Lu, Po-Liang; Lin, Lin; Sheu, Jyh-Horng

    2016-01-01

    Nosocomial infections and increasing multi-drug resistance caused by Acinetobacter baumannii have been recognized as emerging problems worldwide. Moreover, A. baumannii is able to colonize various abiotic materials and medical devices, making it difficult to eradicate and leading to ventilator-associated pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial biofilm formation may be an alternative prophylactic option for the treatment of biofilm-associated A. baumannii infections. Marine environments, which are unlike their terrestrial counterparts, harbor an abundant biodiversity of marine organisms that produce novel bioactive natural products with pharmaceutical potential. In this study, we identified 5-episinuleptolide, which was isolated from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606 and three multi-drug resistant A. baumannii strains. In addition, the anti-biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5-episinuleptolide is effective against only Gram-negative bacteria. The mechanism of biofilm inhibition was demonstrated to correlate to decreased gene expression from the pgaABCD locus, which encodes the extracellular polysaccharide poly-β-(1,6)-N-acetylglucosamine (PNAG). Scanning electron microscopy (SEM) indicated that extracellular matrix of the biofilm was dramatically decreased by treatment with 5-episinuleptolide. Our study showed potentially synergistic activity of combination therapy with 5-episinuleptolide and levofloxacin against biofilm formation and biofilm cells. These data indicate that inhibition of biofilm formation via 5-episinuleptolide may represent another prophylactic option for solving the persistent problem of biofilm-associated A. baumannii infections. PMID:27483290

  7. 5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii.

    PubMed

    Tseng, Sung-Pin; Hung, Wei-Chun; Huang, Chiung-Yao; Lin, Yin-Shiou; Chan, Min-Yu; Lu, Po-Liang; Lin, Lin; Sheu, Jyh-Horng

    2016-01-01

    Nosocomial infections and increasing multi-drug resistance caused by Acinetobacter baumannii have been recognized as emerging problems worldwide. Moreover, A. baumannii is able to colonize various abiotic materials and medical devices, making it difficult to eradicate and leading to ventilator-associated pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial biofilm formation may be an alternative prophylactic option for the treatment of biofilm-associated A. baumannii infections. Marine environments, which are unlike their terrestrial counterparts, harbor an abundant biodiversity of marine organisms that produce novel bioactive natural products with pharmaceutical potential. In this study, we identified 5-episinuleptolide, which was isolated from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606 and three multi-drug resistant A. baumannii strains. In addition, the anti-biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5-episinuleptolide is effective against only Gram-negative bacteria. The mechanism of biofilm inhibition was demonstrated to correlate to decreased gene expression from the pgaABCD locus, which encodes the extracellular polysaccharide poly-β-(1,6)-N-acetylglucosamine (PNAG). Scanning electron microscopy (SEM) indicated that extracellular matrix of the biofilm was dramatically decreased by treatment with 5-episinuleptolide. Our study showed potentially synergistic activity of combination therapy with 5-episinuleptolide and levofloxacin against biofilm formation and biofilm cells. These data indicate that inhibition of biofilm formation via 5-episinuleptolide may represent another prophylactic option for solving the persistent problem of biofilm-associated A. baumannii infections. PMID:27483290

  8. Global dissemination of a multidrug resistant Escherichia coli clone

    PubMed Central

    Petty, Nicola K.; Ben Zakour, Nouri L.; Stanton-Cook, Mitchell; Skippington, Elizabeth; Totsika, Makrina; Forde, Brian M.; Phan, Minh-Duy; Gomes Moriel, Danilo; Peters, Kate M.; Davies, Mark; Rogers, Benjamin A.; Dougan, Gordon; Rodriguez-Baño, Jesús; Pascual, Alvaro; Pitout, Johann D. D.; Upton, Mathew; Paterson, David L.; Walsh, Timothy R.; Schembri, Mark A.; Beatson, Scott A.

    2014-01-01

    Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000–2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL–resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen. PMID:24706808

  9. Molecular characterization of clinical multidrug-resistant Klebsiella pneumoniae isolates

    PubMed Central

    2014-01-01

    Background Klebsiella pneumoniae is a frequent nosocomial pathogen, with the multidrug-resistant (MDR) K. pneumoniae being a major public health concern, frequently causing difficult-to-treat infections worldwide. The aim of this study was to investigate the molecular characterization of clinical MDR Klebsiella pneumoniae isolates. Methods A total of 27 non-duplicate MDR K. pneumoniae isolates with a CTX-CIP-AK resistance pattern were investigated for the prevalence of antimicrobial resistance genes including extended spectrum β-lactamase genes (ESBLs), plasmid-mediated quinolone resistance (PMQR) genes, 16S rRNA methylase (16S-RMTase) genes, and integrons by polymerase chain reaction (PCR) amplification and DNA sequencing. Plasmid replicons were typed by PCR-based replicon typing (PBRT). Multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to characterize the strain relatedness. Results All the isolates co-harbored 3 or more resistance determinants. OqxAB, CTX-M-type ESBLs and RmtB were the most frequent determinants, distributed among19 (70.4%),18 (66.7%) and 8 (29.6%) strains. Fourteen isolates harbored class 1 integrons, with orfD-aacA4 being the most frequent gene cassette array. Class 3 integrons were less frequently identified and contained the gene cassette array of blaGES-1-blaOXA-10-aac(6′)-Ib. IncFII replicon was most commonly found in this collection. One cluster was observed with ≥80% similarity among profiles obtained by PFGE, and one sequence type (ST) by MLST, namely ST11, was observed in the cluster. Conclusion K. pneumoniae carbapenemase (KPC)–producing ST11 was the main clone detected. Of particular concern was the high prevalence of multiple resistance determinants, classs I integrons and IncFII plasmid replicon among these MDR strains, which provide advantages for the rapid development of MDR strains. PMID:24884610

  10. Counting Pyrazinamide in Regimens for Multidrug-Resistant Tuberculosis

    PubMed Central

    Becerra, Mercedes C.; Tierney, Dylan B.; Rich, Michael L.; Bonilla, Cesar; Bayona, Jaime; McLaughlin, Megan M.; Mitnick, Carole D.

    2015-01-01

    Rationale: For treatment of multidrug-resistant tuberculosis, World Health Organization (WHO) guidelines recommend four likely effective drugs plus pyrazinamide (PZA), irrespective of the likely effectiveness of PZA in an individual patient. Whether this regimen should be supplemented in the absence of likely PZA effectiveness is an open question. Objectives: The objectives of this study were to examine (1) whether individuals receiving four likely effective drugs (based on documented susceptibility or no prior exposure) experienced higher mortality during the intensive phase of treatment than those receiving five likely effective drugs and (2) whether the WHO-recommended regimen (four likely effective drugs plus PZA) may be compromised in individuals in whom PZA is not likely effective. Methods: Among 668 patients, we compared the hazard of death across regimen groups characterized by the number of likely effective drugs and whether pyrazinamide was one of the likely effective drugs. Measurements and Main Results: Relative to five likely effective drugs, regimens of four likely effective drugs and the WHO-recommended regimen used in individuals in whom PZA was not likely effective were associated with higher mortality rates (respectively, adjusted hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.35–6.09 and adjusted HR, 2.76; 95% CI, 0.92–8.27). The mortality rate for a regimen of five likely effective drugs with likely effective PZA was similar to that for the regimen of five likely effective drugs without PZA (HR, 1.00; 95% CI, 0.12–8.00). Conclusions: Mortality may be reduced by the inclusion of five likely effective drugs, including an injectable, during the intensive phase of treatment. If PZA is unlikely to be effective in an individual patient, these results suggest adding a different, likely effective drug. PMID:25664920

  11. National action plan to combat multidrug-resistant tuberculosis.

    PubMed

    1992-06-19

    At no time in recent history has tuberculosis (TB) been as great a concern as it is today. TB cases are on the increase, and the most serious aspect of the problem is the recent occurrence of outbreaks of multidrug-resistant (MDR) TB, which pose an urgent public health problem and require rapid intervention. A Task Force composed of representatives of many federal agencies has developed a National Action Plan for addressing this problem. The Task Force identified a number of objectives to be met if MDR-TB is to be successfully combatted. These objectives fall under the categories of a) surveillance and epidemiology--determining the magnitude and nature of the problem; b) laboratory diagnosis--improving the rapidity, sensitivity, and reliability of diagnostic methods for MDR-TB; c) patient management--effectively managing patients who have MDR-TB and preventing patients with drug-susceptible TB from developing drug-resistant disease; d) screening and preventive therapy--identifying persons who are infected with or at risk of developing MDR-TB and preventing them from developing clinically active TB; e) infection control--minimizing the risk of transmission of MDR-TB to patients, workers, and others in institutional settings; f) outbreak control; g) program evaluation--ensuring that TB programs are effective in managing patients and preventing MDR-TB; h) information dissemination/training and education; and i) research to provide new, more effective tools with which to combat MDR-TB. The Action Plan lays out a series of activities to be undertaken at the national level. For each category, the Plan presents statements of problems to be overcome, followed by a summary of the objective to be achieved and steps to be carried out. For each implementation step, responsibility is assigned to the appropriate organization and start-up dates are listed. PMID:1640920

  12. [Adverse drug reactions in multidrug-resistant tuberculosis].

    PubMed

    Palmero, Domingo; Cruz, Víctor; Museli, Tomás; Pavlovsky, Hernán; Fernández, Juan; Waisman, Jaime

    2010-01-01

    Multidrug-resistant tuberculosis (MDRTB) poses difficulties in diagnosis and treatment, including increased frequency of adverse reactions to antituberculosis drugs (ADRAs), which compromise the effectiveness of treatment. This is specially complicated in the treatment of patients co-infected with HIV which includes the antiretroviral therapy plus the treatment of eventual comorbidities. A total of 121 MDRTB patients, 87 HIV-negative and 34 HIV positive, assisted in the Hospital F. J. Muñiz, Buenos Aires, during the period 2003-2007 were retrospectively studied. The incidence of ADRAs among the two groups of patients was compared. All the patients with adherence to treatment (no more than one abandon, recovered) were included in the study. Antituberculosis drugs used were: ethambutol, pyrazinamide, ofloxacin, moxifloxacin, cycloserine, ethionamide, PAS, streptomycin, kanamycin, amikacin and linezolid. The emergence of ADRAs and the proportion of severe reactions attributed to antituberculosis drugs were similar in both groups: 44.8% in HIV negative and 44.1% in HIV positive, but it was observed an additional 23.5% of adverse reactions to antiretroviral therapy in the second group. There were differences in the type of reactions and time of occurrence between the two groups. One HIV positive patient died of epidermolysis. The proportion of adverse reactions in HIV/AIDS patients increased 50% when those attributed to antiretroviral treatment were included. We conclude that the studied population showed a frequency of ADRAs higher than it would be expected in the treatment of susceptible TB, but there was no difference in its frequency among HIV-negative and positive patients. PMID:20920959

  13. ATP7B expression confers multidrug resistance through drug sequestration

    PubMed Central

    Moinuddin, F M; Shinsato, Yoshinari; Komatsu, Masaharu; Mitsuo, Ryoichi; Minami, Kentaro; Yamamoto, Masatatsu; Kawahara, Kohich; Hirano, Hirofumi; Arita, Kazunori; Furukawa, Tatsuhiko

    2016-01-01

    We previously reported that ATP7B is involved in cisplatin resistance and ATP7A confers multidrug resistance (MDR) in cancer cells. In this study, we show that ATP7B expressing cells also are resistant to doxorubicin, SN-38, etoposide, and paclitaxel as well as cisplatin. In ATP7B expressing cells, doxorubicin relocated from the nuclei to the late-endosome at 4 hours after doxorubicin exposure. EGFP-ATP7B mainly colocalized with doxorubicin. ATP7B has six metal binding sites (MBSs) in the N-terminal cytoplasmic region. To investigate the role of the MBSs of ATP7B in doxorubicin resistance, we used three mutant ATP7B (Cu0, Cu6 and M6C/S) expressing cells. Cu0 has no MBSs, Cu6 has only the sixth MBS and M6C/S carries CXXC to SXXS mutation in the sixth MBS. Cu6 expressing cells were less resistance to the anticancer agents than wild type ATP7B expressing cells, and had doxorubicin sequestration in the late-endosome. Cu0- and M6C/S-expressing cells were sensitive to doxorubicin. In these cells, doxorubicin did not relocalize to the late-endosome. EGFP-M6C/S mainly localized to the trans-Golgi network (TGN) even in the presence of copper. Thus the cysteine residues in the sixth MBS of ATP7B are essential for MDR phenotype. Finally, we found that ammonium chloride and tamoxifen suppressed late endosomal sequestration of doxorubicin, thereby attenuating drug resistance. These results suggest that the sequestration depends on the acidity of the vesicles partly. We here demonstrate that ATP7B confers MDR by facilitating nuclear drug efflux and late endosomal drug sequestration. PMID:26988911

  14. A Novel Way of Treating Multidrug-resistant Enterococci

    PubMed Central

    Desai, Hem; Wong, Ryan; Pasha, Ahmed Khurshid

    2016-01-01

    Context: Daptomycin is the only antibiotic available with in vitro bactericidal activity against vancomycin-resistant enterococci (VRE). Its increased use has resulted in cases of decreased daptomycin efficacy. Recent in vitro studies have shown effective use of beta (β)-lactam and daptomycin antibiotics, as a combination therapy, in the treatment of VRE. We describe a case of effective treatment in a patient with VRE infection using dual ampicillin and daptomycin therapy that shows bench-to-bedside application of the abovementioned finding. Case Report: A 76-year-old gentleman with a history of bilateral arthroplasty was admitted with a swollen left knee. Blood cultures were positive for Enterococcus faecium. Left knee joint aspiration showed leukocytosis and alpha defensins. Extensive imaging did not show any other source of infection. Culture sensitivity results showed multidrug-resistant enterococci sensitive to daptomycin. The patient was started on intravenous (IV) daptomycin. His left knee prosthesis was explanted and a spacer was placed. The patient continued to be bacteremic for 10 days after removing the knee prosthesis. The patient was trialed on combination IV ampicillin and daptomycin. His blood culture turned negative 2 days later. The patient was discharged home to continue 6 weeks of IV ampicillin and daptomycin. Conclusion: The exact mechanism of the daptomycin/ampicillin synergy effect is unclear. Current hypothesis suggests that ampicillin causes a reduction in the net positive charge of the bacterial surface, possibly by releasing lipoteichoic acid (LTA) from the cell wall. This process increases the ability of the cationic daptomycin/calcium complex to bind to the cell wall more effectively. Our case shows the clinical application of the same. A prospective randomized control trial to explore the effectiveness of dual antibiotic therapy in vivo is needed. If proven, daptomycin/β-lactam can become a standard of care to treat VRE and decrease

  15. Interleukin-6: A Critical Cytokine in Cancer Multidrug Resistance.

    PubMed

    Ghandadi, Morteza; Sahebkar, Amirhossein

    2016-01-01

    Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other mechanisms such as overexpression of drug-detoxifying enzymes and alterations in pro-survival or pro-death signaling pathways are also responsible for MDR. Inflammatory mediators including interleukin-6 (IL-6) play important roles in various events during inflammation and are also involved in development and progression of several types of cancers. Mounting evidence has suggested a crosstalk between IL-6 and MDR in cancer, highlighting the role of IL-6 in chemotherapy response, and the potential opportunity to control MDR through modulation of IL-6 expression. Upregulation of IL-6 has been shown to promote MDR through activation of Janus kinases (JAK)/signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt), and Ras-MAPK (mitogen-activated protein kinase) pathways. Activation of the aforementioned pathways changes the expression pattern of several genes involved in proliferation, survival and cell cycle regulation, thus facilitating MDR. Conversely, IL-6 inhibition using different strategies (antibodies, siRNA, and antisense transfection) has been shown to improve tumor responsiveness and mitigate MDR in different cancer cell lines. This review focuses on the in vitro, experimental and clinical findings on the role of IL-6 in MDR, and potential therapeutic opportunities arising from this role of IL-6. PMID:26601970

  16. Multidrug-Resistant Nontuberculous Mycobacteria Isolated from Cystic Fibrosis Patients

    PubMed Central

    Cândido, Pedro Henrique Campanini; Nunes, Luciana de Souza; Marques, Elizabeth Andrade; Folescu, Tânia Wrobel; Coelho, Fábrice Santana; de Moura, Vinicius Calado Nogueira; da Silva, Marlei Gomes; Gomes, Karen Machado; Lourenço, Maria Cristina da Silva; Aguiar, Fábio Silva; Chitolina, Fernanda; Armstrong, Derek T.; Leão, Sylvia Cardoso; Neves, Felipe Piedade Gonçalves; Mello, Fernanda Carvalho de Queiroz

    2014-01-01

    Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of pulmonary infections in cystic fibrosis (CF) patients, with an estimated prevalence ranging from 5 to 20%. This work investigated the presence of NTM in sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal clinical supervision at a regional reference center in Rio de Janeiro, Brazil. From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of 129 children were obtained. Molecular identification of NTM was performed by using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene, and susceptibility tests were performed that followed Clinical and Laboratory Standards Institute recommendations. For evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE) and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) was performed. The species identified were Mycobacterium abscessus subsp. bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium fortuitum (n = 3), Mycobacterium marseillense (n = 2), and Mycobacterium timonense (n = 1). Most of the isolates presented resistance to five or more of the antimicrobials tested. Typing profiles were mainly patient specific. The PFGE profiles indicated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in two patients. Given the observed multidrug resistance patterns and the possibility of transmission between patients, we suggest the implementation of continuous and routine investigation of NTM infection or colonization in CF patients, including countries with a high burden of tuberculosis disease. PMID:24920766

  17. Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

    PubMed Central

    Franke, Molly F.; Appleton, Sasha C.; Mitnick, Carole D.; Furin, Jennifer J.; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C.

    2013-01-01

    Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. PMID:23223591

  18. Cellular functions of vaults and their involvement in multidrug resistance.

    PubMed

    Steiner, E; Holzmann, K; Elbling, L; Micksche, M; Berger, W

    2006-08-01

    Vaults are evolutionary highly conserved ribonucleoprotein (RNP) particles with a hollow barrel-like structure. They are 41 x 73 nm in size and are composed of multiple copies of three proteins and small untranslated RNA (vRNA). The main component of vaults represents the 110 kDa major vault protein (MVP), whereas the two minor vault proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (VPARP) and the 240 kDa telomerase-associated protein-1 (TEP1). Vaults are abundantly present in the cytoplasm of eukaryotic cells and they were found to be associated with cytoskeletal elements as well as occasionally with the nuclear envelope. Vaults and MVP have been associated with several cellular processes which are also involved in cancer development like cell motility and differentiation. Due to the over-expression of MVP (also termed lung resistance-related protein or LRP) in several P-glycoprotein (P-gp)-negative chemoresistant cancer cell lines, vaults have been linked to multidrug resistance (MDR). Accordingly, high levels of MVP were found in tissues chronically exposed to xenobiotics. In addition, the expression of MVP correlated with the degree of malignancy in certain cancer types, suggesting a direct involvement in tumor development and/or progression. Based on the finding that MVP binds several phosphatases and kinases including PTEN, SHP-2 as well as Erk, evidence is accumulating that MVP might be involved in the regulation of important cell signalling pathways including the PI3K/Akt and the MAPK pathways. In this review we summarize the current knowledge concerning the vault particle and discuss its possible cellular functions, focusing on the role of vaults in chemotherapy resistance. PMID:16918321

  19. Characteristics of multidrug-resistant tuberculosis in Namibia

    PubMed Central

    2012-01-01

    Background To describe the epidemiology and possible risk factors for the development of multidrug-resistant tuberculosis (MDR-TB) in Namibia. Methods Using medical records and patient questionnaires, we conducted a case-control study among patients diagnosed with TB between January 2007 and March 2009. Cases were defined as patients with laboratory-confirmed MDR-TB; controls had laboratory-confirmed drug-susceptible TB or were being treated with WHO Category I or Category II treatment regimens. Results We enrolled 117 MDR-TB cases and 251 TB controls, of which 100% and 2% were laboratory-confirmed, respectively. Among cases, 97% (113/117) had been treated for TB before the current episode compared with 46% (115/251) of controls (odds ratio [OR] 28.7, 95% confidence interval [CI] 10.3–80.5). Cases were significantly more likely to have been previously hospitalized (OR 1.9, 95% CI 1.1–3.5) and to have had a household member with MDR-TB (OR 5.1, 95% CI 2.1–12.5). These associations remained significant when separately controlled for being currently hospitalized or HIV-infection. Conclusions MDR-TB was associated with previous treatment for TB, previous hospitalization, and having had a household member with MDR-TB, suggesting that TB control practices have been inadequate. Strengthening basic TB control practices, including expanding laboratory confirmation, directly observed therapy, and infection control, are critical to the prevention of MDR-TB. PMID:23273024

  20. Detection of Quorum Sensing Activity in the Multidrug-Resistant Clinical Isolate Pseudomonas aeruginosa Strain GB11

    PubMed Central

    Cheng, Huey Jia; Ee, Robson; Cheong, Yuet Meng; Tan, Wen-Si; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    A multidrug-resistant clinical bacteria strain GB11 was isolated from a wound swab on the leg of a patient. Identity of stain GB11 as Pseudomonas aeruginosa was validated by using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Detection of the production of signaling molecules, N-acylhomoserine lactones (AHLs), was conducted using three different bacterial biosensors. A total of four different AHLs were found to be produced by strain GB11, namely N-butyryl homoserine lactone (C4-HSL), N-hexanoylhomoserine lactone (C6-HSL), N-octanoyl homoserine lactone (C8-HSL) and N-3-oxo-dodecanoylhomoserine lactone (3-oxo-C12-HSL) using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Of these detected AHLs, 3-oxo-C12-HSL was found to be the most abundant AHL produced by P. aeruginosa GB11. PMID:25019635

  1. Bloodstream infections caused by multi-drug resistant Proteus mirabilis: Epidemiology, risk factors and impact of multi-drug resistance.

    PubMed

    Korytny, Alexander; Riesenberg, Klaris; Saidel-Odes, Lisa; Schlaeffer, Fransisc; Borer, Abraham

    2016-06-01

    Background The prevalence of antimicrobial co-resistance among ESBL-producing Enterobactereaceae is extremely high in Israel. Multidrug-resistant Proteus mirabilis strains (MDR-PM), resistant to almost all antibiotic classes have been described. The aim was to determine the risk factors for bloodstream infections caused by MDR-PM and clinical outcomes. Methods A retrospective case-control study. Adult patients with PM bacteremia during 7 years were identified retrospectively and their files reviewed for demographics, underlying diseases, Charlson Comorbidity Index, treatment and outcome. Results One hundred and eighty patients with PM-bloodstream infection (BSI) were included; 90 cases with MDR-PM and 90 controls with sensitive PM (S-PM). Compared to controls, cases more frequently were from nursing homes, had recurrent hospital admissions in the past year and received antibiotic therapy in the previous 3 months, were bedridden and suffered from peripheral vascular disease and peptic ulcer disease (p < 0.001). Two-thirds of the MDR-PM isolates were ESBL-producers vs 4.4% of S-PM isolates (p < 0.001, OR = 47.6, 95% CI = 15.9-142.6). In-hospital crude mortality rate of patients with MDR-PM BSI was 37.7% vs 23.3% in those with S-PM BSI (p = 0.0359, OR = 2, 95% CI = 1.4-3.81). Conclusions PM bacteremia in elderly and functionally-dependent patients is likely to be caused by nearly pan-resistant PM strains in the institution; 51.8% of the patients received inappropriate empiric antibiotic treatment. The crude mortality rate of patients with MDR-PM BSI was significantly higher than that of patients with S-PM BSI. PMID:26763474

  2. In vivo challenging of polymyxins and levofloxacin eye drop against multidrug-resistant Pseudomonas aeruginosa keratitis.

    PubMed

    Tajima, Kazuki; Miyake, Taku; Koike, Naohito; Hattori, Takaaki; Kumakura, Shigeto; Yamaguchi, Tetsuo; Matsumoto, Tetsuya; Fujita, Koji; Kuroda, Masahiko; Ito, Norihiko; Goto, Hiroshi

    2014-06-01

    The purposes of this study were to establish a rabbit multidrug-resistant Pseudomonas aeruginosa (MDRP) keratitis model, and test the efficacy of levofloxacin, colistin methanesulfate (CL-M), colistin sulfate (CL-S) and polymyxin B (PL-B) against MDRP infection. In a rabbit eye, making a 2-mm circular corneal excision, and MDRP strain #601 or representative P. aeruginosa strain IID1210 were instilled into the corneal concavity. IID1210 was used to confirm this model developed P. aeruginosa keratitis. After MDRP keratitis developed, we treated the eyes with levofloxacin, CL-M, CL-S or PL-B eye drops. The infected eyes were evaluated by clinical score, histopathological examination and viable bacterial count (CFU). Rabbits developed MDRP keratitis reproducibly after instilled the bacteria into the corneal lesion. MDRP produced severe keratitis similarly with IID1210, as shown by slit lamp examination and clinical score. In MDRP keratitis models, clinical scores and viable bacterial counts were significantly lower in levofloxacin- and CL-M-treated groups compared with PBS-treated group, but the magnitudes of reduction were not remarkable. However, clinical scores were dramatically lowered in CL-S- and PL-B-treated groups compared with PBS-treated group. CL-S- and PL-B-treated group were kept corneal translucency and little influx of polymorphonuclear neutrophils in histopathological examination. In addition, both CL-S- and PL-B-treated groups were not detected viable bacteria in infected cornea. Using our MDRP keratitis model, we showed that topical levofloxacin and CL-M are not adequately effective, while CL-S and PL-B are efficacious in controlling MDRP keratitis. Especially, PL-B, which is commercially available eye drop, might be most effective against MDRP. PMID:24726376

  3. Modified live Edwardsiella ictaluri vaccine, AQUAVAC-ESC, lacks multidrug resistance plasmids.

    PubMed

    Lafrentz, Benjamin R; Welch, Timothy J; Shoemaker, Craig A; Drennan, John D; Klesius, Phillip H

    2011-12-01

    Plasmid-mediated antibiotic resistance was first discovered in Edwardsiella ictaluri in the early 1990s, and in 2007 an E. ictaluri isolate harboring an IncA/C plasmid was recovered from a moribund channel catfish Ictalurus punctatus infected with the bacterium. Due to the identification of multidrug resistance plasmids in aquaculture and their potential clinical importance, we sought to determine whether the modified live E. ictaluri vaccine strain in AQUAVAC-ESC harbors such plasmids, so that the use of this vaccine will not directly contribute to the pool of bacteria carrying plasmid-borne resistance. Antimicrobial sensitivity testing of the E. ictaluri parent isolate and vaccine strain demonstrated that both were sensitive to 15 of the 16 antimicrobials tested. Total DNA from each isolate was analyzed by polymerase chain reaction (PCR) using a set of 13 primer pairs specific for conserved regions of the IncA/C plasmid backbone, and no specific products were obtained. PCR-based replicon typing of the parent isolate and vaccine strain demonstrated the absence of the 18 commonly occurring plasmid incompatibility groups. These results demonstrate that the vaccine strain does not carry resistance to commonly used antimicrobials and provide strong support for the absence of IncA/C and other commonly occurring plasmid incompatibility groups. Therefore, its use should not directly contribute to the pool of bacteria carrying plasmid-borne resistance. This work highlights the importance of thoroughly investigating potential vaccine strains for the presence of plasmids or other transmissible elements that may encode resistance to antibiotics. PMID:22372247

  4. Crowdsourced Data Indicate Widespread Multidrug Resistance in Skin Flora of Healthy Young Adults.

    PubMed

    Freeman, Scott; Okoroafor, Nnadozie O; Gast, Christopher M; Koval, Mikhail; Nowowiejski, David; O'Connor, Eileen; Harrington, Robert D; Parks, John W; Fang, Ferric C

    2016-03-01

    In a laboratory exercise for undergraduate biology majors, students plated bacteria from swabs of their facial skin under conditions that selected for coagulase-negative Staphylococcus; added disks containing the antibiotics penicillin, oxacillin, tetracycline, and erythromycin; and measured zones of inhibition. Students also recorded demographic and lifestyle variables and merged this information with similar data collected from 9,000 other students who had contributed to the database from 2003 to 2011. Minimum inhibitory concentration (MIC) testing performed at the Harborview Medical Center Microbiology Laboratory (Seattle, WA) indicated a high degree of accuracy for student-generated data; species identification with a matrix-assisted laser desorption ionization (MALDI) Biotyper revealed that over 88% of the cells analyzed by students were S. epidermidis or S. capitus. The overall frequency of resistant cells was high, ranging from 13.2% of sampled bacteria resistant to oxacillin to 61.7% resistant to penicillin. Stepwise logistic regressions suggested that recent antibiotic use was strongly associated with resistance to three of the four antibiotics tested (p = 0.0003 for penicillin, p < 0.0001 for erythromycin and tetracycline), and that age, gender, use of acne medication, use of antibacterial soaps, or makeup use were associated with resistance to at least one of the four antibiotics. Furthermore, drug resistance to one antibiotic was closely linked to resistance to the other three antibiotics in every case (all p values < 0.0001), suggesting the involvement of multidrug-resistant strains. The data reported here suggest that citizen science could not only provide an important educational experience for undergraduates, but potentially play a role in efforts to expand antibiotic resistance (ABR) surveillance. PMID:27047615

  5. The TCA cycle is not required for selection or survival of multidrug-resistant Salmonella

    PubMed Central

    Ricci, Vito; Loman, Nick; Pallen, Mark; Ivens, Alasdair; Fookes, Maria; Langridge, Gemma C.; Wain, John; Piddock, Laura J. V.

    2012-01-01

    Objectives The initial aim of this study was to use a systems biology approach to analyse a ciprofloxacin-selected multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium, L664. Methods The whole genome sequence and transcriptome of L664 were analysed. Site-directed mutagenesis to recreate each mutation was carried out, followed by phenotypic characterization and mutation frequency analysis. As a mutation in the TCA cycle was detected we tested the controversial hypothesis regarding the bacterial response to bactericidal antibiotics, put forward by Kohanski et al. (Cell 2007; 130: 797–810 and Mol Cell 2010; 37: 311–20), that exposure of bacteria to agents such as ciprofloxacin produces reactive oxygen species (ROS), which transiently increase the mutation rate giving rise to MDR bacteria. Results L664 contained a mutation in ramR that conferred MDR. A mutation in tctA affected the TCA cycle and conferred the inability to grow on minimal agar. The virulence of L664 was not attenuated. Ciprofloxacin exposure produced ROS in L664 and SL1344 (tctA::aph), but it was reduced and occurred later. There were no significant differences in the rates of killing or mutations per generation to antibiotic resistance between the strains. Conclusions Whilst we confirm production of ROS in response to ciprofloxacin, we have no data to support the hypothesis that this leads to selection of MDR strains. Our results indicate that the mutations in tctA and glgA were random as they did not pre-exist in the parental strain, and that the mutation in tctA did not provide a survival advantage or disadvantage in the presence of antibiotic. PMID:22186876

  6. A pilot study on water pollution and characterization of multidrug-resistant superbugs from Byramangala tank, Ramanagara district, Karnataka, India.

    PubMed

    Skariyachan, Sinosh; Lokesh, Priyanka; Rao, Reshma; Kumar, Arushi Umesh; Vasist, Kiran S; Narayanappa, Rajeswari

    2013-07-01

    Urbanization and industrialization has increased the strength and qualities of municipal sewage in Bangalore, India. The disposal of sewage into natural water bodies became a serious issue. Byramangala reservoir is one such habitat enormously polluted in South India. The water samples were collected from four hotspots of Byramangala tank in 3 months. The biochemical oxygen demand (BOD) and bacterial counts were determined. The fecal coliforms were identified by morphological, physiological, and biochemical studies. The antibiotics sensitivity profiling of isolated bacteria were further carried out. We have noticed that a high content of BOD in the tank in all the 3 months. The total and fecal counts were found to be varied from 1.6 × 10(6) to 8.2 × 10(6) colony forming unit/ml and >5,500/100 ml, respectively. The variations in BOD and total count were found to be statistically significant at p > 0.05. Many pathogenic bacteria were characterized and most of them were found to be multidrug resistant. Salmonella showed resistance to cefoperazone, cefotaxime, cefixime, moxifloxacin, piperacillin/tazobactam, co-trimoxazole, levofloxacin, trimethoprim, and ceftazidime. Escherichia coli showed resistance to chloramphenicol, trimethoprim, co-trimoxazole, rifampicin, and nitrofurantoin while Enterobacter showed resistant to ampicillin, cefepime, ceftazidime, cefoperazone, and cefotaxime. Klebsiella and Shigella exhibited multiple drug resistance to conventional antibiotics. Staphylococcus showed resistance to vancomycin, methicillin, oxacillin, and tetracycline. Furthermore, Salmonella and Klebsiella are on the verge of acquiring resistance to even the strongest carbapenems-imipenem and entrapenem. Present study revealed that Byramanagala tank has become a cesspool of multidrug-resistant "superbugs" and will be major health concern in South Bangalore, India. PMID:23114918

  7. Nationwide outbreak of multidrug-resistant Salmonella Heidelberg infections associated with ground turkey: United States, 2011.

    PubMed

    Routh, J A; Pringle, J; Mohr, M; Bidol, S; Arends, K; Adams-Cameron, M; Hancock, W T; Kissler, B; Rickert, R; Folster, J; Tolar, B; Bosch, S; Barton Behravesh, C; Williams, I T; Gieraltowski, L

    2015-11-01

    On 23 May 2011, CDC identified a multistate cluster of Salmonella Heidelberg infections and two multidrug-resistant (MDR) isolates from ground turkey retail samples with indistinguishable pulsed-field gel electrophoresis patterns. We defined cases as isolation of outbreak strains in persons with illness onset between 27 February 2011 and 10 November 2011. Investigators collected hypothesis-generating questionnaires and shopper-card information. Food samples from homes and retail outlets were collected and cultured. We identified 136 cases of S. Heidelberg infection in 34 states. Shopper-card information, leftover ground turkey from a patient's home containing the outbreak strain and identical antimicrobial resistance profiles of clinical and retail samples pointed to plant A as the source. On 3 August, plant A recalled 36 million pounds of ground turkey. This outbreak increased consumer interest in MDR Salmonella infections acquired through United States-produced poultry and played a vital role in strengthening food safety policies related to Salmonella and raw ground poultry. PMID:25865382

  8. A novel molecule with notable activity against multi-drug resistant tuberculosis.

    PubMed

    Nair, Vasu; Okello, Maurice O; Mangu, Naveen K; Seo, Byung I; Gund, Machhindra G

    2015-03-15

    Multi-drug resistant tuberculosis (MDR-TB) is emerging as a serious global health problem, which has been elevated through co-infection involving HIV and MDR-Mtb. The discovery of new compounds with anti-MDR TB efficacy and favorable metabolism profiles is an important scientific challenge. Using computational biology and ligand docking data, we have conceived a multifunctional molecule, 2, as a potential anti-MDR TB agent. This compound was produced through a multi-step synthesis. It exhibited significant in vitro activity against MDR-TB (MIC 1.56μg/mL) and its half-life (t1/2) in human liver microsomes was 14.4h. The metabolic profiles of compound 2 with respect to human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes were favorable. Compound 2 also had relatively low in vitro cytotoxicity in uninfected macrophages. It displayed synergistic behavior against MDR-TB in combination with PA-824. Interestingly, compound 2 also displayed in vitro anti-HIV activity. PMID:25677656

  9. Essential Oil from Origanum vulgare Completely Inhibits the Growth of Multidrug-Resistant Cystic Fibrosis Pathogens.

    PubMed

    Pesavento, Giovanna; Maggini, Valentina; Maida, Isabel; Lo Nostro, Antonella; Calonico, Carmela; Sassoli, Chiara; Perrin, Elena; Fondi, Marco; Mengoni, Alessio; Chiellini, Carolina; Vannacci, Alfredo; Gallo, Eugenia; Gori, Luigi; Bogani, Patrizia; Bilia, Anna Rita; Campana, Silvia; Ravenni, Novella; Dolce, Daniela; Firenzuoli, Fabio; Fani, Renato

    2016-06-01

    Essential oils (EOs) are known to inhibit the growth of a wide range of microorganisms. Particularly interesting is the possible use of EOs to treat multidrug-resistant cystic fibrosis (CF) pathogens. We tested the essential oil (EO) from Origanum vulgare for in vitro antimicrobial activity, against three of the major human opportunistic pathogens responsible for respiratory infections in CF patients; these are methicillin-resistant Staphylococcus aureus, Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Antibiotic susceptibility of each strain was previously tested by the standard disk diffusion method. Most strains were resistant to multiple antibiotics and could be defined as multi-drug-resistant (MDR). The antibacterial activity of O. vulgare EO (OEO) against a panel of 59 bacterial strains was evaluated, with MIC and MBC determined at 24, 48 and 72 hours by a microdilution method. The OEO was effective against all tested strains, although to a different extent. The MBC and MIC of OEO for S. aureus strains were either lower or equal to 0.50%, v/v, for A. xylosoxidans strains were lower or equal to 1% and 0.50%, v/v, respectively; and for S. maltophilia strains were lower or equal to 0.25%, v/v. The results from this study suggest that OEO might exert a role as an antimicrobial in the treatment of CF infections. PMID:27534136

  10. Redox Regulation of Multidrug Resistance in Cancer Chemotherapy: Molecular Mechanisms and Therapeutic Opportunities

    PubMed Central

    2009-01-01

    Abstract The development of multidrug resistance to cancer chemotherapy is a major obstacle to the effective treatment of human malignancies. It has been established that membrane proteins, notably multidrug resistance (MDR), multidrug resistance protein (MRP), and breast cancer resistance protein (BCRP) of the ATP binding cassette (ABC) transporter family encoding efflux pumps, play important roles in the development of multidrug resistance. Overexpression of these transporters has been observed frequently in many types of human malignancies and correlated with poor responses to chemotherapeutic agents. Evidence has accumulated showing that redox signals are activated in response to drug treatments that affect the expression and activity of these transporters by multiple mechanisms, including (a) conformational changes in the transporters, (b) regulation of the biosynthesis cofactors required for the transporter's function, (c) regulation of the expression of transporters at transcriptional, posttranscriptional, and epigenetic levels, and (d) amplification of the copy number of genes encoding these transporters. This review describes various specific factors and their relevant signaling pathways that are involved in the regulation. Finally, the roles of redox signaling in the maintenance and evolution of cancer stem cells and their implications in the development of intrinsic and acquired multidrug resistance in cancer chemotherapy are discussed. Antioxid. Redox Signal. 11, 99–133. PMID:18699730

  11. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong; Zhou, Xianguang; Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing; Wang, Jiandong; Zhang, Longjiang; Teng, Zhaogang; Lu, Guangming

    2015-03-01

    Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer.

  12. A Novel Nitrobenzoate Microtubule Inhibitor that Overcomes Multidrug Resistance Exhibits Antitumor Activity.

    PubMed

    Zheng, Yan-Bo; Gong, Jian-Hua; Liu, Xiu-Jun; Wu, Shu-Ying; Li, Yi; Xu, Xian-Dong; Shang, Bo-Yang; Zhou, Jin-Ming; Zhu, Zhi-Ling; Si, Shu-Yi; Zhen, Yong-Su

    2016-01-01

    Multidrug resistance is a major limitation for microtubule-binding agents in cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl-5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity against multidrug-resistant cell lines and its antitumor efficacy in animal models. IMB5046 disrupted microtubule structures in cells and inhibited purified tubulin polymerization in vitro. It bound to the colchicine pocket of tubulin. IMB5046 displayed potent cytotoxicity against multiple tumor cell lines with an IC50 range of 0.037-0.426 μM. Notably, several multidrug-resistant cell lines which were resistant to colchicine, vincristine and paclitaxel remained sensitive to IMB5046. IMB5046 was not a P-glycoprotein substrate. IMB5046 blocked cell cycle at G2/M phase and induced cell apoptosis. Microarray assay indicated that the differentially expressed genes after IMB5046 treatment were highly related to immune system, cell death and cancer. In a mouse xenograft model IMB5046 inhibited the growth of human lung tumor xenograft by 83% at a well-tolerated dose. It is concluded that IMB5046 is a tubulin polymerization inhibitor with novel chemical structure and can overcome multidrug resistance. It is a promising lead compound for cancer chemotherapy, especially for treatment of multidrug-resistant tumors. PMID:27510727

  13. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells

    SciTech Connect

    Horio, M.; Gottesman, M.M.; Pastan, I. )

    1988-05-01

    Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the MDR1 gene, whose product is the plasma membrane P-glycoprotein. Plasma membrane vesicles partially purified from multidrug-resistant human KB carcinoma cells, but not from drug-sensitive cells, accumulate ({sup 3}H)vinblastine in an ATP-dependent manner. This transport is osmotically sensitive, with an apparent K{sub m} of 38 {mu}M for ATP and of {approx} 2 {mu}M for vinblastine. The nonhydrolyzable analog adenosine 5{prime}-({beta},{gamma}-imido)triphosphate does not substitute for ATP but is a competitive inhibitor of ATP for the transport process. Vanadate, and ATPase inhibitor, is a potent noncompetitive inhibitor of transport. These results indicate that hydrolysis of ATP is probably required for active transport vinblastine. Several other drugs to which multidrug-resistant cell lines are resistant inhibit transport, with relative potencies as follows: vincristine > actinomycin D > daunomycin > colchicine = puromycin. Verapamil and quinidine, which reverse the multidrug-resistance phenotype, are good inhibitors of the transport process. These results confirm that multidrug-resistant cells express an energy-dependent plasma membrane transporter for hydrophobic drugs, and establish a system for the detailed biochemical analysis of this transport process.

  14. A Novel Nitrobenzoate Microtubule Inhibitor that Overcomes Multidrug Resistance Exhibits Antitumor Activity

    PubMed Central

    Zheng, Yan-Bo; Gong, Jian-Hua; Liu, Xiu-Jun; Wu, Shu-Ying; Li, Yi; Xu, Xian-Dong; Shang, Bo-Yang; Zhou, Jin-Ming; Zhu, Zhi-Ling; Si, Shu-Yi; Zhen, Yong-Su

    2016-01-01

    Multidrug resistance is a major limitation for microtubule-binding agents in cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl-5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity against multidrug-resistant cell lines and its antitumor efficacy in animal models. IMB5046 disrupted microtubule structures in cells and inhibited purified tubulin polymerization in vitro. It bound to the colchicine pocket of tubulin. IMB5046 displayed potent cytotoxicity against multiple tumor cell lines with an IC50 range of 0.037–0.426 μM. Notably, several multidrug-resistant cell lines which were resistant to colchicine, vincristine and paclitaxel remained sensitive to IMB5046. IMB5046 was not a P-glycoprotein substrate. IMB5046 blocked cell cycle at G2/M phase and induced cell apoptosis. Microarray assay indicated that the differentially expressed genes after IMB5046 treatment were highly related to immune system, cell death and cancer. In a mouse xenograft model IMB5046 inhibited the growth of human lung tumor xenograft by 83% at a well-tolerated dose. It is concluded that IMB5046 is a tubulin polymerization inhibitor with novel chemical structure and can overcome multidrug resistance. It is a promising lead compound for cancer chemotherapy, especially for treatment of multidrug-resistant tumors. PMID:27510727

  15. Applications of nanoparticle drug delivery systems for the reversal of multidrug resistance in cancer

    PubMed Central

    HUANG, YINGHONG; COLE, SUSAN P.C.; CAI, TIANGE; CAI, YU

    2016-01-01

    Multidrug resistance (MDR) to chemotherapy presents a major obstacle in the treatment of cancer patients, which directly affects the clinical success rate of cancer therapy. Current research aims to improve the efficiency of chemotherapy, whilst reducing toxicity to prolong the lives of cancer patients. As with good biocompatibility, high stability and drug release targeting properties, nanodrug delivery systems alter the mechanism by which drugs function to reverse MDR, via passive or active targeting, increasing drug accumulation in the tumor tissue or reducing drug elimination. Given the potential role of nanodrug delivery systems used in multidrug resistance, the present study summarizes the current knowledge on the properties of liposomes, lipid nanoparticles, polymeric micelles and mesoporous silica nanoparticles, together with their underlying mechanisms. The current review aims to provide a reliable basis and useful information for the development of new treatment strategies of multidrug resistance reversal using nanodrug delivery systems. PMID:27347092

  16. The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons

    PubMed Central

    Ravi, Anuradha; Avershina, Ekaterina; Foley, Steven L.; Ludvigsen, Jane; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; McCartney, Anne L.; L’Abée-Lund, Trine M.; Rudi, Knut

    2015-01-01

    Despite the accumulating knowledge on the development and establishment of the gut microbiota, its role as a reservoir for multidrug resistance is not well understood. This study investigated the prevalence and persistence patterns of an integrase gene (int1), used as a proxy for integrons (which often carry multiple antimicrobial resistance genes), in the fecal microbiota of 147 mothers and their children sampled longitudinally from birth to 2 years. The study showed the int1 gene was detected in 15% of the study population, and apparently more persistent than the microbial community structure itself. We found int1 to be persistent throughout the first two years of life, as well as between mothers and their 2-year-old children. Metagenome sequencing revealed integrons in the gut meta-mobilome that were associated with plasmids and multidrug resistance. In conclusion, the persistent nature of integrons in the infant gut microbiota makes it a potential reservoir of mobile multidrug resistance. PMID:26507767

  17. Detection of Multi-drug Resistant Acinetobacter Lwoffii Isolated from Soil of Mink Farm.

    PubMed

    Sun, Na; Wen, Yong Jun; Zhang, Shu Qin; Zhu, Hong Wei; Guo, Li; Wang, Feng Xue; Chen, Qiang; Ma, Hong Xia; Cheng, Shi Peng

    2016-07-01

    There were 4 Acinetobacter lwoffii obtained from soil samples. The antimicrobial susceptibility of the strains to 16 antimicrobial agents was investigated using K-B method. Three isolates showed the multi-drug resistance. The presence of resistance genes and integrons was determined using PCR. The aadA1, aac(3')-IIc, aph(3')-VII, aac(6')-Ib, sul2, cat2, floR, and tet(K) genes were detected, respectively. Three class 1 integrons were obtained. The arr-3-aacA4 and blaPSE-1 gene cassette, which cause resistance to aminoglycoside and beta-lactamase antibiotics. Our results reported the detection of multi-drug resistant and carried resistant genes Acinetobacter lwoffii from soil. The findings suggested that we should pay close attention to the prevalence of multi-drug resistant bacterial species of environment. PMID:27554122

  18. The commensal infant gut meta-mobilome as a potential reservoir for persistent multidrug resistance integrons.

    PubMed

    Ravi, Anuradha; Avershina, Ekaterina; Foley, Steven L; Ludvigsen, Jane; Storrø, Ola; Øien, Torbjørn; Johnsen, Roar; McCartney, Anne L; L'Abée-Lund, Trine M; Rudi, Knut

    2015-01-01

    Despite the accumulating knowledge on the development and establishment of the gut microbiota, its role as a reservoir for multidrug resistance is not well understood. This study investigated the prevalence and persistence patterns of an integrase gene (int1), used as a proxy for integrons (which often carry multiple antimicrobial resistance genes), in the fecal microbiota of 147 mothers and their children sampled longitudinally from birth to 2 years. The study showed the int1 gene was detected in 15% of the study population, and apparently more persistent than the microbial community structure itself. We found int1 to be persistent throughout the first two years of life, as well as between mothers and their 2-year-old children. Metagenome sequencing revealed integrons in the gut meta-mobilome that were associated with plasmids and multidrug resistance. In conclusion, the persistent nature of integrons in the infant gut microbiota makes it a potential reservoir of mobile multidrug resistance. PMID:26507767

  19. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition

    PubMed Central

    2012-01-01

    Background We aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. Methods A retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs. Results Cost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively). Conclusions P. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact. PMID:22621745

  20. Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo

    PubMed Central

    Lu, Wei-Dong; Qin, Yong; Yang, Chuang; Li, Lei

    2013-01-01

    OBJECTIVE: To determine whether curcumin reverses the multidrug resistance of human colon cancer cells in vitro and in vivo. METHODS: In a vincristine-resistant cell line of human colon cancer, the cell viability of curcumin-treated cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Rhodamine123 efflux was evaluated to detect P-glycoprotein transporter activity, and expression of the multidrug resistance protein 1 and survivin genes was analyzed by reverse transcription polymerase chain reaction and western blotting. In addition, xenograft mouse tumors were grown and treated with curcumin. The morphology of the xenografts was investigated by hematoxylin-eosin staining. The in vivo expression of the multidrug resistance gene and P-glycoprotein and survivin genes and proteins was observed using reverse transcription-polymerase chain reaction and western blotting, respectively. RESULTS: Curcumin was not obviously toxic to the vincristine-resistant human colon cancer cells at concentrations less than 25 μM, but the growth of cells was significantly inhibited. At concentrations greater than 25 μM, curcumin was toxic in a concentration-dependent manner. The sensitivity of cells to vincristine, cisplatin, fluorouracil, and hydroxycamptothecin was enhanced, intracellular Rhodamine123 accumulation was increased (p<0.05), and the expression of the multidrug resistance gene and P-glycoprotein were significantly suppressed (p<0.05). The combination of curcumin and vincristine significantly inhibited xenograft growth. The expression of the multidrug resistance protein 1 and survivin genes was significantly reduced in xenografts of curcumin-treated mice and mice treated with both curcumin and vincristine relative to control mice. CONCLUSION: Curcumin has strong reversal effects on the multidrug resistance of human colon carcinoma in vitro and in vivo. PMID:23778405

  1. Draft genome sequence of a multidrug-resistant Chryseobacterium indologenes isolate from Malaysia

    PubMed Central

    Yu, Choo Yee; Ang, Geik Yong; Cheng, Huey Jia; Cheong, Yuet Meng; Yin, Wai-Fong; Chan, Kok-Gan

    2015-01-01

    Chryseobacterium indologenes is an emerging pathogen which poses a threat in clinical healthcare setting due to its multidrug-resistant phenotype and its common association with nosocomial infections. Here, we report the draft genome of a multidrug-resistant C. indologenes CI_885 isolated in 2014 from Malaysia. The 908,704-kb genome harbors a repertoire of putative antibiotic resistance determinants which may elucidate the molecular basis and underlying mechanisms of its resistant to various classes of antibiotics. The genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession number LJOD00000000. PMID:26981402

  2. Draft genome sequence of a multidrug-resistant Chryseobacterium indologenes isolate from Malaysia.

    PubMed

    Yu, Choo Yee; Ang, Geik Yong; Cheng, Huey Jia; Cheong, Yuet Meng; Yin, Wai-Fong; Chan, Kok-Gan

    2016-03-01

    Chryseobacterium indologenes is an emerging pathogen which poses a threat in clinical healthcare setting due to its multidrug-resistant phenotype and its common association with nosocomial infections. Here, we report the draft genome of a multidrug-resistant C. indologenes CI_885 isolated in 2014 from Malaysia. The 908,704-kb genome harbors a repertoire of putative antibiotic resistance determinants which may elucidate the molecular basis and underlying mechanisms of its resistant to various classes of antibiotics. The genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession number LJOD00000000. PMID:26981402

  3. [Relevance of animal models in the development of compounds targeting multidrug resistant cancer].

    PubMed

    Füredi, András; Tóth, Szilárd; Hámori, Lilla; Nagy, Veronika; Tóvári, József; Szakács, Gergely

    2015-12-01

    Anticancer compounds are typically identified in in vitro screens. Unfortunately, the in vitro drug sensitivity of cell lines does not reflect treatment efficiency in animal models, and neither show acceptable correlation to clinical results. While cell lines and laboratory animals can be readily "cured", the treatment of malignancies remains hampered by the multidrug resistance (MDR) of tumors. Genetically engineered mouse models (GEMMs) giving rise to spontaneous tumors offer a new possibility to characterize the evolution of drug resistance mechanisms and to target multidrug resistant cancer. PMID:26665195

  4. The emergence and outbreak of multidrug-resistant typhoid fever in China.

    PubMed

    Yan, Meiying; Li, Xinlan; Liao, Qiaohong; Li, Fang; Zhang, Jing; Kan, Biao

    2016-01-01

    Typhoid fever remains a severe public health problem in developing countries. The emergence of resistant typhoid, particularly multidrug-resistant typhoid infections, highlights the necessity of monitoring the resistance characteristics of this invasive pathogen. In this study, we report a typhoid fever outbreak caused by multidrug-resistant Salmonella enterica serovar Typhi strains with an ACSSxtT pattern. Resistance genes conferring these phenotypes were harbored by a large conjugative plasmid, which increases the threat of Salmonella Typhi and thus requires close surveillance for dissemination of strains containing such genes. PMID:27329848

  5. Scaling-up treatment for HIV/AIDS: lessons learned from multidrug-resistant tuberculosis.

    PubMed

    Gupta, Rajesh; Irwin, Alexander; Raviglione, Mario C; Kim, Jim Yong

    2004-01-24

    The UN has launched an initiative to place 3 million people in developing countries on antiretroviral AIDS treatment by end 2005 (the 3 by 5 target). Lessons for HIV/AIDS treatment scale-up emerge from recent experience with multidrug-resistant tuberculosis. Expansion of treatment for multidrug-resistant tuberculosis through the multipartner mechanism known as the Green Light Committee (GLC) has enabled gains in areas relevant to 3 by 5, including policy development, drug procurement, rational use of drugs, and the strengthening of health systems. The successes of the GLC and the obstacles it has encountered provide insights for building sustainable HIV/AIDS treatment programmes. PMID:14751708

  6. A family cluster of tuberculosis cases, including a case of acquired multidrug resistant tuberculosis.

    PubMed

    Holden, Julie; Trachtman, Louis

    2012-01-01

    Although the number of tuberculosis cases in the US is at an all-time low, with progressive declines seen for the past 17 years, many goals in the tuberculosis elimination process remain unrealized. This report describes a cluster of four tuberculosis cases in a family, including one case of acquired multidrug resistant tuberculosis. It also underscores some important issues in tuberculosis control today, including significant disparities in the foreign-born population with multidrug resistant tuberculosis as a looming problem, as well as utilization of therapeutic drug level monitoring in complicated cases. PMID:22533114

  7. The emergence and outbreak of multidrug-resistant typhoid fever in China

    PubMed Central

    Yan, Meiying; Li, Xinlan; Liao, Qiaohong; Li, Fang; Zhang, Jing; Kan, Biao

    2016-01-01

    Typhoid fever remains a severe public health problem in developing countries. The emergence of resistant typhoid, particularly multidrug-resistant typhoid infections, highlights the necessity of monitoring the resistance characteristics of this invasive pathogen. In this study, we report a typhoid fever outbreak caused by multidrug-resistant Salmonella enterica serovar Typhi strains with an ACSSxtT pattern. Resistance genes conferring these phenotypes were harbored by a large conjugative plasmid, which increases the threat of Salmonella Typhi and thus requires close surveillance for dissemination of strains containing such genes. PMID:27329848

  8. Long-term survival of patients with multidrug-resistant tuberculosis according to treatment outcomes.

    PubMed

    Kwak, Nakwon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Yim, Jae-Joon

    2016-07-01

    Survival times of 219 patients diagnosed with multidrug-resistant tuberculosis were calculated and treatment outcomes compared. Mean survival of 20 patients who failed to be cured was 109.8 months (95% confidence interval [CI], 87.4-132.1), shorter than that of 150 patients who were cured (140.4 months; 95% CI, 136.1-144.7; P < .01) and that of 28 patients classified as treatment completed (138.5 months; 95% CI, 131.0-146.1; P = .02). The results demonstrate that patients with multidrug-resistant tuberculosis with poor treatment outcomes live 9 years, on average. PMID:26922891

  9. Induction of apoptosis and reversal of permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM by ginsenoside Rh2

    PubMed Central

    Zhang, Hui; Gong, Jian; Zhang, Huilai; Kong, Di

    2015-01-01

    Multidrug resistance is a phenomenon that cancer cells develop a cross-resistant phenotype against several unrelated drugs, and permeability glycoprotein derived from the overexpression of multidrug resistance gene 1 has been taken as the most significant cause of multidrug resistance. In the present study, ginsenoside Rh2 was used to reverse permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM cell line. Effects of ginsenoside Rh2 on the apoptotic process and caspase-3 activity of MCF-7 and MCF-7/ADM cell lines were determined using flow cytometry and microplate reader. Methyl thiazolyl tetrazolium test was conducted to assess the IC50 values of ginsenoside Rh2 and adriamycin on MCF-7 and MCF-7/ADM cultures; Rhodamin 123 assay was used to assess the retention of permeability glycoprotein after ginsenoside Rh2 treatment; flow cytometry and real time polymerase chain reaction were used to determine the expression levels of permeability glycoprotein and multidrug resistance gene 1 in drug-resistant cells and their parental cells after exposure to ginsenoside Rh2. The results showed that ginsenoside Rh2, except for inducing apoptosis, had the ability to reverse multidrug resistance in MCF-7/ADM cell line without changing the expression levels of permeability glycoprotein and multidrug resistance gene 1. Our findings provided some valuable information for the application of ginsenoside Rh2 in cancer therapy, especially for multidrug resistance reversal in clinic. PMID:26191135

  10. Detection of multi-drug resistant Escherichia coli in the urban waterways of Milwaukee, WI

    PubMed Central

    Kappell, Anthony D.; DeNies, Maxwell S.; Ahuja, Neha H.; Ledeboer, Nathan A.; Newton, Ryan J.; Hristova, Krassimira R.

    2015-01-01

    Urban waterways represent a natural reservoir of antibiotic resistance which may provide a source of transferable genetic elements to human commensal bacteria and pathogens. The objective of this study was to evaluate antibiotic resistance of Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics covering 10 different families were utilized to determine the phenotypic antibiotic resistance for all 259 E. coli isolates. All obtained isolates were determined to be multi-drug resistant. The E. coli isolates were also screened for the presence of the genetic determinants of resistance including ermB (macrolide resistance), tet(M) (tetracycline resistance), and β-lactamases (blaOXA, blaSHV, and blaPSE). E. coli from urban waterways showed a greater incidence of antibiotic resistance to 8 of 17 antibiotics tested compared to human derived sources. These E. coli isolates also demonstrated a greater incidence of resistance to higher numbers of antibiotics compared to the human derived isolates. The urban waterways demonstrated a greater abundance of isolates with co-occurrence of antibiotic resistance than human derived sources. When screened for five different antibiotic resistance genes conferring macrolide, tetracycline, and β-lactam resistance, clinical E. coli isolates were more likely to harbor ermB and blaOXA than isolates from urban waterway. These results indicate that Milwaukee’s urban waterways may select or allow for a greater incidence of multiple antibiotic resistance organisms and likely harbor a different antibiotic resistance gene pool than clinical sources. The implications of this study are significant to understanding the presence of resistance in urban freshwater environments by supporting the idea that sediment from urban waterways serves as a reservoir of antibiotic resistance. PMID:25972844

  11. Antibacterial Activity of Salvadora persica L. (Miswak) Extracts against Multidrug Resistant Bacterial Clinical Isolates

    PubMed Central

    Al-Ayed, Mohamed Saeed Zayed; Asaad, Ahmed Morad; Qureshi, Mohamed Ansar; Attia, Hany Goda; AlMarrani, Abduljabbar Hadi

    2016-01-01

    Much effort has focused on examining the inhibitory effect of Salvadora persica (miswak) on oral microorganisms, but information concerning its antibacterial activity against other human pathogens, particularly multidrug resistant (MDR) isolates, is scarce. Therefore, this study aimed to assess the in vitro antibacterial activities of Salvadora persica L. extracts against 10 MDR bacterial clinical isolates other than oral pathogens. The antibacterial activity of aqueous and methanol miswak extracts was assessed using the agar dilution and minimum inhibitory concentration (MIC) methods. Overall, the 400 mg/mL of miswak extract was the most effective on all strains. The methanol extract exhibited a stronger antibacterial activity against Gram-negative (3.3–13.6 mm) than Gram-positive (1.8–8.3 mm) bacteria. The lowest MIC value was seen for E. coli (0.39, 1.56 µg/mL), followed by Streptococcus pyogenes (1.56 µg/mL). The highest MIC value (6.25, 12.5 µg/mL) was recorded for methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, and Stenotrophomonas maltophilia. This study demonstrates, for the first time, the moderate to strong antibacterial activity of miswak extracts against all tested MDR-pathogens. Methanol extract appears to be a potent antimicrobial agent that could be considered as complementary and alternative medicine against resistant pathogens. Further studies on a large number of MDR organisms are necessary to investigate and standardize the inhibitory effect of miswak extracts against these emerging pathogens. PMID:26904146

  12. Phosphate-Containing Polyethylene Glycol Polymers Prevent Lethal Sepsis by Multidrug-Resistant Pathogens

    PubMed Central

    Zaborin, Alexander; Defazio, Jennifer R.; Kade, Matthew; Kaiser, Brooke L. Deatherage; Belogortseva, Natalia; Camp, David G.; Smith, Richard D.; Adkins, Joshua N.; Kim, Sangman M.; Alverdy, Alexandria; Goldfeld, David; Firestone, Millicent A.; Collier, Joel H.; Jabri, Bana; Tirrell, Matthew

    2014-01-01

    Antibiotic resistance among highly pathogenic strains of bacteria and fungi is a growing concern in the face of the ability to sustain life during critical illness with advancing medical interventions. The longer patients remain critically ill, the more likely they are to become colonized by multidrug-resistant (MDR) pathogens. The human gastrointestinal tract is the primary site of colonization of many MDR pathogens and is a major source of life-threatening infections due to these microorganisms. Eradication measures to sterilize the gut are difficult if not impossible and carry the risk of further antibiotic resistance. Here, we present a strategy to contain rather than eliminate MDR pathogens by using an agent that interferes with the ability of colonizing pathogens to express virulence in response to host-derived and local environmental factors. The antivirulence agent is a phosphorylated triblock high-molecular-weight polymer (here termed Pi-PEG 15–20) that exploits the known properties of phosphate (Pi) and polyethylene glycol 15-20 (PEG 15-20) to suppress microbial virulence and protect the integrity of the intestinal epithelium. The compound is nonmicrobiocidal and appears to be highly effective when tested both in vitro and in vivo. Structure functional analyses suggest that the hydrophobic bis-aromatic moiety at the polymer center is of particular importance to the biological function of Pi-PEG 15-20, beyond its phosphate content. Animal studies demonstrate that Pi-PEG prevents mortality in mice inoculated with multiple highly virulent pathogenic organisms from hospitalized patients in association with preservation of the core microbiome. PMID:24277029

  13. Multidrug-resistant bacterial infections after liver transplantation: An ever-growing challenge

    PubMed Central

    Santoro-Lopes, Guilherme; de Gouvêa, Erika Ferraz

    2014-01-01

    Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients. Over the last two decades, various multidrug-resistant (MDR) pathogens have emerged as relevant causes of infection in this population. Although this fact reflects the spread of MDR pathogens in health care facilities worldwide, several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units. The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy, which further contributes to the selection of drug resistance. This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options. Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial therapy. The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections. Furthermore, high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae, for which optimal treatment remains undefined. In such a context, the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients. This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients, and summarizes current preventive and therapeutic recommendations. PMID:24876740

  14. Individualizing Risk of Multidrug-Resistant Pathogens in Community-Onset Pneumonia

    PubMed Central

    Falcone, Marco; Russo, Alessandro; Giannella, Maddalena; Cangemi, Roberto; Scarpellini, Maria Gabriella; Bertazzoni, Giuliano; Alarcón, José Martínez; Taliani, Gloria; Palange, Paolo; Farcomeni, Alessio; Vestri, Annarita; Bouza, Emilio; Violi, Francesco; Venditti, Mario

    2015-01-01

    Introduction The diffusion of multidrug-resistant (MDR) bacteria has created the need to identify risk factors for acquiring resistant pathogens in patients living in the community. Objective To analyze clinical features of patients with community-onset pneumonia due to MDR pathogens, to evaluate performance of existing scoring tools and to develop a bedside risk score for an early identification of these patients in the Emergency Department. Patients and Methods This was an open, observational, prospective study of consecutive patients with pneumonia, coming from the community, from January 2011 to January 2013. The new score was validated on an external cohort of 929 patients with pneumonia admitted in internal medicine departments participating at a multicenter prospective study in Spain. Results A total of 900 patients were included in the study. The final logistic regression model consisted of four variables: 1) one risk factor for HCAP, 2) bilateral pulmonary infiltration, 3) the presence of pleural effusion, and 4) the severity of respiratory impairment calculated by use of PaO2/FiO2 ratio. A new risk score, the ARUC score, was developed; compared to Aliberti, Shorr, and Shindo scores, this point score system has a good discrimination performance (AUC 0.76, 95% CI 0.71-0.82) and calibration (Hosmer-Lemeshow, χ2 = 7.64; p = 0.469). The new score outperformed HCAP definition in predicting etiology due to MDR organism. The performance of this bedside score was confirmed in the validation cohort (AUC 0.68, 95% CI 0.60-0.77). Conclusion Physicians working in ED should adopt simple risk scores, like ARUC score, to select the most appropriate antibiotic regimens. This individualized approach may help clinicians to identify those patients who need an empirical broad-spectrum antibiotic therapy. PMID:25860142

  15. Fighting infections due to multidrug-resistant Gram-positive pathogens.

    PubMed

    Cornaglia, G

    2009-03-01

    Growing bacterial resistance in Gram-positive pathogens means that what were once effective and inexpensive treatments for infections caused by these bacteria are now being seriously questioned, including penicillin and macrolides for use against pneumococcal infections and-in hospitals-oxacillin for use against staphylococcal infections. As a whole, multidrug-resistant (MDR) Gram-positive pathogens are rapidly becoming an urgent and sometimes unmanageable clinical problem. Nevertheless, and despite decades of research into the effects of antibiotics, the actual risk posed to human health by antibiotic resistance has been poorly defined; the lack of reliable data concerning the outcomes resulting from antimicrobial resistance stems, in part, from problems with study designs and the methods used in resistence determination. Surprisingly little is known, too, about the actual effectiveness of the many types of intervention aimed at controlling antibiotic resistance. New antibiotics active against MDR Gram-positive pathogens have been recently introduced into clinical practice, and the antibiotic pipeline contains additional compounds at an advanced stage of development, including new glycopeptides, new anti-methicillin-resistant Staphylococcus aureus (MRSA) beta-lactams, and new diaminopyrimidines. Many novel antimicrobial agents are likely to be niche products, endowed with narrow antibacterial spectra and/or targeted at specific clinical problems. Therefore, an important educational goal will be to change the current, long-lasting attitudes of both physicians and customers towards broad-spectrum and multipurpose compounds. Scientific societies, such as the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), must play a leading role in this process. PMID:19335367

  16. Overcoming drug resistance in multi-drug resistant cancers and microorganisms: a conceptual framework.

    PubMed

    Avner, Benjamin S; Fialho, Arsenio M; Chakrabarty, Ananda M

    2012-01-01

    Resistance development against multiple drugs is a common feature among many pathogens--including bacteria such as Pseudomonas aeruginosa, viruses, and parasites--and also among cancers. The reasons are two-fold. Most commonly-used rationally-designed small molecule drugs or monoclonal antibodies, as well as antibiotics, strongly inhibit a key single step in the growth and proliferation of the pathogen or cancer cells. The disease agents quickly change or switch off this single target, or activate the efflux mechanisms to pump out the drug, thereby becoming resistant to the drug. A second problem is the way drugs are designed. The pharmaceutical industry chooses to use, by high-throughput screening, compounds that are maximally inhibitory to the key single step in the growth of the pathogen or cancer, thereby promoting selective pressure. An ideal drug would be one that inhibits multiple steps in the disease progression pathways with less stringency in these steps. Low levels of inhibition at multiple steps provide cumulative strong inhibitory effect, but little incentives or ability on the part of the pathogen/cancer to develop resistance. Such intelligent drug design involving multiple less stringent inhibitory steps is beyond the scope of the drug industry and requires evolutionary wisdom commonly possessed by bacteria. This review surveys assessments of the current clinical situation with regard to drug resistance in P. aeruginosa, and examines tools currently employed to limit this trend. We then provide a conceptual framework in which we explore the similarities between multi-drug resistance in pathogens and in cancers. We summarize promising work on anti-cancer drugs derived from the evolutionary wisdom of bacteria such as P. aeruginosa, and how such strategies can be the basis for how to look for candidate protein/peptide antibiotic drugs from bioengineered bugs. Such multi-domain proteins, unlike diffusible antibiotics, are not diffusible because of their

  17. Charge is Major Determinant of Activation of the Ligand-Responsive Multidrug Resistance Gene Regulator, BmrR.

    PubMed

    Bachas, Sharrol; Kohrs, Bryan; Wade, Herschel

    2016-05-19

    A medium-throughput approach (80+ compounds) to investigate allosteric transcriptional control in the multidrug resistance gene regulator BmrR, with cations, zwitterions, uncharged compounds and anions, is described. Even at the allosteric level, BmrR is quite promiscuous with regard to molecular shape and structure, but it is sensitive to molecular charge. A role for charge is further supported by differences in the activation properties of structurally similar ligands displaying variable charge properties as well as differences in activation by zwitterions and uncharged ligands, which show similar binding affinities. A comparison of allosteric selectivity with the distribution of differently charged ligands in bacterial cellular environments suggests that the selectivity of charge is a major factor in discrimination of xenobiotics, and native biological compounds and metabolites. Interestingly, in eukaryotic cells, the selectivity of cationic ligands might be a protective mechanism against chemical agents that act in a promiscuous fashion. PMID:27010425

  18. Synergistic effect of membrane-active peptides polymyxin B and gramicidin S on multidrug-resistant strains and biofilms of Pseudomonas aeruginosa.

    PubMed

    Berditsch, Marina; Jäger, Thomas; Strempel, Nikola; Schwartz, Thomas; Overhage, Jörg; Ulrich, Anne S

    2015-09-01

    Multidrug-resistant Pseudomonas aeruginosa is a major cause of severe hospital-acquired infections. Currently, polymyxin B (PMB) is a last-resort antibiotic for the treatment of infections caused by Gram-negative bacteria, despite its undesirable side effects. The delivery of drug combinations has been shown to reduce the required therapeutic doses of antibacterial agents and thereby their toxicity if a synergistic effect is present. In this study, we investigated the synergy between two cyclic antimicrobial peptides, PMB and gramicidin S (GS), against different P. aeruginosa isolates, using a quantitative checkerboard assay with resazurin as a growth indicator. Among the 28 strains that we studied, 20 strains showed a distinct synergistic effect, represented by a fractional inhibitory concentration index (FICI) of ≤0.5. Remarkably, several clinical P. aeruginosa isolates that grew as small-colony variants revealed a nonsynergistic effect, as indicated by FICIs between >0.5 and ≤0.70. In addition to inhibiting the growth of planktonic bacteria, the peptide combinations significantly decreased static biofilm growth compared with treatment with the individual peptides. There was also a faster and more prolonged effect when the combination of PMB and GS was used compared with single-peptide treatments on the metabolic activity of pregrown biofilms. The results of the present study define a synergistic interaction between two cyclic membrane-active peptides toward 17 multidrug-resistant P. aeruginosa and biofilms of P. aeruginosa strain PAO1. Thus, the application of PMB and GS in combination is a promising option for a topical medication and in the prevention of acute and chronic infections caused by multidrug-resistant or biofilm-forming P. aeruginosa. PMID:26077259

  19. Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene.

    PubMed Central

    Shen, D W; Fojo, A; Roninson, I B; Chin, J E; Soffir, R; Pastan, I; Gottesman, M M

    1986-01-01

    Mouse NIH 3T3 cells were transformed to multidrug resistance with high-molecular-weight DNA from multidrug-resistant human KB carcinoma cells. The patterns of cross resistance to colchicine, vinblastine, and doxorubicin hydrochloride (Adriamycin; Adria Laboratories Inc.) of the human donor cell line and mouse recipients were similar. The multidrug-resistant human donor cell line contains amplified sequences of the mdr1 gene which are expressed at high levels. Both primary and secondary NIH 3T3 transformants contained and expressed these amplified human mdr1 sequences. Amplification and expression of the human mdr1 sequences and amplification of cotransferred human Alu sequences in the mouse cells correlated with the degree of multidrug resistance. These data suggest that the mdr1 gene is likely to be responsible for multidrug resistance in cultured cells. Images PMID:3796599

  20. Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes.

    PubMed

    Omosa, Leonidah K; Midiwo, Jacob O; Mbaveng, Armelle T; Tankeo, Simplice B; Seukep, Jackson A; Voukeng, Igor K; Dzotam, Joachim K; Isemeki, John; Derese, Solomon; Omolle, Ruth A; Efferth, Thomas; Kuete, Victor

    2016-01-01

    In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3' together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are

  1. Inc A/C Plasmids in Multidrug resistant Salmonella enterica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteria plasmids are fragments of extra-chromosomal double stranded deoxyribonucleic acid (DNA) that can contain a variety of genes beneficial to the survival of the host bacteria. Classification and tracking of plasmids is beneficial because they are potentially a medium of horizontal gene transf...

  2. Isolation and characterization of antimicrobial compounds in plant extracts against multidrug-resistant Acinetobacter baumannii.

    PubMed

    Miyasaki, Yoko; Rabenstein, John D; Rhea, Joshua; Crouch, Marie-Laure; Mocek, Ulla M; Kittell, Patricia Emmett; Morgan, Margie A; Nichols, Wesley Stephen; Van Benschoten, M M; Hardy, William David; Liu, George Y

    2013-01-01

    The number of fully active antibiotic options that treat nosocomial infections due to multidrug-resistant Acinetobacter baumannii (A. baumannii) is extremely limited. Magnolia officinalis, Mahonia bealei, Rabdosia rubescens, Rosa rugosa, Rubus chingii, Scutellaria baicalensis, and Terminalia chebula plant extracts were previously shown to have growth inhibitory activity against a multidrug-resistant clinical strain of A. baumannii. In this study, the compounds responsible for their antimicrobial activity were identified by fractionating each plant extract using high performance liquid chromatography, and determining the antimicrobial activity of each fraction against A. baumannii. The chemical structures of the fractions inhibiting >40% of the bacterial growth were elucidated by liquid chromatography/mass spectrometry analysis and nuclear magnetic resonance spectroscopy. The six most active compounds were identified as: ellagic acid in Rosa rugosa; norwogonin in Scutellaria baicalensis; and chebulagic acid, chebulinic acid, corilagin, and terchebulin in Terminalia chebula. The most potent compound was identified as norwogonin with a minimum inhibitory concentration of 128 µg/mL, and minimum bactericidal concentration of 256 µg/mL against clinically relevant strains of A. baumannii. Combination studies of norwogonin with ten anti-Gram negative bacterial agents demonstrated that norwogonin did not enhance the antimicrobial activity of the synthetic antibiotics chosen for this study. In conclusion, of all identified antimicrobial compounds, norwogonin was the most potent against multidrug-resistant A. baumannii strains. Further studies are warranted to ascertain the prophylactic and therapeutic potential of norwogonin for infections due to multidrug-resistant A. baumannii. PMID:23630600

  3. Modified live Edwardsiella ictaluri vaccine, AQUAVAC-ESC, lacks multidrug resistance plasmids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmid mediated antibiotic resistance was first discovered in Edwardsiella ictaluri in the early 1990’s, and in 2007 an E. ictaluri isolate harboring an IncA/C plasmid was recovered from a moribund channel catfish infected with the bacterium. Due to the identification of multidrug resistance plasm...

  4. First Genome Sequence of a Mexican Multidrug-Resistant Acinetobacter baumannii Isolate

    PubMed Central

    Graña-Miraglia, Lucía; Lozano, Luis; Castro-Jaimes, Semiramis; Cevallos, Miguel A.; Volkow, Patricia

    2016-01-01

    Acinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. Here, we present the draft genome of the first multidrug-resistant A. baumannii isolate, sampled from a tertiary hospital in Mexico City. This genome will provide a starting point for studying the genomic diversity of this species in Mexico. PMID:27013043

  5. Antibiotic exposure can induce various bacterial virulence phenotypes in multidrug-resistant Salmonella enterica serovar Typhimurium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella is one of the most prevalent bacterial foodborne diseases in the United States and causes an estimated 1 million human cases every year. Multidrug-resistant (MDR) Salmonella has emerged as a public health issue as it has been associated with increased morbidity in humans and mortality in...

  6. Multidrug-Resistant Bacteroides fragilis Bacteremia in a US Resident: An Emerging Challenge

    PubMed Central

    Parajuli, Sunita; Siegfried, Justin; Dubrovskaya, Yanina; Rahimian, Joseph

    2016-01-01

    We describe a case of Bacteroides fragilis bacteremia associated with paraspinal and psoas abscesses in the United States. Resistance to b-lactam/b-lactamase inhibitors, carbapenems, and metronidazole was encountered despite having a recent travel history to India as the only possible risk factor for multidrug resistance. Microbiological cure was achieved with linezolid, moxifloxacin, and cefoxitin. PMID:27418986

  7. Geraniol Restores Antibiotic Activities against Multidrug-Resistant Isolates from Gram-Negative Species▿ †

    PubMed Central

    Lorenzi, Vannina; Muselli, Alain; Bernardini, Antoine François; Berti, Liliane; Pagès, Jean-Marie; Amaral, Leonard; Bolla, Jean-Michel

    2009-01-01

    The essential oil of Helichrysum italicum significantly reduces the multidrug resistance of Enterobacter aerogenes, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Combinations of the two most active fractions of the essential oil with each other or with phenylalanine arginine β-naphthylamide yield synergistic activity. Geraniol, a component of one fraction, significantly increased the efficacy of β-lactams, quinolones, and chloramphenicol. PMID:19258278

  8. Multidrug-resistant viridans streptococcus (MDRVS) osteomyelitis of the mandible successfully treated with moxifloxacin.

    PubMed

    Ang, Jocelyn Y; Asmar, Basim I

    2008-05-01

    Multidrug-resistant viridans group streptococcus (MDRVS) strains have emerged as important pathogens. Treatment of MDRVS infections is problematic. The use of fluoroquinolones for treatment of MDRVS osteomyelitis has not been established. We present the first case of MDRVS osteomyelitis of the mandible successfully treated with sequential intravenous then oral moxifloxacin, and review the literature on the subject. PMID:18414152

  9. Comparative genomics of the IncA/C multidrug resistance plasmid family

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multidrug resistance (MDR) plasmids belonging to the IncA/C plasmid family are widely distributed among Salmonella and other enterobacterial isolates from agricultural sources and have, at least once, also been identified in a drug resistant Yersinia pestis isolate (IP275) from Madagascar. Here, we...

  10. Draft Genome Sequences of Two Multidrug Resistant Klebsiella pneumoniae ST258 Isolates Resistant to Colistin

    PubMed Central

    Comandatore, Francesco; Sassera, Davide; Ambretti, Simone; Landini, Maria Paola; Daffonchio, Daniele; Marone, Piero; Sambri, Vittorio; Bandi, Claudio

    2013-01-01

    Sequence type 258 (ST258) is the most widespread multidrug resistant (MDR) Klebsiella pneumoniae strain worldwide. Here, we report the draft genome sequences of two colistin-resistant MDR K. pneumoniae ST258 clinical strains isolated from hospital patients in Italy. These strains are resistant to β-lactams, cephalosporins, fluoroquinolones, aminoglycosides, macrolides, tetracyclines, carbapenems, and colistin. PMID:23405348

  11. Genome Sequence of Riemerella anatipestifer Strain RCAD0122, a Multidrug-Resistant Isolate from Ducks

    PubMed Central

    Song, Xiao-Heng; Zhou, Wang-Shu; Wang, Jiang-Bo; Liu, Ma-Feng; Wang, Ming-Shu; Cheng, An-Chun; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue

    2016-01-01

    Riemerella anatipestifer is an important pathogenic bacterium in waterfowl and other avian species. We present here the genome sequence of R. anatipestifer RCAD0122, a multidrug-resistant strain isolated from infected ducks. The isolate contains at least nine types of antibiotic resistance-associated genes. PMID:27151800

  12. Increased risk for multidrug-resistant tuberculosis in migratory workers, Armenia.

    PubMed

    Truzyan, Nune; Crape, Byron; Grigoryan, Ruzanna; Martirosyan, Hripsime; Petrosyan, Varduhi

    2015-03-01

    To understand use of tuberculosis (TB) services for migrant workers, we conducted a cross-sectional census of 95 migrant workers with TB from Armenia by using medical record reviews and face-to-face interviews. Prolonged time between diagnosis and treatment, treatment interruption, and treatment defaults caused by migrant work might increase the risk for multidrug-resistant TB. PMID:25695488

  13. Fecal Microbiota Transplantation and Successful Resolution of Multidrug-Resistant-Organism Colonization

    PubMed Central

    Sullivan, Eva; Ballon-Landa, Gonzalo

    2015-01-01

    We report a case in which fecal microbiota transplantation (FMT) utilized for relapsing Clostridium difficile colitis successfully eradicated colonization with several multidrug-resistant organisms (MDROs). FMT may have an additive benefit of reducing MDRO carriage and should be further investigated as a potential measure to eradicate additional potentially virulent organisms beyond C. difficile. PMID:25878340

  14. Increased Risk for Multidrug-Resistant Tuberculosis in Migratory Workers, Armenia

    PubMed Central

    Crape, Byron; Grigoryan, Ruzanna; Martirosyan, Hripsime; Petrosyan, Varduhi

    2015-01-01

    To understand use of tuberculosis (TB) services for migrant workers, we conducted a cross-sectional census of 95 migrant workers with TB from Armenia by using medical record reviews and face-to-face interviews. Prolonged time between diagnosis and treatment, treatment interruption, and treatment defaults caused by migrant work might increase the risk for multidrug-resistant TB. PMID:25695488

  15. ACSSuT Multi-Drug Resistance Among Salmonella Isolates of Animal Origin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Multi-drug resistant (MDR) Salmonella Typhimurium DT104 (DT104) emerged in the mid-1990’s in humans and animals with infection resulting in increased morbidity and mortality. DT104 was characterized by resistance to Ampicillin, Chloramphenicol, Streptomycin, Sulfa, and Tetracycline (AC...

  16. Fatal skin and soft tissue infection of multidrug resistant Acinetobacter baumannii: A case report

    PubMed Central

    Ali, Aqsa; Botha, John; Tiruvoipati, Ravindranath

    2014-01-01

    INTRODUCTION Acinetobacter baumannii is usually associated with respiratory tract, urinary tract and bloodstream infections. Recent reports suggest that it is increasingly causing skin and soft tissue infections. It is also evolving as a multidrug resistant organism that can be difficult to treat. We present a fatal case of multidrug resistant A. baumannii soft tissue infection and review of relevant literature. PRESENTATION OF CASE A 41 year old morbidly obese man, with history of alcoholic liver disease presented with left superficial pre-tibial abrasions and cellulitis caused by multidrug resistant (MDR) A. baumannii. In spite of early antibiotic administration he developed extensive myositis and fat necrosis requiring extensive and multiple surgical debridements. He deteriorated despite appropriate antibiotic therapy and multiple surgical interventions with development of multi-organ failure and died. DISCUSSION Managing Acinetobacter infections remains difficult due to the array of resistance and the pathogens ability to develop new and ongoing resistance. The early diagnosis of necrotizing soft tissue infection may be challenging, but the key to successful management of patients with necrotizing soft tissue infection are early recognition and complete surgical debridement. CONCLUSION A. baumannii is emerging as an important cause of severe, life-threatening soft tissue infections. Multidrug resistant A. baumannii soft tissue infections may carry a high mortality in spite of early and aggressive treatment. Clinicians need to consider appropriate early empirical antibiotic coverage or the use of combination therapy to include MDR A. baumannii as a cause of skin and soft tissue infections. PMID:25016080

  17. Whole-Genome Sequence of a Multidrug-Resistant Clinical Isolate of Acinetobacter lwoffii▿

    PubMed Central

    Hu, Yongfei; Zhang, Wei; Liang, Hui; Liu, Liping; Peng, Guojun; Pan, Yuanlong; Yang, Xi; Zheng, Beiwen; Gao, George F.; Zhu, Baoli; Hu, Hongyan

    2011-01-01

    Acinetobacter lwoffii has been considered an opportunistic pathogen that can cause nosocomial infections in humans. Here, we present the genome sequence of A. lwoffii WJ10621, a multidrug-resistant clinical isolate that carries a plasmid with the NDM-1 resistance gene. PMID:21742884

  18. [Coxitis due to multidrug resistant Mycobacterium tuberculosis in a HIV negative patient].

    PubMed

    Palmero, D J; Simboli, N; Alberti, F A; Francos, J L; Güemes Gurtubay, J L; Ochoa, E J; Cardozo, L; Waisman, J L

    2000-01-01

    A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrug-resistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed. PMID:11050817

  19. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    PubMed

    Hameed, Saif; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Goswami, Shyamal K; Prasad, Rajendra

    2011-01-01

    We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR), however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS) based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25) and sphingolipid biosynthesis (AUR1 and SCS7) genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron deprived Candida

  20. Intrinsic Conformational Plasticity of Native EmrE Provides a Pathway for Multidrug Resistance

    PubMed Central

    2015-01-01

    EmrE is a multidrug resistance efflux pump with specificity to a wide range of antibiotics and antiseptics. To obtain atomic-scale insight into the attributes of the native state that encodes the broad specificity, we used a hybrid of solution and solid-state NMR methods in lipid bilayers and bicelles. Our results indicate that the native EmrE dimer oscillates between inward and outward facing structural conformations at an exchange rate (kex) of ∼300 s–1 at 37 °C (millisecond motions), which is ∼50-fold faster relative to the tetraphenylphosphonium (TPP+) substrate-bound form of the protein. These observables provide quantitative evidence that the rate-limiting step in the TPP+ transport cycle is not the outward–inward conformational change in the absence of drug. In addition, using differential scanning calorimetry, we found that the width of the gel-to-liquid crystalline phase transition was 2 °C broader in the absence of the TPP+ substrate versus its presence, which suggested that changes in transporter dynamics can impact the phase properties of the membrane. Interestingly, experiments with cross-linked EmrE showed that the millisecond inward-open to outward-open dynamics was not the culprit of the broadening. Instead, the calorimetry and NMR data supported the conclusion that faster time scale structural dynamics (nanosecond–microsecond) were the source and therefore impart the conformationally plastic character of native EmrE capable of binding structurally diverse substrates. These findings provide a clear example how differences in membrane protein transporter structural dynamics between drug-free and bound states can have a direct impact on the physical properties of the lipid bilayer in an allosteric fashion. PMID:24856154

  1. Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells.

    PubMed

    Mapoung, Sariya; Pitchakarn, Pornsiri; Yodkeeree, Supachai; Ovatlarnporn, Chitchamai; Sakorn, Natee; Limtrakul, Pornngarm

    2016-01-25

    Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies. PMID:26689174

  2. Multidrug Resistant CTX-M-Producing Escherichia coli: A Growing Threat among HIV Patients in India

    PubMed Central

    Padmavathy, Kesavaram; Padma, Krishnan; Rajasekaran, Sikhamani

    2016-01-01

    Extended Spectrum β-Lactamases (ESBLs) confer resistance to third-generation cephalosporins and CTX-M types have emerged as the most prominent ESBLs worldwide. This study was designed to determine the prevalence of CTX-M positive ESBL-producing urinary E. coli isolates from HIV patients and to establish the association of multidrug resistance, phylogeny, and virulence profile with CTX-M production. A total of 57 ESBL producers identified among 76 E. coli strains isolated from HIV patients from South India were screened for blaCTX-M, AmpC production, multidrug resistance, and nine virulence associated genes (VAGs), fimH, pap, afa/dra, sfa/foc, iutA, fyuA, iroN, usp, and kpsMII. The majority (70.2%) of the ESBL producers harbored blaCTX-M and were AmpC coproducers. Among the CTX-M producers, 47.5% were found to be UPEC, 10% harbored as many as 7 VAGs, and 45% possessed kpsMII. Multidrug resistance (CIPRSXTRGENR) was significantly more common among the CTX-M producers compared to the nonproducers (70% versus 41.2%). However, 71.4% of the multidrug resistant CTX-M producers exhibited susceptibility to nitrofurantoin thereby making it an effective alternative to cephalosporins/fluoroquinolones. The emergence of CTX-M-producing highly virulent, multidrug resistant uropathogenic E. coli is of significant public health concern in countries like India with a high burden of HIV/AIDS. PMID:27123344

  3. In vivo uptake of carbon-14-colchicine for identification of tumor multidrug resistance

    SciTech Connect

    Mehta, B.M.; Rosa, E.; Biedler, J.L.

    1994-07-01

    A major limitation in the treatment of cancer with natural product chemotherapeutic agents is the development of multidrug resistance (MDR). Multidrug resistance is attributed to enhanced expression of the multidrug resistance gene MDR1. Colchicine (CHC) is known to be one of the MDR drugs. The authors have previously demonstrated that it is possible to distinguish multidrug resistant tumors from the multidrug-sensitive tumors in vivo on the basis of tritium ({sup 3}H) uptake following injection of {sup 3}H-CHC. The present studies were carried out in xenografted animals using {sup 14}C-CHC which may be more indicative of {sup 11}C-labeled CHC distribution with regard to circulating metabolites, since metabolic processes following injection of (ring C, methoxy-{sup 11}C)-CHC may produce significant amounts of circulating 1l-carbon fragments (i.e., methanol and/or formaldehyde). Experiments were carried out at a dose of 2 mg/kg. Activity concentration per injected dose was approximately twice as great in sensitive as in resistant tumors (p < 0.05) at 60 min following intravenous injection of {sup 14}C-CHC. About 75% of total activity was CHC in the sensitive tumors. The findings are further confirmed by the quantitative autoradiographic evaluation of resistant and sensitive tumors. These studies confirm our previous observations that it is possible to noninvasively distinguish multidrug-resistant tumors from sensitive tumors in vivo based on uptake of an injected MDR drug using a{sup 14}C-labeled CHC at the same position and of comparable specific activity to a {sup 11}C-CHC tracer used for PET imaging. 16 refs., 5 figs., 2 tabs.

  4. Multidrug Resistant CTX-M-Producing Escherichia coli: A Growing Threat among HIV Patients in India.

    PubMed

    Padmavathy, Kesavaram; Padma, Krishnan; Rajasekaran, Sikhamani

    2016-01-01

    Extended Spectrum β-Lactamases (ESBLs) confer resistance to third-generation cephalosporins and CTX-M types have emerged as the most prominent ESBLs worldwide. This study was designed to determine the prevalence of CTX-M positive ESBL-producing urinary E. coli isolates from HIV patients and to establish the association of multidrug resistance, phylogeny, and virulence profile with CTX-M production. A total of 57 ESBL producers identified among 76 E. coli strains isolated from HIV patients from South India were screened for bla CTX-M, AmpC production, multidrug resistance, and nine virulence associated genes (VAGs), fimH, pap, afa/dra, sfa/foc, iutA, fyuA, iroN, usp, and kpsMII. The majority (70.2%) of the ESBL producers harbored bla CTX-M and were AmpC coproducers. Among the CTX-M producers, 47.5% were found to be UPEC, 10% harbored as many as 7 VAGs, and 45% possessed kpsMII. Multidrug resistance (CIP(R)SXT(R)GEN(R)) was significantly more common among the CTX-M producers compared to the nonproducers (70% versus 41.2%). However, 71.4% of the multidrug resistant CTX-M producers exhibited susceptibility to nitrofurantoin thereby making it an effective alternative to cephalosporins/fluoroquinolones. The emergence of CTX-M-producing highly virulent, multidrug resistant uropathogenic E. coli is of significant public health concern in countries like India with a high burden of HIV/AIDS. PMID:27123344

  5. An Autocrine Cytokine/JAK/STAT-Signaling Induces Kynurenine Synthesis in Multidrug Resistant Human Cancer Cells

    PubMed Central

    Campia, Ivana; Buondonno, Ilaria; Castella, Barbara; Rolando, Barbara; Kopecka, Joanna; Gazzano, Elena; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    Background Multidrug resistant cancer cells are hard to eradicate for the inefficacy of conventional anticancer drugs. Besides escaping the cytotoxic effects of chemotherapy, they also bypass the pro-immunogenic effects induced by anticancer drugs: indeed they are not well recognized by host dendritic cells and do not elicit a durable anti-tumor immunity. It has not yet been investigated whether multidrug resistant cells have a different ability to induce immunosuppression than chemosensitive ones. We addressed this issue in human and murine chemosensitive and multidrug resistant cancer cells. Results We found that the activity and expression of indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the conversion of tryptophan into the immunosuppressive metabolite kynurenine, was higher in all the multidrug resistant cells analyzed and that IDO1 inhibition reduced the growth of drug-resistant tumors in immunocompetent animals. In chemoresistant cells the basal activity of JAK1/STAT1 and JAK1/STAT3 signaling was higher, the STAT3 inhibitor PIAS3 was down-regulated, and the autocrine production of STAT3-target and IDO1-inducers cytokines IL-6, IL-4, IL-1β, IL-13, TNF-α and CD40L, was increased. The disruption of the JAK/STAT signaling lowered the IDO1 activity and reversed the kynurenine-induced pro-immunosuppressive effects, as revealed by the restored proliferation of T-lymphocytes in STAT-silenced chemoresistant cells. Conclusions Our work shows that multidrug resistant cells have a stronger immunosuppressive attitude than chemosensitive cells, due to the constitutive activation of the JAK/STAT/IDO1 axis, thus resulting chemo- and immune-evasive. Disrupting this axis may significantly improve the efficacy of chemo-immunotherapy protocols against resistant tumors. PMID:25955018

  6. A Small Multidrug Resistance-like Transporter Involved in the Arabinosylation of Arabinogalactan and Lipoarabinomannan in Mycobacteria*

    PubMed Central

    Larrouy-Maumus, Gérald; Škovierová, Henrieta; Dhouib, Rabeb; Angala, Shiva Kumar; Zuberogoitia, Sophie; Pham, Ha; Villela, Anne Drumond; Mikušová, Katarina; Noguera, Audrey; Gilleron, Martine; Valentínová, Lucia; Korduláková, Jana; Brennan, Patrick. J.; Puzo, Germain; Nigou, Jérôme; Jackson, Mary

    2012-01-01

    The biosynthesis of the major cell envelope glycoconjugates of Mycobacterium tuberculosis is topologically split across the plasma membrane, yet nothing is known of the transporters required for the translocation of lipid-linked sugar donors and oligosaccharide intermediates from the cytoplasmic to the periplasmic side of the membrane in mycobacteria. One of the mechanisms used by prokaryotes to translocate lipid-linked phosphate sugars across the plasma membrane relies on translocases that share resemblance with small multidrug resistance transporters. The presence of an small multidrug resistance-like gene, Rv3789, located immediately upstream from dprE1/dprE2 responsible for the formation of decaprenyl-monophosphoryl-β-d-arabinose (DPA) in the genome of M. tuberculosis led us to investigate its potential involvement in the formation of the major arabinosylated glycopolymers, lipoarabinomannan (LAM) and arabinogalactan (AG). Disruption of the ortholog of Rv3789 in Mycobacterium smegmatis resulted in a reduction of the arabinose content of both AG and LAM that accompanied the accumulation of DPA in the mutant cells. Interestingly, AG and LAM synthesis was restored in the mutant not only upon expression of Rv3789 but also upon that of the undecaprenyl phosphate aminoarabinose flippase arnE/F genes from Escherichia coli. A bacterial two-hybrid system further indicated that Rv3789 interacts in vivo with the galactosyltransferase that initiates the elongation of the galactan domain of AG. Biochemical and genetic evidence is thus consistent with Rv3789 belonging to an AG biosynthetic complex, where its role is to reorient DPA to the periplasm, allowing this arabinose donor to then be used in the buildup of the arabinan domains of AG and LAM. PMID:23038254

  7. Antibacterial and antibiotic-potentiation activities of the methanol extract of some cameroonian spices against Gram-negative multi-drug resistant phenotypes

    PubMed Central

    2012-01-01

    Background The present work was designed to evaluate the antibacterial properties of the methanol extracts of eleven selected Cameroonian spices on multi-drug resistant bacteria (MDR), and their ability to potentiate the effect of some common antibiotics used in therapy. Results The extract of Cinnamomum zeylanicum against Escherichia coli ATCC 8739 and AG100 strains showed the best activities, with the lowest minimal inhibitory concentration (MIC) of 64 μg/ml. The extract of Dorstenia psilurus was the most active when tested in the presence of an efflux pump inhibitor, phenylalanine Arginine-β- Naphtylamide (PAβN), a synergistic effect being observed in 56.25 % of the tested bacteria when it was combined with Erythromycin (ERY). Conclusion The present work evidently provides information on the role of some Cameroonian spices in the fight against multi-resistant bacteria. PMID:22709668

  8. An oligonucleotide microarray to characterize multidrug resistant plasmids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteria plasmids are fragments of extra-chromosomal double stranded deoxyribonucleic acid (DNA) that can contain a variety of genes beneficial to the host organism like antibiotic drug resistance. Many of the Enterobacteriaceae carry multiple drug resistance (MDR) genes on large plasmids of replic...

  9. Identification and characterization of a Streptomyces sp. isolate exhibiting activity against multidrug-resistant coagulase-negative Staphylococci.

    PubMed

    Sadigh-Eteghad, Saeed; Dehnad, Alireza; Shanebandi, Dariush; Khalili, Iraj; Razmarayii, Nasser; Namvaran, Ali

    2011-12-01

    The resistance of 220 coagulase-negative Staphylococci (CNS) (associated with animal disease) to 13 antibiotics were determined using the disk diffusion method. 35.9% of multidrug-resistant coagulase-negative Staphylococci (MR-CNS) exhibited resistance to five or more than five antibiotics; all of these bacteria were resistant to methicillin too. The new Streptomyces sp. ABRIINW111 was isolated from the Zagros Mountains Hamadan, Iran. The 16S rDNA sequence of the isolate indicated that it has 98% similarity to S. levis, but some mutations in the alpha and gamma regions of the 16S rDNA sequence emphasize the probability of the existence of a new species. Preliminary and secondary antibacterial screenings revealed that the isolate is active against gram negative and positive bacteria. The diethyl ether extracted metabolite of the Streptomyces sp. ABRIINW111 showed an effective antibacterial activity against MR-CNS. So the diethyl ether extract of the new Streptomyces sp. strain ABRIINW111 can inhibit the MR-CNS in vitro, and it can offer a new approach to treat MR-CNS infectious patients. PMID:21744110

  10. Presence of Multidrug-Resistant Shiga Toxin-Producing Escherichia coli, Enteropathogenic E. coli and Enterotoxigenic E. coli, on Raw Nopalitos (Opuntia ficus-indica L.) and in Nopalitos Salads from Local Retail Markets in Mexico.

    PubMed

    Gómez-Aldapa, Carlos A; Cerna-Cortes, Jorge F; Rangel-Vargas, Esmeralda; Torres-Vitela, Mdel Refugio; Villarruel-López, Angelica; Gutiérrez-Alcántara, Eduardo J; Castro-Rosas, Javier

    2016-05-01

    The presence of multidrug-resistant pathogenic bacteria in food is a significant public health concern. Diarrheagenic Escherichia coli pathotypes (DEPs) are foodborne bacteria. In Mexico, DEPs have been associated with diarrheal illness. There is no information about the presence of multidrug-resistant DEPs on fresh vegetables and in cooked vegetable salads in Mexico. "Nopalitos" (Opuntia ficus-indica L.) is a Cactacea extensively used as a fresh green vegetable throughout Mexico. The presence of generic E. coli and multidrug-resistant DEPs on raw whole and cut nopalitos and in nopalitos salad samples was determined. One hundred raw whole nopalitos (without prickles) samples, 100 raw nopalitos cut into small square samples, and 100 cooked nopalitos salad samples were collected from markets. Generic E. coli was determined using the most probable number procedures. DEPs were identified using two multiplex polymerase chain reaction procedures. Susceptibility to 16 antibiotics was tested for the isolated DEP strains by standard test. Of the 100 whole nopalitos samples, 100 cut nopalitos samples, and 100 nopalitos salad samples, generic E. coli and DEPs were identified, respectively, in 80% and 10%, 74% and 10%, and 64% and 8%. Eighty-two DEP strains were isolated from positive nopalitos samples. The identified DEPs included Shiga toxin-producing E. coli (STEC), enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). All isolated strains exhibited resistance to at least six antibiotics. To the best of our knowledge, this is the first report of the presence of multidrug-resistant and antibiotic resistance profiles of STEC, ETEC, and EPEC on raw nopalitos and in nopalitos salads in Mexico. PMID:26954710

  11. [Epidemiology of multi-drug resistant gramnegative bacilli].

    PubMed

    Ruiz-Garbajosa, P; Cantón, R

    2016-09-01

    Current antimicrobial resistance in Gram negative bacilli is particularly worrisome due to development of resistance to all available antimicrobial agents. This situation dramatically limits therapeutic options. The microorganisms acquire a multiresistance phenotype as a consequence of different complex processes in which the antimicrobials acts as selective driver of resistance. Dissemination of multiresistant bacteria is driven by the expansion of the high-risk clones. These clones can be selected in the presence of antimicrobials allowing their persistence over time. PMID:27608308

  12. Bundled strategies against infection after liver transplantation: Lessons from multidrug-resistant Pseudomonas aeruginosa.

    PubMed

    Sato, Asahi; Kaido, Toshimi; Iida, Taku; Yagi, Shintaro; Hata, Koichiro; Okajima, Hideaki; Takakura, Shunji; Ichiyama, Satoshi; Uemoto, Shinji

    2016-04-01

    Infection is a life-threatening complication after liver transplantation (LT). A recent outbreak of multidrug-resistant Pseudomonas aeruginosa triggered changes in our infection control measures. This study investigated the usefulness of our bundled interventions against postoperative infection after LT. This before-and-after analysis enrolled 130 patients who underwent living donor or deceased donor LT between January 2011 and October 2014. We initiated 3 measures after January 2013: (1) we required LT candidates to be able to walk independently; (2) we increased the hand hygiene compliance rate and contact precautions; and (3) we introduced procalcitonin (PCT) measurement for a more precise determination of empirical antimicrobial treatment. We compared factors affecting the emergence of drug-resistant microorganisms, such as the duration of antimicrobial and carbapenem therapy and hospital stay, and outcomes such as bacteremia and death from infection between before (n = 77) and after (n = 53) the LT suspension period. The utility of PCT measurement was also evaluated. Patients' backgrounds were not significantly different before and after the protocol revision. Incidence of bacteremia (44% versus 25%; P = 0.02), detection rate of multiple bacteria (18% versus 4%; P = 0.01), and deaths from infections (12% versus 2%; P =  0.04) significantly decreased after the protocol revision. Duration of antibiotic (42.3 versus 25.1 days; P =  0.002) and carbapenem administration (15.1 versus 5.2 days; P < 0.001) and the length of postoperative hospital stay (85.4 versus 63.5 days; P =  0.048) also decreased after the protocol revision. PCT mean values were significantly higher in the bacteremia group (10.10 ng/mL), compared with the uneventful group (0.65 ng/mL; P =  0.002) and rejection group (2.30 ng/mL; P =  0.02). One-year overall survival after LT significantly increased in the latter period (71% versus 94%; P =  0

  13. Synthesis and study of cytotoxic activity of 1,2,4-trioxane- and egonol-derived hybrid molecules against Plasmodium falciparum and multidrug-resistant human leukemia cells.

    PubMed

    Reiter, Christoph; Capcı Karagöz, Aysun; Fröhlich, Tony; Klein, Volker; Zeino, Maen; Viertel, Katrin; Held, Jana; Mordmüller, Benjamin; Emirdağ Öztürk, Safiye; Anıl, Hüseyin; Efferth, Thomas; Tsogoeva, Svetlana B

    2014-03-21

    Malaria and cancer cause the death of millions of people every year. To combat these two diseases, it is important that new pharmaceutically active compounds have the ability to overcome multidrug resistance in cancer and Plasmodium falciparum strains. In search of effective anti-cancer and anti-malaria hybrids that possess improved properties compared to their parent compounds, a series of novel 1,2,4-trioxane-based hybrids incorporating egonol and/or ferrocene fragments were synthesized and tested in vitro against P. falciparum strains, CCRF-CEM cells and the multidrug-resistant P-glycoprotein-over-expressing CEM/ADR5000 cells. The most active compounds against P. falciparum strains were artesunic acid homodimers 12 and 13 (IC50 of 0.32 and 0.30 nM, respectively), whereas novel hybrids 7 (1,2,4-trioxane-ferrocene-egonol), 9 (1,2,4-trioxane-ferrocene) and 11 (artesunic acid-egonol) showed a remarkable cytotoxicity toward CCRF-CEM cells (IC50 of 0.07, 0.25 and 0.18 μM, respectively). A cooperative and synergistic effect of the three moieties 1,2,4-trioxane, ferrocene and egonol in hybrid molecule 7 is significant and is obviously stronger than in hybrids 9 (1,2,4-trioxane-ferrocene) and 11 (artesunic acid-egonol), which comprises of only two of the three considered parent compounds. Interestingly, hybrid 9 containing a 1,2,4-trioxane and a ferrocene fragment has shown to be the most effective among the studied hybrids against the tested multidrug-resistant leukemia CEM/ADR5000 cells (IC50 of 0.57 μM) and possesses a degree of cross-resistance of 2.34. PMID:24561670

  14. Characterization of multidrug-resistant Escherichia coli by antimicrobial resistance profiles, plasmid replicon typing, and pulsed-field gel electrophoresis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: Plasmid characterization has particular clinical importance because genes encoding significant traits including antimicrobial resistance are frequently carried on plasmids. The objective of this study was to examine the distribution of multidrug resistance (MDR) in Escherichia coli in relation ...

  15. Bactericidal Monoclonal Antibodies Specific to the Lipopolysaccharide O Antigen from Multidrug-Resistant Escherichia coli Clone ST131-O25b:H4 Elicit Protection in Mice

    PubMed Central

    Szijártó, Valéria; Guachalla, Luis M.; Visram, Zehra C.; Hartl, Katharina; Varga, Cecília; Mirkina, Irina; Zmajkovic, Jakub; Badarau, Adriana; Zauner, Gerhild; Pleban, Clara; Magyarics, Zoltán; Nagy, Eszter

    2015-01-01

    The Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-resistant extraintestinal infections. We generated humanized monoclonal antibodies (MAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These MAbs bound to the surface of live bacterial cells irrespective of the capsular type expressed. In a serum bactericidal assay in vitro, MAbs induced >95% bacterial killing in the presence of human serum as the complement source. Protective efficacy at low antibody doses was observed in a murine model of bacteremia. The mode of action in vivo was investigated by using aglycosylated derivatives of the protective MAbs. The significant binding to live E. coli cells and the in vitro and in vivo efficacy were corroborated in assays using bacteria grown in human serum to mimic relevant clinical conditions. Given the dry pipeline of novel antibiotics against multidrug-resistant Gram-negative pathogens, passive immunization with bactericidal antibodies offers a therapeutic alternative to control infections caused by E. coli ST131-O25b:H4. PMID:25779571

  16. Isolation and characterization of a bacteriophage phiEap-2 infecting multidrug resistant Enterobacter aerogenes

    PubMed Central

    Li, Erna; Wei, Xiao; Ma, Yanyan; Yin, Zhe; Li, Huan; Lin, Weishi; Wang, Xuesong; Li, Chao; Shen, Zhiqiang; Zhao, Ruixiang; Yang, Huiying; Jiang, Aimin; Yang, Wenhui; Yuan, Jing; Zhao, Xiangna

    2016-01-01

    Enterobacter aerogenes (Enterobacteriaceae) is an important opportunistic pathogen that causes hospital-acquired pneumonia, bacteremia, and urinary tract infections. Recently, multidrug-resistant E. aerogenes have been a public health problem. To develop an effective antimicrobial agent, bacteriophage phiEap-2 was isolated from sewage and its genome was sequenced because of its ability to lyse the multidrug-resistant clinical E. aerogenes strain 3-SP. Morphological observations suggested that the phage belongs to the Siphoviridae family. Comparative genome analysis revealed that phage phiEap-2 is related to the Salmonella phage FSL SP-031 (KC139518). All of the structural gene products (except capsid protein) encoded by phiEap-2 had orthologous gene products in FSL SP-031 and Serratia phage Eta (KC460990). Here, we report the complete genome sequence of phiEap-2 and major findings from the genomic analysis. Knowledge of this phage might be helpful for developing therapeutic strategies against E. aerogenes. PMID:27320081

  17. 20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

    PubMed

    Liu, Junhua; Wang, Xu; Liu, Peng; Deng, Rongxin; Lei, Min; Chen, Wantao; Hu, Lihong

    2013-07-15

    Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. PMID:23683834

  18. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain

    PubMed Central

    Eldholm, Vegard; Monteserin, Johana; Rieux, Adrien; Lopez, Beatriz; Sobkowiak, Benjamin; Ritacco, Viviana; Balloux, Francois

    2015-01-01

    The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally. PMID:25960343

  19. Molecular modeling of the human multidrug resistance protein 1 (MRP1/ABCC1)

    SciTech Connect

    DeGorter, Marianne K.; Conseil, Gwenaelle; Deeley, Roger G.; Campbell, Robert L.; Cole, Susan P.C.

    2008-01-04

    Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to elucidate its transport mechanism, but only low resolution structural data are currently available. Consequently, comparative modeling has been used to generate models of human MRP1 based on the crystal structure of the ABC transporter Sav1866 from Staphylococcus aureus. In these Sav1866-based models, the arrangement of transmembrane helices differs strikingly from earlier models of MRP1 based on the structure of the bacterial lipid transporter MsbA, both with respect to packing of the twelve helices and their interactions with the nucleotide binding domains. The functional importance of Tyr{sup 324} in transmembrane helix 6 predicted to project into the substrate translocation pathway was investigated.

  20. Isolation and characterization of a bacteriophage phiEap-2 infecting multidrug resistant Enterobacter aerogenes.

    PubMed

    Li, Erna; Wei, Xiao; Ma, Yanyan; Yin, Zhe; Li, Huan; Lin, Weishi; Wang, Xuesong; Li, Chao; Shen, Zhiqiang; Zhao, Ruixiang; Yang, Huiying; Jiang, Aimin; Yang, Wenhui; Yuan, Jing; Zhao, Xiangna

    2016-01-01

    Enterobacter aerogenes (Enterobacteriaceae) is an important opportunistic pathogen that causes hospital-acquired pneumonia, bacteremia, and urinary tract infections. Recently, multidrug-resistant E. aerogenes have been a public health problem. To develop an effective antimicrobial agent, bacteriophage phiEap-2 was isolated from sewage and its genome was sequenced because of its ability to lyse the multidrug-resistant clinical E. aerogenes strain 3-SP. Morphological observations suggested that the phage belongs to the Siphoviridae family. Comparative genome analysis revealed that phage phiEap-2 is related to the Salmonella phage FSL SP-031 (KC139518). All of the structural gene products (except capsid protein) encoded by phiEap-2 had orthologous gene products in FSL SP-031 and Serratia phage Eta (KC460990). Here, we report the complete genome sequence of phiEap-2 and major findings from the genomic analysis. Knowledge of this phage might be helpful for developing therapeutic strategies against E. aerogenes. PMID:27320081

  1. Role of tipranavir in treatment of patients with multidrug-resistant HIV

    PubMed Central

    Courter, Joshua D; Teevan, Colleen J; Li, Michael H; Girotto, Jennifer E; Salazar, Juan C

    2010-01-01

    The worldwide emergence of multidrug-resistant human immunodeficiency virus (HIV)-1 strains has the driven the development of new antiretroviral (ARV) agents. Over the past 5 years, HIV-entry and integrase inhibitor ARVs, as well as improved non-nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), have become available for treatment. It is important to assess how these new ARVs might be most judiciously used, paying close attention to viral susceptibility patterns, pharmacodynamic parameters, and the likelihood that patients will adhere to their therapy. Herein we review published material in Medline, EMBASE, and ISI for each antiretroviral agent/classes currently approved and summarize the available data on their efficacy, safety, and pharmacologic parameters. We focus on the role of tipranavir, a recently approved nonpeptidic PI, for treating HIV-infected children, adolescents, and adults with a history of multidrug-resistant HIV. PMID:20957134

  2. [AA-type amyloidosis secondary to multidrug resistant pulmonary tuberculosis: implications for therapy].

    PubMed

    Baux, E; Henard, S; Alauzet, C; Goehringer, F; Laurain, C; Champigneulle, J; Vaillant, P; Hardy, A; Rabaud, C; May, T

    2015-10-01

    Multidrug resistant pulmonary tuberculosis was diagnosed to a 32-year-old man. An AA-amyloidosis was subsequently diagnosed on the renal biopsy performed for nephrotic syndrome and macroscopic hematuria. A 6-drug antibiotic treatment was delivered quickly after first results of genotypic antibiogram given the renal failure, and was secondarily adapted to the phenotypic antibiogram. Multidrug therapy was fairly well tolerated. Clinical and biological improving were slow. Although tuberculosis is a classic cause of amyloidosis, this is the first case reporting an association between a multidrug resistant case and an amyloidosis in adults. This case also raises the question of MDR probabilistic treatments in situations whether a vital organ prognosis is engaged. PMID:26198876

  3. Novel type of Streptococcus pneumoniae causing multidrug-resistant acute otitis media in children.

    PubMed

    Xu, Qingfu; Pichichero, Michael E; Casey, Janet R; Zeng, Mingtao

    2009-04-01

    After our recent discovery of a Streptococcus pneumoniae 19A "superbug" (Legacy strain) that is resistant to all Food and Drug Administration-approved antimicrobial drugs for treatment of acute otitis media (AOM) in children, other S. pneumoniae isolates from children with AOM were characterized by multilocus sequence typing (MLST). Among 40 isolates studied, 16 (40%) were serotype 19A, and 9 (23%) were resistant to multiple antimicrobial drugs. Two others had unreported sequence types (STs) that expressed the 19A capsule, and 8 (88%) of the 9 multidrug-resistant strains were serotype 19A, including the Legacy strain with the new ST-2722. In genetic relatedness, ST-2722 belonged to a cluster of reported strains of S. pneumoniae in which all strains had 6 of the same alleles as ST-156. The multidrug-resistant strains related to ST-156 expressed different capsular serotypes: 9V, 14, 11A, 15C, and 19F. PMID:19331730

  4. Primary Extrapulmonary Multidrug-Resistant Tuberculosis of the Sternum without HIV Infection

    PubMed Central

    Rawal, Gautam

    2016-01-01

    Skeletal tuberculosis (TB) accounts for about 9% of all TB cases. Tuberculosis of the sternum is not a common presentation. The case of primary multidrug-resistant (MDR) TB of the sternum is even rare. So far no such case has been reported in the medical literature. Herein, we present the very first case of primary extrapulmonary MDR TB of the sternum in a 21-year-old immunocompetent Indian female who presented with chest pain and an increased swelling over the anterior chest with an intermittently discharging sinus. She was diagnosed with multidrug-resistant tuberculosis of the sternum without the active pulmonary disease. Conservative management with oral multidrug antitubercular therapy (ATT) completely cured the patient. PMID:26894135

  5. Meayamycin Inhibits pre-mRNA Splicing and Exhibits Picomolar Activity Against Multidrug Resistant Cells

    PubMed Central

    Albert, Brian J.; McPherson, Peter A.; O'Brien, Kristine; Czaicki, Nancy L.; DeStefino, Vincent; Osman, Sami; Li, Miaosheng; Day, Billy W.; Grabowski, Paula J.; Moore, Melissa J.; Vogt, Andreas; Koide, Kazunori

    2009-01-01

    FR901464 is a potent antitumor natural product that binds to the SF3b complex and inhibits pre-mRNA splicing. Its analogue, meayamycin, is two orders of magnitude more potent as an antiproliferative agent against human breast cancer MCF-7 cells. Here, we report the picomolar antiproliferative activity of meayamycin against various cancer cell lines and multidrug resistant cells. Time-dependence studies implied that meayamycin may form a covalent bond with its target protein(s). Meayamycin inhibited pre-mRNA splicing in HEK-293 cells but not alternative splicing in a neuronal system. Meayamycin exhibited specificity toward human lung cancer cells compared to non-tumorigenic human lung fibroblasts and retained picomolar growth inhibitory activity against multi-drug resistant cells. These data suggest that meayamycin is a useful chemical probe to study pre-mRNA splicing in live cells and is a promising lead as an anticancer agent. PMID:19671752

  6. Jatrophane diterpenoid esters from Euphorbia sororia serving as multidrug resistance reversal agents.

    PubMed

    Lu, Dongli; Liu, Yongqiang; Aisa, Haji Akber

    2014-01-01

    Six (1-6) new jatrophane diterpenoid esters together with four known compounds (7-10) were isolated from the acetone extract of fructus Euphorbia sororia. Their structures were elucidated by the spectral technology, including the 2D NMR experiments (HMQC, HMBC and NOESY). The absolute configuration of compound 1 and compound 7 were first confirmed by X-ray crystallographic analysis. Compounds 1-7 were assayed for their antiproliferative activity in human cancer cell lines: human mammary adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549). All the compounds were inactive for the cell lines. The multidrug-resistance reversal activity was also tested on KBv200 cells and compound 2 displayed strong multidrug resistance reversal activity, outperforming verapamil at 10 μM. PMID:24291755

  7. A Case of Disseminated Multidrug-Resistant Tuberculosis involving the Brain

    PubMed Central

    Chang, Ji Young; Lee, Yoon Pyo; Chung, Min Kyung; Seo, Eui Kyo; Koo, Hea Soo

    2016-01-01

    We report a case of a 23-year-old female immigrant from China who was diagnosed with multidrug-resistant tuberculosis affecting her lung and brain, resistant to the standard first-line therapeutics and streptomycin. She was treated with prothionamide, moxifloxacin, cycloserine, and kanamycin. However, her headache and brain lesion worsened. After the brain biopsy, the patient was confirmed with intracranial tuberculoma. Linezolid was added to intensify the treatment regimen, and steroid was added for the possibility of paradoxical response. Kanamycin was discontinued 6 months after initiation of the treatment; she was treated for 18 months with susceptible drugs and completely recovered. To our knowledge, this case is the first multidrug-resistant tuberculosis that disseminated to the brain in Korea. PMID:27104015

  8. AIDS and multidrug-resistant tuberculosis: an epidemic transforms an old disease.

    PubMed

    Farley, T A

    1992-08-01

    Since 1985, tuberculosis case counts in the United States have increased, primarily because of the influence of the HIV epidemic. In addition, during this time outbreaks of multidrug-resistant tuberculosis among patients with AIDS or HIV infection have been reported in New York City and Florida. These outbreaks have occurred in hospitals and prisons and have been characterized by high case fatality rates, disease transmission within the institutions, and high infection rates in health care workers. The increase in tuberculosis rates and the outbreaks have raised concern that multidrug-resistant tuberculosis could become a widespread problem in the United States. Dealing with tuberculosis in the 1990s will require reconsideration of our current methods of tuberculosis prevention, diagnosis, treatment, and control. PMID:1453093

  9. Outbreak of mastitis in sheep caused by multi-drug resistant Enterococcus faecalis in Sardinia, Italy.

    PubMed

    Sanciu, G; Marogna, G; Paglietti, B; Cappuccinelli, P; Leori, G; Rappelli, P

    2013-03-01

    An outbreak of infective mastitis due to Enterococcus faecalis occurred in an intensive sheep farm in north Sardinia (Italy). E. faecalis, which is only rarely isolated from sheep milk, was unexpectedly found in 22·3% of positive samples at microbiological examination. Forty-five out of the 48 E. faecalis isolates showed the same multi-drug resistance pattern (cloxacillin, streptomycin, kanamycin, clindamycin, oxytetracycline). E. faecalis isolates were analysed by pulsed-field gel electrophoresis, and all 45 multi-drug resistant strains showed an indistinguishable macrorestiction profile, indicating their clonal origin. To our knowledge, this is the first report of an outbreak of mastitis in sheep caused by E. faecalis. PMID:22595402

  10. Molecular characterization of multidrug-resistant Shigella spp. of food origin.

    PubMed

    Ahmed, Ashraf M; Shimamoto, Tadashi

    2015-02-01

    Shigella spp. are the causative agents of food-borne shigellosis, an acute enteric infection. The emergence of multidrug-resistant clinical isolates of Shigella presents an increasing challenge for clinicians in the treatment of shigellosis. Several studies worldwide have characterized the molecular basis of antibiotic resistance in clinical Shigella isolates of human origin, however, to date, no such characterization has been reported for Shigella spp. of food origin. In this study, we characterized the genetic basis of multidrug resistance in Shigella spp. isolated from 1600 food samples (800 meat products and 800 dairy products) collected from different street venders, butchers, retail markets, and slaughterhouses in Egypt. Twenty-four out of 27 Shigella isolates (88.9%) showed multidrug resistance phenotypes to at least three classes of antimicrobials. The multidrug-resistant Shigella spp. were as follows: Shigella flexneri (66.7%), Shigella sonnei (18.5%), and Shigella dysenteriae (3.7%). The highest resistance was to streptomycin (100.0%), then to kanamycin (95.8%), nalidixic acid (95.8%), tetracycline (95.8%), spectinomycin (93.6%), ampicillin (87.5%), and sulfamethoxazole/trimethoprim (87.5%). PCR and DNA sequencing were used to screen and characterize integrons and antibiotic resistance genes. Our results indicated that 11.1% and 74.1% of isolates were positive for class 1 and class 2 integrons, respectively. Beta-lactamase-encoding genes were identified in 77.8% of isolates, and plasmid-mediated quinolone resistance genes were identified in 44.4% of isolates. These data provide useful information to better understand the molecular basis of antimicrobial resistance in Shigella spp. To the best of our knowledge, this is the first report of the molecular characterization of antibiotic resistance in Shigella spp. isolated from food. PMID:25485847

  11. Role of OmpA in the Multidrug Resistance Phenotype of Acinetobacter baumannii

    PubMed Central

    Fàbrega, Anna; Roca, Ignasi; Sánchez-Encinales, Viviana; Vila, Jordi; Pachón, Jerónimo

    2014-01-01

    Acinetobacter baumannii has emerged as a nosocomial pathogen with an increased prevalence of multidrug-resistant strains. The role of the outer membrane protein A (OmpA) in antimicrobial resistance remains poorly understood. In this report, disruption of the ompA gene led to decreased MICs of chloramphenicol, aztreonam, and nalidixic acid. We have characterized, for the first time, the contribution of OmpA in the antimicrobial resistance phenotype of A. baumannii. PMID:24379205

  12. Lab-on-Chip-Based Platform for Fast Molecular Diagnosis of Multidrug-Resistant Tuberculosis

    PubMed Central

    Cabibbe, Andrea M.; Miotto, Paolo; Moure, Raquel; Alcaide, Fernando; Feuerriegel, Silke; Pozzi, Gianni; Nikolayevskyy, Vladislav; Drobniewski, Francis; Niemann, Stefan; Reither, Klaus

    2015-01-01

    We evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistant tuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDRplus assay for Mycobacterium tuberculosis complex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use. PMID:26246486

  13. Effect of honey on multidrug resistant organisms and its synergistic action with three common antibiotics.

    PubMed

    Karayil, S; Deshpande, S D; Koppikar, G V

    1998-01-01

    A total of 15 bacterial strains (7 Pseudomonas & 8 Klebsiella species) isolated from various samples which showed multi-drug resistance were studied to verify in vitro antibacterial action of honey on the principle of Minimum Inhibitory Concentration (MIC) & its synergism with 3 common antibiotics--Gentamicin, Amikacin & Ceftazidime. The MIC of honey with saline for both organisms was found to be 1:2. The synergistic action was seen in the case of Pseudomonas spp. and not with Klebsiella spp. PMID:10703581

  14. Attitudes and perceptions of health care workers in Northeastern Germany about multidrug-resistant organisms.

    PubMed

    Marschall, P; Hübner, N-O; Maletzki, S; Wilke, F; Dittmann, K; Kramer, A

    2016-06-01

    There were 256 health care workers in 39 facilities who were interviewed about their perceptions of the quality of care of patients with and without multidrug-resistant organisms based on a standardized questionnaire. There are remarkable differences in the responses between facility types (acute care hospitals, long-term care hospitals, rehabilitation hospitals, and home care services). Hygiene management must be specifically tailored to the requirements of each facility. PMID:26897700

  15. IMPACT OF SEPSIS CLASSIFICATION AND MULTIDRUG RESISTANCE STATUS ON OUTCOME AMONG PATIENTS TREATED WITH APPROPRIATE THERAPY

    PubMed Central

    Burnham, Jason P.; Lane, Michael A.; Kollef, Marin H.

    2015-01-01

    Objective To assess the impact of sepsis classification and multidrug resistance status on outcome in patients receiving appropriate initial antibiotic therapy. Design A retrospective cohort study. Setting Barnes-Jewish Hospital, a 1250-bed teaching hospital. Patients Individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock that received appropriate initial antimicrobial therapy between June 2009 and December 2013. Interventions Clinical outcomes were compared according to multidrug resistance status, sepsis classification, demographics, severity of illness, comorbidities, and antimicrobial treatment. Measurements and Main Results We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were non-survivors. Mortality increased significantly with increasing severity of sepsis (3.5%, 9.9%, and 28.6%, for sepsis, severe sepsis, and septic shock, respectively, p<0.05). Time to antimicrobial therapy was not significantly associated with outcome. APACHE II was more predictive of mortality than age-adjusted Charlson comorbidity index. Multidrug resistance status did not result in excess mortality. Length of intensive care unit and hospital stay increased with more severe sepsis. In multivariate logistic regression analysis, African-American race, sepsis severity, APACHE II score, solid organ cancer, cirrhosis, and transfer from an outside hospital were all predictors of mortality. Conclusions Our results support sepsis severity, but not multidrug resistance status as being an important predictor of death when all patients receive appropriate initial antibiotic therapy. Future sepsis trials should attempt to provide appropriate antimicrobial therapy and take sepsis severity into careful account when determining outcomes. PMID:25855900

  16. Does Alcohol Consumption during Multidrug-resistant Tuberculosis Treatment Affect Outcome?

    PubMed Central

    Duraisamy, Karthickeyan; Mrithyunjayan, Sunilkumar; Ghosh, Smita; Nair, Sreenivas Achuthan; Balakrishnan, Shibu; Subramoniapillai, Jayasankar; Oeltmann, John E.; Moonan, Patrick K.; Kumar, Ajay M. V.

    2015-01-01

    Rationale India reports the largest number of multidrug-resistant tuberculosis cases in the world; yet, no longitudinal study has assessed factors related to treatment outcomes under programmatic conditions in the public sector. Objectives To describe demographic, clinical, and risk characteristics associated with treatment outcomes for all patients with multidrug-resistant tuberculosis registered in the Revised National Tuberculosis Control Programme, Kerala State, India from January 1, 2009 to June 30, 2010. Methods Cox regression methods were used to calculate adjusted hazard ratios with 95% confidence intervals (CIs) to assess factors associated with an unsuccessful treatment outcome. Measurements and Main Results Of 179 patients with multidrug-resistant tuberculosis registered, 112 (63%) had successful treatment outcomes (77 bacteriologically cured, 35 treatment completed) and 67 (37%) had unsuccessful treatment outcomes (30 died, 26 defaulted, 9 failed treatment, 1 stopped treatment because of drug-related adverse events, and 1 developed extensively drug-resistant tuberculosis). The hazard for unsuccessful outcome was significantly higher among patients who consumed alcohol during treatment (adjusted hazard ratio, 4.3; 95% CI, 1.1–17.6) than those who did not. Persons who consumed alcohol during treatment, on average, missed 18 more intensive-phase doses (95% CI, 13–22) than those who did not. Although many patients had diabetes (33%), were ever smokers (39%), or had low body mass index (47%), these factors were not associated with outcome. Conclusion Overall treatment success was greater than global and national averages; however, outcomes among patients consuming alcohol remained poor. Integration of care for multidrug-resistant tuberculosis and alcoholism should be considered to improve treatment adherence and outcomes. PMID:24735096

  17. Multidrug-resistant Salmonella enterica serotype Typhi, Gulf of Guinea Region, Africa.

    PubMed

    Baltazar, Murielle; Ngandjio, Antoinette; Holt, Kathryn Elizabeth; Lepillet, Elodie; Pardos de la Gandara, Maria; Collard, Jean-Marc; Bercion, Raymond; Nzouankeu, Ariane; Le Hello, Simon; Dougan, Gordon; Fonkoua, Marie-Christine; Weill, François-Xavier

    2015-04-01

    We identified 3 lineages among multidrug-resistant (MDR) Salmonella enterica serotype Typhi isolates in the Gulf of Guinea region in Africa during the 2000s. However, the MDR H58 haplotype, which predominates in southern Asia and Kenya, was not identified. MDR quinolone-susceptible isolates contained a 190-kb incHI1 pST2 plasmid or a 50-kb incN pST3 plasmid. PMID:25811307

  18. A case of acute postoperative keratitis after deep anterior lamellar keratoplasty by multidrug resistant Klebsiella

    PubMed Central

    Bajracharya, Leena; Sharma, Binita; Gurung, Reeta

    2015-01-01

    A healthy lady of 42 years underwent deep anterior lamellar keratoplasty for granular dystrophy. The very next day, it was complicated by development of infectious keratitis. The organism was identified as multidrug resistant Klebsiella pneumoniae. Donor corneal button may be implicated in the transmission of infection in an otherwise uneventful surgery and follow-up. Nosocomial infections are usually severe, rapidly progressive and difficult to treat. Finally, the lady had to undergo therapeutic penetrating keratoplasty for complete resolution of infection. PMID:26044477

  19. Multidrug-Resistant Salmonella enterica Serotype Typhi, Gulf of Guinea Region, Africa

    PubMed Central

    Baltazar, Murielle; Ngandjio, Antoinette; Holt, Kathryn Elizabeth; Lepillet, Elodie; Pardos de la Gandara, Maria; Collard, Jean-Marc; Bercion, Raymond; Nzouankeu, Ariane; Le Hello, Simon; Dougan, Gordon; Fonkoua, Marie-Christine

    2015-01-01

    We identified 3 lineages among multidrug-resistant (MDR) Salmonella enterica serotype Typhi isolates in the Gulf of Guinea region in Africa during the 2000s. However, the MDR H58 haplotype, which predominates in southern Asia and Kenya, was not identified. MDR quinolone-susceptible isolates contained a 190-kb incHI1 pST2 plasmid or a 50-kb incN pST3 plasmid. PMID:25811307

  20. Complexation study and anticellular activity enhancement by doxorubicin-cyclodextrin complexes on a multidrug-resistant adenocarcinoma cell line.

    PubMed

    Al-Omar, A; Abdou, S; De Robertis, L; Marsura, A; Finance, C

    1999-04-19

    Ability of molecular complexes of [Doxorubicin (DX)-cyclodextrin (Cd)] to enhance the anticellular activity of antineoplastic drug Doxorubicin and to reverse its multidrug resistance has been investigated. A spectroscopic study of the alpha, beta, and gamma-[DX-Cds] complexes has been investigated in relation to their biological effects on a multidrug resistant (MDR) human rectal adenocarcinoma cell line (HRT-18). A ten fold enhancement of DX anticellular activity in presence of beta-cyclodextrin alone was detected. PMID:10328296

  1. Assessment of multidrug resistance on cell coculture patterns using scanning electrochemical microscopy.

    PubMed

    Kuss, Sabine; Polcari, David; Geissler, Matthias; Brassard, Daniel; Mauzeroll, Janine

    2013-06-01

    The emergence of resistance to multiple unrelated chemotherapeutic drugs impedes the treatment of several cancers. Although the involvement of ATP-binding cassette transporters has long been known, there is no in situ method capable of tracking this transporter-related resistance at the single-cell level without interfering with the cell's environment or metabolism. Here, we demonstrate that scanning electrochemical microscopy (SECM) can quantitatively and noninvasively track multidrug resistance-related protein 1-dependent multidrug resistance in patterned adenocarcinoma cervical cancer cells. Nonresistant human cancer cells and their multidrug resistant variants are arranged in a side-by-side format using a stencil-based patterning scheme, allowing for precise positioning of target cells underneath the SECM sensor. SECM measurements of the patterned cells, performed with ferrocenemethanol and [Ru(NH3)6](3+) serving as electrochemical indicators, are used to establish a kinetic "map" of constant-height SECM scans, free of topography contributions. The concept underlying the work described herein may help evaluate the effectiveness of treatment administration strategies targeting reduced drug efflux. PMID:23686580

  2. Heat Shock-Independent Induction of Multidrug Resistance by Heat Shock Factor 1†

    PubMed Central

    Tchénio, Thierry; Havard, Marilyne; Martinez, Luis A.; Dautry, François

    2006-01-01

    The screening of two different retroviral cDNA expression libraries to select genes that confer constitutive doxorubicin resistance has in both cases resulted in the isolation of the heat shock factor 1 (HSF1) transcription factor. We show that HSF1 induces a multidrug resistance phenotype that occurs in the absence of heat shock or cellular stress and is mediated at least in part through the constitutive activation of the multidrug resistance gene 1 (MDR-1). This drug resistance phenotype does not correlate with an increased expression of heat shock-responsive genes (heat shock protein genes, or HSPs). In addition, HSF1 mutants lacking HSP gene activation are also capable of conferring multidrug resistance, and only hypophosphorylated HSF1 complexes accumulate in transduced cells. Our results indicate that HSF1 can activate MDR-1 expression in a stress-independent manner that differs from the canonical heat shock-activated mechanism involved in HSP induction. We further provide evidence that the induction of MDR-1 expression occurs at a posttranscriptional level, revealing a novel undocumented role for hypophosphorylated HSF1 in posttranscriptional gene regulation. PMID:16382149

  3. High heterogeneity of plasma membrane microfluidity in multidrug-resistant cancer cells

    NASA Astrophysics Data System (ADS)

    Boutin, Céline; Roche, Yann; Millot, Christine; Deturche, Régis; Royer, Pascal; Manfait, Michel; Plain, Jérôme; Jeannesson, Pierre; Millot, Jean-Marc; Jaffiol, Rodolphe

    2009-05-01

    Diffusion-time distribution analysis (DDA) has been used to explore the plasma membrane fluidity of multidrug-resistant cancer cells (LR73 carcinoma cells) and also to characterize the influence of various membrane agents present in the extracellular medium. DDA is a recent single-molecule technique, based on fluorescence correlation spectroscopy (FCS), well suited to retrieve local organization of cell membrane. The method was conducted on a large number of living cells, which enabled us to get a detailed overview of plasma membrane microviscosity, and plasma membrane micro-organization, between the cells of the same line. Thus, we clearly reveal the higher heterogeneity of plasma membrane in multidrug-resistant cancer cells in comparison with the nonresistant ones (denoted sensitive cells). We also display distinct modifications related to a membrane fluidity modulator, benzyl alcohol, and two revertants of multidrug resistance, verapamil and cyclosporin-A. A relation between the distribution of the diffusion-time values and the modification of membrane lateral heterogeneities is proposed.

  4. Green Tea Catechin-Based Complex Micelles Combined with Doxorubicin to Overcome Cardiotoxicity and Multidrug Resistance

    PubMed Central

    Cheng, Tangjian; Liu, Jinjian; Ren, Jie; Huang, Fan; Ou, Hanlin; Ding, Yuxun; Zhang, Yumin; Ma, Rujiang; An, Yingli; Liu, Jianfeng; Shi, Linqi

    2016-01-01

    Chemotherapy for cancer treatment has been demonstrated to cause some side effects on healthy tissues and multidrug resistance of the tumor cells, which greatly limits therapeutic efficacy. To address these limitations and achieve better therapeutic efficacy, combination therapy based on nanoparticle platforms provides a promising approach through delivering different agents simultaneously to the same destination with synergistic effect. In this study, a novel green tea catechin-based polyion complex (PIC) micelle loaded with doxorubicin (DOX) and (-)-Epigallocatechin-3-O-gallate (EGCG) was constructed through electrostatic interaction and phenylboronic acid-catechol interaction between poly(ethylene glycol)-block-poly(lysine-co-lysine-phenylboronic acid) (PEG-PLys/PBA) and EGCG. DOX was co-loaded in the PIC micelles through π-π stacking interaction with EGCG. The phenylboronic acid-catechol interaction endowed the PIC micelles with high stability under physiological condition. Moreover, acid cleavability of phenylboronic acid-catechol interaction in the micelle core has significant benefits for delivering EGCG and DOX to same destination with synergistic effects. In addition, benefiting from the oxygen free radicals scavenging activity of EGCG, combination therapy with EGCG and DOX in the micelle core could protect the cardiomyocytes from DOX-mediated cardiotoxicity according to the histopathologic analysis of hearts. Attributed to modulation of EGCG on P-glycoprotein (P-gp) activity, this kind of PIC micelles could effectively reverse multidrug resistance of cancer cells. These results suggested that EGCG based PIC micelles could effectively overcome DOX induced cardiotoxicity and multidrug resistance. PMID:27375779

  5. Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor.

    PubMed Central

    Raggers, R J; Vogels, I; van Meer, G

    2001-01-01

    The human multidrug-resistance (MDR1) P-glycoprotein (Pgp) is an ATP-binding-cassette transporter (ABCB1) that is ubiquitously expressed. Often its concentration is high in the plasma membrane of cancer cells, where it causes multidrug resistance by pumping lipophilic drugs out of the cell. In addition, MDR1 Pgp can transport analogues of membrane lipids with shortened acyl chains across the plasma membrane. We studied a role for MDR1 Pgp in transport to the cell surface of the signal-transduction molecule platelet-activating factor (PAF). PAF is the natural short-chain phospholipid 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. [(14)C]PAF synthesized intracellularly from exogenous alkylacetylglycerol and [(14)C]choline became accessible to albumin in the extracellular medium of pig kidney epithelial LLC-PK1 cells in the absence of vesicular transport. Its translocation across the apical membrane was greatly stimulated by the expression of MDR1 Pgp, and inhibited by the MDR1 inhibitors PSC833 and cyclosporin A. Basolateral translocation was not stimulated by expression of the basolateral drug transporter MRP1 (ABCC1). It was insensitive to the MRP1 inhibitor indomethacin and to depletion of GSH which is required for MRP1 activity. While efficient transport of PAF across the apical plasma membrane may be physiologically relevant in MDR1-expressing epithelia, PAF secretion in multidrug-resistant tumours may stimulate angiogenesis and thereby tumour growth. PMID:11463358

  6. Pluronic mixed micelles overcoming methotrexate multidrug resistance: in vitro and in vivo evaluation

    PubMed Central

    Chen, Yanzuo; Sha, Xianyi; Zhang, Wei; Zhong, Weitong; Fan, Zhuoyang; Ren, Qiuyue; Chen, Liangcen; Fang, Xiaoling

    2013-01-01

    A Pluronic polymeric mixed micelle delivery system was developed in this study by using Pluronic P105 and F127 block copolymers to encapsulate the antitumor compound, methotrexate (MTX). The MTX-loaded Pluronic P105/F127 mixed micelle exhibited the spherical shape with about 22 nm in diameter, high encapsulation efficiency (about 85%) and pH-dependent in vitro drug release. In this study, A-549 and KBv cell lines were selected as multidrug resistance tumor cell models, while H-460 and KB cell lines were chosen as sensitive tumor cells. The MTX-loaded Pluronic P105/F127 mixed micelle exhibited significant higher in vitro cytotoxicity in multidrug resistant tumor cells than that of control (MTX injection) mainly because of higher cellular uptake of MTX. The pharmacokinetic studies indicated that the Pluronic micelles significantly prolonged systemic circulation time of MTX compared to MTX injection. Moreover, a much stronger antitumor efficacy in KBv tumor xenografts nude mice was observed in the MTX-loaded Pluronic P105/F127 mixed micelle group, than MTX. Collectively, Pluronic P105/F127 mixed micelles could significantly enhance the antitumor activity of MTX and might be a promising drug delivery platform for multidrug resistance modulation. PMID:23620663

  7. Vitamin E derivative-based multifunctional nanoemulsions for overcoming multidrug resistance in cancer.

    PubMed

    Zheng, Nannan; Gao, Yanan; Ji, Hongyu; Wu, Linhua; Qi, Xuejing; Liu, Xiaona; Tang, Jingling

    2016-08-01

    The multidrug resistance (MDR), including intrinsic and acquired multidrug resistance, is a major problem in tumor chemotherapy. Here, we proposed a strategy for modulating intrinsic and/or acquired multidrug resistance by altering the levels of Bax and Bcl-2 expression and inhibiting the transport function of P-gp, increasing the intracellular concentration of its substrate anticancer drugs. Vitamin E derivative-based nanoemulsions containing paclitaxel (MNEs-PTX) were fabricated in this study, and in vitro anticancer efficacy of the nanoemulsion system was evaluated in the paclitaxel-resistant human ovarian carcinoma cell line A2780/Taxol. The MNEs-PTX exhibited a remarkably enhanced antiproliferation effect on A2780/Taxol cells than free paclitaxel (PTX) (p < 0.01). Compared with that in the Taxol group, MNEs-PTX further decreased mitochondrial potential. Vitamin E derivative-based multifunctional nanoemulsion (MNEs) obviously increased intracellular accumulation of rhodamine 123 (P-gp substrate). Overexpression of Bcl-2 is generally associated with tumor drug resistance, we found that MNEs could reduce Bcl-2 protein level and increase Bax protein level. Taken together, our findings suggest that anticancer drugs associated with MNEs could play a role in the development of MDR in cancers. PMID:26710274

  8. Assessment of multidrug resistance on cell coculture patterns using scanning electrochemical microscopy

    PubMed Central

    Kuss, Sabine; Polcari, David; Geissler, Matthias; Brassard, Daniel; Mauzeroll, Janine

    2013-01-01

    The emergence of resistance to multiple unrelated chemotherapeutic drugs impedes the treatment of several cancers. Although the involvement of ATP-binding cassette transporters has long been known, there is no in situ method capable of tracking this transporter-related resistance at the single-cell level without interfering with the cell’s environment or metabolism. Here, we demonstrate that scanning electrochemical microscopy (SECM) can quantitatively and noninvasively track multidrug resistance-related protein 1–dependent multidrug resistance in patterned adenocarcinoma cervical cancer cells. Nonresistant human cancer cells and their multidrug resistant variants are arranged in a side-by-side format using a stencil-based patterning scheme, allowing for precise positioning of target cells underneath the SECM sensor. SECM measurements of the patterned cells, performed with ferrocenemethanol and [Ru(NH3)6]3+ serving as electrochemical indicators, are used to establish a kinetic “map” of constant-height SECM scans, free of topography contributions. The concept underlying the work described herein may help evaluate the effectiveness of treatment administration strategies targeting reduced drug efflux. PMID:23686580

  9. Modeling epidemics of multidrug-resistant M. tuberculosis of heterogeneous fitness.

    PubMed

    Cohen, Ted; Murray, Megan

    2004-10-01

    Mathematical models have recently been used to predict the future burden of multidrug-resistant tuberculosis (MDRTB). These models suggest the threat of multidrug resistance to TB control will depend on the relative 'fitness' of MDR strains and imply that if the average fitness of MDR strains is considerably less than that of drug-sensitive strains, the emergence of resistance will not jeopardize the success of tuberculosis control efforts. Multidrug resistance in M. tuberculosis is conferred by the sequential acquisition of a number of different single-locus mutations that have been shown to have heterogeneous phenotypic effects. Here we model the impact of initial fitness estimates on the emergence of MDRTB assuming that the relative fitness of MDR strains is heterogeneous. We find that even when the average relative fitness of MDR strains is low and a well-functioning control program is in place, a small subpopulation of a relatively fit MDR strain may eventually outcompete both the drug-sensitive strains and the less fit MDR strains. These results imply that current epidemiological measures and short-term trends in the burden of MDRTB do not provide evidence that MDRTB strains can be contained in the absence of specific efforts to limit transmission from those with MDR disease. PMID:15378056

  10. Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?

    PubMed Central

    Bastian, I.; Rigouts, L.; Van Deun, A.; Portaels, F.

    2000-01-01

    Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis. These "DOTS-plus for MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be individualized rather than standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing; reliable supplies of a wide range of expensive second-line agents would have to be supplied; operational studies would be required to determine the indications for and format of the expanded programmes; financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments. PMID:10743297

  11. Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling.

    PubMed

    Jones, P M; George, A M

    2005-04-30

    Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein. PMID:15826647

  12. Inhibition of multidrug resistant Listeria monocytogenes by peptides isolated from combinatorial phage display libraries.

    PubMed

    Flachbartova, Z; Pulzova, L; Bencurova, E; Potocnakova, L; Comor, L; Bednarikova, Z; Bhide, M

    2016-01-01

    The aim of the study was to isolate and characterize novel antimicrobial peptides from peptide phage library with antimicrobial activity against multidrug resistant Listeria monocytogenes. Combinatorial phage-display library was used to affinity select peptides binding to the cell surface of multidrug resistant L. monocytogenes. After several rounds of affinity selection followed by sequencing, three peptides were revealed as the most promising candidates. Peptide L2 exhibited features common to antimicrobial peptides (AMPs), and was rich in Asp, His and Lys residues. Peptide L3 (NSWIQAPDTKSI), like peptide L2, inhibited bacterial growth in vitro, without any hemolytic or cytotoxic effects on eukaryotic cells. L1 peptide showed no inhibitory effect on Listeria. Structurally, peptides L2 and L3 formed random coils composed of α-helix and β-sheet units. Peptides L2 and L3 exhibited antimicrobial activity against multidrug resistant isolates of L. monocytogenes with no haemolytic or toxic effects. Both peptides identified in this study have the potential to be beneficial in human and veterinary medicine. PMID:27296960

  13. Genomic structure, gene expression, and promoter analysis of human multidrug resistance-associated protein 7

    SciTech Connect

    Kao, Hsin-Hsin; Chang, Ming-Shi; Cheng, Jan-Fang; Huang, Jin-Ding

    2002-03-15

    The multidrug resistance-associated protein (MRP) subfamily transporters associated with anticancer drug efflux are attributed to the multidrug-resistance of cancer cells. The genomic organization of human multidrug resistance-associated protein 7 (MRP7) was identified. The human MRP7 gene, consisting of 22 exons and 21 introns, greatly differs from other members of the human MRP subfamily. A splicing variant of human MRP7, MRP7A, expressed in most human tissues, was also characterized. The 1.93-kb promoter region of MRP7 was isolated and shown to support luciferase activity at a level 4- to 5-fold greater than that of the SV40 promoter. Basal MRP7 gene expression was regulated by 2 regions in the 5-flanking region at 1,780 1,287 bp, and at 611 to 208 bp. In Madin-Darby canine kidney (MDCK) cells, MRP7 promoter activity was increased by 226 percent by genotoxic 2-acetylaminofluorene and 347 percent by the histone deacetylase inhibitor, trichostatin A. The protein was expressed in the membrane fraction of transfected MDCK cells.

  14. Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia

    PubMed Central

    Ghaderpour, Aziz; Ho, Wing Sze; Chew, Li-Lee; Bong, Chui Wei; Chong, Ving Ching; Thong, Kwai-Lin; Chai, Lay Ching

    2015-01-01

    E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry. PMID:26483759

  15. Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia.

    PubMed

    Ghaderpour, Aziz; Ho, Wing Sze; Chew, Li-Lee; Bong, Chui Wei; Chong, Ving Ching; Thong, Kwai-Lin; Chai, Lay Ching

    2015-01-01

    E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry. PMID:26483759

  16. Bisbenzylisoquinolines as modulators of chloroquine resistance in Plasmodium falciparum and multidrug resistance in tumor cells.

    PubMed

    Frappier, F; Jossang, A; Soudon, J; Calvo, F; Rasoanaivo, P; Ratsimamanga-Urverg, S; Saez, J; Schrevel, J; Grellier, P

    1996-06-01

    Ten naturally occurring bisbenzylisoquinolines (BBIQ) and two dihydro derivatives belonging to five BBIQ subgroups were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance to chloroquine of strain FcB1. The same alkaloids were also assessed in vitro for their potentiating activity against vinblastine with the multidrug-resistant clone CCRF-CEM/VLB, established from lymphoblastic acute leukemia. Three of the BBIQ tested had 50% inhibitory concentrations of less than 1 microM. The most potent antimalarial agent was cocsoline (50% inhibitory concentration, 0.22 microM). Regarding the chloroquine-potentiating effect, fangchinoline exhibited the highest biological activity whereas the remaining compounds displayed either antagonistic or slight synergistic effects. Against the multidrug-resistant cancer cell line, fangchinoline was also by far the most active compound. Although there were clear differences between the activities of tested alkaloids, no relevant structure-activity relationship could be established. Nevertheless, fangchinoline appears to be a new biochemical tool able to help in the comprehension of the mechanism of both chloroquine resistance in P. falciparum and multidrug resistance in tumor cells. PMID:8726022

  17. Bisbenzylisoquinolines as modulators of chloroquine resistance in Plasmodium falciparum and multidrug resistance in tumor cells.

    PubMed Central

    Frappier, F; Jossang, A; Soudon, J; Calvo, F; Rasoanaivo, P; Ratsimamanga-Urverg, S; Saez, J; Schrevel, J; Grellier, P

    1996-01-01

    Ten naturally occurring bisbenzylisoquinolines (BBIQ) and two dihydro derivatives belonging to five BBIQ subgroups were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance to chloroquine of strain FcB1. The same alkaloids were also assessed in vitro for their potentiating activity against vinblastine with the multidrug-resistant clone CCRF-CEM/VLB, established from lymphoblastic acute leukemia. Three of the BBIQ tested had 50% inhibitory concentrations of less than 1 microM. The most potent antimalarial agent was cocsoline (50% inhibitory concentration, 0.22 microM). Regarding the chloroquine-potentiating effect, fangchinoline exhibited the highest biological activity whereas the remaining compounds displayed either antagonistic or slight synergistic effects. Against the multidrug-resistant cancer cell line, fangchinoline was also by far the most active compound. Although there were clear differences between the activities of tested alkaloids, no relevant structure-activity relationship could be established. Nevertheless, fangchinoline appears to be a new biochemical tool able to help in the comprehension of the mechanism of both chloroquine resistance in P. falciparum and multidrug resistance in tumor cells. PMID:8726022

  18. Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel-7402/5-fluorouracil cells

    PubMed Central

    LING, SUNBIN; TIAN, YU; ZHANG, HAIQUAN; JIA, KAIQI; FENG, TINGTING; SUN, DEGUANG; GAO, ZHENMING; XU, FEI; HOU, ZHAOYUAN; LI, YAN; WANG, LIMING

    2014-01-01

    Metformin exhibits anti-proliferative effects in tumor cells in vitro and in vivo. The present study investigated the ability of metformin to reverse multidrug resistance (MDR) in human hepatocellular carcinoma Bel-7402/5-fluorouracil (5-Fu; Bel/Fu) cells. The synergistic anti-proliferative effect of metformin combined with 5-Fu was evaluated using a Cell Counting kit-8 assay. The variation in apoptotic rates and cell cycle distribution were evaluated using a flow cytometric assay and variations in target gene and protein expression were monitored using reverse transcription-polymerase chain reaction and western blot analysis. The results demonstrated that metformin had a synergistic anti-proliferative effect with 5-Fu in the Bel/Fu cells. The variations in the number of apoptotic cells and distribution of the cell cycle were consistent with the variability in cell viability. Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1α (HIF-1α) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1α/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma. PMID:25310259

  19. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil

    SciTech Connect

    Safa, A.R. )

    1988-10-01

    Verapamil, a phenylalkylamine calcium channel blocker, has been shown to reverse multidrug resistance in tumor cells, possibly by increasing drug retention through interaction with an outward drug transporter of the resistant cells. In this study two photoactive radioactive analogs of verapamil, N-(p-azido(3,5-{sup 3}H)benzoyl)aminomethyl verapamil and N-(p-azido(3-{sup 125}I)salicyl)aminomethyl verapamil, were synthesized and used to identify the possible biochemical target(s) for verapamil in multidrug-resistance DC-3F/VCRd-5L Chinese hamster lung cells selected for resistance to vincristine. The results show that a specifically labeled 150- to 180-kDa membrane protein in resistant cells was immunoprecipitated with a monoclonal antibody specific for P-glycoprotein. Phenylalkylamine binding specificity was established by competitive blocking of specific photolabeling with the nonradioactive photoactive analogs as well as with verapamil. Photoaffinity labeling was also inhibited by 50 {mu}M concentrations of the calcium channel blockers nimodipine, nifedipine, nicardipine, azidopine, bepridil, and diltiazem and partially by prenylamine. Moreover, P-glycoprotein labeling was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at 0.2 {mu}M compared to that by verapamil at 8 {mu}M. These data provide direct evidence that P-glycoprotein has broad drug recognition capacity and that it serves as a molecular target for calcium channel blocker action in reversing multidrug resistance.

  20. Poly(ethylene glycol)-conjugated multi-walled carbon nanotubes as an efficient drug carrier for overcoming multidrug resistance

    SciTech Connect

    Cheng Jinping; Meziani, Mohammed J.; Sun Yaping; Cheng, Shuk Han

    2011-01-15

    The acquisition of multidrug resistance poses a serious problem in chemotherapy, and new types of transporters have been actively sought to overcome it. In the present study, poly(ethylene glycol)-conjugated (PEGylated) multi-walled carbon nanotubes (MWCNTs) were prepared and explored as drug carrier to overcome multidrug resistance. The prepared PEGylated MWCNTs penetrated into mammalian cells without damage plasma membrane, and its accumulation did not affect cell proliferation and cell cycle distribution. More importantly, PEGylated MWCNTs accumulated in the multidrug-resistant cancer cells as efficient as in the sensitive cancer cells. Intracellular translocation of PEGylated MWCNTs was visualized in both multidrug-resistant HepG2-DR cells and sensitive HepG2 cells, as judged by both fluorescent and transmission electron microscopy. PEGylated MWCNTs targeted cancer cells efficiently and multidrug-resistant cells failed to remove the intracellular MWCNTs. However, if used in combination with drugs without conjugation, PEGylated MWCNTs prompted drug efflux in MDR cells by stimulating the ATPase activity of P-glycoprotein. This study suggests that PEGylated MWCNTs can be developed as an efficient drug carrier to conjugate drugs for overcoming multidrug resistance in cancer chemotherapy.

  1. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog

    SciTech Connect

    Akiyama, S.; Cornwell, M.M.; Kuwano, M.; Pastan, I.; Gottesman, M.M.

    1988-02-01

    Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-(3-/sup 125/I)salicyl)-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N-solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P-glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts.

  2. Antibacterial activities of selected Cameroonian spices and their synergistic effects with antibiotics against multidrug-resistant phenotypes

    PubMed Central

    2011-01-01

    Background The emergence of multi-drug resistant (MDR) phenotypes is a major public health problem today in the treatment of bacterial infections. The present study was designed to evaluate the antibacterial activities of the methanol extracts of eleven Cameroonian spices on a panel of twenty nine Gram negative bacteria including MDR strains. Methods The phytochemical analysis of the extracts was carried out by standard tests meanwhile the liquid micro-broth dilution was used for all antimicrobial assays. Results Phytochemical analysis showed the presence of alkaloids, phenols and tannins in all plants extracts. The results of the antibacterial assays indicated that all tested extracts exert antibacterial activities, with the minimum inhibitory concentration (MIC) values varying from 32 to 1024 μg/ml. The extracts from Dichrostachys glomerata, Beilschmiedia cinnamomea, Aframomum citratum, Piper capense, Echinops giganteus, Fagara xanthoxyloïdes and Olax subscorpioïdea were the most active. In the presence of efflux pump inhibitor, PAßN, the activity of the extract from D. glomerata significantly increased on 69.2% of the tested MDR bacteria. At MIC/5, synergistic effects were noted with the extract of D. glomerata on 75% of the tested bacteria for chloramphenicol (CHL), tetracycline (TET) and norfloxacin (NOR). With B. cinnamomea synergy were observed on 62.5% of the studied MDR bacteria with CHL, cefepime (FEP), NOR and ciprofloxacin (CIP) and 75% with erythromycin (ERY). Conclusion The overall results provide information for the possible use of the studied extracts of the spices in the control of bacterial infections involving MDR phenotypes. PMID:22044718

  3. Antibiotic strategies in the era of multidrug resistance.

    PubMed

    Karam, George; Chastre, Jean; Wilcox, Mark H; Vincent, Jean-Louis

    2016-01-01

    The rapid emergence and dissemination of antibiotic-resistant microorganisms in ICUs worldwide threaten adequate antibiotic coverage of infected patients in this environment. The causes of this problem are multifactorial, but the core issues are clear: the emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Because a significant increase in mortality is observed when antibiotic therapy is delayed in infected ICU patients, initial therapy should be broad enough to cover all likely pathogens. Receipt of unnecessary prolonged broad-spectrum antibiotics, however, should be avoided. Local microbiologic data are extremely important to predict the type of resistance that may be present for specific causative bacteria, as is prior antibiotic exposure, and antibiotic choices should thus be made at an individual patient level. PMID:27329228

  4. Nanobiotechnological Approaches Against Multidrug Resistant Bacterial Pathogens: An Update.

    PubMed

    Shaikh, Sibhghatulla; Shakil, Shazi; Abuzenadah, Adel M; Rizvi, Syed Mohd Danish; Roberts, Philip Michael; Mushtaq, Gohar; Kamal, Mohammad Amjad

    2015-01-01

    Multiple drug resistant bacteria remain the greatest challenge in public health care. Globally, infections produced by such resistant strains are on the rise. Recent advent of genetic tolerance to antibiotics in many pathogens such as multiple drug resistant Staphylococcus aureus is a matter of concern, prompting researchers and pharmaceutical companies to search for new molecules and unconventional antibacterial agents. Recent advances in nanotechnology offer new opportunities to develop formulations based on metallic nanoparticles with different shapes and sizes and variable antimicrobial properties. This article is an extensive literature review that covers the latest approaches in the development of new and unconventional antibacterial agents using nanobiotechnological approaches which will better equip scientists and clinicians to face the challenges in view of dwindling stocks of effective and potent antimicrobial agents and formulations. PMID:26419545

  5. Single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) and risk of chronic myeloid leukemia.

    PubMed

    Yaya, Kassogue; Hind, Dehbi; Meryem, Quachouh; Asma, Quessar; Said, Benchekroun; Sellama, Nadifi

    2014-11-01

    Multidrug resistance gene 1 (MDR1) is known for its involvement in the detoxification through the active transport of toxic compounds from diverse origins outside the cells. These compounds could cause injury to cell DNA, which might lead in cancer like chronic myeloid leukemia (CML). Individual inherited genetic differences related to polymorphism in detoxification enzymes could be an important factor not only in carcinogen metabolism but also in susceptibility of cancer. The present study aimed to investigate the association of three single nucleotide polymorphisms (SNPs) of the MDR1 gene in the susceptibility of CML. We successively have determined the genotype profiles of 1236 C>T (exon 12); 2677 G>T (exon 21), and 3435 C>T (exon 26) SNPs by PCR-RFLP in 89 patients and 99 unrelated healthy controls. Logistic regression was used to assess the effect of each SNP on the development of CML. Interestingly, in exon 12, the 1236 TT was significantly associated with the susceptibility of CML when compared to the wild type 1236 CC (OR 2.7; 95% CI 1-7.32, p = 0.041). Additionally, the recessive model 1236 TT vs. 1236 CC/CT showed a risk of 3.3 fold (p = 0.011) with CML. In exon 26, the 3435 CT genotype was associated with a reduced risk of CML (OR 0.5; 95% CI 0.3-1, p = 0.042). In exon 21, the 2677 GT genotype seems to have a protective effect (OR 0.6; 95% CI 0.32-1.1, p = 0.074). Diplolotypes analysis has demonstrated no effect in susceptibility of CML, but 1236 CT/3435 CC and 1236 CC/2677 GT were associated with a protective effect. The haplotypes analysis showed no particular trend (global association p = 0.33). Our findings demonstrate that 1236 TT in exon 12 might contribute in the susceptibility of CML, while the 3435 CT in exon 26 as well as 1236 CT/3435 CC and 1236 CC/2677 GT combinations might be protective factors. PMID:25087925

  6. Potential multidrug resistance gene POHL: an ecologically relevant indicator in marine sponges.

    PubMed

    Krasko, A; Kurelec, B; Batel, R; Müller, I M; Müller, W E

    2001-01-01

    Sponges are sessile filter feeders found in all aquatic habitats from the tropics to the arctic. Against potential environmental hazards, they are provided with efficient defense systems, e.g., protecting chaperones and/or the P-170/multidrug resistance pump system. Here we report on a further multidrug resistance pathway that is related to the pad one homologue (POH1) mechanism recently identified in humans. It is suggested that proteolysis is involved in the inactivation of xenobiotics by the POH1 system. Two cDNAs were cloned, one from the demosponge Geodia cydonium and a second from the hexactinellid sponge Aphrocallistes vastus. The cDNA from G. cydonium, termed GCPOHL, encodes a deduced polypeptide with a size of 34,591 Da and that from A. vastus, AVPOHL, a protein of a calculated M(r) of 34,282. The two sponge cDNAs are highly similar to each other as well as to the known sequences from fungi (Schizosaccharomyces pombe and Saccharomyces cerevisiae) and other Metazoa (from Schistosoma mansoni to humans). Under controlled laboratory conditions, the expression of the potential multidrug resistance gene POHL is, in G. cydonium, strongly upregulated in response to the toxins staurosporin (20 microM) or taxol (50 microM); the first detectable transcripts appear after 1 d and reach a maximum after 3 to 5 d of incubation. The relevance of the expression pattern of the G. cydonium gene POHL for the assessment of pollution in the field was determined at differently polluted sites in the area around Rovinj (Croatia; Mediterranean Sea, Adriatic Sea). The load of the selected sites was assessed by measuring the potency of XAD-7 concentrates of water samples taken from those places to induce the level of benzo[a]pyrene monooxygenase (BaPMO) in fish and to impair the multidrug resistance (MDR)/P-170 extrusion pump in clams. These field experiments revealed that the levels of inducible BaPMO activity in fish and of the MDR potential by the water concentrates are highly

  7. Sensitive, resistant and multi-drug resistant Acinetobacter baumanii at Saudi Arabia hospital eastern region.

    PubMed

    Ahmed, Mughis Uddin; Farooq, Reshma; Al-Hawashim, Nadia; Ahmed, Motasim; Yiannakou, Nearchos; Sayeed, Fatima; Sayed, Ali Rifat; Lutfullah, Sualiha

    2015-05-01

    Since the Physicians start use of antibiotics long ago with un-notice drug resistance. However actual problem was recognized about 85 years ago. Antibiotic resistant and Multi-drug resistant bacterial strains are at rise throughout the world. It is physicians and researchers to take scientific research based appropriate action to overcome this ever-spreading problem. This study is designed to find out sensitive (S), resistant (R) and multi-drug resistant (MDR) Acinetobacter baumanii strain along with other isolates in the resident patients of Eastern Region of Saudi Arabia. Pseudomonas aeruginosa is excluded from other gram-negative organisms isolated from different sites as it will be dealt separately. This study is based in was retrospective observations designed to collect data of different stains of Acinetobacter baumanii with reference to their Sensitivity (S), Resistance (R), Multi-Drug Resistance (MDR) along with other Gram negative isolated from different sites (from 1st January 2004 to 31st December 2011) at King Abdulaziz Hospital located Eastern Region of Kingdom of Saudi Arabia (KSA). All necessary techniques were used to culture and perform sensitivity of these isolates. There were 4532 isolates out of which 3018 (67%) were from patients. Out of Acinetobacter baumanii infected were 906 (20%) while other 3626 (80%) isolates were miscellaneous. Numbers of patients or cases were 480 (53%) out of 906 isolates and numbers of patients or cases in other organisms were 2538 (70%) out of 3626 isolates. Acinetobacter baumanii infected patients 221 (46%) were male and 259 (54%) were female and the male and female ratio of 1:1.2. In other organisms this male female ratio was almost same. There was steady rise in number of patients and the hence the isolates from 2004 to 2011. Majority of the bacterial strains were isolated as single organism but some were isolated as double or triple or quadruple or more organisms from different sites. Sensitive, Resistant and Multi-Drug Resistant Acinetobacter baumanii have been isolated from different sites. The other Gram negative isolates included Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Klebsiella oxytoca, Serratia marcescens and Stenotrophomonas maltophilia. A significant rise in R and MDR but there is rise in R and MDR Acinetobacter baumanii Strains has been interceded other isolates. It is important to adopt proper and sustainable policies and guideline regarding antibiotics prescription and used. We should also check our infection control practices in our hospital or healthcare settings. We should start antibiotics stewardship in our hospital in order to reducing or overcoming antibiotics Resistant (R) and Multi-Drug Resistant (MDR) strains prevalence. PMID:26004714

  8. The modulation of ABC transporter-mediated multidrug resistance in cancer: a review of the past decade.

    PubMed

    Kathawala, Rishil J; Gupta, Pranav; Ashby, Charles R; Chen, Zhe-Sheng

    2015-01-01

    ATP-binding cassette (ABC) transporters represent one of the largest and oldest families of membrane proteins in all extant phyla from prokaryotes to humans, which couple the energy derived from ATP hydrolysis essentially to translocate, among various substrates, toxic compounds across the membrane. The fundamental functions of these multiple transporter proteins include: (1) conserved mechanisms related to nutrition and pathogenesis in bacteria, (2) spore formation in fungi, and (3) signal transduction, protein secretion and antigen presentation in eukaryotes. Moreover, one of the major causes of multidrug resistance (MDR) and chemotherapeutic failure in cancer therapy is believed to be the ABC transporter-mediated active efflux of a multitude of structurally and mechanistically distinct cytotoxic compounds across membranes. It has been postulated that ABC transporter inhibitors known as chemosensitizers may be used in combination with standard chemotherapeutic agents to enhance their therapeutic efficacy. The current paper reviews the advance in the past decade in this important domain of cancer chemoresistance and summarizes the development of new compounds and the re-evaluation of compounds originally designed for other targets as transport inhibitors of ATP-dependent drug efflux pumps. PMID:25554624

  9. Bactericidal activity and mechanism of action of copper-sputtered flexible surfaces against multidrug-resistant pathogens.

    PubMed

    Ballo, Myriam K S; Rtimi, Sami; Mancini, Stefano; Kiwi, John; Pulgarin, César; Entenza, José M; Bizzini, Alain

    2016-07-01

    Using direct current magnetron sputtering (DCMS), we generated flexible copper polyester surfaces (Cu-PES) and investigated their antimicrobial activity against a range of multidrug-resistant (MDR) pathogens including eight Gram-positive isolates (three methicillin-resistant Staphylococcus aureus [MRSA], four vancomycin-resistant enterococci, one methicillin-resistant Staphylococcus epidermidis) and four Gram-negative strains (one extended-spectrum β-lactamase-producing [ESBL] Escherichia coli, one ESBL Klebsiella pneumoniae, one imipenem-resistant Pseudomonas aeruginosa, and one ciprofloxacin-resistant Acinetobacter baumannii). Bactericidal activity (≥3 log10 CFU reduction of the starting inoculum) was reached within 15-30 min exposure to Cu-PES. Antimicrobial activity of Cu-PES persisted in the absence of oxygen and against both Gram-positive and Gram-negative bacteria containing elevated levels of catalases, indicating that reactive oxygen species (ROS) do not play a primary role in the killing process. The decrease in cell viability of MRSA ATCC 43300 and Enterococcus faecalis V583 correlated with the progressive loss of cytoplasmic membrane integrity both under aerobic and anaerobic conditions, suggesting that Cu-PES mediated killing is primarily induced by disruption of the cytoplasmic membrane function. Overall, we here present novel antimicrobial copper surfaces with improved stability and sustainability and provide further insights into their mechanism of killing. PMID:27020284

  10. Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant staphylococci.

    PubMed

    Mohammad, Haroon; Mayhoub, Abdelrahman S; Cushman, Mark; Seleem, Mohamed N

    2015-04-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant S. aureus (VRSA) clinical isolates. In addition, the anti-biofilm activity of the novel thiazoles was investigated against S. epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to resensitize VRSA to vancomycin, reducing its MIC by 512-fold in two strains. In addition, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively, the results obtained demonstrate that compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm. PMID:25315757

  11. Prediction of multi-drug resistance transporters using a novel sequence analysis method [version 2; referees: 2 approved

    DOE PAGESBeta

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; Gosink, Luke; Lindemann, Stephen R.

    2015-03-09

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequencesimilarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first showmore » that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.« less

  12. Prediction of multi-drug resistance transporters using a novel sequence analysis method [version 2; referees: 2 approved

    SciTech Connect

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; Gosink, Luke; Lindemann, Stephen R.

    2015-03-09

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequencesimilarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.

  13. Associations between multidrug resistance, plasmid content, and virulence potential among extraintestinal pathogenic and commensal Escherichia coli from humans and poultry.

    PubMed

    Johnson, Timothy J; Logue, Catherine M; Johnson, James R; Kuskowski, Michael A; Sherwood, Julie S; Barnes, H John; DebRoy, Chitrita; Wannemuehler, Yvonne M; Obata-Yasuoka, Mana; Spanjaard, Lodewijk; Nolan, Lisa K

    2012-01-01

    The emergence of plasmid-mediated multidrug resistance (MDR) among enteric bacteria presents a serious challenge to the treatment of bacterial infections in humans and animals. Recent studies suggest that avian Escherichia coli commonly possess the ability to resist multiple antimicrobial agents, and might serve as reservoirs of MDR for human extraintestinal pathogenic Escherichia coli (ExPEC) and commensal E. coli populations. We determined antimicrobial susceptibility profiles for 2202 human and avian E. coli isolates, then sought for associations among resistance profile, plasmid content, virulence factor profile, and phylogenetic group. Avian-source isolates harbored greater proportions of MDR than their human counterparts, and avian ExPEC had higher proportions of MDR than did avian commensal E. coli. MDR was significantly associated with possession of the IncA/C, IncP1-α, IncF, and IncI1 plasmid types. Overall, inferred virulence potential did not correlate with drug susceptibility phenotype. However, certain virulence genes were positively associated with MDR, including ireA, ibeA, fyuA, cvaC, iss, iutA, iha, and afa. According to the total dataset, isolates segregated significantly according to host species and clinical status, thus suggesting that avian and human ExPEC and commensal E. coli represent four distinct populations with limited overlap. These findings suggest that in extraintestinal E. coli, MDR is most commonly associated with plasmids, and that these plasmids are frequently found among avian-source E. coli from poultry production systems. PMID:21988401

  14. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches

    PubMed Central

    Karaiskos, Ilias; Giamarellou, Helen

    2014-01-01

    Introduction: In the era of multidrug-resistant, extensively drug-resistant (XDR) and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the threat of untreatable infections particularly those caused by carbapenemase-producing bacteria, that is, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Therefore, all the presently available antibiotics, as well as for the near future compounds, are presented and discussed. Areas covered: Current knowledge concerning mechanisms of action, in vitro activity and interactions, pharmacokinetic/pharmacodynamics, clinical efficacy and toxicity issues for revived and novel antimicrobial agents overcoming current resistance mechanisms, including colistin, tigecycline, fosfomycin, temocillin, carbapenems, and antibiotics still under development for the near future such as plazomicin, eravacycline and carbapenemase inhibitors is discussed. Expert opinion: Colistin is active in vitro and effective in vivo against XDR carbapenemase-producing microorganisms in the critically ill host, whereas tigecycline, with the exception of P. aeruginosa, has a similar spectrum of activity. The efficacy of combination therapy in bacteremias and ventilator-associated pneumonia caused by K. pneumoniae carbapenemase producers seems to be obligatory, whereas in cases of P. aeruginosa and A. baumannii its efficacy is questionable. Fosfomycin, which is active against P. aeruginosa and K. pneumoniae, although promising, shares poor experience in XDR infections. The in vivo validity of the newer potent compounds still necessitates the evaluation of Phase III clinical trials particularly in XDR infections. PMID:24766095

  15. Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant staphylococci

    PubMed Central

    Mohammad, Haroon; Mayhoub, Abdelrahman S.; Cushman, Mark; Seleem, Mohamed N.

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates. Additionally, the anti-biofilm activity of the novel thiazoles was investigated against Staphylococcus epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to re-sensitize VRSA to vancomycin, reducing its minimum inhibitory concentration (MIC) by 512-fold in two strains. Additionally, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively the results obtained demonstrate compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm. PMID:25315757

  16. In Vitro antibacterial and antibiotic-potentiation activities of four edible plants against multidrug-resistant gram-negative species

    PubMed Central

    2013-01-01

    Background The present study was designed to investigate the antibacterial activities of the methanol extracts of four Cameroonian edible plants, locally used to treat microbial infections, and their synergistic effects with antibiotics against a panel of twenty nine Gram-negative bacteria including Multi-drug resistant (MDR) phenotypes expressing active efflux pumps. Methods The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of the extracts [alone and in the presence of the efflux pumps inhibitor (EPI) Phenylalanine-Arginine β-Naphtylamide (PAβN)], and those of antibiotics in association with the two of the most active ones, Piper nigrum and Telfairia occidentalis. The preliminary phytochemical screening of the extracts was conducted according to the standard phytochemical methods. Results Phytochemical analysis showed the presence of alkaloids and flavonoids in all studied extracts. Other chemical classes of secondary metabolites were selectively present in the extracts. The results of the MIC determination indicated that the crude extracts from P. nigrum and V. amygdalina were able to inhibit the growth of all the twenty nine studied bacteria within a concentration range of 32 to 1024 μg/mL. At a similar concentration range (32 to 1024 μg/mL) the extract from T. occidentalis inhibited the growth of 93.1% of the tested microorganisms. At MIC/2 and MIC/5, synergistic effects were noted between the extracts from P. nigrum and T. occidentalis and seven of the tested antibiotics on more than 70% of the tested bacteria. Conclusion The overall results of the present study provide information for the possible use of the studied edible plants extracts in the control of bacterial infections including MDR phenotypes. PMID:23885762

  17. Whole genome sequencing for deciphering the resistome of Chryseobacterium indologenes, an emerging multidrug-resistant bacterium isolated from a cystic fibrosis patient in Marseille, France.

    PubMed

    Cimmino, T; Rolain, J-M

    2016-07-01

    We decipher the resistome of Chryseobacterium indologenes MARS15, an emerging multidrug-resistant clinical strain, using the whole genome sequencing strategy. The bacterium was isolated from the sputum of a hospitalized patient with cystic fibrosis in the Timone Hospital in Marseille, France. Genome sequencing was done with Illumina MiSeq using a paired-end strategy. The in silico analysis was done by RAST, the resistome by the ARG-ANNOT database and detection of polyketide synthase (PKS) by ANTISMAH. The genome size of C. indologenes MARS15 is 4 972 580 bp with 36.4% GC content. This multidrug-resistant bacterium was resistant to all β-lactams, including imipenem, and also to colistin. The resistome of C. indologenes MARS15 includes Ambler class A and B β-lactams encoding bla CIA and bla IND-2 genes and MBL (metallo-β-lactamase) genes, the CAT (chloramphenicol acetyltransferase) gene and the multidrug efflux pump AcrB. Specific features include the presence of an urease operon, an intact prophage and a carotenoid biosynthesis pathway. Interestingly, we report for the first time in C. indologenes a PKS cluster that might be responsible for secondary metabolite biosynthesis, similar to erythromycin. The whole genome sequence analysis provides insight into the resistome and the discovery of new details, such as the PKS cluster. PMID:27222716

  18. Tetrandrine and fangchinoline, bisbenzylisoquinoline alkaloids from Stephania tetrandra can reverse multidrug resistance by inhibiting P-glycoprotein activity in multidrug resistant human cancer cells.

    PubMed

    Sun, Yan Fang; Wink, Michael

    2014-01-01

    The overexpression of ABC transporters is a common reason for multidrug resistance (MDR) in cancer cells. In this study, we found that the isoquinoline alkaloids tetrandrine and fangchinoline from Stephania tetrandra showed a significant synergistic cytotoxic effect in MDR Caco-2 and CEM/ADR5000 cancer cells in combination with doxorubicin, a common cancer chemotherapeutic agent. Furthermore, tetrandrine and fangchinoline increased the intracellular accumulation of the fluorescent P-glycoprotein (P-gp) substrate rhodamine 123 (Rho123) and inhibited its efflux in Caco-2 and CEM/ADR5000 cells. In addition, tetrandrine and fangchinoline significantly reduced P-gp expression in a concentration-dependent manner. These results suggest that tetrandrine and fangchinoline can reverse MDR by increasing the intracellular concentration of anticancer drugs, and thus they could serve as a lead for developing new drugs to overcome P-gp mediated drug resistance in clinic cancer therapy. PMID:24856768

  19. Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1

    PubMed Central

    van Gorkom, B A P; Timmer-Bosscha, H; de Jong, S; van der Kolk, D M; Kleibeuker, J H; de Vries, E G E

    2002-01-01

    Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines, possibly increase colorectal cancer risk. Anthracyclines interfere with topoisomerase II, intercalate DNA and are substrates for P-glycoprotein and multidrug resistance-associated protein 1. P-glycoprotein and multidrug resistance-associated protein 1 protect colonic epithelial cells against xenobiotics. The aim of this study was to analyse the interference of anthranoids with these natural defence mechanisms and the direct cytotoxicity of anthranoids in cancer cell lines expressing these mechanisms in varying combinations. A cytotoxicity profile of rhein, aloe emodin and danthron was established in related cell lines exhibiting different levels of topoisomerases, multidrug resistance-associated protein 1 and P-glycoprotein. Interaction of rhein with multidrug resistance-associated protein 1 was studied by carboxy fluorescein efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic in the multidrug resistance-associated protein 1 overexpressing GLC4/ADR cell line compared to GLC4. Multidrug resistance-associated protein 1 inhibition with MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by rhein. No P-glycoprotein dependent rhein efflux was observed, nor was topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR mechanisms. Rhein is a substrate for multidrug resistance-associated protein 1 and induces apoptosis. It could therefore render the colonic epithelium sensitive to cytotoxic agents, apart from being toxic in itself. British Journal of Cancer (2002) 86, 1494–1500. DOI: 10.1038/sj/bjc/6600255 www.bjcancer.com © 2002 Cancer Research UK PMID:11986786

  20. Use of Ceftolozane/Tazobactam in the Treatment of Multidrug-resistant Pseudomonas aeruginosa Bloodstream Infection in a Pediatric Leukemia Patient.

    PubMed

    Aitken, Samuel L; Kontoyiannis, Dimitrios P; DePombo, April M; Bhatti, Micah M; Tverdek, Frank P; Gettys, Suzanne C; Nicolau, David P; Nunez, Cesar A

    2016-09-01

    Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P. aeruginosa bloodstream infection in a pediatric leukemia patient with ceftolozane/tazobactam and provides the first description of its pharmacokinetics in pediatrics. PMID:27254038

  1. Amikacin Concentrations Predictive of Ototoxicity in Multidrug-Resistant Tuberculosis Patients

    PubMed Central

    Modongo, Chawangwa; Pasipanodya, Jotam G.; Zetola, Nicola M.; Williams, Scott M.; Sirugo, Giorgio

    2015-01-01

    Aminoglycosides, such as amikacin, are used to treat multidrug-resistant tuberculosis. However, ototoxicity is a common problem and is monitored using peak and trough amikacin concentrations based on World Health Organization recommendations. Our objective was to identify clinical factors predictive of ototoxicity using an agnostic machine learning method. We used classification and regression tree (CART) analyses to identify clinical factors, including amikacin concentration thresholds that predicted audiometry-confirmed ototoxicity among 28 multidrug-resistant pulmonary tuberculosis patients in Botswana. Amikacin concentrations were measured for all patients. The quantitative relationship between predictive factors and the probability of ototoxicity were then identified using probit analyses. The primary predictors of ototoxicity on CART analyses were cumulative days of therapy, followed by cumulative area under the concentration-time curve (AUC), which improved on the primary predictor by 87%. The area under the receiver operating curve was 0.97 on the test set. Peak and trough were not predictors in any tree. When algorithms were forced to pick peak and trough as primary predictors, the area under the receiver operating curve fell to 0.46. Probit analysis revealed that the probability of ototoxicity increased sharply starting after 6 months of therapy to near maximum at 9 months. A 10% probability of ototoxicity occurred with a threshold cumulative AUC of 87,232 days · mg · h/liter, while that of 20% occurred at 120,000 days · mg · h/liter. Thus, cumulative amikacin AUC and duration of therapy, and not peak and trough concentrations, should be used as the primary decision-making parameters to minimize the likelihood of ototoxicity in multidrug-resistant tuberculosis. PMID:26248372

  2. Transcriptional and proteomic analyses of two-component response regulators in multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Zhou, Lei; Yang, Liu; Zeng, Xianfei; Danzheng, Jiacuo; Zheng, Qing; Liu, Jiayun; Liu, Feng; Xin, Yijuan; Cheng, Xiaodong; Su, Mingquan; Ma, Yueyun; Hao, Xiaoke

    2015-07-01

    Two-component systems (TCSs) have been reported to exhibit a sensing and responding role under drug stress that induces drug resistance in several bacterial species. However, the relationship between TCSs and multidrug resistance in Mycobacterium tuberculosis has not been comprehensively analysed to date. In this study, 90 M. tuberculosis clinical isolates were analysed using 15-loci mycobacterial interspersed repetitive unit (MIRU)-variable number tandem repeat (VNTR) typing and repetitive extragenic palindromic (rep)-PCR-based DNA fingerprinting. The results showed that all of the isolates were of the Beijing lineage, and strains with a drug-susceptible phenotype had not diverged into similar genotype clusters. Expression analysis of 13 response regulators of TCSs using real-time PCR and tandem mass spectrometry (MS/MS) proteomic analysis demonstrated that four response regulator genes (devR, mtrA, regX3 and Rv3143) were significantly upregulated in multidrug-resistant (MDR) strains compared with the laboratory strain H37Rv as well as drug-susceptible and isoniazid-monoresistant strains (P<0.05). DNA sequencing revealed that the promoter regions of devR, mtrA, regX3 and Rv3143 did not contain any mutations. Moreover, expression of the four genes could be induced by most of the four first-line antitubercular agents. In addition, either deletion or overexpression of devR in Mycobacterium bovis BCG did not alter its sensitivity to the four antitubercular drugs. This suggests that upregulation of devR, which is common in MDR-TB strains, might be induced by drug stress and hypoxic adaptation following the acquisition of multidrug resistance. PMID:25937537

  3. TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug-Resistant Breast Cancer.

    PubMed

    Song, Jie; Huang, Houcai; Xia, Zhi; Wei, Yingjie; Yao, Nan; Zhang, Li; Yan, Hongmei; Jia, Xiaobin; Zhang, Zhenhai

    2016-09-01

    The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS-Icariside II-phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer. PMID:26293804

  4. Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells.

    PubMed

    Mo, Lihong; Pospichalova, Vendula; Huang, Zhiqing; Murphy, Susan K; Payne, Sturgis; Wang, Fang; Kennedy, Margaret; Cianciolo, George J; Bryja, Vitezslav; Pizzo, Salvatore V; Bachelder, Robin E

    2015-01-01

    Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in stage III/IV ovarian cancer patients, ascites is associated with cancer progression. However, whether ascites drives multidrug resistance in ovarian cancer cells awaits elucidation. Here, we demonstrate that when cultured with ascites derived from ovarian cancer-bearing mice, a murine ovarian cancer cell line became less sensitive to paclitaxel, a first line chemotherapeutic agent for ovarian cancer patients. Moreover, incubation of murine ovarian cancer cells in vitro with ascites drives efflux function in these cells. Functional studies show ascites-driven efflux is suppressible by specific inhibitors of either of two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer Related Protein (BCRP)]. To demonstrate relevance of our findings to ovarian cancer patients, we studied relative efflux in human ovarian cancer cells obtained from either patient ascites or from primary tumor. Immortalized cell lines developed from human ascites show increased susceptibility to efflux inhibitors (MRP1, BCRP) compared to a cell line derived from a primary ovarian cancer, suggesting an association between ascites and efflux function in human ovarian cancer. Efflux in ascites-derived human ovarian cancer cells is associated with increased expression of ABC transporters compared to that in primary tumor-derived human ovarian cancer cells. Collectively, our findings identify a novel activity for ascites in promoting ovarian cancer multidrug resistance. PMID:26148191

  5. Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction.

    PubMed

    Nishikawa, Joy L; Boeszoermenyi, Andras; Vale-Silva, Luis A; Torelli, Riccardo; Posteraro, Brunella; Sohn, Yoo-Jin; Ji, Fei; Gelev, Vladimir; Sanglard, Dominique; Sanguinetti, Maurizio; Sadreyev, Ruslan I; Mukherjee, Goutam; Bhyravabhotla, Jayaram; Buhrlage, Sara J; Gray, Nathanael S; Wagner, Gerhard; Näär, Anders M; Arthanari, Haribabu

    2016-02-25

    Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. Aberrant function of transcription activators has been implicated in several diseases. However, therapeutic targeting efforts have been hampered by a lack of detailed molecular knowledge of the mechanisms of gene activation by disease-associated transcription activators. We previously identified an activator-targeted three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11/Med15 Mediator subunits in fungi. The Gal11/Med15 KIX domain engages pleiotropic drug resistance transcription factor (Pdr1) orthologues, which are key regulators of the multidrug resistance pathway in Saccharomyces cerevisiae and in the clinically important human pathogen Candida glabrata. The prevalence of C. glabrata is rising, partly owing to its low intrinsic susceptibility to azoles, the most widely used antifungal agent. Drug-resistant clinical isolates of C. glabrata most commonly contain point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway represents a linchpin in C. glabrata multidrug resistance. Here we perform sequential biochemical and in vivo high-throughput screens to identify small-molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Determining the NMR structure of the C. glabrata Gal11A KIX domain provides a detailed understanding of the molecular mechanism of Pdr1 gene activation and multidrug resistance inhibition by iKIX1. We have demonstrated the feasibility of small-molecule targeting of a

  6. Molecular Characterization of Multidrug-Resistant Isolates of Mycobacterium tuberculosis from Patients in North India

    PubMed Central

    Siddiqi, Noman; Shamim, Mohammed; Hussain, Seema; Choudhary, Rakesh Kumar; Ahmed, Niyaz; Prachee; Banerjee, Sharmistha; Savithri, G. R.; Alam, Mahfooz; Pathak, Niteen; Amin, Amol; Hanief, Mohammed; Katoch, V. M.; Sharma, S. K.; Hasnain, Seyed E.

    2002-01-01

    The World Health Organization has identified India as a major hot-spot region for Mycobacterium tuberculosis infection. We have characterized the sequences of the loci associated with multidrug resistance in 126 clinical isolates of M. tuberculosis from India to identify the respective mutations. The loci selected were rpoB (rifampin), katG and the ribosomal binding site of inhA (isoniazid), gyrA and gyrB (ofloxacin), and rpsL and rrs (streptomycin). We found known as well as novel mutations at these loci. Few of the mutations at the rpoB locus could be correlated with the drug resistance levels exhibited by the M. tuberculosis isolates and occurred with frequencies different from those reported earlier. Missense mutations at codons 526 to 531 seemed to be crucial in conferring a high degree of resistance to rifampin. We identified a common Arg463Leu substitution in the katG locus and certain novel insertions and deletions. Mutations were also mapped in the ribosomal binding site of the inhA gene. A Ser95Thr substitution in the gyrA locus was the most common mutation observed in ofloxacin-resistant isolates. A few isolates showed other mutations in this locus. Seven streptomycin-resistant isolates had a silent mutation at the lysine residue at position 121. While certain mutations are widely present, pointing to the magnitude of the polymorphisms at these loci, others are not common, suggesting diversity in the multidrug-resistant M. tuberculosis strains prevalent in this region. Our results additionally have implications for the development of methods for multidrug resistance detection and are also relevant in the shaping of future clinical treatment regimens and drug design strategies. PMID:11796356

  7. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Hazbón, Manzour Hernando; Brimacombe, Michael; Bobadilla del Valle, Miriam; Cavatore, Magali; Guerrero, Marta Inírida; Varma-Basil, Mandira; Billman-Jacobe, Helen; Lavender, Caroline; Fyfe, Janet; García-García, Lourdes; León, Clara Inés; Bose, Mridula; Chaves, Fernando; Murray, Megan; Eisenach, Kathleen D; Sifuentes-Osornio, José; Cave, M Donald; Ponce de León, Alfredo; Alland, David

    2006-08-01

    The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. PMID:16870753

  8. Multidrug resistance-associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate.

    PubMed

    Homolya, László; Váradi, András; Sarkadi, Balázs

    2003-01-01

    Many endogenous or xenobiotic lipophilic substances are eliminated from the cells by the sequence of oxidation, conjugation to an anionic group (glutathione, glucuronate or sulfate) and transport across the plasma membrane into the extracellular space. The latter step is mediated by integral membrane glycoproteins belonging to the superfamily of ATP-Binding Cassette (ABC) transporters. A subfamily, referred as ABCC, includes the famous/infamous cystic fibrosis transmembrane regulator (CFTR), the sulfonylurea receptors (SUR 1 and 2), and the multidrug resistance-associated proteins (MRPs). The name of the MRPs refers to their potential role in clinical multidrug resistance, a phenomenon that hinders the effective chemotherapy of tumors. The MRPs that have been functionally characterized so far share the property of ATP-dependent export pumps for conjugates with glutathione (GSH), glucuronate or sulfate. MRP1 and MRP2 are also mediating the cotransport of unconjugated amphiphilic compounds together with free GSH. MRP3 preferentially transports glucuronides but not glutathione S-conjugates or free GSH. MRP1 and MRP2 also contribute to the control of the intracellular glutathione disulfide (GSSG) level. Although these proteins are low affinity GSSG transporters, they can play essential role in response to oxidative stress when the activity of GSSG reductase becomes rate limiting. The human MRP4, MRP5 and MRP6 have only partially been characterized. However, it has been revealed that MRP4 can function as an efflux pump for cyclic nucleotides and nucleoside analogues, used as anti-HIV drugs. MRP5 also transports GSH conjugates, nucleoside analogues, and possibly heavy metal complexes. Transport of glutathione S-conjugates mediated by MRP6, the mutation of which causes pseudoxantoma elasticum, has recently been shown. In summary, numerous members of the multidrug resistance-associated protein family serve as export pumps that prevent the accumulation of anionic conjugates

  9. Genome Evolution and Plasticity of Serratia marcescens, an Important Multidrug-Resistant Nosocomial Pathogen

    PubMed Central

    Iguchi, Atsushi; Nagaya, Yutaka; Pradel, Elizabeth; Ooka, Tadasuke; Ogura, Yoshitoshi; Katsura, Keisuke; Kurokawa, Ken; Oshima, Kenshiro; Hattori, Masahira; Parkhill, Julian; Sebaihia, Mohamed; Coulthurst, Sarah J.; Gotoh, Naomasa; Thomson, Nicholas R.; Ewbank, Jonathan J.; Hayashi, Tetsuya

    2014-01-01

    Serratia marcescens is an important nosocomial pathogen that can cause an array of infections, most notably of the urinary tract and bloodstream. Naturally, it is found in many environmental niches, and is capable of infecting plants and animals. The emergence and spread of multidrug-resistant strains producing extended-spectrum or metallo beta-lactamases now pose a threat to public health worldwide. Here we report the complete genome sequences of two carefully selected S. marcescens strains, a multidrug-resistant clinical isolate (strain SM39) and an insect isolate (strain Db11). Our comparative analyses reveal the core genome of S. marcescens and define the potential metabolic capacity, virulence, and multidrug resistance of this species. We show a remarkable intraspecies genetic diversity, both at the sequence level and with regards genome flexibility, which may reflect the diversity of niches inhabited by members of this species. A broader analysis with other Serratia species identifies a set of approximately 3,000 genes that characterize the genus. Within this apparent genetic diversity, we identified many genes implicated in the high virulence potential and antibiotic resistance of SM39, including the metallo beta-lactamase and multiple other drug resistance determinants carried on plasmid pSMC1. We further show that pSMC1 is most closely related to plasmids circulating in Pseudomonas species. Our data will provide a valuable basis for future studies on S. marcescens and new insights into the genetic mechanisms that underlie the emergence of pathogens highly resistant to multiple antimicrobial agents. PMID:25070509

  10. Emergence of Multidrug Resistance and Metallo-beta-lactamase Producing Acinetobacter baumannii Isolated from Patients in Shiraz, Iran

    PubMed Central

    Moghadam, MN; Motamedifar, M; Sarvari, J; Sedigh, Ebrahim-Saraie H; Mousavi, Same M; Moghadam, FN

    2016-01-01

    Background: Metallo-beta-lactamase (MβL) enzymes production is one of the most important resistance mechanisms against carbapenems in some bacteria including Acinetobacter baumannii. Aims: This study was aimed to determine the antimicrobial susceptibility and the prevalence of MβL among carbapenem-resistant isolates of A. baumannii. Materials and Methods: In this cross-sectional study from October 2012 to April 2013, 98 isolates were identified as A. baumannii using Microgen™ kits and confirmed by molecular method. These isolates were tested for antimicrobial susceptibilities by disk diffusion method according to the Clinical and Laboratory Standards Institute guidelines. Carbapenem-resistant isolates were further detected phenotypically by MβL minimal inhibitory concentration (MIC)-test strips, and subsequently positive MβL isolates were confirmed by polymerase chain reaction (PCR). Results: Overall, 98% (96/98) of A. baumannii isolates were detected as carbapenem-resistant by MIC test. Highest sensitivity to the tested antibiotic with 42.9% (42/98) was observed to colistin. Of 96 carbapenem-resistant isolates, 43 were phenotypically positive for MβL; out of 43 isolates, 37 were confirmed for the presence of MβL genes by PCR. Conclusion: The frequency of drug resistance among the clinical samples of A. baumannii isolated in our study against most of the antibiotics was very high. Moreover, all MβL producing isolates were multidrug resistance. Therefore, systematic surveillance to detect MβL producing bacteria and rational prescription and use of carbapenems could be helpful to prevent the spread of carbapenem resistance. PMID:27398247

  11. Emergence of a Multidrug-Resistant Shiga Toxin-Producing Enterotoxigenic Escherichia coli Lineage in Diseased Swine in Japan.

    PubMed

    Kusumoto, Masahiro; Hikoda, Yuna; Fujii, Yuki; Murata, Misato; Miyoshi, Hirotsugu; Ogura, Yoshitoshi; Gotoh, Yasuhiro; Iwata, Taketoshi; Hayashi, Tetsuya; Akiba, Masato

    2016-04-01

    EnterotoxigenicEscherichia coli(ETEC) and Shiga toxin-producingE. coli(STEC) are important causes of diarrhea and edema disease in swine. The majority of swine-pathogenicE. colistrains belong to a limited range of O serogroups, including O8, O138, O139, O141, O147, O149, and O157, which are the most frequently reported strains worldwide. However, the circumstances of ETEC and STEC infections in Japan remain unknown; there have been few reports on the prevalence or characterization of swine-pathogenicE. coli In the present study, we determined the O serogroups of 967E. coliisolates collected between 1991 and 2014 from diseased swine in Japan, and we found that O139, O149, O116, and OSB9 (O serogroup ofShigella boydiitype 9) were the predominant serogroups. We further analyzed these four O serogroups using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, and virulence factor profiling. Most of the O139 and O149 strains formed serogroup-specific PFGE clusters (clusters I and II, respectively), whereas the O116 and OSB9 strains were grouped together in the same cluster (cluster III). All of the cluster III strains belonged to a single sequence type (ST88) and carried genes encoding both enterotoxin and Shiga toxin. This PFGE cluster III/ST88 lineage exhibited a high level of multidrug resistance (to a median of 10 antimicrobials). Notably, these bacteria were resistant to fluoroquinolones. Thus, this lineage should be considered a significant risk to animal production due to the toxigenicity and antimicrobial resistance of these bacteria. PMID:26865687

  12. Afatinib reverses multidrug resistance in ovarian cancer via dually inhibiting ATP binding cassette subfamily B member 1

    PubMed Central

    Wang, Sheng-qi; Liu, Shi-ting; Zhao, Bo-xin; Yang, Fu-heng; Wang, Ya-tian; Liang, Qian-ying; Sun, Ya-bin; Liu, Yuan; Song, Zhi-hua; Cai, Yun; Li, Guo-feng

    2015-01-01

    ABCB1-mediated multidrug resistance (MDR) remains a major obstacle to successful chemotherapy in ovarian cancer. Herein, afatinib at nontoxic concentrations significantly reversed ABCB1-mediated MDR in ovarian cancer cells in vitro (p < 0.05). Combining paclitaxel and afatinib caused tumor regressions and tumor necrosis in A2780T xenografts in vivo. More interestingly, unlike reversible TKIs, afatinib had a distinctive dual-mode action. Afatinib not only inhibited the efflux function of ABCB1, but also attenuated its expression transcriptionally via down-regulation of PI3K/AKT and MAPK/p38-dependent activation of NF-κB. Furthermore, apart from a substrate binding domain, afatinib could also bind to an ATP binding domain of ABCB1 through forming hydrogen bonds with Gly533, Gly534, Lys536 and Ala560 sites. Importantly, mutations in these four binding sites of ABCB1 and the tyrosine kinase domain of EGFR were not correlated with the reversal activity of afatinib on MDR. Given that afatinib is a clinically approved drug, our results suggest combining afatinib with chemotherapeutic drugs in ovarian cancer. This study can facilitate the rediscovery of superior MDR reversal agents from molecular targeted drugs to provide a more effective and safer way of resensitizing MDR. PMID:26317651

  13. Progesterone interacts with P-glycoprotein in multidrug-resistant cells and in the endometrium of gravid uterus.

    PubMed

    Yang, C P; DePinho, S G; Greenberger, L M; Arceci, R J; Horwitz, S B

    1989-01-15

    P-Glycoprotein (P-GP) plays a pivotal role in maintaining the multidrug-resistant (MDR) phenotype. This membrane glycoprotein is overproduced in MDR cells and the endometrium of the mouse gravid uterus (Arceci, R.J., Croop, J.M., Horwitz, S.B., and Housman, D. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 4350-4354). This latter observation and an interest in endogenous substrates for P-GP led to a study of the interaction of steroids with P-GP found in the endometrium of the mouse gravid uterus and in MDR cells derived from the murine macrophage-like cell J774.2. [3H]Azidopine labeling of P-GP from these two sources was inhibited by various steroids, particularly progesterone. Progesterone also markedly inhibited [3H]vinblastine binding to membrane vesicles prepared from MDR cells, enhanced vinblastine accumulation in MDR cells, and increased the sensitivity of MDR cells to vinblastine. In addition, we have demonstrated that the hydrophobicity of a steroid is important in determining its effect on inhibition of drug binding to P-GP. It is concluded that progesterone, a relatively nontoxic endogenous steroid, interacts with P-GP and is capable of reversing drug resistance in MDR cells. PMID:2562956

  14. Cytotoxicity of the Sesquiterpene Lactones Neoambrosin and Damsin from Ambrosia maritima Against Multidrug-Resistant Cancer Cells

    PubMed Central

    Saeed, Mohamed; Jacob, Stefan; Sandjo, Louis P.; Sugimoto, Yoshikazu; Khalid, Hassan E.; Opatz, Till; Thines, Eckhard; Efferth, Thomas

    2015-01-01

    Multidrug resistance is a prevailing phenomenon leading to chemotherapy treatment failure in cancer patients. In the current study two known cytotoxic pseudoguaianolide sesquiterpene lactones; neoambrosin (1) and damsin (2) that circumvent MDR were identified. The two cytotoxic compounds were isolated using column chromatography, characterized using 1D and 2D NMR, MS, and compared with literature values. The isolated compounds were investigated for their cytotoxic potential using resazurin assays and thereafter confirmed with immunoblotting and in silico studies. MDR cells overexpressing ABC transporters (P-glycoprotein, BCRP, ABCB5) did not confer cross-resistance toward (1) and (2), indicating that these compounds are not appropriate substrates for any of the three ABC transporters analyzed. Resistance mechanisms investigated also included; the loss of the functions of the TP53 and the mutated EGFR. The HCT116 p53-/- cells were sensitive to 1 but resistant to 2. It was interesting to note that resistant cells transfected with oncogenic ΔEGFR exhibited hypersensitivity CS toward (1) and (2) (degrees of resistances were 0.18 and 0.15 for (1) and (2), respectively). Immunoblotting and in silico analyses revealed that 1 and 2 silenced c-Src kinase activity. It was hypothesized that inhibition of c-Src kinase activity may explain CS in EGFR-transfected cells. In conclusion, the significant cytotoxicity of 1 and 2 against different drug-resistant tumor cell lines indicate that they may be promising candidates to treat refractory tumors. PMID:26617519

  15. Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

    PubMed Central

    Yu, Xiwei; Yang, Guang; Shi, Yijie; Su, Chang; Liu, Ming; Feng, Bo; Zhao, Liang

    2015-01-01

    Nowadays, multidrug resistance and side effects of drugs limit the effectiveness of chemotherapies in clinics. P-glycoprotein (P-gp) (MDR1), as a member of the ATP-binding cassette family, acts on transporting drugs into cell plasma across the membrane of cancer cells and leads to the occurrence of multidrug resistance, thus resulting in the failure of chemotherapy in cancer. The main aims of this research were to design a nanodelivery system for accomplishing the effective co-delivery of gene and antitumor drug and overcoming multidrug resistance effect. In this study, shMDR1 and gefitinib-encapsulating chitosan nanoparticles with sustained release, small particle size, and high encapsulation efficiency were prepared. The serum stability, protection from nuclease, and transfection efficiency of gene in vitro were investigated. The effects of co-delivery of shMDR1 and gefitinib in nanoparticles on reversing multidrug resistance were also evaluated by investigating the cytotoxicity, cellular uptake mechanism, and cell apoptosis on established gefitinib-resistant cells. The results demonstrated that chitosan nanoparticles entrapping gefitinib and shMDR1 had the potential to overcome the multidrug resistance and improve cancer treatment efficacy, especially toward resistant cells. PMID:26648717

  16. Effect of different agents onto multidrug resistant cells revealed by fluorescence correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Boutin, C.; Roche, Y.; Jaffiol, R.; Millot, J.-M.; Millot, C.; Plain, J.; Deturche, R.; Jeannesson, P.; Manfait, M.; Royer, P.

    Fluorescence correlation spectroscopy (FCS), which is a sensitive and non invasive technique, has been used to characterize the plasma membrane fluidity and heterogeneity of multidrug resistant living cells. At the single cell level, the effects of different membrane agents present in the extra-cellular medium have been analyzed. Firstly, we reveal a modification of plasma membrane microviscosity according to the addition of a fluidity modulator, benzyl alcohol. In the other hand, revertant such as verapamil and cyclosporin-A appears to act more specifically on the slow diffusion sites as microdomains.

  17. Spread of multidrug-resistant Pseudomonas aeruginosa clones in a university hospital.

    PubMed

    Koutsogiannou, Maria; Drougka, Eleanna; Liakopoulos, Apostolos; Jelastopulu, Eleni; Petinaki, Efthimia; Anastassiou, Evangelos D; Spiliopoulou, Iris; Christofidou, Myrto

    2013-02-01

    An outbreak of multidrug-resistant Pseudomonas aeruginosa (MDRPA) infections in a university hospital is described. Phenotypic and genotypic analysis of 240 isolates revealed that 152 patients, mainly in the intensive care unit (ICU), were colonized or infected with MDRPA, the majority with O11. All metallo-β-lactamase (MBL)-positive isolates carried the bla(VIM-2) or bla(VIM-1) gene. One or more type III secretion system toxin genes were detected in most isolates. Five dominant pulsed-field gel electrophoresis (PFGE) types were characterized, associated with ST235, ST111, ST253, ST309, and ST639. PMID:23241381

  18. Vancomycin for multi-drug resistant Enterococcus faecium cholangiohepatitis in a cat.

    PubMed

    Pressel, Michelle A; Fox, Leslie E; Apley, Michael D; Simutis, Frank J

    2005-10-01

    A 12-year-old, neutered male domestic shorthair cat was evaluated with a life-long history of intermittent, predominantly small bowel diarrhea and a 3 day history of hematochezia. At presentation, the cat had increased liver enzyme activities and an inflammatory leukogram. Histopathology demonstrated inflammatory bowel disease (IBD), cholangiohepatitis and pancreatitis. The cholangiohepatitis was associated with a multi-drug resistant Enterococcus faecium. Gallbladder agenesis was also documented. Treatment with vancomycin was safely instituted for 10 days. Clinical signs resolved, however, cure of the bacterial cholangiohepatitis was not achieved. The risk of vancomycin resistant enterococci (VRE) in human and veterinary medicine is discussed. PMID:16182186

  19. [Molecular genetic and bacteriological methods for the diagnosis of multidrug resistant M. tuberculosis].

    PubMed

    Agaev, F F; Aliev, K A; Salimova, N A; Abuzarov, R M; Gasymov, I A; Griadunov, D A

    2009-01-01

    For the early diagnosis of multidrug resistant tuberculosis, 67 sputum samples obtained from primary patients with different clinical forms of pulmonary tuberculosis were examined by the molecular genetic test using the TB-Biochip test system. Having a high sensitivity and specificity, the molecular genetic test for determining the drug sensitivity of Mycobacterium tuberculosis substantially accelerates its diagnosis (2-3 days) before the real-time mode of a patient's admission to the clinic. The method allows identification of mutations in the rpoB (resistance to R), katG, inhG, and ahpC (resistance to H) genes, which permits timely correction of performed specific treatment. PMID:19886013

  20. The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis

    PubMed Central

    Somoskovi, Akos

    2015-01-01

    To realize the most benefit from multidrug-resistant tuberculosis (MDR-TB) screening, all nucleic acid amplification test (NAAT)-positive respiratory specimens should be universally tested. Once an MDR-TB diagnosis is established, additional testing is warranted to provide details about the detected mutations. The lab-on-chip technology described by A. M. Cabibbe et al. (J Clin Microbiol 53:3876–3880, 2015, http://dx.doi.org/10.1128/JCM.01824-15) potentially provides this much needed information. PMID:26378276

  1. First report of an OXA-48-producing multidrug-resistant Proteus mirabilis strain from Gaza, Palestine.

    PubMed

    Chen, Liang; Al Laham, Nahed; Chavda, Kalyan D; Mediavilla, Jose R; Jacobs, Michael R; Bonomo, Robert A; Kreiswirth, Barry N

    2015-07-01

    We report the first multidrug-resistant Proteus mirabilis strain producing the carbapenemase OXA-48 (Pm-OXA-48) isolated at Al-Shifa hospital in Gaza, Palestine. Draft genome sequencing of Pm-OXA-48 identified 16 antimicrobial resistance genes, encoding resistance to β-lactams, aminoglycosides, fluoroquinolones, phenicols, streptothricin, tetracycline, and trimethoprim-sulfamethoxazole. Complete sequencing of the bla(OXA-48)-harboring plasmid revealed that it is a 72 kb long IncL/M plasmid, harboring carbapenemase gene bla(OXA-48), extended spectrum β-lactamase gene bla(CTX-M-14), and aminoglycoside resistance genes strA, strB, and aph(3')-VIb. PMID:25896692

  2. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain

    PubMed Central

    Halim, Mohd Zakihalani A.; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-01-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. PMID:26981419

  3. The multidrug resistance (mdr1) gene product functions as an ATP channel.

    PubMed Central

    Abraham, E H; Prat, A G; Gerweck, L; Seneveratne, T; Arceci, R J; Kramer, R; Guidotti, G; Cantiello, H F

    1993-01-01

    The multidrug resistance (mdr1) gene product, P-glycoprotein, is responsible for the ATP-dependent extrusion of a variety of compounds, including chemotherapeutic drugs, from cells. The data presented here show that cells with increased levels of the P-glycoprotein release ATP to the medium in proportion to the concentration of the protein in their plasma membrane. Furthermore, measurements of whole-cell and single-channel currents with patch-clamp electrodes indicate that the P-glycoprotein serves as an ATP-conducting channel in the plasma membrane. These findings suggest an unusual role for the P-glycoprotein. PMID:7678345

  4. Diterpene Constituents of Euphorbia exigua L. and Multidrug Resistance Reversing Activity of the Isolated Diterpenes.

    PubMed

    Rédei, Dóra; Boros, Klára; Forgo, Peter; Molnár, Joseph; Kele, Zoltán; Pálinkó, István; Pinke, Gyula; Hohmann, Judit

    2015-08-01

    Phytochemical investigation of the MeOH extract obtained from the aerial parts of the annual weed Euphorbia exigua L. resulted in the isolation of two novel (1, 2) and one known (3) jatrophane diterpenes. Their structures were established by extensive 1D- and 2D-NMR spectroscopy and HR-ESI-MS. The isolated compounds were evaluated for multidrug resistance (MDR) reversing activity on human MDR gene-transfected L5178 mouse lymphoma cells; and all three compounds were found to modulate the intracellular drug accumulation. PMID:26265573

  5. Management of emerging multidrug-resistant tuberculosis in a low-prevalence setting.

    PubMed

    Catho, G; Couraud, S; Grard, S; Bouaziz, A; Sénéchal, A; Valour, F; Perpoint, T; Braun, E; Biron, F; Ferry, T; Chidiac, C; Freymond, N; Perrot, E; Souquet, P-J; Maury, J-M; Tronc, F; Veziris, N; Lina, G; Dumitrescu, O; Ader, F

    2015-05-01

    Multidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies. PMID:25708551

  6. First Two Cases of Fungal Infections Associated with Multi-drug Resistant Yeast, Fereydounia khargensis.

    PubMed

    Tap, Ratna Mohd; Ramli, Nur Yasmin; Sabaratnam, Parameswari; Hashim, Rohaidah; Bakri, Ahmed Rafezzan Ahmed; Bee, Lim Bee; Ginsapu, Stephanie Jane; Ahmad, Rahimah; Razak, Mohd Fuat Abd; Ahmad, Norazah

    2016-08-01

    The number of new fungal pathogens is increasing due to growing population of immunocompromised patients and advanced identification techniques. Fereydounia khargensis is a yeast and was first described in 2014 from environmental samples. As far as we know, this is the first report of human infections associated with F. khargensis. The yeasts were isolated from blood of a HIV-positive patient and pleural fluid of chronic renal failure patient. Amplification and sequencing of the internal transcribed spacer and the large subunit regions confirmed the identity of the isolates. Both isolates showed multi-drug resistance to antifungal agents tested. PMID:27010640

  7. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain.

    PubMed

    Halim, Mohd Zakihalani A; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-03-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. PMID:26981419

  8. [Molecular physiology of receptor mediated endocytosis and its role in overcoming multidrug resistance].

    PubMed

    Severin, E S; Posypanova, G A

    2011-06-01

    Receptor-mediated endocytosis plays important role in the selective uptake of proteins at the plasma membrane of eukaryotic cells. Endocytosis regulates many processes of cell signalling by controlling the number of functional receptors on the cell surface. The article reviews the mechanism of clathrin-dependent endocytosis and the possibility of using this phenomenon for the targeted delivery of drugs. Use of certain proteins as targeting component of drug delivery systems can significantly improve the selectivity of this drug, as well as to overcome the multidrug resistance of cells resulting from the activity of the ABC-transporters. PMID:21874867

  9. Two pimarane diterpenoids from Ephemerantha lonchophylla and their evaluation as modulators of the multidrug resistance phenotype.

    PubMed

    Na, G X; Wang, T S; Yin, L; Pan, Y; Guo, Y L; LeBlanc, G A; Reinecke, M G; Watson, W H; Krawiec, M

    1998-01-01

    Two new pimarane diterpenoids, lonchophylloids A (1) and B (2), were isolated from the stems of Ephemerantha lonchophylla. The structures of 1 and 2 were established predominantly through the application of extensive 1H-and 13C-NMR, 1D- and 2D-homonuclear and heteronuclear correlation NMR experiments, and X-ray diffraction methods. Consistent with structure--activity predictions, both compounds were capable of sensitizing cells that expressed the multidrug resistance phenotype to the toxicity of the anticancer drug doxorubicin. PMID:9461658

  10. Identification of selenocompounds with promising properties to reverse cancer multidrug resistance.

    PubMed

    Domínguez-Álvarez, Enrique; Gajdács, Márió; Spengler, Gabriella; Palop, Juan Antonio; Marć, Małgorzata Anna; Kieć-Kononowicz, Katarzyna; Amaral, Leonard; Molnár, Joseph; Jacob, Claus; Handzlik, Jadwiga; Sanmartín, Carmen

    2016-06-15

    In previous studies, 56 novel selenoesters and one cyclic selenoanhydride with chemopreventive, antiproliferative and cytotoxic activity were described. Herein, the selenoanhydride and selected selenoesters were evaluated for their ability to reverse the cancer multidrug resistance (MDR) using the ABCB1 efflux pump inhibition assay in mouse MDR T-lymphoma cells. Results showed that the selenoanhydride (1) and the selenoesters with ketone terminal fragments (9-11) exerted (1.7-3.6)-fold stronger efflux pump inhibitory action than the reference verapamil. In addition, those four derivatives triggered apoptotic events in more than 80% of the examined MDR mouse cells. PMID:27156771

  11. Selective Conditions for a Multidrug Resistance Plasmid Depend on the Sociality of Antibiotic Resistance

    PubMed Central

    Wood, A. Jamie; Brockhurst, Michael A.

    2016-01-01

    Multidrug resistance (MDR) plasmids frequently carry antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show here that the antibiotic concentrations selecting for the RK2 plasmid in Escherichia coli depend upon the sociality of the drug resistance: the selection for selfish drug resistance (efflux pump) occurred at very low drug concentrations, just 1.3% of the MIC of the plasmid-free antibiotic-sensitive strain, whereas selection for cooperative drug resistance (modifying enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain. PMID:26787694

  12. Multidrug-resistant tuberculosis outbreak on an HIV ward--Madrid, Spain, 1991-1995.

    PubMed

    1996-04-26

    Beginning in 1990, outbreaks of multidrug-resistant tuberculosis (MDR-TB) have been reported in hospitals and prisons in the eastern United States (1). During June 1991-January 1995, MDR-TB was diagnosed in 47 patients and one health-care worker at a 120-bed, infectious disease referral hospital in urban Madrid; on April 19, 1995, the Spanish Field Epidemiology Training Program was asked to investigate this outbreak. This report summarizes the findings of this investigation, which suggested that nosocomial transmission of MDR-TB occurred on a hospital ward for patients with human immunodeficiency virus (HIV) infection. PMID:8602134

  13. Characterization of an IncA/C Multidrug Resistance Plasmid in Vibrio alginolyticus.

    PubMed

    Ye, Lianwei; Li, Ruichao; Lin, Dachuan; Zhou, Yuanjie; Fu, Aisi; Ding, Qiong; Chan, Edward Wai Chi; Yao, Wen; Chen, Sheng

    2016-05-01

    Cephalosporin-resistant Vibrio alginolyticus was first isolated from food products, with β-lactamases encoded by blaPER-1, blaVEB-1, and blaCMY-2 being the major mechanisms mediating their cephalosporin resistance. The complete sequence of a multidrug resistance plasmid, pVAS3-1, harboring the blaCMY-2 and qnrVC4 genes was decoded in this study. Its backbone exhibited genetic homology to known IncA/C plasmids recoverable from members of the family Enterobacteriaceae, suggesting its possible origin in Enterobacteriaceae. PMID:26976864

  14. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal

    PubMed Central

    Choi, Cheol-Hee

    2005-01-01

    One of the major problems related with anticancer chemotherapy is resistance against anticancer drugs. The ATP-binding cassette (ABC) transporters are a family of transporter proteins that are responsible for drug resistance and a low bioavailability of drugs by pumping a variety of drugs out cells at the expense of ATP hydrolysis. One strategy for reversal of the resistance of tumor cells expressing ABC transporters is combined use of anticancer drugs with chemosensitizers. In this review, the physiological functions and structures of ABC transporters, and the development of chemosensitizers are described focusing on well-known proteins including P-glycoprotein, multidrug resistance associated protein, and breast cancer resistance protein. PMID:16202168

  15. Partial synthesis and biological evaluation of bisbenzylisoquinoline alkaloids derivatives: potential modulators of multidrug resistance in cancer.

    PubMed

    He, Ping; Sun, Hua; Jian, Xi-Xian; Chen, Qiao-Hong; Chen, Dong-Lin; Liu, Geng-Tao; Wang, Feng-Peng

    2012-01-01

    A series of new bisbenzylisoquinoline alkaloids was partially synthesized from tetrandrine and fangchinoline and evaluated for their ability to reverse P-glycoprotein-mediated multidrug resistance (MDR) in cancer cells. All the test compounds increased the intracellular accumulation rate of rhodamine 123 in MDR cells (Bel7402 and HCT8), and most exhibited more potent MDR-reversing activity relative to the reference compound verapamil. Compounds 8, 10, 13, and 14 enhanced intracellular accumulation of doxorubicin in Bel7402 and HCT8 cells. PMID:22587798

  16. Reversal of the multidrug resistance by drug combination using multifunctional liposomes

    NASA Astrophysics Data System (ADS)

    Patel, Niravkumar R.

    One of the major obstacles to the success of cancer chemotherapy is the multi-drug resistance (MDR) that results due mainly to the over-expression of drug efflux transporter pumps such as P-glycoprotein (P-gp). Highly efficacious third generation P-gp inhibitors, like tariquidar, have shown promising results against MDR. However, P-gp is also expressed in normal tissues like the blood-brain barrier, gastrointestinal tract, liver and kidney. It is therefore important to limit the exposure of P-gp inhibitors to normal tissues and increase their co-localization with anticancer agents in tumor tissues to maximize the efficacy of a P-gp inhibitor. To minimize non-specific binding and increase its delivery to tumor tissues, liposomes, self-assembling phospholipid vesicles, were chosen as a drug delivery vehicle. The liposome has been identified as a system capable of carrying molecules with diverse physicochemical properties. It can also alter the pharmacokinetic profile of loaded molecules which is a concern with both tariquidar and paclitaxel. Liposomes can easily be surface-modified rendering them cell-specific as well as organelle-specific. The main objective of present study was to develop an efficient liposomal delivery system which would deliver therapeutic molecules of interest to tumor tissues and avoid interaction with normal tissues. In this study, the co-delivery of tariquidar and paclitaxel into tumor cells to reverse the MDR using long-circulating cationic liposomes was investigated. SKOV-3TR, the resistant variant of SKOV-3 and MCF-7/ADR, the resistant variant of MCF-7 were used as model cell lines. Uniform liposomal formulations were generated with high incorporation efficiency and no apparent decrease in tariquidar potency towards P-gp. Tariquidar- and paclitaxel- co-loaded long-circulating liposomes showed significant re-sensitization of SKOV-3TR and MCF-7/ADR for paclitaxel in vitro. Further modification of these liposomes with antitumor 2C5 resulted

  17. Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance.

    PubMed

    Pape, Veronika F S; Tóth, Szilárd; Füredi, András; Szebényi, Kornélia; Lovrics, Anna; Szabó, Pál; Wiese, Michael; Szakács, Gergely

    2016-07-19

    There is a constant need for new therapies against multidrug