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Sample records for adequate antibiotic therapy

  1. [Sepsis management -- antibiotic therapy].

    PubMed

    Welte, T

    2004-11-26

    Sepsis is one of the most frequent infectious problems at Intensive Care Units, and sepsis is associated with significant mortality. The latter could not be markedly reduced in the last years, despite a number of advances in the field of volume substitution, catecholamines, and endocrinologic therapy. The reason might be that important steps towards overcoming of sepsis are the surgical resection of infectious foci and an adequate antibiotic treatment. A critical role plays the growing resistance of pathogens against the common antibiotics. Since no major progress in the development of new antibiotics can be expected for the next years, sepsis treatment must be focused on prevention of infection, and on an optimised application of current antibiotic substances. The key factors are a broad and high dose initial treatment, a de-escalation strategy according to the clinical course, and -with exceptions- a limitation of treatment to 7 to 10 days. Rotation of antibiotics should be performed, if problems with resistances exist or no specialist for infectious diseases is available on the Intensive Care Unit.

  2. Systemic antibiotic therapy in periodontics

    PubMed Central

    Kapoor, Anoop; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak

    2012-01-01

    Systemic antibiotics in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy. PMID:23559912

  3. [Antibiotic therapy in psittacines].

    PubMed

    Krautwald, M E

    1989-01-01

    The use of different antibiotics in psittacines is described. Among other aspects especially the anatomy of the bird and its consequence for the application of medicaments is taken into account. The use of antibiotics in psittacines often turns out to be difficult because of missing data about their pharmacokinetics, dosage, period of application and their compatibility. In order to deal with the increasing number of pet-birds in the veterinary practice, further examinations have to be conducted. PMID:2655172

  4. Nebulized antibiotics. An adequate option for treating ventilator-associated respiratory infection?

    PubMed

    Rodríguez, A; Barcenilla, F

    2015-03-01

    Ventilator-associated tracheobronchitis (VAT) is a frequent complication in critical patients. The 90% of those who develop it receive broad-spectrum antibiotic (ATB) treatment, without any strong evidence of its favorable impact. The use of nebulized ATB could be a valid treatment option, to reduce the use of systemic ATB and the pressure of selection on the local flora. Several studies suggest that an adequate nebulization technique can ensure high levels of ATB even in areas of lung consolidation, and to obtain clinical and microbiological cure. New studies are needed to properly assess the impact of treatment with nebulized ATB on the emergence of resistance.

  5. [Duration of antibiotic therapy in bacterial meningitis].

    PubMed

    Pereira, P Ricardo; Borges, Fernando; Mansinho, Kamal

    2013-01-01

    The duration of antibiotic therapy in bacterial meningitis is a controversial issue. Antibiotic regimens have changed over time along with the criteria used to determine the ideal antibiotic therapy duration. The authors aim to make an historical overview on this matter and simultaneously add the evidence of recent studies, pointing out some issues in results interpretation, namely, their design and the associated demographic and epidemiological questions. Clinical assays on this subject, with statistically significant results, are quite recent. Most of the scientific knowledge has been acquired empirically through the times. The actual investigation paradigm, in what concerns to antibiotic therapy in bacterial meningitis, lays on the dichotomy: "short versus long duration regimens". Nevertheless, so far, the existing studies have not completely cleared this doubt. Thus, despite some evidence suggests that short duration antibiotic regimens are effective for some patients, in patients with severe disease presentations or with other morbidities its use may be questioned.

  6. [Inhaled antibiotic therapy in cystic fibrosis].

    PubMed

    Girón Moreno, Rosa M; Salcedo Posadas, Antonio; Mar Gómez-Punter, Rosa

    2011-06-01

    Cystic fibrosis is the most frequent fatal genetically-transmitted disease among Caucasians. Chronic bronchial infection, especially by Pseudomonas aeruginosa, is the main cause of morbidity and mortality in this disease. Aerosolized antibiotic therapy achieves high drug concentrations in the airway with low toxicity, allowing chronic use. Currently, two antibiotics have been approved for inhalation therapy, tobramycin inhalation solution and colistimethate sodium aerosol. There is less evidence from clinical trials for the latter. The main indication for these drugs is chronic bronchial colonization by P. aeruginosa, although there is increasing evidence of the importance of the primary infection by this bacterium, whether treated by oral or intravenous antibiotics or not. More controversial is the use of aerosolized antibiotic therapy in bacterial prophylaxis or respiratory exacerbations. For many years, intravenous formulations of distinct antibiotics for aerosolized use have been employed, which are in distinct phases of research for use in nebulizer therapy. In addition to being used to treat P. aeruginosa infection, aerosolized antibiotics have been used to treat other pathogens such as methicillin-resistant Staphylococus aureus, Mycobacterium abscessus and Aspergillus fumigatus. PMID:21703474

  7. [Antipyocyanic antibiotic therapy. Principles and efficacy factors].

    PubMed

    Cohen, R

    2006-10-01

    Pseudomonas aeruginosa is among the bacterial species one of the most resistant "naturally" to antibiotics and one of which acquires most easily resistance to antibiotics. The major principle of the treatment of the infections due to P. aeruginosa is the use of antibiotic association to decrease the risk of emergence of resistant strains. Pharmacokinetic-pharmacodynamic parameters of antimicrobials with antipseudomonal activity are gaining importance as a mean of optimization of antibiotic therapy: tobramycin among the aminosides, ceftazidime among the beta-lactam antibiotics and ciprofloxacin among the quinolones have the best profile. The new mechanisms of pathogenicity or resistance (biofilm secretion, quorum sensing, hypermutator phenomenon) far from being opposed to the rules of prescription reinforce and complicate them.

  8. Therapy of acute gastroenteritis: role of antibiotics.

    PubMed

    Zollner-Schwetz, I; Krause, R

    2015-08-01

    Acute infectious diarrhoea remains a very common health problem, even in the industrialized world. One of the dilemmas in assessing patients with acute diarrhoea is deciding when to test for aetiological agents and when to initiate antimicrobial therapy. The management and therapy of acute gastroenteritis is discussed in two epidemiological settings: community-acquired diarrhoea and travellers' diarrhoea. Antibiotic therapy is not required in most patients with acute gastroenteritis, because the illness is usually self-limiting. Antimicrobial therapy can also lead to adverse events, and unnecessary treatments add to resistance development. Nevertheless, empirical antimicrobial therapy can be necessary in certain situations, such as patients with febrile diarrhoeal illness, with fever and bloody diarrhoea, symptoms persisting for >1 week, or immunocompromised status.

  9. [Antibiotic Stewardship].

    PubMed

    Lanckohr, Christian; Ellger, Björn

    2016-02-01

    The adequate management of infections is an important task in critical care medicine which has an effect on patient outcome. As a result, the prevalence of antiinfective therapy is high in intensive care units. In the face of an unsettling development of worldwide microbial resistance, an optimization and reduction of antiinfective therapy is necessary. Antibiotic stewardship tries to improve antiinfective therapy with an interdisciplinary approach. One overall objective of antibiotic stewardship is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Intensive care units are important fields of action for antibiotic stewardship interventions. This article reviews available evidence and some practical aspects for antibiotic stewardship.

  10. Antibiotic Therapy for Infective Endocarditis in Childhood

    PubMed Central

    Calza, Leonardo; Manfredi, Roberto; Chiodo, Francesco

    2006-01-01

    Infective endocarditis is relatively uncommon in childhood, but its epidemiology has changed in the past three to four decades and its incidence has been increasing in recent years. With the improved survival rates of children with congenital heart diseases and the overall decreased frequency of rheumatic valvular heart disease in developed countries, congenital cardiac abnormalities now represent the predominant underlying condition for infective endocarditis in children over the age of two years in Western Europe and Northern America. Moreover, the complex management of neonatal and pediatric intensive care unit patients has increased the risk of catheter-related endocarditis. More specifically, the surgical correction of congenital heart alterations is associated with the risk of postoperative infections. Endocarditis in children may be difficult to diagnosis and manage. Emerging resistant bacteria, such as methicillin- or vancomycin-resistant staphylococci and vancomycin-resistant enterococci, are becoming a new challenge for conventional antibiotic therapy. Newer antimicrobial compounds recently introduced in clinical practice, such as streptogramins and oxazolidinones, may be effective alternatives in children with endocarditis sustained by Gram-positive cocci resistant to glycopeptides. Home intravenous therapy has become an acceptable approach for stable patients who are at low risk for embolic complications. However, further clinical studies are needed in order to assess efficacy and safety of these antimicrobial agents in children. This review should help outline the most appropriate antimicrobial treatments for infective endocarditis in children. PMID:23118646

  11. Gut Check: IFNγ Delays Mucosal Recovery during Antibiotic Therapy.

    PubMed

    Chung, Lawton K; Bliska, James B

    2016-08-10

    Antibiotic therapy has been largely ineffective in improving clinical outcomes following Salmonellosis, yet the reasons why remain obscure. In this issue of Cell Host & Microbe, Dolowschiak et al. (2016) report that IFNγ produced by NK and T cells following antibiotic treatment of acute Salmonella infection limits mucosal remission. PMID:27512899

  12. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy.

    PubMed

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B H

    2016-04-01

    Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa.

  13. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy.

    PubMed

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B H

    2016-04-01

    Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa. PMID:27019964

  14. Antibiotic Therapy for Very Low Birth Weigh Newborns in NICU

    PubMed Central

    Afjeh, Seyyed-Abolfazl; Sabzehei, Mohammad-Kazem; Fahimzad, Seyyed-Ali-Reza; Shiva, Farideh; Shamshiri, Ahmad-Reza; Esmaili, Fatemeh

    2016-01-01

    Background Prolonged empiric antibiotics therapy in neonates results in several adverse consequences including widespread antibiotic resistance, late onset sepsis (LOS), necrotizing enterocolitis (NEC), prolonged hospital course (HC) and increase in mortality rates. Objectives To assess the risk factors and the outcome of prolonged empiric antibiotic therapy in very low birth weight (VLBW) newborns. Materials and Methods Prospective study in VLBW neonates admitted to NICU and survived > 2 W, from July 2011 - June 2012. All relevant perinatal and postnatal data including duration of antibiotics therapy (Group I < 2W vs Group II > 2W) and outcome up to the time of discharge or death were documented and compared. Results Out of 145 newborns included in the study, 62 were in group I, and 83 in Group II. Average duration of antibiotic therapy was 14 days (range 3 - 62 days); duration in Group I and Group II was 10 ± 2.3 vs 25.5 ± 10.5 days. Hospital stay was 22.3 ± 11.5 vs 44.3 ± 14.7 days, respectively. Multiple regression analysis revealed following risk factors as significant for prolonged empiric antibiotic therapy: VLBW especially < 1000 g, (P < 0.001), maternal Illness (P = 0.003), chorioamnionitis (P = 0.048), multiple pregnancy (P = 0.03), non-invasive ventilation (P < 0.001) and mechanical ventilation (P < 0.001). Seventy (48.3%) infants developed LOS; 5 with NEC > stage II, 12 (8.3%) newborns died. Infant mortality alone and with LOS/NEC was higher in group II as compared to group I (P < 0.002 and < 0.001 respectively). Conclusions Prolonged empiric antibiotic therapy caused increasing rates of LOS, NEC, HC and infant mortality. PMID:27307961

  15. [LOCAL ANTIBIOTIC THERAPY OF OSTEOMYELITIS USING NONABSORBABLE IMPLANT (REVIEW)].

    PubMed

    Tuleubaev, B; Saginova, D; Abiyev, T; Davletbaev, M; Koshanova, A

    2016-06-01

    Despite the variety of treatments available, including surgical procedures and antimicrobial therapy, bone infections is still a medical problem, because they are difficult to treat. Optimal treatment should stabilize the bone, promote the biological recovery of bone defects and destroy bacterial infection. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. In contrast, the antibiotic impregnated bone cements or fillers can act as a local anti-infective drug delivery system, which not only fills the dead space after debridement, but also provide high concentrations of antibiotics in a potential site of infection, no increase levels of antibiotics in serum. The review analyzed the use of antibiotic-impregnated cement as local delivery of antibiotics systems. Gentamycin impregnated polymethylmethacrylate (PMMA) beads, for the topical treatment of orthopedic infections clinically used for over 30 years. Application of antibiotic delivery systems using cement in the infected region is common method of treatment that continues to improve. On the downside of PMMA is that the material does not biodegradable requires subsequent invasive procedures necessary to remove the implant. PMID:27441531

  16. Applications of medical informatics in antibiotic therapy.

    PubMed

    Evans, R S; Pestotnik, S L

    1994-01-01

    The Infectious Disease Society of America is concerned about the excessive and inappropriate use of antibiotics in U.S. hospitals. Applications of Medical Informatics can help improve the use of antibiotics and help improve patient care by monitoring and managing enormous amounts of patient information. Monitoring the duration of every antibiotic ordered in the hospital or keeping tract of the antibiotic susceptibilities for five years are examples of tasks better performed by computers. The impact of computers in medicine is seen by some as disappointing. The computer revolution has not had the impact in medicine experienced by other areas. The acceptance and use of computers by medicine will be evolutionary rather than revolutionary. In 1979, the MYCIN project demonstrated that the computer could aid physicians in the selection of antibiotics. However, MYCIN was never clinically used because physicians were require to enter all patient information into the computer. The development of computerized medical records is an essential step to further the development and implementation of computer-aided decision support. The science of Medical Informatics is still relatively new but is emerging as a distinct academic field. A few hospitals are now installing information systems and have determined that these systems will play an essential role in their ability to survive into the next century. The telephone and the automobile have been recognized as two of the most important tools for improving medical care during the past 100 years. People could more readily get medical care and the time to transmit medical information was greatly reduced through physician use of the telephone and automobile. The computer is a tool that can be used to help physicians manage the great amount of medical information being generated every day. The computer can also alert the physician of patient conditions that need attention. However, it is the physician who must use and apply the

  17. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  18. Antibiotic and anti-inflammatory therapies for cystic fibrosis.

    PubMed

    Chmiel, James F; Konstan, Michael W; Elborn, J Stuart

    2013-10-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed.

  19. Antibiotic therapy of aortic graft infection: treatment and prevention recommendations.

    PubMed

    Hodgkiss-Harlow, Kelley D; Bandyk, Dennis F

    2011-12-01

    Surgical site infection (SSI) after aortic intervention, an uncommon but serious vascular condition, requires patient-specific antibiotic therapy. Effective treatment and prevention requires the vascular surgeon to be cognizant of changing SSI microbiology, advances in antibiotic delivery, and patient characteristics. The majority of aortic graft infections are caused by Gram-positive bacteria, with methicillin-resistant Staphylococcus aureus now the prevalent pathogen. Nasal carriage of methicillin-sensitive or methicillin-resistant S aureus strains, diabetes mellitus, recent hospitalization, a failed arterial reconstruction, and the presence of a groin incision are important SSI risk factors. Overall, the aortic SSI rate is higher than predicted by the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance risk category system; ranging from 5% after open or endovascular aortic interventions to as high as 10% to 15% after aortofemoral bypass or uni-aortoiliac grafting with femorofemoral bypass. Perioperative measures to reduce S aureus nares and skin colonization, administration of antibiotic prophylaxis, meticulous wound closure/care, and therapy directed to optimize patient host defense regulation mechanisms (eg, temperature, oxygenation, blood sugar) can minimize SSI occurrence. Antibiotic therapy for aortic graft infection should utilize bactericidal drugs that penetrate bacteria biofilms and can be delivered to the surgical site both parenterally and locally in the form of antibiotic-impregnated beads or prosthetic grafts.

  20. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    PubMed

    Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

    2015-03-01

    Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections.

  1. Failure of antibiotic therapy in acute otitis media.

    PubMed

    Babin, Emmanuel; Lemarchand, Vincent; Moreau, Sylvain; Goullet de Rugy, Marc; Valdazo, André; Bequignon, Arnaud

    2003-03-01

    The aim of this retrospective study was to determine the possible causes of failure of antibiotic therapy in children with acute otitis media (AOM). Thirty-nine samples of middle-ear fluid were obtained by myringotomy from 31 children suffering from AOM, unrelieved by antibiotic therapy administered for over 48 hours. The samples were analysed by the usual microbiological techniques, including cultures, tests for beta-lactamase producing strains and the determination of the minimal inhibitory concentration of penicillin for Streptococcus pneumoniae. In 14 samples, no bacterial strains were detected in the cultures of middle-ear fluid; and in two samples the cultures revealed two strains of bacteria. The bacteria most frequently identified were Haemophilus influenzae, found in 11 samples, and Streptococcus pneumoniae, found in seven samples, of which four produced strains with reduced susceptibility to penicillin. The failure of antibiotic therapy in AOM appears to be related to the increased resistance of Haemophilus influenzae and to the reduced susceptibility of Streptococcus pneumoniae to penicillin. Other factors contributing to the failure of antibiotic therapy in AOM may be the viruses or the bacteria that produce multiple pathogens in the middle ear.

  2. [Sense and nonsense in antibiotic therapy for respiratory tract infections].

    PubMed

    Domej, W; Flögel, E; Tilz, G P; Demel, U

    2005-07-01

    Whether an antibiotic successfully eradicates pathogens depends on the pathogens involved, on pharmacokinetics and bioavailability in the target tissue, and on the antimicrobial resistance of the pathogen. Other determinants are drug interactions, individual risk factors, age and compliance with respect to correct dosage and duration of therapy. In many cases, antimicrobial therapy is begun on an empirical basis, because the responsible pathogen can be identified in only half of all respiratory infections. The eradication of the pathogen has to be the first aim if treatment is to be curative and the development of resistance prevented. Long-term prevention of antimicrobial resistance will require a more critical prospective evaluation of the prescription of antibiotics. This paper considers rational and irrational measures in the antimicrobial therapy of respiratory infections. PMID:15815891

  3. [Antibiotics, azelaic acid and benzoyl peroxide in topical acne therapy].

    PubMed

    Fluhr, Joachim W; Degitz, Klaus

    2010-03-01

    Benzoyl peroxide was introduced as a basic treatment already in acne therapy 1934. The mechanism of action is the reduction of anaerobe bacteria by strong oxidation processes. No resistancies have been ever reported. BPO is available in 2.5, 5 and 10 % formulations. Its efficacy is slightly related to the strength of concentrations, but the side effect profile with burning, erythema and desquamation is increasing with concentrations. BPO 5% mostly is efficient enough to control acne of grades I to II according to the Kligman & Plewig classification. BPO my bleach clothes and hair. It is the most costeffective topical drug in acne of grades I-II. Inflammatory acne of the papular-pustular type I-II can also be treated by topical antibiotics such as erythromycin, clindamycin, and, less frequent and today not anymore recommended tetracyclines. Mechanism of action is not alone an antibacterial but anti inflammatory effect. The efficacy and penetration of the topical antibiotics between the groups are similar. Randomized studies have shown that concentrations of 2-4% are equivalent to oral tetracycline and minocycline in mild to moderate acne. Combinatory formulations with BPO and with retinoids enhance the efficacy significantly. Topical antibiotics plus BPO show less bacterial resistancies as topical antibiotics alone. Antibiotics should therefore not be used as monotherapy. Moreover gram negative folliculitis may develop. Azelaic acid is acting as an antimicrobial and can also reduce comedones. It can also be used in pregnancy and during the lactation period.

  4. [Antibiotics, azelaic acid and benzoyl peroxide in topical acne therapy].

    PubMed

    Fluhr, Joachim W; Degitz, Klaus

    2010-03-01

    Benzoyl peroxide was introduced as a basic treatment already in acne therapy 1934. The mechanism of action is the reduction of anaerobe bacteria by strong oxidation processes. No resistancies have been ever reported. BPO is available in 2.5, 5 and 10 % formulations. Its efficacy is slightly related to the strength of concentrations, but the side effect profile with burning, erythema and desquamation is increasing with concentrations. BPO 5% mostly is efficient enough to control acne of grades I to II according to the Kligman & Plewig classification. BPO my bleach clothes and hair. It is the most costeffective topical drug in acne of grades I-II. Inflammatory acne of the papular-pustular type I-II can also be treated by topical antibiotics such as erythromycin, clindamycin, and, less frequent and today not anymore recommended tetracyclines. Mechanism of action is not alone an antibacterial but anti inflammatory effect. The efficacy and penetration of the topical antibiotics between the groups are similar. Randomized studies have shown that concentrations of 2-4% are equivalent to oral tetracycline and minocycline in mild to moderate acne. Combinatory formulations with BPO and with retinoids enhance the efficacy significantly. Topical antibiotics plus BPO show less bacterial resistancies as topical antibiotics alone. Antibiotics should therefore not be used as monotherapy. Moreover gram negative folliculitis may develop. Azelaic acid is acting as an antimicrobial and can also reduce comedones. It can also be used in pregnancy and during the lactation period. PMID:20482689

  5. Antibiotic lock therapy: review of technique and logistical challenges

    PubMed Central

    Justo, Julie Ann; Bookstaver, P Brandon

    2014-01-01

    Antibiotic lock therapy (ALT) for the prevention and treatment of catheter-related bloodstream infections is a simple strategy in theory, yet its real-world application may be delayed or avoided due to technical questions and/or logistical challenges. This review focuses on these latter aspects of ALT, including preparation information for a variety of antibiotic lock solutions (ie, aminoglycosides, beta-lactams, fluoroquinolones, folate antagonists, glycopeptides, glycylcyclines, lipopeptides, oxazolidinones, polymyxins, and tetracyclines) and common clinical issues surrounding ALT administration. Detailed data regarding concentrations, additives, stability/compatibility, and dwell times are summarized. Logistical challenges such as lock preparation procedures, use of additives (eg, heparin, citrate, or ethylenediaminetetraacetic acid), timing of initiation and therapy duration, optimal dwell time and catheter accessibility, and risks of ALT are also described. Development of local protocols is recommended in order to avoid these potential barriers and encourage utilization of ALT where appropriate. PMID:25548523

  6. Outpatient parenteral antibiotic therapy (OPAT) in different countries: a comparison.

    PubMed

    Esposito, S; Noviello, S; Leone, S; Tice, A; Seibold, G; Nathwani, D; Scaglione, F

    2004-11-01

    In order to assess how outpatient parenteral antibiotic therapy (OPAT) is managed in different countries, we analyzed the data collected in the USA, UK and Italy by the International OPAT Registry using an ad hoc Access/Excel Microsoft program. The analysis of data concerned 9826 patients in the USA, 981 in the UK and 620 in Italy. Differences were observed in several aspects of OPAT management such as the infections treated and the antibiotics utilized. The duration of therapy also differed: it was much longer in Italy (56.0 average days), than in the USA (22.5 days) and UK (19.9 days). Delivery model, delivery route and infusion devices show substantial differences. The present analysis shows that OPAT is carried out with substantial differences in different countries probably according to different programmes and guidelines adopted. PMID:15519480

  7. The management of infections and antibiotic therapy: a European survey.

    PubMed

    Halls, G A

    1993-06-01

    A survey was undertaken in the five largest European countries in 1990/91 to measure the incidence of infectious diseases and record their antibiotic treatment, and usage as prophylaxis in acute general hospitals with over 300 beds. A representative sample of between 1234 and 1954 patient records were received for each country, with each participating clinician providing eight to ten records. Data were projected up to national totals. There were similarities between the patients across the countries, 50% of patients received surgery at some time in their hospital stay and in 45% the first antibiotic usage was as prophylaxis. In one fifth of the 55% treated for an infection, that infection was hospital acquired, but these 20% of patients accounted for 30% of total days in hospital for patients treated for infection. Infections of the lower respiratory tract, urinary tract and abdomen accounted for 75% of all infection cases. In 85% of infection cases, initial treatment was empirical. Overall, no culture and sensitivity data were reported by the end of treatment in over 50% of patients, with appreciable variation between the countries. In the UK, 60% of in-patient treatment was with oral antibiotics; in Italy, over 80% was injectable with over half that intramuscular. Germany had the highest rate of intravenous administration at nearly 60% of treatment days. Combination usage was highest, with over 30% of patient treatment days, in France and Spain, but Germany and Italy had the lowest usage at 21% and 16%. Mean duration of administration of antibiotics was shortest in the UK, eight days for infection and four days for prophylaxis, with France the longest at 12 days for infection, and Italy for prophyalxis at over five days. The UK had the highest rate of discharge on antibiotic treatment at over 30% of patients. Initial therapy was effective in about 90% of patients, but the UK, with the shortest durations and the greatest use of older antibiotics often as

  8. Home iv antibiotic therapy through a medical day care unit.

    PubMed

    Gourdeau, M; Deschênes, L; Caron, M; Desmarais, M

    1993-05-01

    An out-patient parenteral antibiotic therapy program provided through a medical day care unit was evaluated in a tertiary care hospital. From July 11, 1988 to December 31, 1990, 122 patients were treated either on site at the unit or at home with self-administered intravenous antibiotics. In all, 142 courses of parenteral antibiotics (mostly cephalosporins and clindamycin) were given for a total of 124 infections, mostly bone and soft tissue infections (67 of 124, 54%). The duration of out-patient therapy ranged from two to 62 days with a mean duration of 9.4 days if treated at the unit, or 13.2 days in the home care model (1476 patient-days). Vein access was peripheral and catheters remained functional for an average of 4.9 days (range 0.5 to 22 days). Only two patients experienced adverse drug reactions that necessitated modification of treatment. One other case was readmitted to the hospital for surgical debridement. The average cost per patient-day was $66 compared with $375 for in-hospital therapy. This program proved to be safe, efficient, and cost-effective.

  9. Home iv antibiotic therapy through a medical day care unit

    PubMed Central

    Gourdeau, Marie; Deschênes, Louise; Caron, Martine; Desmarais, Marc

    1993-01-01

    An out-patient parenteral antibiotic therapy program provided through a medical day care unit was evaluated in a tertiary care hospital. From July 11, 1988 to December 31, 1990, 122 patients were treated either on site at the unit or at home with self-administered intravenous antibiotics. In all, 142 courses of parenteral antibiotics (mostly cephalosporins and clindamycin) were given for a total of 124 infections, mostly bone and soft tissue infections (67 of 124, 54%). The duration of out-patient therapy ranged from two to 62 days with a mean duration of 9.4 days if treated at the unit, or 13.2 days in the home care model (1476 patient-days). Vein access was peripheral and catheters remained functional for an average of 4.9 days (range 0.5 to 22 days). Only two patients experienced adverse drug reactions that necessitated modification of treatment. One other case was readmitted to the hospital for surgical debridement. The average cost per patient-day was $66 compared with $375 for in-hospital therapy. This program proved to be safe, efficient, and cost-effective. PMID:22346440

  10. Opportunistic microorganisms in patients undergoing antibiotic therapy for pulmonary tuberculosis

    PubMed Central

    Querido, Silvia Maria Rodrigues; Back-Brito, Graziella Nuernberg; dos Santos, Silvana Soléo Ferreira; Leão, Mariella Vieira Pereira; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

    2011-01-01

    Antimicrobial therapy may cause changes in the resident oral microbiota, with the increase of opportunistic pathogens. The aim of this study was to compare the prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the oral cavity of fifty patients undergoing antibiotic therapy for pulmonary tuberculosis and systemically healthy controls. Oral rinsing and subgingival samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol, mannitol agar and MacConkey agar, and incubated for 48 h at 37°C. Candida spp. and coagulase-positive staphylococci were identified by phenotypic tests, C. dubliniensis, by multiplex PCR, and coagulase-negative staphylococci, Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of Candida spp. was significantly higher in tuberculosis patients, and C. albicans was the most prevalent specie. No significant differences in the prevalence of other microorganisms were observed. In conclusion, the antimicrobial therapy for pulmonary tuberculosis induced significant increase only in the amounts of Candida spp. PMID:24031759

  11. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    NASA Astrophysics Data System (ADS)

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

    2009-03-01

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

  12. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    SciTech Connect

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Woo, Shiao; Mohan, Radhe; Yepes, Pablo

    2009-03-10

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

  13. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    PubMed Central

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

    2010-01-01

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy. PMID:20844607

  14. The Comparison of Procalcitonin Guidance Administer Antibiotics with Empiric Antibiotic Therapy in Critically Ill Patients Admitted in Intensive Care Unit.

    PubMed

    Najafi, Atabak; Khodadadian, Ali; Sanatkar, Mehdi; Shariat Moharari, Reza; Etezadi, Farhad; Ahmadi, Arezoo; Imani, Farsad; Khajavi, Mohammad Reza

    2015-01-01

    The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS). A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23). Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups. PMID:26553084

  15. The Comparison of Procalcitonin Guidance Administer Antibiotics with Empiric Antibiotic Therapy in Critically Ill Patients Admitted in Intensive Care Unit.

    PubMed

    Najafi, Atabak; Khodadadian, Ali; Sanatkar, Mehdi; Shariat Moharari, Reza; Etezadi, Farhad; Ahmadi, Arezoo; Imani, Farsad; Khajavi, Mohammad Reza

    2015-01-01

    The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS). A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23). Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups.

  16. Efficacy of Postoperative Prophylactic Antibiotic Therapy in Third Molar Surgery

    PubMed Central

    Reddy B, Praveen

    2014-01-01

    Introduction: Surgical extraction of mandibular third molar is the most frequently performed procedure in oral surgery. This procedure is associated with significant postoperative sequelae such as trismus, swelling, pain and infection. The need of antibiotic therapy during the removal of mandibular third molar has been a contentious issue. Method: This study investigated a regimen by using amoxycillin and metronidazole in one group and without using antibiotics in the other. Both the groups were assessed postoperatively on the 1st, 2nd, 5th, 7th and 10th days by the same observer for post operative mouth opening (interincisal distance), presence of a purulent discharge at the site of surgery, pain and swelling. Result: Overall, no statistically significant difference was seen between both the treatment groups when interincisal distance, pain, swelling and purulent discharge were considered. Conclusion: The results of this study failed to show any advantage which was associated with the routine postoperative use of antibiotics in asymptomatic third molar surgeries. PMID:24995236

  17. Antibiotics

    MedlinePlus

    Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

  18. Adequate margin definition for scanned particle therapy in the incidence of intrafractional motion

    NASA Astrophysics Data System (ADS)

    Knopf, Antje-Christin; Boye, Dirk; Lomax, Antony; Mori, Shininchiro

    2013-09-01

    Advanced 4D dose calculations (4DDCs) for scanned particle therapy show that in the incidence of motion, it is insufficient to use target contours defined on one reference CT phase. ICRU Report 62 (ICRU 1999 ICRU Report 62 (Bethesda, MD: ICRU)) advises that variations in size, shape and position of CTVs relative to anatomic reference points have to be considered for internal target volumes (ITVs). In addition to geometrical margin adaption, changes of water equivalent path length have to be considered for particle therapy. Different ITV concepts have been applied to six representative patients (liver and lung indications) based on 4DCT. Geometrical ITVs (gITV) were calculated by combining deformed CTVs over all motion phases. To take into account path length changes, range adapted ITVs (raITV) were established as the union of range adapted CTVs in all phases. For gated delivery, gat_gITVs and gat_raITVs were calculated. Extensive 4DDCs have been performed for two exemplary patients to illustrate that neither re-scanning nor gating can sufficiently compensate for motion effects if no appropriate margins are employed and to evaluate the effectiveness of gITVs and raITVs. CTVs significantly differ from gITVs and raITVs in size (up to a factor 2 in volume). But also raITVs and gITVs differ significantly in size and are spatially displaced, particularly for lung patients. raITVs show a strong field dependence in shape. All volumes are reduced in size when gating is applied and considered during margin adaption. 4D dose distributions show big improvements when gITV or raITV are used compared to CTVs. However, the use of either gITVs or raITVs do not result in significant differences. If raITVs are used, slightly better target coverage is gained at the cost of more healthy tissue exposure. Our results emphasize that adapted target volumes have to be used for scanned particle therapy in the presence of motion. However, even though gITVs and raITVs differ significantly in

  19. Effect of an Undergraduate Special Problems Elective upon Student Knowledge of Antibiotic Therapy.

    ERIC Educational Resources Information Center

    MacCosbe, Paul E.; Segelman, Alvin B.

    1984-01-01

    The knowledge of antibiotic therapy among students taking an elective course in antibiotic prescription following a course in antibiotics and infectious diseases was compared with those not taking the follow-up elective course, and it was determined that the elective course reinforced existing knowledge. (MSE)

  20. [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid].

    PubMed

    Worret, Wolf-Ingo; Fluhr, Joachim W

    2006-04-01

    Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite the fact that only few randomized trials have been published, BPO is considered the standard in topical acne treatment. Anaerobic bacteria are reduced by oxidative mechanisms and the induction of resistant strains is reduced. Topical formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect is dose-dependent, but the irritation increases with higher concentrations. Usually 5 % BPO is sufficient to control acne grade I-II. Due to its strong oxidative potential, patients should be advised that BPO may bleach colored and dark clothing, bedding and even hair. BPO is safe for use in pregnant and lactating females because it is degraded to benzoic acid. It is a cost-effective treatment for acne grade I-II. Patients with papulopustular acne grade I-II, particularly with marked inflammation, show satisfactory improvement with topical antibiotic treatment. The following compounds are available and effective: erythromycin, clindamycin and tetracycline (the latter being less frequently used). A review in 1990 suggested that topical tetracycline was ineffective in the treatment of acne. Along with eliminating Propionibacterium acnes, the main mechanism of topical antibiotics is their antiinflammatory effect. All three penetrate the epidermal barrier well and are similarly efficacious. Randomized trials have shown that in concentrations of 2-4 %, their effects are comparable to oral tetracycline and minocycline. Combination therapy with retinoids or benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and reduce comedones, while topical antibiotics primarily address inflammation. One side effect of topical antibacterial treatment is an increase in drug-resistant resident skin flora with gram-negative microorganisms prevailing, which can lead to gram-negative folliculitis. All three antibiotics fluoresce under black light which may produce interesting

  1. [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid].

    PubMed

    Worret, Wolf-Ingo; Fluhr, Joachim W

    2006-04-01

    Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite the fact that only few randomized trials have been published, BPO is considered the standard in topical acne treatment. Anaerobic bacteria are reduced by oxidative mechanisms and the induction of resistant strains is reduced. Topical formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect is dose-dependent, but the irritation increases with higher concentrations. Usually 5 % BPO is sufficient to control acne grade I-II. Due to its strong oxidative potential, patients should be advised that BPO may bleach colored and dark clothing, bedding and even hair. BPO is safe for use in pregnant and lactating females because it is degraded to benzoic acid. It is a cost-effective treatment for acne grade I-II. Patients with papulopustular acne grade I-II, particularly with marked inflammation, show satisfactory improvement with topical antibiotic treatment. The following compounds are available and effective: erythromycin, clindamycin and tetracycline (the latter being less frequently used). A review in 1990 suggested that topical tetracycline was ineffective in the treatment of acne. Along with eliminating Propionibacterium acnes, the main mechanism of topical antibiotics is their antiinflammatory effect. All three penetrate the epidermal barrier well and are similarly efficacious. Randomized trials have shown that in concentrations of 2-4 %, their effects are comparable to oral tetracycline and minocycline. Combination therapy with retinoids or benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and reduce comedones, while topical antibiotics primarily address inflammation. One side effect of topical antibacterial treatment is an increase in drug-resistant resident skin flora with gram-negative microorganisms prevailing, which can lead to gram-negative folliculitis. All three antibiotics fluoresce under black light which may produce interesting

  2. Tigecycline use in the outpatient parenteral antibiotic therapy setting.

    PubMed

    Ingram, P R; Rawlins, M D M; Murray, R J; Roberts, J A; Manning, L

    2016-10-01

    In the context of globally increasing antimicrobial resistance, tigecycline appears to be a useful therapeutic option. The need for prolonged courses for complex infections has prompted consideration of its use via outpatient parenteral antibiotic therapy (OPAT) programmes, although clinical outcomes when used in this setting remain unknown. We retrospectively reviewed the patient characteristics and outcomes of 11 patients who received tigecycline, most commonly delivered as 100 mg once daily, via OPAT at three tertiary Australian hospitals. Rates of co-morbidity and prior antibiotic use were high. Patients had a wide range of infections including bone and/or joint (n = 5), intra-abdominal (n = 3), lower respiratory tract (n = 2) and parapharyngeal abscess (n = 1). Mycobacterial species (n = 5) were the most frequent pathogen, and multi-resistant organisms were common (n = 4). The median OPAT duration was 14 days (IQR 6-30). Nausea was encountered in 45 % of cases. At completion of OPAT, 1 patient (9 %) was cured, 2 (18 %) had improved and 8 (73 %) failed therapy. Failure occurred due to either progression or non-response of infection (n = 4), re-admission (n = 3), premature cessation of tigecycline due to nausea (n = 3) or death (n = 1). Whilst OPAT delivery of tigecycline is a therapeutic option, when used as second-line therapy for complex, often multi-resistant infections in patients with multiple comorbidities, high rates of clinical failure, readmissions and adverse effects, especially nausea, should be anticipated.

  3. [Rational antibiotic therapy in the dental office: Practical guidelines for decision-making].

    PubMed

    Zadik, Y

    2016-04-01

    Although most dental and periodontal diseases are caused by bacteria, the usual therapy is mechanical/surgical rather than antimicrobial medications. However, sometimes antibiotic administration may be necessary in addition to or as an alternative to the surgical/mechanical treatment. Many studies have shown that the misuse of antibiotics by dentists may be mostly attributed to unnecessity or inefficient regimen, and could contribute to bacterial resistance to antibiotics. The article presents practical guidelines to the administration of antibiotics in the dental office.

  4. [Nutrition, probiotics, antibiotics, antioxidative therapy, endoscopy in chronic pancreatitis].

    PubMed

    Mössner, J

    2006-10-18

    Treatment of chronic pancreatitis is dependent on the stage of the disease and consists of several arms: treatment of pain when ever possible according to its pathogenesis; treatment of complications primarily by interventional endoscopy, in cases of failure by surgery; therapy of exocrine insufficiency with porcine pancreatic extracts; treatment of endocrine insufficiency with insulin. Pseudocysts can be drained according to their location by either the transgastric, transduodenal, transpapillary or transcutaneous route. Distal prepapillary stenoses of the main pancreatic duct can be handled by placement of a plastic stent; similarily to treatment of biliary strictures. Stones leading to obstruction of the main pancreatic duct can be disintegrated by extracorporeal shock wave lithotripsy (ESWL) and the fragments removed by endoscopy after papillotomy. Transgastral endoscopic drainage of retroperitoneal necroses is still experimental. Prospective randomized multicenter trials comparing surgery with interventional endoscopy are still lacking. Failure of endoscopic therapy or suspicion of tumor is clearly an indication for surgery. There is no need for a specific diet in patients with chronic pancreatitis without having diabetes. In severe attacks, clinically similar to acute pancreatitis, enteral nutrition via a jejunal tube is replacing parenteral nutrition. However, prospective comparative trials are still mandatory. Prophylactic application of antibiotics in patients with pancreatic necrosis is again under debate. Whether probiotics are capable to decrease the risk of secondary pancreatic infection of necrosis has not been thoroughly studied. The hypothesis that capture of oxygen free radicals by drugs such as selenium may prevent frequency and severity of acute relapses has also not been proven.

  5. The history and evolution of outpatient parenteral antibiotic therapy (OPAT).

    PubMed

    Williams, David N; Baker, Cristina A; Kind, Allan C; Sannes, Mark R

    2015-09-01

    Outpatient parenteral antibiotic therapy (OPAT) is now a widely accepted and safe therapeutic option for carefully selected patients. Benefits include cost savings and improved patient satisfaction; risks include failure to adhere to care, unexpected changes in the underlying infection, and adverse drug and intravenous access events. We report on our 40-year experience with OPAT in a single healthcare system in the USA and highlight OPAT developments in several countries. We compared data on patients treated in our programme over two time periods: Period 1 from 1978 to 1990; and Period 2, calendar year 2014. In Period 2 paediatric patients were excluded. Between Periods 1 and 2, changes included an almost three-fold increase in the number of patients treated per year (80 vs. 229), treatment of more patients with severe orthopaedic-related infections (20% vs. 38%), a marked increase in the use of peripherally inserted central catheters to administer antibiotics (20% vs. 98%), a shorter duration of inpatient stay and a longer duration of OPAT (13 days vs. 24 days). Other changes in Period 2 included treatment of 20% of patients without antecedent hospitalisation, and use of carbapenems rather than cephalosporins as the most frequently administered agents. OPAT was safe, with rehospitalisation rates of 6% and 1% in Periods 1 and 2, respectively. We recommend increased access to structured OPAT teams and the development of standard definitions and criteria for important outcome measures (e.g. clinical 'cure' and unplanned hospital re-admissions). These steps are critical for patient safety and financial stewardship of resources.

  6. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality

    PubMed Central

    2012-01-01

    Introduction Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. Methods This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). Results We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). Conclusions β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric

  7. A survey on antibiotic therapy knowledge among physicians of a tertiary care and university hospital.

    PubMed

    Gentile, Ivan; Landolfo, Danilo; Buonomo, Antonio Riccardo; Crispo, Manuel; Iula, Vita Dora; Minei, Giuseppina; Catania, Maria Rosaria; Borgia, Guglielmo

    2015-03-01

    Antibiotic therapy has resulted in major progress in the fight against infectious diseases and is associated with an improved quality of life and increased survival. However, the emergence of resistant bacterial strains represents an inevitable consequence of antibiotic treatment and yields a loss of beneficial effects. Due to the scarce availability of new molecules in the near future, physicians have to learn how to best use currently available molecules. The aim of the present study was to evaluate the criteria that physicians use in choosing targeted antibiotic therapy. To achieve this goal, we used a questionnaire comprising seven questions. The questionnaire was administered, with the guarantee of anonymity, to a pool of physicians at the Federico II University Hospital of Naples who could prescribe antibiotics. Of the physicians interviewed, 68% chose antibiotic therapy autonomously or in cooperation with other doctors of the same structure, whereas 30% of interviewees referred to the infectious diseases consultant (8% after the first bacterial isolation and 22% after antibiotic therapy failure). The definition and meaning of minimum inhibitory concentration (MIC) were known to the vast majority of physicians (82% and 83%, respectively). In contrast, few of the interviewees knew the definition or meaning of breakpoint (16% and 17%, respectively). The key question of the questionnaire focused on the main criterion for antibiotic choice: 68% of interviewees gave an incorrect answer, most interviewees considering only the lowest MIC value for the isolated bacterium as the fundamental parameter in antibiotic choice. Our study shows that antibiotic therapy in a teaching hospital is often chosen using inappropriate criteria. Due to the well-known effects of the wrong antibiotic choice on therapeutic failure rate and on healthcare cost, information and training programmes for physicians who prescribe antibiotics are urgently needed.

  8. Fighting urinary tract infections with antibiotic and non-antibiotic therapies.

    PubMed

    Peri, Lluis

    2016-06-25

    Urinary tract infections (UTIs) place a considerable burden on the patient and are associated with substantial economic cost. Treatment of UTIs is mainly achieved using antibiotics, however, the rise in antibiotic resistance is concerning and the use of non-antimicrobial prophylaxis offers alternative treatment methods.

  9. Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy

    PubMed Central

    2013-01-01

    Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has

  10. [Old and new antibiotics for therapy of multidrug resistant bacteria].

    PubMed

    Pintado, V

    2016-09-01

    The lack of new antibiotics for multidrug-resistant bacteria is a matter of concern in microorganisms such as Pseudomonas aeruginosa, ESBL- and carbapenemase-producing Enterobacteriaceae, Acinetobacter baumannii, methicillin-resistant Staphylococcous aureus and vancomycin-resistant Enterococcus faecium. This situation has conditioned the reuse of "old" antibiotics (colistin, fosfomycin), the use of more recent antibiotics with new indications or dosage regimens (tigecycline, meropenem) and the introduction of "new" antibiotics (β-lactams, lipoglycopeptides, oxazolidinones) that are the subject of this review. PMID:27608312

  11. [Acute otitis media and antibiotics. Evidence-based guidelines for antibiotic therapy?].

    PubMed

    Thorøe, J; Lous, J

    1999-09-27

    Antibiotic treatment of acute otitis media is controversial. The questions are when to treat, with which antibiotic, and for how long? Within the last years three reviews attempting to discuss these questions have been published. All three found only a marginal effect of antibiotic treatment. The effect was less earache after the first day. The meta-analyses showed that between eight and 22 children had to be treated before one had any benefit of the treatment. The randomized studies did not find a greater effect of amoxicillin than of penicillin. The marginal effect of antibiotics on acute otitis media supports watchful waiting and individualized care and follow-up. There is a need for well-organized, randomized, placebo-controlled trials including the youngest children and the more severe cases of acute otitis media where the effect of antibiotic treatment may turn out to be most beneficial.

  12. Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections

    PubMed Central

    Barra, Federica; Roscetto, Emanuela; Soriano, Amata A.; Vollaro, Adriana; Postiglione, Ilaria; Pierantoni, Giovanna Maria; Palumbo, Giuseppe; Catania, Maria Rosaria

    2015-01-01

    Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O2, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores. PMID:26343645

  13. IV antibiotic therapy in the community: clinically effective and cost effective.

    PubMed

    Barker, Annie; Lyden-Rodgers, Mary

    This article discusses how the introduction of new ways of working has resulted in a more cost-effective service for the delivery of intravenous (IV) antibiotic therapy in a community setting. When community IV therapy was originally initiated in the trust, the system involved two nurses to check calculations and oversee the administration of IV antibiotic therapy. However, as the demand for IV therapy escalated, and with some patients requiring multiple visits, pressures on community nursing teams created challenges relating to capacity and demand. This service improvement project involved two phases. Phase one examined patient safety and the administration of IV antibiotics by one nurse. Phase two reviewed the administration of IV antibiotic via a timed bolus route. Following the analysis, the implementation of these initiatives demonstrated maximisation of resources, a release of nurses' time to care and improvements to the patient experience. PMID:27145545

  14. Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans

    SciTech Connect

    Datz, F.L.; Thorne, D.A.

    1986-12-01

    Although /sup 111/In-labeled leukocytes have been shown to be a useful technique for detecting infection, it has been postulated that antibiotic therapy may reduce the sensitivity of the leukocyte scan. Many patients with suspected bacterial infections are placed on antibiotics before a definite site of infection has been identified. Three hundred twelve leukocyte scans on 271 patients were retrospectively reviewed and classified as positive or negative, and as to whether or not they were being treated with antibiotics at the time the leukocyte scan was performed. The overall sensitivity, considering all 312 studies, was 90%. One hundred sixty-nine patient studies were on patients receiving antibiotics; 143 studies were on patients not on antibiotics. The sensitivity of the leukocyte scan was 88.7% in patients on antibiotic therapy; it was 92.1% in those who were not receiving antibiotics. The differences in sensitivity between the two groups were not significantly different (p less than 0.05). We conclude that antibiotic therapy does not affect the sensitivity of the /sup 111/In-labeled leukocyte scan.

  15. Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study

    PubMed Central

    Álvarez-Lerma, Francisco; Alvarez, Bernabe; Luque, Pilar; Ruiz, Francisco; Dominguez-Roldan, Jose-Maria; Quintana, Elisabet; Sanz-Rodriguez, Cesar

    2006-01-01

    Introduction Antibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance. Methods To assess a carbapenem-based de-escalating strategy in nosocomial pneumonia (NP), a prospective observational study was conducted in critically ill patients with NP treated empirically with imipenem ± aminoglycoside/glycopeptide in 24 intensive care units of Spanish general hospitals. Overall, 244 patients were assessable (91% with late-onset NP). The primary outcome was therapeutic success 7–9 days post therapy. Results Microbial identification – based on cultures of tracheal aspirates in 82% of patients, cultures of protected specimen brush in 33%, and cultures of bronchoalveolar lavage in 4% – was only available for 131 (54%) patients. Initial antibiotics were inadequate for 23 (9%) patients. Of the remaining patients, antibiotics were streamlined in 56 (23%) patients and remained unchanged in 14 (6%) patients based on microbiology data, in 38 (16%) patients despite microbiology data favouring de-escalation, and in 113 (46%) patients due to unknown aetiology. Overall, de-escalation was implemented in only 23% of patients with potentially multiresistant pathogens, compared with 68% of patients with the remaining pathogens (P < 0.001). Response rates were 53% for patients continuously treated with imipenem-based regimens and 50% for the de-escalated patients. Higher Acute Physiology, Age, and Chronic Health Evaluation II scores were associated with greater mortality, whereas adequate empiric antibiotic therapy protected against fatal outcomes. No increase of superinfection rates caused by emerging pathogens was observed. The costs associated with de-escalation were mainly dependent on the duration of hospitalization. Conclusion This study

  16. Point: antibiotic therapy is not the answer for patients with persisting symptoms attributable to lyme disease.

    PubMed

    Auwaerter, Paul G

    2007-07-15

    It is not well understood why some patients develop a subjective syndrome that includes considerable fatigue, musculoskeletal aches, and neurocognitive dysfunction after receiving standard antibiotic courses for the treatment of Lyme disease. Some practitioners use the term "chronic Lyme disease" and order prolonged courses of oral and parenteral antibiotics, believing that persistent infection with Borrelia burgdorferi is responsible. However, well-performed prospective studies have found neither evidence of chronic infection nor a benefit worthy of long-term antibiotic therapy for these patients. Such extended antibiotic therapy poses hazards and cannot be viewed as acceptable. The term "chronic Lyme disease" should be discarded as misleading; rather, the term "post-Lyme disease syndrome" better reflects the postinfectious nature of this condition. Further research is necessary to understand possible mechanisms of these chronic symptoms following Lyme disease as well as to find effective therapies.

  17. Osmotic therapies added to antibiotics for acute bacterial meningitis

    PubMed Central

    Wall, Emma CB; Ajdukiewicz, Katherine MB; Heyderman, Robert S; Garner, Paul

    2014-01-01

    Background Every day children and adults throughout the world die from acute community-acquired bacterial meningitis, particularly in low-income countries. Survivors are at risk of deafness, epilepsy and neurological disabilities. Osmotic therapies have been proposed as an adjunct to improve mortality and morbidity from bacterial meningitis. The theory is that they will attract extra-vascular fluid by osmosis and thus reduce cerebral oedema by moving excess water from the brain into the blood. The intention is to thus reduce death and improve neurological outcomes. Objectives To evaluate the effects on mortality, deafness and neurological disability of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults. Search methods We searched CENTRAL 2012, Issue 11, MEDLINE (1950 to November week 3, 2012), EMBASE (1974 to November 2012), CINAHL (1981 to November 2012), LILACS (1982 to November 2012) and registers of ongoing clinical trials (April 2012). We also searched conference abstracts and contacted researchers in the field. Selection criteria Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. Data collection and analysis Two review authors independently screened the search results and selected trials for inclusion. We collected data from each study for mortality, deafness, seizures and neurological disabilities. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. Main results Four trials were included comprising 1091 participants. All compared glycerol (a water-soluble sugar alcohol) with a control; in three trials this was a placebo, and in one a small amount of 50% dextrose. Three trials included comparators of dexamethasone alone or in combination with glycerol. As dexamethasone appeared to have no modifying effect, we aggregated results across arms where both

  18. Culture-inappropriate antibiotic therapy decreases quality of life improvement after sinus surgery

    PubMed Central

    Zhang, Zi; Palmer, James N.; Morales, Knashawn H.; Howland, Timothy J.; Doghramji, Laurel J.; Adappa, Nithin D.; Chiu, Alexander G.; Cohen, Noam A.; Lautenbach, Ebbing

    2014-01-01

    Background Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality of life (QOL) improvement following functional endoscopic sinus surgery (FESS). Methods This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between 10/1/2007 to 12/31/2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22 item Sinonasal Outcome Test scores from preoperative visit to 1-, 3- and 6-month post-FESS. Clinically significant difference was defined as at least ½ SD of baseline QOL score in the reference group. Mixed-effects regression models were performed. Results Seven percent of patients (n=27) had culture-inappropriate antibiotic therapy, and additional 5% (n=19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences. Conclusions Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome. PMID:24415647

  19. Empiric antibiotic therapy in a child with cancer and suspected septicemia

    PubMed Central

    Caselli, Desiree; Paolicchi, Olivia

    2012-01-01

    Improved outcome in the treatment of childhood cancer results not only from more aggressive and tailored cancer-directed therapy, but also from improved supportive therapy and treatment of life-threatening infectious complications. Prompt and aggressive intervention with empiric antibiotics has reduced mortality in this group of patients. Physical examination, blood tests, and blood cultures must be performed, and antibiotic therapy must be administered as soon as possible. Beta-lactam monotherapy, such as piperacillin-tazobactam or cefepime, may be an appropriate empiric therapy of choice for all clinically stable patients with neutropenic fever. An anti-pseudomonal beta-lactam antibiotic plus gentamicin is recommended for patients with systemic compromise. PMID:22690308

  20. Synthesis and characterization of magnetite/silver/antibiotic nanocomposites for targeted antimicrobial therapy.

    PubMed

    Ivashchenko, Olena; Lewandowski, Mikołaj; Peplińska, Barbara; Jarek, Marcin; Nowaczyk, Grzegorz; Wiesner, Maciej; Załęski, Karol; Babutina, Tetyana; Warowicka, Alicja; Jurga, Stefan

    2015-10-01

    The article is devoted to preparation and characterization of magnetite/silver/antibiotic nanocomposites for targeted antimicrobial therapy. Magnetite nanopowder was produced by thermochemical technique; silver was deposited on the magnetite nanoparticles in the form of silver clusters. Magnetite/silver nanocomposite was investigated by XRD, SEM, TEM, AFM, XPS, EDX techniques. Adsorptivity of magnetite/silver nanocomposite towards seven antibiotics from five different groups was investigated. It was shown that rifampicin, doxycycline, ceftriaxone, cefotaxime and doxycycline may be attached by physical adsorption to magnetite/silver nanocomposite. Electrostatic surfaces of antibiotics were modeled and possible mechanism of antibiotic attachment is considered in this article. Raman spectra of magnetite, magnetite/silver and magnetite/silver/antibiotic were collected. It was found that it is difficult to detect the bands related to antibiotics in the magnetite/silver/antibiotic nanocomposite spectra due to their overlap by the broad carbon bands of magnetite nanopowder. Magnetic measurements revealed that magnetic saturation of the magnetite/silver/antibiotic nanocomposites decreased on 6-19 % in comparison with initial magnetite nanopowder. Pilot study of antimicrobial properties of the magnetite/silver/antibiotic nanocomposites were performed towards Bacillus pumilus.

  1. [Consequences of antibiotic therapy to the intestinal ecosystem].

    PubMed

    Andremont, A

    2000-05-01

    Ecological impact of antibiotherapy results from the interaction between microorganisms in the ecosystems and antibiotics at which they are exposed. The amount of antibiotics use in the world is continuously increasing. The fraction devoted to human care is only about half the total amount. There are multiple other fields of usage, in agriculture, breeding and veterinary medicine. Bacterial ecosystems exposed at antibiotherapy in man are mainly the skin and the gastrointestinal and respiratory tracts. The gastrointestinal system is quantitatively predominant and the consequences of the bacterial imbalance induced by antibiotics are potentially severe. It is the reason why it is the most extensively studied, in the literature and in the present review. The origin of resistant bacteria will be briefly discussed.

  2. Metformin as a potential combination therapy with existing front-line antibiotics for Tuberculosis.

    PubMed

    Vashisht, Rohit; Brahmachari, Samir K

    2015-01-01

    Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) remains a global health concern. The evolution of various multi-drug resistant strains through genetic mutations or drug tolerant strains through bacterial persistence renders existing antibiotics ineffective. Hence there is need for the development of either new antibiotics or rationalizing approved drugs that can be utilized in combination with existing antibiotics as a therapeutic strategy. A comprehensive systems level mapping of metabolic complexity in Mtb revels a putative role of NDH-I in the formation of bacterial persistence under the influence of front-line antibiotics. Possibilities of targeting bacterial NDH-I with existing FDA approved drug for type-II diabetes, Metformin, along with existing front-line antibiotics is discussed and proposed as a potential combination therapy for TB. PMID:25880846

  3. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

    PubMed

    Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

  4. Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.

    PubMed

    Unger, Nathan R; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline.

  5. Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.

    PubMed

    Unger, Nathan R; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

  6. Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy

    PubMed Central

    Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

  7. Department of pharmacy-initiated program for streamlining empirical antibiotic therapy.

    PubMed

    Pastel, D A; Chang, S; Nessim, S; Shane, R; Morgan, M A

    1992-07-01

    The outcome of a department of pharmacy-initiated "streamlining" study designed to promote cost-conscious modifications of empirically selected antibiotic therapy is described. Two hundred forty-one evaluable adult patients started on restricted-use antibiotics at this university-affiliated community private teaching hospital were enrolled in a 9-week prospective streamlining study. Patients were alternately assigned to a Control (i.e., no pharmacist-initiated streamlining recommendations offered based on culture and susceptibility reports) or a Pharmacist Intervention group (i.e., pharmacist offers recommendations to streamline therapy). A statistically significant greater number of patients had their empiric antibiotic treatment courses modified to more appropriate antibiotic choices after receipt of culture and susceptibility reports among private prescribers in the Pharmacist Intervention group (83%) than in the Control group (38%) (p = .006). Additionally, pharmacists were overall successful in gaining prescriber acceptance for 64% of recommended changes of empiric antibiotic treatment courses before the receipt of culture and susceptibility reports (e.g., dose and/or frequency changes). There was no program effect observed with respect to improved physician response to microbiologic data that would allow streamlining empirical antibiotic choices in the Housestaff (i.e., medical or surgical residents), or infectious disease consultant prescriber groups. Projected overall annual cost savings that would be achieved as a result of continued efforts by pharmacists directed at streamlining empirical "restricted" antibiotic regimens is approximately +40,000.

  8. De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study

    PubMed Central

    Moraes, Rafael Barberena; Guillén, Julián Alberto Viteri; Zabaleta, William Javier Castillo; Borges, Flavia Kessler

    2016-01-01

    Objective To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. Methods The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Results Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. Conclusion The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates. PMID:27626951

  9. Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease

    PubMed Central

    2014-01-01

    Background Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy. Methods Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy. Results Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment. Conclusions Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy. PMID:24731247

  10. Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review

    PubMed Central

    2014-01-01

    Background The role of oral antibiotic therapy in treating infective endocarditis (IE) is not well established. Methods We searched MEDLINE, EMBASE and Scopus for studies in which oral antibiotic therapy was used for the treatment of IE. Results Seven observational studies evaluating the use oral beta-lactams (five), oral ciprofloxacin in combination with rifampin (one), and linezolid (one) for the treatment of IE caused by susceptible bacteria reported cure rates between 77% and 100%. Two other observational studies using aureomycin or sulfonamide, however, had failure rates >75%. One clinical trial comparing oral amoxicillin versus intravenous ceftriaxone for streptococcal IE reported 100% cure in both arms but its reporting had serious methodological limitations. One small clinical trial (n = 85) comparing oral ciprofloxacin and rifampin versus conventional intravenous antibiotic therapy for uncomplicated right-sided S. aureus IE in intravenous drug users (IVDUs) reported cure rates of 89% and 90% in each arm, respectively (P =0.9); however, drug toxicities were more common in the latter group (62% versus 3%; P <0.01). Major limitations of this trial were lack of allocation concealment and blinding at the delivery of the study drug(s) and assessment of outcomes. Conclusion Reported cure rates for IE treated with oral antibiotic regimens vary widely. The use of oral ciprofloxacin in combination with rifampin for uncomplicated right-sided S. aureus IE in IVDUs is supported by one small clinical trial of relatively good quality and could be considered when conventional IV antibiotic therapy is not possible. PMID:24624933

  11. Hospital outcomes associated with guideline recommended antibiotic therapy for pediatric pneumonia

    PubMed Central

    Thomson, Joanna; Ambroggio, Lilliam; Kurowski, Eileen Murtagh; Statile, Angela; Graham, Camille; Courter, Joshua D.; Sheehan, Brieanne; Iyer, Srikant; White, Christine M.; Shah, Samir S.

    2014-01-01

    Background Recent national guidelines recommend use of narrow spectrum antibiotic therapy as empiric treatment for children hospitalized with community-acquired pneumonia. However, clinical outcomes associated with adoption of this recommendation have not been studied. Methods This retrospective cohort study included children 3 months -18 years, hospitalized with CAP from May 2, 2011 through July 30, 2012. Primary exposure of interest was empiric antibiotic therapy, classified as guideline recommended or not. Primary outcomes were length of stay (LOS), total hospital costs, and inpatient pharmacy costs. Secondary outcomes included broadened antibiotic therapy, emergency department revisits, and readmissions. Multivariable linear regression and Fisher’s exact test were performed to determine the association of guideline recommended antibiotic therapy on outcomes. Results Empiric guideline recommended therapy was prescribed to 168 (76%) of 220 patients. Median hospital LOS was 1.3 days (IQR: 0.9-1.9 days); median total costs of index hospitalization were $4,097 (IQR: $2,657-$6,054); median inpatient pharmacy costs were $91 (IQR: $40-$183). Between patients who did and did not receive guideline recommended therapy, there were no differences in LOS (adjusted −5.8% change; 95% CI: −22.1, 12.8), total costs (adjusted −10.9% change; 95% CI: −27.4, 9.4), or inpatient pharmacy costs (adjusted 14.8% change; 95% CI: −43.4, 27.1). Secondary outcomes were rare with no difference in unadjusted analysis between patients who did and did not receive guideline recommended therapy. Conclusions Use of guideline recommended antibiotic therapy was not associated with unintended negative consequences; there were no changes in LOS, total costs, or inpatient pharmacy costs. PMID:25263758

  12. Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance.

    PubMed

    Nichol, Daniel; Jeavons, Peter; Fletcher, Alexander G; Bonomo, Robert A; Maini, Philip K; Paul, Jerome L; Gatenby, Robert A; Anderson, Alexander R A; Scott, Jacob G

    2015-09-01

    The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different β-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2-4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically 'steer' the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic-resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy.

  13. Challenges and future prospects of antibiotic therapy: from peptides to phages utilization

    PubMed Central

    Mandal, Santi M.; Roy, Anupam; Ghosh, Ananta K.; Hazra, Tapas K.; Basak, Amit; Franco, Octavio L.

    2014-01-01

    Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. New classes of antibiotics with different actions against MDR pathogens need to be developed urgently. In this context, this review focuses on several ways and future directions to search for the next generation of safe and effective antibiotics compounds including antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics, lipopolysaccharide, and efflux pump inhibitors to control the infections caused by MDR pathogens. PMID:24860506

  14. Can We Stop Antibiotic Therapy When Signs and Symptoms Have Resolved in Diabetic Foot Infection Patients?

    PubMed Central

    Chu, Yuejie; Wang, Chao; Zhang, Jinghang; Wang, Penghua; Xu, Jun; Ding, Min; Li, Xiwen; Hou, Xiaoli; Feng, Shuhong; Li, Xuemei

    2015-01-01

    The study aimed to investigate whether we can stop antibiotic therapy when signs and symptoms have resolved in diabetic foot infection (DFI) patients with different grades of peripheral arterial disease (PAD) and those without PAD, and to determine whether the severity of PAD and infection has an effect on antibiotic therapy duration. A prospective randomized controlled trial of DFI patients was carried out. Patients were randomized into 2 groups when signs and symptoms had resolved: continuing antibiotics group (CAG) and discontinuing antibiotics group (DAG). The recurrence and clinical outcomes were recorded. The recurrence rate of mild infection with mild/moderate PAD was similar in the 2 groups. Compared with CAG, the recurrence rate of mild infection with severe PAD was higher in DAG (P = .030), also for moderate/severe infection with PAD (mild/moderate [P = .032]; severe [P = .008]). No difference was found in the 2 groups (either mild or moderate/severe) for those without PAD. The clinical outcomes of mild infection in patients were similar in the 2 groups. For moderate/severe infection, the healing rate was higher (73.3% vs 48.3%), and the rate of minor/major amputation and death was lower (23.8% vs 49.4%; 6.9% vs 20.7%; 2.0% vs 13.8%) in the CAG. When the clinical signs and symptoms of infection have resolved, it might be appropriate to stop antibiotics for DFI patients without PAD, and also for patients with mild infection with mild/moderate PAD. For patients with mild infection with severe PAD and moderate/severe infection with PAD, we should perhaps continue antibiotic treatment. Continuing antibiotic therapy could improve clinical outcomes for patients with moderate/severe infection. PMID:26248828

  15. Antibiotic or bacterial therapy in post-giardiasis irritable bowel syndrome.

    PubMed

    Morken, Mette Helvik; Valeur, Jørgen; Norin, Elisabeth; Midtvedt, Tore; Nysaeter, Gunnar; Berstad, Arnold

    2009-01-01

    OBJECTIVE. Intestinal infection with Giardia lamblia may lead to therapy-resistant, long-lasting post-giardiasis irritable bowel syndrome (IBS). We report two open pilot studies aiming to treat this condition, using either antibiotics or bacterio-therapy. MATERIAL AND METHODS. Twenty-eight patients with persistent abdominal symptoms, following clearance of G. lamblia infection, were investigated. Eighteen received treatment with rifaximin plus metronidazole (8-10 days) whereas 10 received a suspension of live faecal flora, installed into the duodenum during gastro-duodenoscopy. Customary abdominal symptoms and symptoms following a lactulose breath test were quantified by questionnaires. Hydrogen and methane production after lactulose were analysed in expired air and excretion of fat and short-chain fatty acids (SCFAs) was examined in faeces. RESULTS. As compared with pre-treatment values, total customary symptom scores were barely significantly reduced (p = 0.07) after antibiotics, but were highly significantly reduced (p = 0.0009) after bacterio-therapy. However, symptom improvement following bacterio-therapy did not persist 1 year later. Hydrogen breath excretion was slightly reduced after antibiotics, but not after bacterio-therapy. Compared with healthy persons, faecal excretion of fat was significantly increased in Giardia-cured patients. SCFAs were increased in the bacterio-therapy group, and were not influenced by therapy. CONCLUSIONS. Both antibiotics and bacterio-therapy were ineffective with respect to cure of post-giardiasis IBS. High faecal excretion of fat and SCFAs suggests that intestinal malabsorption of fat and carbohydrates may play a role in the IBS-like complaints of these patients.

  16. A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens

    PubMed Central

    Wittebole, Xavier; De Roock, Sophie; Opal, Steven M

    2014-01-01

    The seemingly inexorable spread of antibiotic resistance genes among microbial pathogens now threatens the long-term viability of our current antimicrobial therapy to treat severe bacterial infections such as sepsis. Antibiotic resistance is reaching a crisis situation in some bacterial pathogens where few therapeutic alternatives remain and pan-resistant strains are becoming more prevalent. Non-antibiotic therapies to treat bacterial infections are now under serious consideration and one possible option is the therapeutic use of specific phage particles that target bacterial pathogens. Bacteriophage therapy has essentially been re-discovered by modern medicine after widespread use of phage therapy in the pre-antibiotic era lost favor, at least in Western countries, after the introduction of antibiotics. We review the current therapeutic rationale and clinical experience with phage therapy as a treatment for invasive bacterial infection as novel alternative to antimicrobial chemotherapy. PMID:23973944

  17. High Diagnostic Accuracy of Nitrite Test Paired with Urine Sediment can Reduce Unnecessary Antibiotic Therapy

    PubMed Central

    Ferry, Sven A.; E. Holm, Stig; Ferry, B. Magnus; Monsen, Tor J.

    2015-01-01

    Background: Urinary tract infections (UTIs) are common bacterial infections dominated by lower UTI in women (LUTIW). Symptoms only are insufficient for diagnosis and accordingly, near patient diagnostic tests confidently confirming significant bacteriuria are desirable. The nitrite test (NIT) has low sensitivity, while bacterial and leukocyte counts disjunctively paired in urine sediment microscopy (SED) have high sensitivity. Similar symptomatic cure rates are found post antibiotic vs. placebo therapy in patients with negative cultures. Consequently, prescription on symptoms only implies unnecessary antibiotic therapy. Aims: to evaluate the diagnostic outcomes of NIT, SED and NIT disjunctively paired with SED (NIT+SED) vs. urine culture, with special focus on bladder incubation time (BIT), and to assess if NIT+SED can reduce unnecessary antibiotic therapy. Methods: A diagnostic, primary care, multicentre study including 1070 women with symptoms suggestive of lower UTI. Results: Significant bacteriuria was found in 77%. The BIT highly influenced the diagnostic outcomes and the optimal duration was ≥4h with sensitivity of 66, 90 and 95% for NIT, SED and NIT+SED, respectively. SED performed only in NIT negative specimens could reduce unnecessary antibiotics by 10% vs. prescription on symptoms only. The number needed to test with SED to reduce one unnecessary antibiotic course was five patients at BIT ≥4h and six patients at ≤3h or overall. Conclusion: The BIT highly influences the diagnostic outcomes with the highest accuracy of NIT+SED. Diagnosis of LUTIW with NIT+SED can reduce unnecessary antibiotic therapy and subsequently decrease antimicrobial resistance. Trial registration: The Swedish Medical Product Agency 1995 03 01:151:01783/94. PMID:26668667

  18. Antibiotics

    NASA Astrophysics Data System (ADS)

    Anhalt, John P.

    A 28-year-old man was transferred to our hospital and underwent surgery for resection of an aortic graft infected with Klebsiella pneumoniae. Antimicrobial therapy consisted of amikacin, cefazolin, chloramphenicol, sulfamethoxazole, and trimethoprim. A request for amikacin and sulfamethoxazole assays was received by the laboratory along with information that the patient had received tobramycin until 24 h before the serum was obtained.

  19. [Eradication therapy of antibiotic-resistant strains of Helicobacter pylori].

    PubMed

    Shcherbakov, P L; Belousova, N L; Shcherbakova, M Iu; Kashnikov, V S

    2010-01-01

    Treatment of inflammatory diseases of the upper digestive tract, associated with Helicobacter pylori has recently greatly complicated by the presence of significant number of resistant strains of this microorganism to traditionally used drugs for eradication therapy. Average resistance to metronidazole and clarithromycin in Russia is about 30 and 25% respectively. The article presents the experience of treating patients with metronidazole resistant strains of H. pylori with using triple therapy, which included a drug used nitrofurans--nifuroxazide in suspension, proton pump inhibitors and clarithromycin. PMID:21485525

  20. Managing an outpatient parenteral antibiotic therapy team: challenges and solutions

    PubMed Central

    Halilovic, Jenana; Christensen, Cinda L; Nguyen, Hien H

    2014-01-01

    Outpatient parenteral antimicrobial therapy (OPAT) programs should strive to deliver safe, cost effective, and high quality care. One of the keys to developing and sustaining a high quality OPAT program is to understand the common challenges or barriers to OPAT delivery. We review the most common challenges to starting and managing an OPAT program and give practical advice on addressing these issues. PMID:24971015

  1. Probiotics to minimize the disruption of faecal microbiota in healthy subjects undergoing antibiotic therapy.

    PubMed

    Engelbrektson, Anna; Korzenik, Joshua R; Pittler, Arlyn; Sanders, Mary E; Klaenhammer, Todd R; Leyer, Gregory; Kitts, Christopher L

    2009-05-01

    A novel combination of culturing and DNA-based terminal restriction fragment length polymorphism (TRFLP) analysis was used to investigate the effect of probiotics on antibiotic-induced gut microbiota alterations to determine if a probiotic preparation containing bifidobacteria and lactobacilli, taken during and after antibiotic therapy, can minimize antibiotic disturbance of faecal microbiota. Healthy subjects administered amoxicillin/clavulanate were randomized and concomitantly received a placebo or probiotic mixture. The primary end point was similarity of faecal microbiota as determined by culturing and TRFLP from subjects taking probiotics compared to those taking a placebo measured by comparing data from baseline to post-treatment for each subject. TRFLP analysis revealed a high subject to subject variation in the baseline faecal microbiota. The most common antibiotic-induced disturbance was a relative increase in Clostridium, Eubacterium, Bacteroides and Enterobacteraceae. The mean similarity to the baseline increased over time in both treatment groups, although the probiotic group was less disturbed according to both TRFLP and culture data. The culture method revealed that post-antibiotic faecal microbiota in probiotic-consuming subjects were more similar to the baseline microbiota than the control group (P=0.046). Changes in Enterobactereaceae (P=0.006) and Bifidobacterium (P=0.030) counts were significantly different between the groups. Analysis of TRFLP data reinforced the trend between groups but was not statistically significant (P=0.066). This study indicates this mixture of probiotics promotes a more rapid return to pre-antibiotic baseline faecal bacterial microbiota.

  2. Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance

    PubMed Central

    Nichol, Daniel; Jeavons, Peter; Fletcher, Alexander G.; Bonomo, Robert A.; Maini, Philip K.; Paul, Jerome L.; Gatenby, Robert A.; Anderson, Alexander R.A.; Scott, Jacob G.

    2015-01-01

    The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different β-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2–4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically ‘steer’ the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic–resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy. PMID:26360300

  3. Surgical Debridement Is Superior to Sole Antibiotic Therapy in a Novel Murine Posttraumatic Osteomyelitis Model

    PubMed Central

    Wallner, Christoph; Ismer, Britta; Schira, Jessica; Abraham, Stephanie; Harati, Kamran; Lehnhardt, Marcus; Behr, Björn

    2016-01-01

    Introduction Bone infections after trauma, i.e. posttraumatic osteomyelitis, pose one of the biggest problems of orthopedic surgery. Even after sufficient clinical therapy including vast debridement of infected bone and antibiotic treatment, regeneration of postinfectious bone seems to be restricted. One explanation includes the large sized defects resulting from sufficient debridement. Furthermore, it remains unclear if inflammatory processes after bone infection do affect bone regeneration. For continuing studies in this field, an animal model is needed where bone regeneration after sufficient treatment can be studied in detail. Methods For this purpose we created a stable infection in murine tibiae by Staphylococcus aureus inoculation. Thereafter, osteomyelitic bones were debrided thoroughly and animals were subsequently treated with antibiotics. Controls included debrided, non-infected, as well as infected animals exclusively treated with antibiotics. To verify sufficient treatment of infected bone, different assessments detecting S. aureus were utilized: agar plates, histology and RT-qPCR. Results All three detection methods revealed massive reduction or eradication of S. aureus within debrided bones 1 and 2 weeks postoperatively, whereas sole antibiotic therapy could not provide sufficient treatment of osteomyelitic bones. Debrided, previously infected bones showed significantly decreased bone formation, compared to debrided, non-infected controls. Discussion Thus, the animal model presented herein provides a reliable and fascinating tool to study posttraumatic osteomyelitis for clinical therapies. PMID:26872128

  4. Revealing the dynamics of polymicrobial infections: implications for antibiotic therapy

    PubMed Central

    Rogers, Geraint B.; Hoffman, Lucas R.; Whiteley, Marvin; Daniels, Thomas W.V.; Carroll, Mary P.; Bruce, Kenneth D.

    2011-01-01

    As a new generation of culture-independent analytical strategies emerge, the amount of data on polymicrobial infections will increase dramatically. For these data to inform clinical thinking, and in turn to maximise benefits for patients, an appropriate framework for their interpretation is required. Here, we use cystic fibrosis (CF) lower airway infections as a model system to examine how conceptual and technological advances can address two clinical questions that are central to improved management of CF respiratory disease. Firstly, can markers of the microbial community be identified that predict a change in infection dynamics and clinical outcomes? Secondly, can these new strategies directly characterize the impact of antimicrobial therapies, allowing treatment efficacy to be both assessed and optimized? PMID:20554204

  5. Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci.

    PubMed

    Dastgheyb, Sana S; Eckmann, David M; Composto, Russell J; Hickok, Noreen J

    2013-12-01

    Staphylococcal infections have become difficult to treat due to antibiotic insensitivity and resistance. Antimicrobial combination therapies may minimize acquisition of resistance and photodynamic therapy is an attractive candidate for these combinations. In this manuscript, we explore combined use of antibiotics and meso-tetra (4-aminophenyl) porphine (TAPP), a cationic porphyrin, for treatment of Staphylococcus aureus contamination. We characterize the antimicrobial activity of photoactivated TAPP and show that activity is largely lost in the presence of a radical scavenger. Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for S. aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis. Chloramphenicol+methylene blue, another photosensitizer, also show additivity against S. aureus. In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. aureus. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentrations of photo-activated TAPP could be used to boost the activity of waning antibiotics. This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy.

  6. Management of chronic suppurative osteomyelitis in a patient with pycnodysostosis by intra-lesional antibiotic therapy

    PubMed Central

    Kamat, Saurabh; Sankar, Kannan; Eswari, Natt Janakiraman; Gahlawat, Vikas; Jude, Bernard Nithin Joseph; Negi, Anjna

    2015-01-01

    Pycnodysostosis is a rare sclerosing bone disorder characterized by short stature, brachycephaly, short/stubby fingers, open cranial sutures/fontanelle, and diffuse osteosclerosis, where multiple fractures of long bones and osteomyelitis of the jaw are common complications. We present a rare case of pycnodysostosis with chronic suppurative osteomyelitis of the mandible in a 36-year-old woman; which was nonsurgically managed by a conservative approach involving a novel protocol referred to as intra-lesional antibiotic therapy. PMID:26283855

  7. [Antibiotic therapy by suppurative diseases of the abdominal cavity and soft tissues].

    PubMed

    Sazhin, V P; Bodrova, N G; Klimov, D E; Iurishchev, V A; Avdovenko, A L; Sazhin, I V

    2010-01-01

    Microbial background of the departments of abdominal and septic surgery was monitored and analyzed. More the 950 samples from each department was worked out. Therefore, it was determined, that gram-negative bacteria were more typical for the abdominal pathology, whereas, soft tissue infection was represented by gram-positive strains. Compliant antibioticogramms were performed and analyzed. For achieving effective prophylactic and empiric antibiotic therapy, data-based formular lists of antibacterial drugs were performed.

  8. Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies.

    PubMed

    Taylor, Patrick K; Yeung, Amy T Y; Hancock, Robert E W

    2014-12-10

    The growth of bacteria as structured aggregates termed biofilms leads to their protection from harsh environmental conditions such as physical and chemical stresses, shearing forces, and limited nutrient availability. Because of this highly adapted ability to survive adverse environmental conditions, bacterial biofilms are recalcitrant to antibiotic therapies and immune clearance. This is particularly problematic in hospital settings where biofilms are a frequent cause of chronic and device-related infections and constitute a significant burden on the health-care system. The major therapeutic strategy against infections is the use of antibiotics, which, due to adaptive resistance, are often insufficient to clear biofilm infections. Thus, novel biofilm-specific therapies are required. Specific features of biofilm development, such as surface adherence, extracellular matrix formation, quorum sensing, and highly regulated biofilm maturation and dispersal are currently being studied as targets to be exploited in the development of novel biofilm-specific treatments. Using Pseudomonas aeruginosa for illustrative purposes, this review highlights the antibiotic resistance mechanisms of biofilms, and discusses current research into novel biofilm-specific therapies.

  9. Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy.

    PubMed

    Cosgrove, Sara E; Li, David X; Tamma, Pranita D; Avdic, Edina; Hadhazy, Eric; Wakefield, Teresa; Gherna, Michael; Carroll, Karen C

    2016-09-01

    Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) is a rapid diagnostic assay that can identify certain organisms growing in blood cultures 30-90 min from the time of positive Gram-stain. Existing studies have demonstrated a clinical utility with this assay when antibiotic stewardship programs assist clinicians with interpreting the results. However, the benefit of these rapid assays in the absence of concomitant antibiotic stewardship involvement is unclear. In this randomized study of 220 patients with enterococcal or streptococcal bacteremia, we found that PNA FISH, in the absence of concomitant input from an antibiotic stewardship program, had no impact on time to effective or optimal therapy, length of hospital stay, or in-hospital mortality. Our results suggest that in the absence of guidance from an antibiotic stewardship program, the clinical benefits of rapid diagnostic microbiological tools may be reduced. PMID:27412814

  10. Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy.

    PubMed

    Cosgrove, Sara E; Li, David X; Tamma, Pranita D; Avdic, Edina; Hadhazy, Eric; Wakefield, Teresa; Gherna, Michael; Carroll, Karen C

    2016-09-01

    Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) is a rapid diagnostic assay that can identify certain organisms growing in blood cultures 30-90 min from the time of positive Gram-stain. Existing studies have demonstrated a clinical utility with this assay when antibiotic stewardship programs assist clinicians with interpreting the results. However, the benefit of these rapid assays in the absence of concomitant antibiotic stewardship involvement is unclear. In this randomized study of 220 patients with enterococcal or streptococcal bacteremia, we found that PNA FISH, in the absence of concomitant input from an antibiotic stewardship program, had no impact on time to effective or optimal therapy, length of hospital stay, or in-hospital mortality. Our results suggest that in the absence of guidance from an antibiotic stewardship program, the clinical benefits of rapid diagnostic microbiological tools may be reduced.

  11. Decline in the frequencies of Borrelia burgdorferi OspA161 175-specific T cells after antibiotic therapy in HLA-DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory lyme arthritis.

    PubMed

    Kannian, Priya; Drouin, Elise E; Glickstein, Lisa; Kwok, William W; Nepom, Gerald T; Steere, Allen C

    2007-11-01

    Synovitis in patients with antibiotic-refractory Lyme arthritis persists for months to several years after antibiotic therapy. This course, which may result from infection-induced autoimmunity, is associated with T cell recognition of Borrelia burgdorferi outer surface protein A (OspA(161-175)) and with HLA-DR molecules that bind this epitope, including the DRB1*0401 molecule. In this study, we used tetramer reagents to determine the frequencies of OspA(161-175)-specific T cells in samples of PBMC and synovial fluid mononuclear cells (SFMC) from 13 DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory arthritis. Initially, three of the six patients (50%) with antibiotic-responsive arthritis and four of the seven patients (57%) with antibiotic-refractory arthritis had frequencies of OspA(161-175)-specific CD4(+) T cells in peripheral blood above the cutoff value of 4 per 10(5) cells. Among the five patients with concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean frequency of such cells was 16 times higher in SFMC, reaching levels as high as 1,177 per 10(5) cells. In the two patients in each patient group in whom serial samples were available, the frequencies of OspA(161-175)-specific T cells declined to low or undetectable levels during or soon after antibiotic therapy, months before the resolution of synovitis in the two patients with antibiotic-refractory arthritis. Thus, the majority of patients with Lyme arthritis initially have increased frequencies of OspA(161-175)-specific T cells. However, the marked decline in the frequency of such cells with antibiotic therapy suggests that persistent synovitis in the refractory group is not perpetuated by these cells.

  12. Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients.

    PubMed

    Join-Lambert, Olivier; Duchatelet, Sabine; Delage, Maïa; Miskinyte, Snaigune; Coignard, Hélène; Lemarchand, Nicolas; Alemy-Carreau, Murielle; Lortholary, Olivier; Nassif, Xavier; Hovnanian, Alain; Nassif, Aude

    2015-11-01

    Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases.

  13. Antibiotic Therapy for Premature Rupture of Membranes and Preterm Labor and Effect on Fetal Outcome.

    PubMed

    Seelbach-Goebel, B

    2013-12-01

    In Germany almost 10 % of children are born before the end of 37th week of gestation. In at least one quarter of these cases, ascending infection of the vagina plays a causative role, particularly during the early weeks of gestation. If, in addition to the decidua, the amniotic membrane, amniotic fluid and the umbilical cord are also affected, infection not only triggers uterine contractions and premature rupture of membranes but also initiates a systemic inflammatory reaction on the part of the fetus, which can increase neonatal morbidity. Numerous studies and meta-analyses have found that antibiotic therapy prolongs pregnancy and reduces neonatal morbidity. No general benefit of antibiotic treatment was found for premature uterine contractions. But it is conceivable that a subgroup of pregnant women would benefit from antibiotic treatment. It is important to identify this subgroup of women and offer them targeted treatment. This overview summarizes the current body of evidence on antibiotic treatment for impending preterm birth and the effect on neonatal outcomes.

  14. Periorbital cellulitis in children: Analysis of outcome of intravenous antibiotic therapy.

    PubMed

    Gonçalves, Rita; Menezes, Carlos; Machado, Rute; Ribeiro, Isabel; Lemos, José A

    2016-08-01

    Periorbital cellulitis is a relatively common ocular disease in the pediatric population. Early diagnosis of this disease with a prompt intervention is critical to avoid vision and life-threatening complications. In the last years, medical therapy has been expanding for the treatment of orbital cellulitis, instead of the standard surgical approach. The purpose of this study was to describe the outcome of treatment with intravenous antibiotic of periorbital cellulitis in children. A retrospective review of all children admitted with periorbital cellulitis in our hospital between January 2002 and July 2013 was conducted. Cases were divided in two subgroups, pre-septal and post-septal infection. The demographics, clinical findings, treatment and outcomes were analyzed. In total 110 children were included, 93 with pre-septal and 17 with post-septal cellulitis. The mean age was 3.5 years in children with pre-septal cellulitis and 5.5 years in those with post-septal cellulitis (p = 0.149). For both subgroups the most common predisposing factor was sinusitis. Intravenous antibiotic therapy was successful in all except one patient with an orbital abscess who required surgical intervention. In our study complete recovery was achieve in all (except for one) children with periorbital cellulitis treated with intravenous antibiotics only. PMID:27192038

  15. Value and Clinical Impact of an Infectious Disease-Supervised Outpatient Parenteral Antibiotic Therapy Program

    PubMed Central

    Petrak, Russell M.; Skorodin, Nathan C.; Fliegelman, Robert M.; Hines, David W.; Chundi, Vishnu V.; Harting, Brian P.

    2016-01-01

    Background. Outpatient parenteral antibiotic therapy (OPAT) is a safe and effective modality for treating serious infections. This study was undertaken to define the value of OPAT in a multicentered infectious disease (ID) private practice setting. Methods. Over a period of 32 months, 6120 patients were treated using 19 outpatient ID offices in 6 states. Analysis included patient demographics, indications of OPAT, diagnoses, therapeutic agent, duration of therapy, and site of therapy initiation. Outcomes were stratified by therapeutic success, clinical relapse, therapeutic complications, and hospitalizations after initiating therapy. Statistical analysis included an ordinal logistic regression analysis. Results. Forty-three percent of patients initiated therapy in an outpatient office, and 57% began therapy in a hospital. Most common diagnoses treated were bone and joint (32.2%), abscesses (18.8%), cellulitis (18.5%), and urinary tract infection (10.8%). Ninety-four percent of patients were successfully treated, and only 3% were hospitalized after beginning therapy. Most common cause of treatment failure was a relapse of primary infection (60%), progression of primary infection (21%), and therapeutic complication (19%). Conclusions. An ID-supervised OPAT program is safe, efficient, and clinically effective. By maximizing the delivery of outpatient care, OPAT provides a tangible value to hospitals, payers, and patients. This program is a distinctive competency available to ID physicians who offer this service to patients. PMID:27807591

  16. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.

    PubMed

    Quigley, Eamonn M M

    2011-03-01

    Several recent observations have raised the possibility that disturbances in the gut microbiota and/or a low-grade inflammatory state may contribute to symptomatology and the etiology of irritable bowel syndrome (IBS). Consequent on these hypotheses, several therapeutic categories have found their way into the armamentarium of those who care for IBS sufferers. These agents include probiotics, prebiotics, antibiotics, and anti-inflammatory agents.

  17. Evaluating the need, timing and best choice of antibiotic therapy for acute otitis media and tonsillopharyngitis infections in children.

    PubMed

    Pichichero, M E

    2000-12-01

    Deciding whether an antibiotic is necessary, when to begin therapy and selecting an optimal drug is an everyday challenge in clinical practice. In vitro susceptibility testing which determines the minimum concentration necessary for a particular antibiotic to inhibit or kill most strains of a bacterial species and pharmacodynamic modeling are useful but have limitations. The need for antibiotic therapy for acute otitis media (AOM) has been recently questioned. However, explanations for uniformly positive results with many antibiotic and placebo comparative trials include overdiagnosis of AOM at study entry, inclusion of patients with mild or uncomplicated AOM and broad criteria for the definition of clinical success. Recurrent and persistent AOM does not have as favorable a natural history as uncomplicated AOM; children below 2 years of age benefit most from antibiotic therapy. Selecting the best choice among the many antibiotics that can be used to treat AOM has become more complex over the last decade due to escalating antibiotic resistance among the pathogens that cause this infection. Broader spectrum antibiotics such as cefdinir, the newly introduced third generation cephalosporin, have their most prominent use in the treatment of persistent and recurrent AOM. In the early 1950s and 1960s penicillin clearly was the best available agent for the treatment of group A streptococcal (GAS) infections. In the 1970s the situation began to change as cephalosporin antibiotics became available. Superior eradication rates with cephalosporins such as cefdinir have now been well-documented. The leading hypothesis to explain the widening gap in efficacy between penicillin and cephalosporins relates to two major concepts: the presence of copathogens and differential alteration of the normal microbial ecology in the throat as a consequence of the selected therapy. There are positive and negative consequences to early initiation of antibiotic therapy for GAS tonsillopharyngitis

  18. Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity

    PubMed Central

    Hannan, Thomas J.; MacPhee, Roderick A.; Schwartz, Drew J.; Macklaim, Jean M.; Gloor, Gregory B.; Razvi, Hassan; Reid, Gregor; Hultgren, Scott J.; Burton, Jeremy P.

    2015-01-01

    ABSTRACT The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections. PMID:25827417

  19. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

  20. Vancomycin-Variable Enterococci Can Give Rise to Constitutive Resistance during Antibiotic Therapy

    PubMed Central

    Thaker, Maulik N.; Kalan, Lindsay; Waglechner, Nicholas; Eshaghi, Alireza; Patel, Samir N.; Poutanen, Susan; Willey, Barbara; Coburn, Bryan; McGeer, Allison; Low, Donald E.

    2014-01-01

    Vancomycin-resistant enterococci (VRE) are notorious clinical pathogens restricting the use of glycopeptide antibiotics in the clinic setting. Routine surveillance to detect VRE isolated from patients relies on PCR bioassays and chromogenic agar-based test methods. In recent years, we and others have reported the emergence of enterococcal strains harboring a “silent” copy of vancomycin resistance genes that confer a vancomycin-susceptible phenotype (vancomycin-susceptible enterococci [VSE]) and thus escape detection using drug sensitivity screening tests. Alarmingly, these strains are able to convert to a resistance phenotype (VSE→VRE) during antibiotic treatment, severely compromising the success of therapy. Such strains have been termed vancomycin-variable enterococci (VVE). We have investigated the molecular mechanisms leading to the restoration of resistance in VVE isolates through the whole-genome sequencing of resistant isolates, measurement of resistance gene expression, and quantification of the accumulation of drug-resistant peptidoglycan precursors. The results demonstrate that VVE strains can revert to a VRE phenotype through the constitutive expression of the vancomycin resistance cassette. This is accomplished through a variety of changes in the DNA region upstream of the resistance genes that includes both a deletion of a likely transcription inhibitory secondary structure and the introduction of a new unregulated promoter. The VSE→VRE transition of VVE can occur in patients during the course of antibiotic therapy, resulting in treatment failure. These VVE strains therefore pose a new challenge to the current regimen of diagnostic tests used for VRE detection in the clinic setting. PMID:25512425

  1. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization. PMID:27125562

  2. Successful treatment of renal allograft and bladder malakoplakia with minimization of immunosuppression and prolonged antibiotic therapy.

    PubMed

    Graves, Angela L; Texler, Michael; Manning, Laurens; Kulkarni, Hemant

    2014-04-01

    Malakoplakia is an unusual granulomatous inflammatory disorder associated with diminished bactericidal action of leucocytes that occurs in immunosuppressed hosts. Cases of renal allograft malakoplakia are generally associated with a poor graft and patient survival. We present the case of a 56-year-old female with allograft and bladder malakoplakia occurring two years after renal transplantation complicated by an early antibody mediated rejection. Following a number of symptomatic urinary tract infections caused by resistant Gram-negative bacilli, a diagnosis of malakoplakia was made by biopsy of a new mass lesion of the renal allograft. Cystoscopy also revealed malakoplakia of the bladder wall. Immunosuppressant regimen was modified. Mycophenolate mofetil was ceased, prednisolone reduced to 5 mg/day and tacrolimus concentrations were carefully monitored to maintain trough serum concentrations of 2-4 μg/L. Concurrently, she received a prolonged course of intravenous antibiotics followed by 13 months of dual oral antibiotic therapy with fosfomycin and faropenem. This joint approach resulted in almost complete resolution of allograft malakoplakia lesions and sustained regression of bladder lesions on cystoscopy with histological resolution in bladder lesions. Her renal function has remained stable throughout the illness. If treated with sustained antimicrobial therapy and reduction of immunosuppression, cases of allograft malakoplakia may not necessarily be associated with poor graft survival. PMID:24460630

  3. Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

    PubMed

    Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

    2013-01-01

    This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

  4. Prophylactic broad spectrum antibiotics as a new anti-myeloma therapy.

    PubMed

    Valkovic, Toni; Nacinovic, Antica Duletic; Petranovic, Duska

    2013-12-01

    Multiple myeloma is a common, yet incurable, haematological neoplasm. The reciprocal communication between malignant plasma cells, other cell types, and the extracellular matrix in the bone marrow micro-eco system is mediated by cell-cell and cell-matrix adhesion, as well as the production of different soluble factors, and is crucial for tumour growth and drug resistance. Inflammation and pro-inflammatory cytokines contribute to the clonal expansion of neoplastic plasmacytes. This extremely complex pathogenesis of multiple myeloma gives us the opportunity to promote numerous novel drugs and approaches based on the paradigm of targeted therapy. Immune dysfunction is a hallmark of multiple myeloma. Intrinsic and therapy-related immunosuppression leads to an increased risk of recurrent infection, the major cause of mortality. However, little data is available regarding the possible influence of infection on the biology and progression of multiple myeloma. Some authors have shown that pathogenic microorganisms can activate tool-like receptors on myeloma cells, as well as the robust production of pro-inflammatory cytokines; together these factors can contribute to myeloma growth, survival, and progression. Therefore, we proposed a simple, inexpensive, and new approach for anti-myeloma therapy that, to the best of our knowledge, is the first one concerning the prophylactic, long-term use of broad-spectrum antibiotics during the course of disease regardless of the chosen concomitant regimens. Prophylactic treatment with antibiotics should suppress the pro-inflammatory milieu produced during recurrent bacterial infections and prevent the activation of tool-like receptors on tumour cells, which are important factors responsible for tumour growth and survival in patients with multiple myeloma.

  5. Clinical pilot study: efficacy of triple antibiotic therapy in Blastocystis positive irritable bowel syndrome patients

    PubMed Central

    2014-01-01

    Background Blastocystis species are common human enteric parasites. Carriage has been linked to Irritable Bowel Syndrome (IBS). Treatment of Blastocystis spp. with antimicrobials is problematic and insensitive diagnostic methods and re-infection complicate assessment of eradication. We investigated whether triple antibiotic therapy comprising diloxanide furoate, trimethoprim/sulfamethoxazole and secnidazole (TAB) given to diarrhoea-predominant IBS (D-IBS) patients positive for Blastocystis would achieve eradication. Methods In a longitudinal, prospective case study 10 D-IBS Blastocystis-positive patients took 14 days of diloxanide furoate 500 mg thrice daily, trimethoprim/sulfamethoxazole 160/80 mg twice daily and secnidazole 400 mg thrice daily. Faecal specimens were collected at baseline, day 15 and 4 weeks after completion of TAB. Specimens were analysed using faecal smear, culture and polymerase chain reaction (PCR) of the 16 SSU rRNA. Patients kept a concurrent clinical diary. Results Six (60%) patients cleared Blastocystis spp. after TAB, including three who had failed previous therapy. Subtypes detected were ST3 (60%), ST4 (40%), ST1 (20%) and ST7, 8 (10%); four patients had mixed ST infections. Serum immunoglobulin A (IgA) levels were low in 40% of patients. Higher rates of Blastocystis clearance were observed in patients symptomatic for less than a year (Mann–Whitney, p = 0.032, 95% confidence) with no associations found with age, previous antibiotic therapy, faecal parasite load, ST, IgA level or clinical improvement. Conclusions Clearance of Blastocystis spp. was achieved with TAB in 60% of D-IBS patients, an improvement over conventional monotherapy. Higher clearance rates are needed to facilitate investigation of the relevance of this parasite in clinically heterogenous IBS. PMID:25349629

  6. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  7. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis.

    PubMed

    Jepsen, Karin; Jepsen, Søren

    2016-06-01

    This review gives an update of the current scientific evidence on the efficacy of the adjunctive use of systemic and local antibiotics/antimicrobials in the treatment of periodontitis. In particular, it addresses whether their use can improve the results of nonsurgical mechanical therapy in mild-to-moderate forms of the disease. Large numbers of randomized clinical trials and systematic reviews with meta-analyses have clearly established that adjunctive systemic antibiotics, combined with mechanical debridement, offer clinical improvements additional to those obtained with scaling and root planing alone. These effects are more pronounced in aggressive periodontitis and in initially deep pockets, whereas more limited additional improvements, of 0.3 mm for additional pocket reduction and 0.2 mm for additional clinical attachment gain, have been documented for moderately deep sites (4-6 mm) in patients with chronic periodontitis. The marginal clinical benefit in patients with moderate disease has to be balanced against possible side effects. Notably, it has to be realized that an increasing number of warnings have been articulated against the unrestricted use of antibiotics in treating periodontal diseases because of the emerging global public health issue of bacterial resistance. The effects of the adjunctive local administration of antimicrobials have also been very well documented in several systematic reviews. Overall, in persistent or recurrent localized deep sites, the application of antimicrobials by sustained-delivery devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and 0.3 mm in clinical attachment level gain. In conclusion, the slight additional benefits of adjunctive antimicrobials, which were shown for moderate forms of periodontitis, have to be balanced against their side effects and therefore their prescription should be limited as much as possible. PMID:27045432

  8. Antibiotic time-lag combination therapy with fosfomycin for postoperative intra-abdominal abscesses.

    PubMed

    Kusachi, Shinya; Nagao, Jiro; Saida, Yoshihisa; Watanabe, Manabu; Okamoto, Yasushi; Asai, Koji; Nakamura, Yoichi; Enomoto, Toshiyuki; Arima, Yoichi; Kiribayashi, Takaharu; Watanabe, Ryohei; Saito, Tomoaki; Uramatsu, Masashi; Sato, Junko

    2011-02-01

    The first-line treatment for intra-abdominal abscess is source control. Sometimes, however, source control is too invasive for relatively small abscesses and is not feasible due to the risk of injury to some organs. Based on reports that fosfomycin (FOM) can break up biofilms to enhance the permeability of other antibiotics, we investigated the FOM time-lag combination therapy (FOM-TLCT). We enrolled 114 patients who had intra-abdominal abscess after gastrointestinal surgery and examined the efficacy of FOM-TLCT using the same therapeutic antibiotic (TA) as that which had been used previously, but had proven ineffective, at the same dose schedule. The efficacy endpoint determination was carried out as follows: among the systemic inflammatory response syndrome (SIRS)-positive cases, even after administration of TA, excellent outcome was defined as SIRS negative within 7 days of FOM-TLCT with TA without the need for other treatment, including other antibiotics or drainage. Of the 114 patients enrolled, 104 cases (SIRS positive 73; SIRS negative 31) were assessed. Ten patients were excluded; four had received TA at higher doses, three had received different TAs, and three were considered to have bacteria resistant to TAs. Among these patients, 86.3% (63/73) of the SIRS-positive cases were classified as excellent, and 90.3% (28/31) of the SIRS-negative cases were classified as effective. In total, the efficacy rate was 87.5% (91/104). The total no-response rates were 12.5% (13/104). FOM-TLCT seems to be effective for treating refractory intra-abdominal abscess.

  9. Infectious prosthetic hip joint loosening: bacterial species involved in its aetiology and their antibiotic resistance profiles against antibiotics recommended for the therapy of implant-associated infections.

    PubMed

    Bogut, Agnieszka; Niedźwiadek, Justyna; Strzelec-Nowak, Dagmara; Blacha, Jan; Mazurkiewicz, Tomasz; Marczyński, Wojciech; Kozioł-Montewka, Maria

    2014-04-01

    Reliable microbiological diagnosis along with surgery and prolonged antibiotic therapy are key elements in the management of prosthetic-joint infections (PJIs). The purpose of this study was to characterize antibiotic resistance profiles of bacteria involved in the aetiology of PJIs. A total of 33 bacterial isolates cultured from 31 patients undergoing exchange of total hip prostheses were analyzed. The diagnostic approach toward isolation of prosthesis- associated microorganisms included sonication of retrieved implants and conventional cultures of periprosthetic tissues and synovial fluid. The in vitro resistance profiles of bacterial isolates were determined in relation to antibiotics recommended for the therapy of PJIs using the disc diffusion method, E-tests(®) and broth microdilution system. Coagulase-negative staphylococci (CNS) were predominant microorganisms followed by Staphylococcus aureus, Enterobacter cloacae, Streptococcus mitis, and Propionibacterium acnes. Twenty out of 30 and 12 out of 30 staphylococcal isolates were methicillin- and multi-drug resistant, respectively. Only two isolates were rifampicinresistant. All staphylococci were susceptible to glycopeptides and linezolid. This paper stresses the pathogenic role of staphylococci in patients suffering from implant loosening and reports high methicillin- and multidrug-resistance rates in these bacteria. Hence, antimicrobial susceptibility tests of individual bacterial isolates must always be performed to guide selection of the optimal therapeutic option.

  10. A Positive Prospective Trial of Antibiotic Therapy in Advanced Stage, Non-Bulky Indolent Lymphoma

    PubMed Central

    Portlock, Carol S; Hamlin, Paul A; Gerecitano, John F; Noy, Ariela; Palomba, Maria Lia; Walkley, Janelle; Corcoran, Stacie; Migliacci, Jocelyn; Schoder, Heiko; Papanicolaou, Genovefa; Markowitz, Arnold J

    2016-01-01

    Background We have prospectively studied a three month course of clarithromycin (substituted by Prevpac®, lansoprazole/ amoxicillin/ clarithromycin, in the first two wks when stool H pylori+) for non-bulky, advanced stage indolent lymphoma. These patients are often candidates for expectant monitoring and it is during this period that a window of opportunity may exist to identify and treat associated infections. Methods All previously untreated patients with a new diagnosis of indolent lymphoma (FL and non-FL) meeting GELF criteria were treated with 12 weeks of clarithromycin. There were 32 evaluable patients, 4 of whom had stool H pylori. Results At one month post-antibiotic therapy, we have observed lymphoma responses in 7 of 32 patients (21.9%). Two additional patients had objective response during followup (28.1% overall response). The median treatment free survival for antibiotic responders is 69.9 months and for non-responders, 30.6 months (p = 0.019). Conclusion Three response patterns have been noted, perhaps suggestive of an immune-mediated response -- prompt PET negative; flair with delayed PET negative response; and gradual continuous improvement. This prospective study appears promising, may be a step toward developing a lymphoma prevention strategy by reducing “antigen drive,” and deserves further clinical/biological study. http://clinicaltrials.gov/show/NCT00461084 PMID:26798624

  11. Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy.

    PubMed

    Koido, Shigeo; Ohkusa, Toshifumi; Kajiura, Takayuki; Shinozaki, Junko; Suzuki, Manabu; Saito, Keisuke; Takakura, Kazuki; Tsukinaga, Shintaro; Odahara, Shunichi; Yukawa, Toyokazu; Mitobe, Jimi; Kajihara, Mikio; Uchiyama, Kan; Arakawa, Hiroshi; Tajiri, Hisao

    2014-01-01

    Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy. PMID:24489770

  12. Long-Term Alteration of Intestinal Microbiota in Patients with Ulcerative Colitis by Antibiotic Combination Therapy

    PubMed Central

    Koido, Shigeo; Ohkusa, Toshifumi; Kajiura, Takayuki; Shinozaki, Junko; Suzuki, Manabu; Saito, Keisuke; Takakura, Kazuki; Tsukinaga, Shintaro; Odahara, Shunichi; Yukawa, Toyokazu; Mitobe, Jimi; Kajihara, Mikio; Uchiyama, Kan; Arakawa, Hiroshi; Tajiri, Hisao

    2014-01-01

    Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy. PMID:24489770

  13. Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins.

    PubMed

    Kling, Angela; Lukat, Peer; Almeida, Deepak V; Bauer, Armin; Fontaine, Evelyne; Sordello, Sylvie; Zaburannyi, Nestor; Herrmann, Jennifer; Wenzel, Silke C; König, Claudia; Ammerman, Nicole C; Barrio, María Belén; Borchers, Kai; Bordon-Pallier, Florence; Brönstrup, Mark; Courtemanche, Gilles; Gerlitz, Martin; Geslin, Michel; Hammann, Peter; Heinz, Dirk W; Hoffmann, Holger; Klieber, Sylvie; Kohlmann, Markus; Kurz, Michael; Lair, Christine; Matter, Hans; Nuermberger, Eric; Tyagi, Sandeep; Fraisse, Laurent; Grosset, Jacques H; Lagrange, Sophie; Müller, Rolf

    2015-06-01

    The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification.

  14. Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin.

    PubMed

    Heinsen, Femke-Anouska; Knecht, Henrik; Neulinger, Sven C; Schmitz, Ruth A; Knecht, Carolin; Kühbacher, Tanja; Rosenstiel, Philip C; Schreiber, Stefan; Friedrichs, Anette K; Ott, Stephan J

    2015-07-01

    Gut microbiota play a key role in the host's health system. Broad antibiotic therapy is known to disrupt the microbial balance affecting pathogenic as well as host-associated microbes. The aim of the present study was to investigate the influence of antibiotic paromomycin on the luminal and mucosa-associated microbiota at the DNA (abundance) and RNA (potential activity) level as well as to identify possible differences. The influence of antibiotic treatment on intestinal microbiota was investigated in 5 healthy individuals (age range: 20-22 years). All participants received the antibiotic paromomycin for 3 d. Fecal samples as well as sigmoidal biopsies were collected before and immediately after cessation of antibiotic treatment as well as after a recovery phase of 42 d. Compartment- and treatment status-specific indicator operational taxonomic units (OTUs) as well as abundance- and activity-specific patterns were identified by 16S rRNA and 16S rRNA gene amplicon libraries and high-throughput pyrosequencing. Microbial composition of lumen and mucosa were significantly different at the DNA compared to the RNA level. Antibiotic treatment resulted in changes of the microbiota, affecting the luminal and mucosal bacteria in a similar way. Several OTUs were identified as compartment- and/or treatment status-specific. Abundance and activity patterns of some indicator OTUs differed considerably. The study shows fundamental changes in composition of gut microbiota under antibiotic therapy at both the potential activity and the abundance level at different treatment status. It may help to understand the complex processes of gut microbiota changes involved in resilience mechanisms and on development of antibiotic-associated clinical diseases. PMID:26178862

  15. Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

    PubMed

    Fitzpatrick, J M; Biswas, J S; Edgeworth, J D; Islam, J; Jenkins, N; Judge, R; Lavery, A J; Melzer, M; Morris-Jones, S; Nsutebu, E F; Peters, J; Pillay, D G; Pink, F; Price, J R; Scarborough, M; Thwaites, G E; Tilley, R; Walker, A S; Llewelyn, M J

    2016-03-01

    Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

  16. Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

    PubMed Central

    Heinsen, Femke-Anouska; Knecht, Henrik; Neulinger, Sven C; Schmitz, Ruth A; Knecht, Carolin; Kühbacher, Tanja; Rosenstiel, Philip C; Schreiber, Stefan; Friedrichs, Anette K; Ott, Stephan J

    2015-01-01

    Gut microbiota play a key role in the host's health system. Broad antibiotic therapy is known to disrupt the microbial balance affecting pathogenic as well as host-associated microbes. The aim of the present study was to investigate the influence of antibiotic paromomycin on the luminal and mucosa-associated microbiota at the DNA (abundance) and RNA (potential activity) level as well as to identify possible differences. The influence of antibiotic treatment on intestinal microbiota was investigated in 5 healthy individuals (age range: 20–22 years). All participants received the antibiotic paromomycin for 3 d. Fecal samples as well as sigmoidal biopsies were collected before and immediately after cessation of antibiotic treatment as well as after a recovery phase of 42 d. Compartment- and treatment status-specific indicator operational taxonomic units (OTUs) as well as abundance- and activity-specific patterns were identified by 16S rRNA and 16S rRNA gene amplicon libraries and high-throughput pyrosequencing. Microbial composition of lumen and mucosa were significantly different at the DNA compared to the RNA level. Antibiotic treatment resulted in changes of the microbiota, affecting the luminal and mucosal bacteria in a similar way. Several OTUs were identified as compartment- and/or treatment status-specific. Abundance and activity patterns of some indicator OTUs differed considerably. The study shows fundamental changes in composition of gut microbiota under antibiotic therapy at both the potential activity and the abundance level at different treatment status. It may help to understand the complex processes of gut microbiota changes involved in resilience mechanisms and on development of antibiotic-associated clinical diseases. PMID:26178862

  17. Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

    PubMed

    Fitzpatrick, J M; Biswas, J S; Edgeworth, J D; Islam, J; Jenkins, N; Judge, R; Lavery, A J; Melzer, M; Morris-Jones, S; Nsutebu, E F; Peters, J; Pillay, D G; Pink, F; Price, J R; Scarborough, M; Thwaites, G E; Tilley, R; Walker, A S; Llewelyn, M J

    2016-03-01

    Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors. PMID:26577143

  18. Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

    PubMed

    Hadinoto, Kunn; Cheow, Wean Sin

    2014-04-01

    Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified.

  19. Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

    PubMed

    Abel zur Wiesch, Pia; Kouyos, Roger; Abel, Sören; Viechtbauer, Wolfgang; Bonhoeffer, Sebastian

    2014-06-01

    The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden. Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance. However, theoretical and clinical studies came to different conclusions regarding the usefulness of rotating first-line therapy (cycling). Here, we performed a quantitative pathogen-specific meta-analysis of clinical studies comparing cycling to standard practice. We searched PubMed and Google Scholar and identified 46 clinical studies addressing the effect of cycling on nosocomial infections, of which 11 met our selection criteria. We employed a method for multivariate meta-analysis using incidence rates as endpoints and find that cycling reduced the incidence rate/1000 patient days of both total infections by 4.95 [9.43-0.48] and resistant infections by 7.2 [14.00-0.44]. This positive effect was observed in most pathogens despite a large variance between individual species. Our findings remain robust in uni- and multivariate metaregressions. We used theoretical models that reflect various infections and hospital settings to compare cycling to random assignment to different drugs (mixing). We make the realistic assumption that therapy is changed when first line treatment is ineffective, which we call "adjustable cycling/mixing". In concordance with earlier theoretical studies, we find that in strict regimens, cycling is detrimental. However, in adjustable regimens single resistance is suppressed and cycling is successful in most settings. Both a meta-regression and our theoretical model indicate that "adjustable cycling" is especially useful to suppress emergence of multiple resistance. While our model predicts that cycling periods of one month perform well, we expect that too long cycling periods are detrimental. Our results suggest that "adjustable cycling

  20. Termite usage associated with antibiotic therapy: enhancement of aminoglycoside antibiotic activity by natural products of Nasutitermes corniger (Motschulsky 1855)

    PubMed Central

    Coutinho, Henrique DM; Vasconcellos, Alexandre; Lima, Micheline A; Almeida-Filho, Geraldo G; Alves, Rômulo RN

    2009-01-01

    Background Several species from Insecta are used as remedies. Among these species, the termite Nasutitermes corniger is commonly used in traditional medicine in Northeast Brazil. The present work tests the modifying antibiotic activity of Nasutitermes corniger, a termite used in folk medicine in Northeastern region of Brazil. Methods Chlorpromazine and decocts of N. corniger were collected from two different plant species used in the traditional medicine were tested for their antimicrobial activity against strains of Escherichia coli resistant to aminoglycosides. The growth of two bacterial strains of E. coli was tested using decocts and chlorpromazine alone or associeted with aminogycosides. Results The MIC and MBC values were ≥1024 μg/ml for both strains of E. coli assayed. A significant synergism was observed between both decocts and chlorpromazine when assyed with neomycin. This synergism with neomycin indicates the involvement of an efflux system in the resistance to this aminoglycoside. Conclusion Therefore it is suggested that natural products from N. corniger could be used as a source of zoo-derived natural products with modifying antibiotic activity to aminoglycosides, being a new weapon against the bacterial resistance to antibiotics. PMID:19761599

  1. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial

    PubMed Central

    Schuetz, Philipp; Christ-Crain, Mirjam; Wolbers, Marcel; Schild, Ursula; Thomann, Robert; Falconnier, Claudine; Widmer, Isabelle; Neidert, Stefanie; Blum, Claudine A; Schönenberger, Ronald; Henzen, Christoph; Bregenzer, Thomas; Hoess, Claus; Krause, Martin; Bucher, Heiner C; Zimmerli, Werner; Müller, Beat

    2007-01-01

    Background: Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections. Methods and design: We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections <28 days of duration. Patients with no informed consent, not fluent in German, a previous hospital stay within 14 days, severe immunosuppression or chronic infection, intravenous drug use or a terminal condition are excluded. Randomization to either guidelines-enforced management or procalcitonin-guided antibiotic therapy is stratified by centre and type of lower respiratory tract infections. During hospitalization, all patients are reassessed at days 3, 5, 7 and at the day of discharge. After 30 and 180 days, structured phone interviews by blinded medical students are conducted. Depending on the randomization allocation, initiation and discontinuation of antibiotics is encouraged or discouraged based on evidence-based guidelines or procalcitonin cut off ranges, respectively. The primary endpoint is the risk of combined disease-specific failure after 30 days. Secondary outcomes are antibiotic exposure, side effects from antibiotics, rate and duration of hospitalization, time to clinical stability, disease activity scores and cost effectiveness. The study hypothesis is that

  2. Empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures.

    PubMed

    Scholte, J B J; Duong, H L; Linssen, C; Van Dessel, H; Bergmans, D; van der Horst, R; Savelkoul, P; Roekaerts, P; van Mook, W

    2015-11-01

    The purpose of this investigation was to explore the presumed relationship between the days of hospitalisation and microorganisms identified by endotracheal aspirate cultures in relation to adequate empirical treatment strategies of pneumonia in the intensive care unit (ICU). All potentially pathogenic microorganisms identified by (surveillance) cultures of endotracheal aspirates obtained in the ICUs of two Dutch teaching hospitals in 2007 and 2012 were retrospectively collected and analysed. Antibiotic susceptibilities to 11 antibiotics were calculated for several time points (days or weeks) after hospital admission and expressed per patient-day. In total, 4184 potentially pathogenic microorganisms identified in 782 patients were analysed. Prevalence of the classic early-onset pneumonia-causing microorganisms decreased from 55 % on the first four days to 34 % on days 4-6 after hospital admission (p < 0.0001). Susceptibility to amoxicillin/clavulanic acid was below 70 % on all days. Except for days 0 and 12, susceptibility to ceftriaxone was below 80 %. The overall susceptibility to piperacillin/tazobactam was 1518/1973 (77 %) in 2007 vs. 727/1008 (67 %) in 2012 (p < 0.0001). After day 8 of hospital admission, susceptibility to piperacillin/tazobactam therapy was below 80 % in 2012. After one week of hospital admission, susceptibilities to antibiotics were lower in the hospital that included that antibiotic in the local empirical treatment protocols as compared to the hospitals in which that antibiotic was not or infrequently included: 90/434 (21 %) vs. 117/398 (29 %); p = 0.004 for amoxicillin/clavulanic acid and 203/433 (47 %) vs. 253/398 (64 %); p < 0.001 for ceftriaxone. No cut-off in the number of days after hospital admission could be identified to distinguish early-onset from late-onset pneumonia. Consequently, the choice of empirical antibiotics should probably not be based on the time of onset.

  3. Effects of intramammary antibiotic therapy during the dry period on the performance of Lacaune dairy sheep under intensive management.

    PubMed

    Hernandez, Fernando; Elvira, Laura; Fernández, Beatriz; Egea, Marta; Gonzalez-Bulnes, Antonio; Gonzalez-Martin, Juan V; Astiz, Susana

    2015-02-01

    Often the only way to ensure profitability of Lacaune dairy sheep is intensive management, which requires appropriate dry-period treatment to ensure animal productivity and health. The present study aimed to investigate the effects of intramammary antibiotic dry therapy on the performance and health of Lacaune sheep under intensive management. We recorded data for 5981 complete lactation periods that followed a dry period. A total of 2402 lactation periods were preceded by a dry period involving intramammary administration of 300 mg of cephapirin benzathine (antibiotic group) and 3579 lactation periods were preceded by dry periods with no treatment (control group). The following on-farm yield data were collected for individual lactation periods: length of the subsequent lactation period; total milk yield per lactation period; daily milk yield and length of the subsequent dry period. Data on confounding factors that might affect productivity were also recorded, including the individual ewe, number of lactation periods and length of the previous dry period. Milk quality was assessed using data on somatic cell count (SCC) and content of protein and fat taken from the Spanish National Official Milk Yield Recording System. Antibiotic dry therapy significantly improved total yield per lactation period, which was 429±151·1 l in the antibiotic group and 412±165·5 l in the control group, as well as the daily milk yield, which was 1986±497·0 and 1851±543·2 ml/d, respectively (both P<0·0001). The initial dry period was significantly longer in the antibiotic group than in the control group, and dry period length correlated inversely with yield variables such us total yield per lactation period (r=-0·055; P<0·0001) and yield per day in milk (r=-0·039; P<0·0001). As a result, milk yield records systematically underestimated the positive effects of antibiotic dry therapy. Antibiotic dry therapy also significantly improved milk quality. Milk from the antibiotic

  4. Bacteriophage therapy for membrane biofouling in membrane bioreactors and antibiotic-resistant bacterial biofilms.

    PubMed

    Bhattacharjee, Ananda Shankar; Choi, Jeongdong; Motlagh, Amir Mohaghegh; Mukherji, Sachiyo T; Goel, Ramesh

    2015-08-01

    To demonstrate elimination of bacterial biofilm on membranes to represent wastewater treatment as well as biofilm formed by antibiotic-resistant bacterial (ARB) to signify medical application, an antibiotic-resistant bacterium and its lytic bacteriophage were isolated from a full-scale wastewater treatment plant. Based on gram staining and complete 16 S rDNA sequencing, the isolated bacterium showed a more than 99% homology with Delftia tsuruhatensis, a gram-negative bacterium belonging to β-proteobacteria. The Delftia lytic phage's draft genome revealed the phage to be an N4-like phage with 59.7% G + C content. No transfer RNAs were detected for the phage suggesting that the phage is highly adapted to its host Delftia tsuruhatensis ARB-1 with regard to codon usage, and does not require additional tRNAs of its own. The gene annotation of the Delftia lytic phage found three different components of RNA polymerase (RNAP) in the genome, which is a typical characteristic of N4-like phages. The lytic phage specific to D. tsuruhatensis ARB-1 could successfully remove the biofilm formed by it on a glass slide. The water flux through the membrane of a prototype lab-scale membrane bioreactor decreased from 47 L/h m(2) to ∼15 L/h m(2) over 4 days due to a biofilm formed by D. tsuruhatensis ARB-1. However, the flux increased to 70% of the original after the lytic phage application. Overall, this research demonstrated phage therapy's great potential to solve the problem of membrane biofouling, as well as the problems posed by pathogenic biofilms in external wounds and on medical instruments. PMID:25728819

  5. Bacteriophage therapy for membrane biofouling in membrane bioreactors and antibiotic-resistant bacterial biofilms.

    PubMed

    Bhattacharjee, Ananda Shankar; Choi, Jeongdong; Motlagh, Amir Mohaghegh; Mukherji, Sachiyo T; Goel, Ramesh

    2015-08-01

    To demonstrate elimination of bacterial biofilm on membranes to represent wastewater treatment as well as biofilm formed by antibiotic-resistant bacterial (ARB) to signify medical application, an antibiotic-resistant bacterium and its lytic bacteriophage were isolated from a full-scale wastewater treatment plant. Based on gram staining and complete 16 S rDNA sequencing, the isolated bacterium showed a more than 99% homology with Delftia tsuruhatensis, a gram-negative bacterium belonging to β-proteobacteria. The Delftia lytic phage's draft genome revealed the phage to be an N4-like phage with 59.7% G + C content. No transfer RNAs were detected for the phage suggesting that the phage is highly adapted to its host Delftia tsuruhatensis ARB-1 with regard to codon usage, and does not require additional tRNAs of its own. The gene annotation of the Delftia lytic phage found three different components of RNA polymerase (RNAP) in the genome, which is a typical characteristic of N4-like phages. The lytic phage specific to D. tsuruhatensis ARB-1 could successfully remove the biofilm formed by it on a glass slide. The water flux through the membrane of a prototype lab-scale membrane bioreactor decreased from 47 L/h m(2) to ∼15 L/h m(2) over 4 days due to a biofilm formed by D. tsuruhatensis ARB-1. However, the flux increased to 70% of the original after the lytic phage application. Overall, this research demonstrated phage therapy's great potential to solve the problem of membrane biofouling, as well as the problems posed by pathogenic biofilms in external wounds and on medical instruments.

  6. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla

    2016-01-01

    Objectives Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits. Conclusions Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment. PMID:26981575

  7. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach

    PubMed Central

    Pérez-Cobas, Ana Elena; Gosalbes, María José; Friedrichs, Anette; Knecht, Henrik; Artacho, Alejandro; Eismann, Kathleen; Otto, Wolfgang; Rojo, David; Bargiela, Rafael; von Bergen, Martin; Neulinger, Sven C; Däumer, Carolin; Heinsen, Femke-Anouska; Latorre, Amparo; Barbas, Coral; Seifert, Jana; dos Santos, Vitor Martins; Ott, Stephan J; Ferrer, Manuel; Moya, Andrés

    2013-01-01

    Objective Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy. Methods The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated. Results Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation. Conclusions This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and

  8. β-Lactam antibiotics and vancomycin inhibit the growth of planktonic and biofilm Candida spp.: an additional benefit of antibiotic-lock therapy?

    PubMed

    Sidrim, José J C; Teixeira, Carlos E C; Cordeiro, Rossana A; Brilhante, Raimunda S N; Castelo-Branco, Débora S C M; Bandeira, Silviane P; Alencar, Lucas P; Oliveira, Jonathas S; Monteiro, André J; Moreira, José L B; Bandeira, Tereza J P G; Rocha, Marcos F G

    2015-04-01

    The aim of this study was to evaluate the effects of cefepime, meropenem, piperacillin/tazobactam (TZP) and vancomycin on strains of Candida albicans and Candida tropicalis in planktonic and biofilm forms. Twenty azole-derivative-resistant strains of C. albicans (n=10) and C. tropicalis (n=10) were tested. The susceptibility of planktonic Candida spp. to the antibacterial agents was investigated by broth microdilution. The XTT reduction assay was performed to evaluate the viability of growing and mature biofilms following exposure to these drugs. Minimum inhibitory concentrations (MICs) ranged from 0.5 mg/mL to 2 mg/mL for cefepime, TZP and vancomycin and from 0.5 mg/mL to 1 mg/mL for meropenem and the drugs also caused statistically significant reductions in biofilm cellular activity both in growing and mature biofilm. Since all of the tested drugs are commonly used in patients with hospital-acquired infections and in those with catheter-related infections under antibiotic-lock therapy, it may be possible to obtain an additional benefit from antibiotic-lock therapy with these drugs, namely the control of Candida biofilm formation.

  9. Rapid identification and antibiotic susceptibility testing of Salmonella enterica serovar Typhi isolated from blood: implications for therapy.

    PubMed

    Saha, S K; Darmstadt, G L; Baqui, A H; Hanif, M; Ruhulamin, M; Santosham, M; Nagatake, T; Black, R E

    2001-10-01

    The turnaround time (TAT) for Salmonella enterica serovar Typhi identification and reporting of the antibiotic susceptibility profile was determined for 391 cases of typhoid fever, using the lysis direct plating or lysis centrifugation method of blood culture along with rapid antimicrobial susceptibility testing. The TAT was more rapid (TAT for 90% of the patients [TAT(90)] = 30 h; TAT(100) Antibiotic susceptibility profiles, determined by the rapid antimicrobial susceptibility testing method, of randomly selected 60 S. enterica serovar Typhi isolates were identical to those determined by overnight conventional testing. Preliminary assessment of the impact of the reduced TAT on physician practices revealed that initial empirical therapy was prescribed at the time of presentation in most cases (87 of 108 [81%]) despite awareness that the final report would be available on the following day. Patients treated empirically with first-line antibiotics and shown subsequently to be infected with a multidrug-resistant strain benefited most (8 cases), since therapy was changed appropriately on the following day. In an additional 21 cases, therapy with an appropriate antibiotic was initiated after culture results were available. Thus, in approximately one-fourth (29 of 108 [27%]) of the cases, a change in management to an agent active for treatment of the isolate was made after receipt of the test results. However, in no case was therapy changed from a second-line to a first-line agent, even if the isolate was reported on the day after presentation to be sensitive to first-line therapy (33 cases). Ways in which to utilize rapid-TAT result reporting in order to positively influence physicians' prescribing in Bangladesh are the subject of ongoing research.

  10. Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

    PubMed Central

    Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

    2013-01-01

    Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•− and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

  11. Clinical and Economic Consequences of Failure of Initial Antibiotic Therapy for Patients with Community-Onset Complicated Intra-Abdominal Infections

    PubMed Central

    Chong, Yong Pil; Bae, In-Gyu; Lee, Sang-Rok; Chung, Jin-Won; Jun, Jae-Bum; Choo, Eun Ju; Moon, Soo-youn; Lee, Mi Suk; Jeon, Min Hyok; Song, Eun Hee; Lee, Eun Jung; Park, Seong Yeon; Kim, Yang Soo

    2015-01-01

    Objectives Complicated intra-abdominal infection (cIAI) is infection that extends beyond the hollow viscus of origin into the peritoneal space, and is associated with either abscess formation or peritonitis. There are few studies that have assessed the actual costs and outcomes associated with failure of initial antibiotic therapy for cIAI. The aims of this study were to evaluate risk factors and impact on costs and outcomes of failure of initial antibiotic therapy for community-onset cIAI. Methods A retrospective study was performed at eleven tertiary-care hospitals. Hospitalized adults with community-onset cIAI who underwent an appropriate source control procedure between August 2008 and September 2011 were included. Failure of initial antibiotic therapy was defined as a change of antibiotics due to a lack of improvement of the clinical symptoms and signs associated with cIAI in the first week. Results A total of 514 patients hospitalized for community-onset cIAI were included in the analysis. The mean age of the patients was 53.3 ± 17.6 years, 72 patients (14%) had health care-associated infection, and 48 (9%) experienced failure of initial antibiotic therapy. Failure of initial antibiotic therapy was associated with increased costs and morbidity. After adjustment for covariates, patients with unsuccessful initial therapy received an additional 2.9 days of parenteral antibiotic therapy, were hospitalized for an additional 5.3 days, and incurred $3,287 in additional inpatient charges. Independent risk factors for failure of initial antibiotic therapy were health care-associated infection, solid cancer, and APACHE II ≥13. Conclusions To improve outcomes and costs in patients with community-onset cIAI, rapid assessment of health care-associated risk factors and severity of disease, selection of an appropriate antibiotic regimen accordingly, and early infection source control should be performed. PMID:25910171

  12. Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy.

    PubMed

    Guillard, Thomas; Pons, Stéphanie; Roux, Damien; Pier, Gerald B; Skurnik, David

    2016-07-01

    "Antibiotic resistance is usually associated with a fitness cost" is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high-throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti-bacterial immunotherapies that have the potential to by-pass the classic antibiotics.

  13. A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients

    PubMed Central

    Roberts, Jason A.; Stove, Veronique; Verstraete, Alain G.; Lipman, Jeffrey; De Waele, Jan J.

    2015-01-01

    De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics. PMID:26014946

  14. A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients.

    PubMed

    Carlier, Mieke; Roberts, Jason A; Stove, Veronique; Verstraete, Alain G; Lipman, Jeffrey; De Waele, Jan J

    2015-08-01

    De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics.

  15. Cheilitis glandularis in an African-American woman: response to antibiotic therapy.

    PubMed

    Bender, Matthew M; Rubenstein, Melissa; Rosen, Ted

    2005-01-01

    A 52-year-old black woman presented with a 2-day history of lower lip swelling 5 days after starting a new medication, lisinopril. She had never experienced similar episodes in the past. She denied shortness of breath, tightening of the throat, swelling of the tongue, generalized cutaneous eruption, urticaria, or pruritus. She also denied symptoms consistent with facial paresis. Her past medical history was significant for hepatitis C infection, coronary artery disease, and hypertriglyceridemia. She had a 15 pack-year smoking history and denied both alcohol and drug abuse. She had never received a blood transfusion and was HIV negative. Physical examination disclosed a tender, swollen, and erythematous lower lip with induration, oozing, and crusting (Figure 1). Pinpoint openings evident throughout the lip surface exuded a clear, sticky, mucoid secretion. Tongue, parotid glands, and regional lymph nodes were normal. The working diagnosis was angioedema secondary to lisinopril. The presumptive offending drug was discontinued, and conservative therapy (topical clobetasol ointment, oral ranitidine, and oral fexofenadine) was initiated. Despite treatment, signs and symptoms persisted unabated. One week after initial presentation, a punch biopsy of her lower lip was taken to rule out granulomatous cheilitis and sarcoidosis. Histopathology included diffuse lymphohistiocytic infiltrate, minimal microabscess formation, and notable absence of granulomata. There was neither hypertrophy nor detectable abnormality of the salivary glands, with the exception of infiltrating mononuclear cells. Based on the clinical history and compatible pathologic findings, a diagnosis of cheilitis glandularis was made. Specifically, crusting and erosion clinically suggested a diagnosis of the superficial suppurative subtype of cheilitis glandularis. The patient received oral penicillin (dicloxacillin, 1.0 g/d) combined with oral fluoroquinolone (ciprofloxacin, 1.0 g/d). Within 2 weeks of

  16. Combination Therapy with Antibiotics and Anthrax Immune Globulin Intravenous (AIGIV) Is Potentially More Effective than Antibiotics Alone in Rabbit Model of Inhalational Anthrax

    PubMed Central

    Kammanadiminti, Srinivas; Patnaikuni, Ravi Kumar; Comer, Jason; Meister, Gabriel; Sinclair, Chris; Kodihalli, Shantha

    2014-01-01

    Background We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. Methods Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain) and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV) or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30–96 hours) after anthrax exposure. Results The majority of treated animals (>88%) survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. Conclusions The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin. PMID:25226075

  17. Interdisciplinary science and the design of a single-dose antibiotic therapy.

    PubMed

    Curatolo, William

    2011-09-01

    Azithromycin is a unique antibiotic due to its serum half-life of 69 h. This half-life is long enough to permit administration of an entire course of therapy in a single dose, if the gastrointestinal (GI) side effects of such a high dose can be minimized. A series of exploratory clinical pharmacology studies were carried out to understand the site-specific absorption and toleration constraints involved in delivering a 2 g oral single-dose regimen. These studies demonstrated that (a) GI side effects were locally mediated in the GI tract, (b) the duodenum was more sensitive than the ileocecal region, and (c) colonic absorption was limited. A novel controlled release suspension dosage form was designed to meet these constraints, and was shown to deliver the desired systemic dose with acceptable toleration. This dosage form, Zmax®, is an oral powder-for-constitution which possesses two major features: (a) 200 μm controlled release microspheres which release the drug as they transit down the small intestine, and (b) alkalizing agents which raise the pH of the gastric milieu for ~20 min to minimize gastric release of the drug (which has high solubility at low pH), in order to minimize exposure of the drug to the sensitive duodenal region. The ability to provide a high single dose of azithromycin results in "front-loading" the mononuclear and polymorphonuclear leukocytes which concentrate the drug and carry it to sites of infection. This provides high drug concentrations early on at infection sites, when the bacterial burden is greatest, potentially improving efficacy and potentially overcoming resistant bacterial strains. Finally, this revolutionary single dose formulation gives 100% compliance, which maximizes the likelihood of therapeutic success.

  18. Herbal therapy associated with antibiotic therapy: potentiation of the antibiotic activity against methicillin – resistant Staphylococcus aureus by Turnera ulmifolia L

    PubMed Central

    Coutinho, Henrique DM; Costa, José GM; Lima, Edeltrudes O; Falcão-Silva, Vivyanne S; Siqueira, José P

    2009-01-01

    Background Staphylococcus genus is widely spread in nature being part of the indigenous microbiota of skin and mucosa of animal and birds. Some Staphylococcus species are frequently recognized as etiological agents of many animal and human opportunistic infections This is the first report testing the antibiotic resistance-modifying activity of Turnera ulmifolia against methicillin-resistant Staphylococcus aureus – MRSA strain. Methods In this study an ethanol extract of Turnera ulmifolia L. and chlorpromazine were tested for their antimicrobial activity alone or in combination with aminoglycosides against an MRSA strain. Results The synergism of the ethanol extract and aminoglycosides were verified using microdillution method. A synergistic effect of this extract on gentamicin and kanamycin was demonstrated. Similarly, a potentiating effect of chlorpromazine on kanamycin, gentamicin and neomycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides. Conclusion It is therefore suggested that extracts from Turnera ulmifolia could be used as a source of plant-derived natural products with resistance-modifying activity, constituting a new weapon against the problem of bacterial resistance to antibiotics demonstrated in MRSA strains. PMID:19426487

  19. Maggot therapy in "lower-extremity hospice" wound care: fewer amputations and more antibiotic-free days.

    PubMed

    Armstrong, David G; Salas, Precious; Short, Brian; Martin, Billy R; Kimbriel, Heather R; Nixon, Brent P; Boulton, Andrew J M

    2005-01-01

    We sought to assess, in a case-control model, the potential efficacy of maggot debridement therapy in 60 nonambulatory patients (mean +/- SD age, 72.2 +/- 6.8 years) with neuroischemic diabetic foot wounds (University of Texas grade C or D wounds below the malleoli) and peripheral vascular disease. Twenty-seven of these patients (45%) healed during 6 months of review. There was no significant difference in the proportion of patients healing in the maggot debridement therapy versus control group (57% versus 33%). Of patients who healed, time to healing was significantly shorter in the maggot therapy than in the control group (18.5 +/- 4.8 versus 22.4 +/- 4.4 weeks). Approximately one in five patients (22%) underwent a high-level (above-the-foot) amputation. Patients in the control group were three times as likely to undergo amputation (33% versus 10%). Although there was no significant difference in infection prevalence in patients undergoing maggot therapy versus controls (80% versus 60%), there were significantly more antibiotic-free days during follow-up in patients who received maggot therapy (126.8 +/- 30.3 versus 81.9 +/- 42.1 days). Maggot debridement therapy reduces short-term morbidity in nonambulatory patients with diabetic foot wounds.

  20. Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center.

    PubMed

    Marín, Mar; Gudiol, Carlota; Garcia-Vidal, Carol; Ardanuy, Carmen; Carratalà, Jordi

    2014-05-01

    Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the

  1. Emergence of cross-resistance to imipenem and other beta-lactam antibiotics in Pseudomonas aeruginosa during therapy.

    PubMed

    Pagani, L; Landini, P; Luzzaro, F; Debiaggi, M; Romero, E

    1990-01-01

    The emergence of resistance to imipenem and other beta-lactams by Pseudomonas aeruginosa was investigated with two pairs of isolates. Two of these isolates were susceptible to imipenem and other beta-lactam antibiotics, such as moxalactam, ceftriaxone and cefotaxime, while the other two had developed resistance to those antibiotics during imipenem therapy. So far imipenem-resistant isolates have not demonstrated cross-resistance to other beta-lactam agents. We examined in these clinical isolates the possible mechanisms of resistance due to permeability modifications, either in outer membrane proteins (porins) or to LPS (lipopolysaccharides) complex. Particularly we analysed possible modification of physico-chemical properties of outer membrane proteins, such as changes in their hydrophobicity and electrical charge. beta-lactamase production was also studied. Results showed that resistance to imipenem may be related to loss or modifications in hydrophobicity of an outer membrane protein of about 46 Kdal; other modifications concerned hydrophobicity of the porin OMP F and, in one strain, the LPS complex appears to be responsible for resistance to other beta-lactam antibiotics together in combination with the production of beta-lactamases.

  2. Does antibiotic lock therapy prevent catheter-associated bacteremia in hemodialysis?

    PubMed

    Jiménez, Macarena; Madrid, Trinidad

    2015-01-22

    Central venous catheter-related blood stream infection is a major cause of morbidity and mortality in patients with renal disease treated with hemodialysis. Antibiotic lock solutions can be effective in preventing this complication in patients with hemodialysis. Searching in Epistemonikos database, which is maintained by screening more than twenty databases, we identified eight systematic reviews including seventeen randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that antibiotic lock solutions probably decrease catheter-related blood stream infection in hemodialysis patients.

  3. Diabetic foot infection: a critical review of recent randomized clinical trials on antibiotic therapy.

    PubMed

    Crouzet, J; Lavigne, J P; Richard, J L; Sotto, A

    2011-09-01

    Controlled clinical trials are essential tools for evaluating the efficacy of antibiotic treatment against infection, but the results of such trials critically depend on sensitive, reproducible, and feasible outcome measures. We reviewed randomized controlled trials on the antibiotic treatment of diabetic foot infection published between 1999 and 2009 in terms of quality and endpoints. Discrepancies in study design, inclusion criteria, statistical methodology, and the varying definitions of both clinical and microbiological endpoints between the published studies, make it difficult to compare them, as well as to determine which regimen may be the most appropriate for patients with diabetic foot infection.

  4. Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial

    PubMed Central

    Vogel, Thomas; Verreault, René; Gourdeau, Marie; Morin, Michèle; Grenier-Gosselin, Lise; Rochette, Louis

    2004-01-01

    Background The optimal duration of antibiotic therapy in older patients with uncomplicated urinary tract infection (UTI) is still a matter of debate. The aim of this randomized controlled double-blind noninferiority trial was to compare the efficacy and safety of 3-day and 7-day courses of oral ciprofloxacin for uncomplicated symptomatic UTI in older women. Methods A total of 183 women at least 65 years of age with acute uncomplicated UTI were recruited from ambulatory clinics and hospital acute care units. Patients with pyelonephritis, contraindications to fluoroquinolones, recent use of antibiotics, urinary tract abnormalities and diabetes mellitus were excluded. Women were randomly assigned to receive either ciprofloxacin 250 mg twice daily orally for 3 days followed by placebo for 4 days (the 3-day group, 93 patients) or ciprofloxacin 250 mg twice daily orally for 7 days (the 7-day group, 90 patients). Bacterial eradication, clinical improvement and occurrence of adverse events were determined 2 days after completion of treatment, and occurrence of reinfection or relapse were determined 6 weeks after completion of treatment. Bacterial eradication and relapse were determined by urine culture. Double-blind procedures were maintained throughout data collection. Results The proportion of patients with bacterial eradication at 2 days after treatment was 98% (91/93) in the 3-day group and 93% (83/89) in the 7-day group (p = 0.16). The frequency of adverse events, including drowsiness, headache, nausea or vomiting, and loss of appetite, was significantly lower in the 3-day group. Interpretation These results suggest that a 3-day course of antibiotic therapy is not inferior to a 7-day course for treatment of uncomplicated symptomatic UTI in older women, and that the shorter course is better tolerated. PMID:14970093

  5. Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

    PubMed

    Lima, Stella Sala Soares; Nobre, Vandack; de Castro Romanelli, Roberta Maia; Clemente, Wanessa Trindade; da Silva Bittencourt, Henrique Neves; Melo, Ana Catarina Mourão; Salomão, Luciana Caetano Botelho; Serufo, José Carlos

    2016-06-01

    Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting. PMID:27118539

  6. Mastitis therapy and antimicrobial susceptibility: a multispecies review with a focus on antibiotic treatment of mastitis in dairy cattle.

    PubMed

    Barlow, John

    2011-12-01

    Mastitis occurs in numerous species. Antimicrobial agents are used for treatment of infectious mastitis in dairy cattle, other livestock, companion animals, and humans. Mastitis is an economically important disease of dairy cattle and most mastitis research has focused on epidemiology and control of bovine mastitis. Antibiotic treatment of clinical and subclinical mastitis in dairy cattle is an established component of mastitis control programs. Research on the treatment of clinical and subclinical mastitis in other dairy species such as sheep and goats has been less frequent, although the general principles of mastitis therapy in small ruminants are similar to those of dairy cattle. Research on treatment of clinical mastitis in humans is limited and as for other species empirical treatment of mastitis appears to be common. While antimicrobial susceptibility testing is recommended to direct treatment decisions in many clinical settings, the use of susceptibility testing for antibiotic selection for mastitis treatments of dairy cattle has been challenged in a number of publications. The principle objective of this review is to summarize the literature evaluating the question, "Does antimicrobial susceptibility predict treatment outcome for intramammary infections caused by common bacterial pathogens?" This review also addresses current issues related to antimicrobial use and treatment decisions for mastitis in dairy cattle. Information on treatment of mastitis in other species, including humans, is included although research appears to be limited. Issues related to study design, gaps in current knowledge and opportunities for future research are identified for bovine mastitis therapy.

  7. Cystoscopy and intravesical bacille Calmette-Guérin therapy in antibiotic-naïve patients with bladder cancer with asymptomatic bacteriuria: An update.

    PubMed

    Herr, Harry W

    2016-06-01

    Urologists often insist on sterile urine before invasive outpatient urological procedures, and urine culture and antibiotics are usually given before cystoscopy or instillation of bacille Calmette-Guérin (BCG) therapy, especially in patients who have positive urine cultures. Our experience suggests that cystoscopy and induction BCG therapy can be performed safely, even in patients with asymptomatic bacteriuria, without pretreatment or prophylactic antibiotics. The rate of subsequent febrile urinary tract infection is <4% in both infected and uninfected patients. Pretreatment antibacterial therapy does not appear to be necessary before these two outpatient urological procedures in patients with bladder cancer. Such strategy facilitates timely interventions and reduces the possibility of antibiotic resistance. PMID:27489733

  8. A cohort study of bacteremic pneumonia: The importance of antibiotic resistance and appropriate initial therapy?

    PubMed

    Guillamet, Cristina Vazquez; Vazquez, Rodrigo; Noe, Jonas; Micek, Scott T; Kollef, Marin H

    2016-08-01

    Bacteremic pneumonia is usually associated with greater mortality. However, risk factors associated with hospital mortality in bacteremic pneumonia are inadequately described.The study was a retrospective cohort study, conducted in Barnes-Jewish Hospital (2008-2015). For purposes of this investigation, antibiotic susceptibility was determined according to ceftriaxone susceptibility, as ceftriaxone represents the antimicrobial agent most frequently recommended for hospitalized patients with community-acquired pneumonia as opposed to nosocomial pneumonia. Two multivariable analyses were planned: the first model included resistance to ceftriaxone as a variable, whereas the second model included the various antibiotic-resistant species (methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae).In all, 1031 consecutive patients with bacteremic pneumonia (mortality 37.1%) were included. The most common pathogens associated with infection were S aureus (34.1%; methicillin resistance 54.0%), Enterobacteriaceae (28.0%), P aeruginosa (10.6%), anaerobic bacteria (7.3%), and Streptococcus pneumoniae (5.6%). Compared with ceftriaxone-susceptible pathogens (46.8%), ceftriaxone-resistant pathogens (53.2%) were significantly more likely to receive inappropriate initial antibiotic treatment (IIAT) (27.9% vs 7.1%; P < 0.001) and to die during hospitalization (41.5% vs 32.0%; P = 0.001). The first logistic regression analysis identified IIAT with the greatest odds ratio (OR) for mortality (OR 2.2, 95% confidence interval [CI] 1.5-3.2, P < 0.001). Other independent predictors of mortality included age, mechanical ventilation, immune suppression, prior hospitalization, prior antibiotic administration, septic shock, comorbid conditions, and severity of illness. In the second multivariable analysis that included the antibiotic-resistant species, IIAT was still associated with excess mortality, and P aeruginosa infection was identified as an

  9. Successful treatment of biofilm infections using shock waves combined with antibiotic therapy

    PubMed Central

    Gnanadhas, Divya Prakash; Elango, Monalisha; Janardhanraj, S.; Srinandan, C. S.; Datey, Akshay; Strugnell, Richard A.; Gopalan, Jagadeesh; Chakravortty, Dipshikha

    2015-01-01

    Many bacteria secrete a highly hydrated framework of extracellular polymer matrix on suitable substrates and embed within the matrix to form a biofilm. Bacterial biofilms are observed on many medical devices, endocarditis, periodontitis and lung infections in cystic fibrosis patients. Bacteria in biofilm are protected from antibiotics and >1,000 times of the minimum inhibitory concentration may be required to treat biofilm infections. Here, we demonstrated that shock waves could be used to remove Salmonella, Pseudomonas and Staphylococcus biofilms in urinary catheters. The studies were extended to a Pseudomonas chronic pneumonia lung infection and Staphylococcus skin suture infection model in mice. The biofilm infections in mice, treated with shock waves became susceptible to antibiotics, unlike untreated biofilms. Mice exposed to shock waves responded to ciprofloxacin treatment, while ciprofloxacin alone was ineffective in treating the infection. These results demonstrate for the first time that, shock waves, combined with antibiotic treatment can be used to treat biofilm infection on medical devices as well as in situ infections. PMID:26658706

  10. Basis for selecting optimum antibiotic regimens for secondary peritonitis.

    PubMed

    Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

    2016-01-01

    Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

  11. Antibiotic therapy and Clostridium difficile infection – primum non nocere – first do no harm

    PubMed Central

    Crowther, Grace S; Wilcox, Mark H

    2015-01-01

    Treatment options for Clostridium difficile infection (CDI) remain limited despite this usually nosocomial infection posing an urgent threat to public health. A major paradox of the management of CDI is the use of antimicrobial agents to treat infection, which runs the risk of prolonged gut microbiota perturbation and so recurrence of infection. Here, we explore alternative CDI treatment and prevention options currently available or in development. Notably, strategies that aim to reduce the negative effects of antibiotics on gut microbiota offer the potential to alter current antimicrobial stewardship approaches to preventing CDI. PMID:26396535

  12. Antibiotic-free nanotherapeutics: hypericin nanoparticles thereof for improved in vitro and in vivo antimicrobial photodynamic therapy and wound healing.

    PubMed

    Nafee, Noha; Youssef, Alaa; El-Gowelli, Hanan; Asem, Heba; Kandil, Sherif

    2013-09-15

    Hypericin (HY) is a naturally-occurring, potent photosensitizer. However, its lipophilicity limits its therapeutic applications. Our attempt is, thus, to develop a biodegradable nanocarrier for hypericin capable of preserving its antibacterial photoactivity. Amphiphilic block copolymers were synthesized to prepare hypericin-laden nanoparticles (HY-NPs). The antimicrobial photoactivity of HY-NPs was assessed; in vitro against biofilm and planktonic cells of methicillin resistant Staphylococcus aureus (MRSA) clinical isolates and in vivo on infected wounds in rats. Nanoparticles of 45 nm in diameter ensured higher amounts of reactive oxygen species upon irradiation. HY-NPs demonstrated superior inhibition of biofilm over planktonic cells. In vivo wound healing studies in rats revealed faster healing, better epithelialization, keratinization and development of collagen fibers when HY-NPs were applied. Determination of growth factors and inflammatory mediators in the wound area confirmed superior healing potential of nanoencapsulated hypericin suggesting that hypericin can join the era of antibiotic-free antimicrobial therapy.

  13. An investigation of the impact of intramammary antibiotic dry cow therapy on clinical coliform mastitis.

    PubMed

    Bradley, A J; Green, M J

    2001-07-01

    The efficacy of an intramammary antibiotic dry cow preparation with significant gram-negative spectrum (product A; Leo Red Dry Cow, Leo Animal Health, UK) was compared with a product with no gram-negative efficacy (product B; Orbenin Extra DC, Pfizer Ltd, UK) as assessed by control of coliform mastitis in the first 100 d of the lactation. The efficacy of both products was also compared for control of noncoliform mastitis and for the ability to control existing and new intramammary infections as measured by individual cow somatic cell counts. Cows treated with product A were significantly less likely to develop clinical Escherichia coli or coliform mastitis during the dry period or the first 100 d of lactation than cows treated with product B. Cows treated with product A were no more likely to develop clinical mastitis due to a noncoliform organism than were cows treated with product B. There was no significant difference between the two groups as measured by individual cow somatic cell count changes across the dry period. This study is the first to have demonstrated the clinical efficacy of an intramammary antibiotic dry cow preparation, as measured by reduction in gram-negative clinical mastitis in the subsequent lactation. These findings demonstrate that selection of a dry cow intramammary preparation with a significant gram-negative spectrum can influence the incidence of clinical coliform mastitis in the subsequent lactation. This finding should be one of the factors taken into account when selecting products. PMID:11467813

  14. A novel approach for emerging and antibiotic resistant infections: Innate defense regulators as an agnostic therapy.

    PubMed

    North, John R; Takenaka, Shunsuke; Rozek, Annett; Kielczewska, Agnieszka; Opal, Steven; Morici, Lisa A; Finlay, B Brett; Schaber, Christopher J; Straube, Richard; Donini, Oreola

    2016-05-20

    Innate Defense Regulators (IDRs) are short synthetic peptides that target the host innate immune system via an intracellular adaptor protein which functions at key signaling nodes. In this work, further details of the mechanism of action of IDRs have been discovered. The studies reported here show that the lead clinical IDR, SGX94, has broad-spectrum activity against Gram-negative and Gram-positive bacterial infections caused by intracellular or extracellular bacteria and also complements the actions of standard of care antibiotics. Based on in vivo and primary cell culture studies, this activity is shown to result from the primary action of SGX94 on tissue-resident cells and subsequent secondary signaling to activate myeloid-derived cells, resulting in enhanced bacterial clearance and increased survival. Data from non-clinical and clinical studies also show that SGX94 treatment modulates pro-inflammatory and anti-inflammatory cytokine levels, thereby mitigating the deleterious inflammatory consequences of innate immune activation. Since they act through host pathways to provide both broad-spectrum anti-infective capability as well as control of inflammation, IDRs are unlikely to be impacted by resistance mechanisms and offer potential clinical advantages in the fight against emerging and antibiotic resistant bacterial infections. PMID:27015977

  15. Iv antibiotic therapy in an outpatient setting: report of a joint venture program.

    PubMed

    Eron, L J

    1988-05-01

    Intracare, a joint venture between infectious disease consultants and Fairfax Hospital, Virginia, represents an ambulatory model for the delivery of intravenous antibiotics on an outpatient basis. This article reviews the cost effectiveness and clinical effectiveness of the program in the first 2,096 enrollees over a 6-year period. The most commonly treated infection was osteomyelitis and the most frequently used antibiotic was ceftriaxone sodium. The infections responded satisfactorily in 89% of patients in the program. A total of 39,829 hospital days were saved, which represented a cost savings for hospital bed charges alone of $15,931,600. The authors conclude that because of changes in the hospital environment--constraints on the expansion of hospital beds, and the reservation of hospital beds for the most acutely ill patients (a future prediction resulting from an increased elderly population)--Intracare may serve as a prototype of a clinic rendering all types of outpatient care to chronically ill or less acutely ill patients who would ordinarily have been hospitalized.

  16. Reassessment of frequency of occurrence of typhoid fever and cost efficacy analysis of antibiotic therapy.

    PubMed

    Sridhar, C B; Kulkarni, R D

    1995-10-01

    Typhoid fever has assumed importance due to the increased incidence of drug resistance in India. The exact magnitude of the problem is not accurately known. The objective of this study was to collect retrospectively the data on the incidence and frequency of typhoid fever among hospital admissions at St. Johns Medical College Hospital (SJMCH), Bangalore during the year 1987 to 1992 and also to study the sensitivity pattern and the use of antibiotics. The study was also aimed at comparison of immunogenicity and tolerance of conventional vaccine to the newer polysaccharide vaccine. It was found that the incidence of typhoid fever showed change from epidemic to endemic situation with outbreaks of epidemics. Sensitivity pattern also showed change during the same period and antibiotic resistance was increasingly demonstrated from 1989. Cost per patient and total cost to the hospital due to increased admissions also showed progressive increase. The polysaccharide vaccine (recently made available in India) had very low adverse reaction profile with higher immunogenicity as compared to conventional vaccine. Its single dose effect with long lasting immunity indicates it probable usefulness in the eradication of disease.

  17. The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy.

    PubMed

    Magalhães, Andreia P; Azevedo, Nuno F; Pereira, Maria O; Lopes, Susana P

    2016-02-01

    The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested. PMID:26637419

  18. The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy.

    PubMed

    Magalhães, Andreia P; Azevedo, Nuno F; Pereira, Maria O; Lopes, Susana P

    2016-02-01

    The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.

  19. Good practice recommendations for paediatric outpatient parenteral antibiotic therapy (p-OPAT) in the UK: a consensus statement.

    PubMed

    Patel, Sanjay; Abrahamson, Ed; Goldring, Stephen; Green, Helen; Wickens, Hayley; Laundy, Matt

    2015-02-01

    There is compelling evidence to support the rationale for managing children on intravenous antimicrobial therapy at home whenever possible, including parent and patient satisfaction, psychological well-being, return to school/employment, reductions in healthcare-associated infection and cost savings. As a joint collaboration between the BSAC and the British Paediatric Allergy, Immunity and Infection Group, we have developed good practice recommendations to highlight good clinical practice and governance within paediatric outpatient parenteral antibiotic therapy (p-OPAT) services across the UK. These guidelines provide a practical approach for safely delivering a p-OPAT service in both secondary care and tertiary care settings, in terms of the roles and responsibilities of members of the p-OPAT team, the structure required to deliver the service, identifying patients and pathologies that are suitable for p-OPAT, ensuring appropriate vascular access, antimicrobial choice and delivery and the clinical governance aspects of delivering a p-OPAT service. The process of writing a business case to support the introduction of a p-OPAT service is also addressed.

  20. The early antibiotic therapy in septic patients--milestone or sticking point?

    PubMed

    Bernhard, Michael; Lichtenstern, Christoph; Eckmann, Christian; Weigand, Markus A

    2014-01-01

    Sepsis is one of the oldest and most elusive syndromes in medicine. Every effort should be made to treat these patients with the best available evidence. As a milestone, empiric antimicrobial therapy is essential in order to reduce morbidity and mortality of septic patients. As a sticking point, the use of broad-spectrum antimicrobial agents may be associated with induction of resistance among common pathogens. PMID:25672873

  1. Preventing Infective Complications following Leech Therapy: Elimination of Symbiotic Aeromonas spp. from the Intestine of Hirudo verbana Using Antibiotic Feeding

    PubMed Central

    Litwinowicz, Agata

    2014-01-01

    Abstract Background: Hirudotherapy is often used successfully in modern medicine, especially in plastic and reconstructive surgery. However, Aeromonas infections are the most common complications of post-operative leech application. Hence, prophylactic antibiotic administration is recommended before and during leech therapy. It has been confirmed that patient safety and achieving the desired therapeutic effect depend mainly on the microbiologic purity of the animals used. The aims of this study were to find a safe and practical way to eradicate symbiotic Aeromonas spp. occuring in the intestine of Hirudo verbana. Methods: Leeches were fed artificially with 1.5 mL of sterile defibrinated sheep blood supplemented with ciprofloxacin (CIP) or cefotaxime (CTX), at bacteriostatic concentrations of 0.2 mcg/mL or 1.5 mcg/mL, and bactericidal concentrations of 20 mcg/mL or 50 mcg/mL, respectively. Bacteria were isolated from the leech intestines before and after feeding at different time intervals: 1, 7, 14, 21, and 28 d. Results: Biochemical identification of bacterial isolates from water samples and intestines of H. verbana using the API-NE20 test showed that A. veronii biovar sobria was predominant. Bacteria belonging to the genus Aeromonas were detected in all control leeches. The results showed that optimum eradication of bacteria from leech intestines was obtained using 20 mcg/mL of CIP and 50 mcg/mL of CTX, which decreased the number of Aeromonas spp. to undetectable levels for two weeks after feeding in all treated leeches. A statistically significant reduction in the number of bacterial colonies (p<0.0001) was observed in leeches treated with bacteriostatic concentrations of CIP or CTX; no bacterial growth was found on the plates after only seven days of feeding with antibiotics. All water samples in which the leeches were kept before treatment were contaminated with Aeromonas spp., whereas these samples were negative after antibiotic feeding of

  2. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  3. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

  4. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques

    PubMed Central

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L.; Frank, Daniel N.; Ma, Dongzhu; Policicchio, Benjamin B.; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S.; Trichel, Anita; Ribeiro, Ruy M.; Tracy, Russell; Wilson, Cara; Landay, Alan L.; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  5. Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance

    PubMed Central

    2013-01-01

    Introduction Several guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria. Methods This is an observational cohort study of 956 immunocompetent patients with CAP admitted to ICUs in France and entered into a prospective database between 1997 and 2010. Patients with chronic obstructive pulmonary disease were excluded. Multivariate analysis adjusted for disease severity, gender, and co-morbidities was used to compare the impact on 60-day mortality of receiving adequate initial antibiotics and of receiving one versus two initial antibiotics. Results Initial adequate antibiotic therapy was significantly associated with better survival (subdistribution hazard ratio (sHR), 0.63; 95% confidence interval (95% CI), 0.42 to 0.94; P = 0.02); this effect was strongest in patients with Streptococcus pneumonia CAP (sHR, 0.05; 95% CI, 0.005 to 0.46; p = 0.001) or septic shock (sHR: 0.62; 95% CI 0.38 to 1.00; p = 0.05). Dual therapy was associated with a higher frequency of initial adequate antibiotic therapy. However, no difference in 60-day mortality was found between monotherapy (β-lactam) and either of the two dual-therapy groups (β-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups. Conclusions Initial adequate antibiotic therapy markedly decreased 60-day mortality. Dual therapy improved the likelihood of initial adequate therapy but did not predict decreased 60-day mortality. Dual therapy did not increase the risk of nosocomial pneumonia or multidrug-resistant bacteria. PMID:24200097

  6. Antibiotic Resistance

    MedlinePlus

    ... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

  7. The Beta Lactam Antibiotics as an Empirical Therapy in a Developing Country: An Update on Their Current Status and Recommendations to Counter the Resistance against Them

    PubMed Central

    Thakuria, Bhaskar; Lahon, Kingshuk

    2013-01-01

    In a developing country like India, where the patients have to bear the cost of their healthcare, the microbiological culture and the sensitivity testing of each and every infection is not feasible. Moreover, there are lacunae in the data storage, management and the sharing of knowledge with respect to the microorganisms which are prevalent in the local geographical area and with respect to the antibiotics which are effective against them. Thus, an empirical therapy for treating infections is imperative in such a setting. The beta lactam antibiotics have been widely used for the empirical treatment of infections since the the discovery of penicillin. Many generations of beta lactams have been launched with, the claims of a higher sensitivity and less resistance, but their sensitivity has drastically decreased over time. Thus, the preference for beta lactams, especially the cephalosporins, as an empirical therapy, among the prescribers was justified initially, but the current sensitivity patterns do not support their empirical use in hospital and community acquired infections. There is a need for increasing the awareness and the attitudinal change among the prescribers, screening of the antibiotic prescriptions, the strict implementation of antibiotic policies in hospital settings, restricting the hospital supplies and avoiding the prescriptions of beta lactams, a regular census of the local sensitivity patterns to formulate and update the antibiotic policies, upgradation of the laboratory facilities for a better and faster detection of the isolates, proper collection, analyses and sharing of the data and the encouragement of the research and development of newer antibiotics with novel mechanisms of action. PMID:23905143

  8. Effectiveness of sequential intravenous-to-oral antibiotic switch therapy in hospitalized patients with gram-positive infection: the SEQUENCE cohort study.

    PubMed

    Rodriguez-Pardo, D; Pigrau, C; Campany, D; Diaz-Brito, V; Morata, L; de Diego, I C; Sorlí, L; Iftimie, S; Pérez-Vidal, R; García-Pardo, G; Larrainzar-Coghen, T; Almirante, B

    2016-08-01

    Switching from intravenous to oral antibiotic therapy may improve inpatient management and reduce hospital stays and the complications of intravenous treatment. We aimed to assess the effectiveness of intravenous-to-oral antibiotic switch therapy and an early discharge algorithm in hospitalized patients with gram-positive infection. We performed a prospective cohort study with a retrospective comparison cohort, recruited from eight tertiary, acute-care Spanish referral hospitals. All patients included had culture-confirmed methicillin-resistant gram-positive infection, or methicillin-susceptible gram-positive infection and beta-lactam allergy and had received intravenous treatment with glycopeptides, lipopeptides, or linezolid. The study comprised two cohorts: the prospective cohort to assess the effectiveness of a sequential intravenous-to-oral antibiotic switch algorithm and early discharge, and a retrospective cohort in which the algorithm had not been applied, used as the comparator. A total of 247 evaluable patients were included; 115 in the prospective and 132 in the retrospective cohort. Forty-five retrospective patients (34 %) were not changed to oral antibiotics, and 87 (66 %) were changed to oral antibiotics without following the proposed algorithm. The duration of hospitalization was significantly shorter in the prospective cohort compared to the retrospective group that did not switch to oral drugs (16.7 ± 18.7 vs 23 ± 13.4 days, P  < 0.001). No differences were observed regarding the incidence of catheter-related bacteraemia (4.4 % vs 2.6 %, P = 0.621). Our results suggest that an intravenous-to-oral antibiotic switch strategy is effective for reducing the length of hospital stay in selected hospitalized patients with gram-positive infection.

  9. Evaluation of Genome-Wide Expression Profiles of Blood and Sputum Neutrophils in Cystic Fibrosis Patients Before and After Antibiotic Therapy

    PubMed Central

    Conese, Massimo; Castellani, Stefano; Lepore, Silvia; Palumbo, Orazio; Manca, Antonio; Santostasi, Teresa; Polizzi, Angela Maria; Copetti, Massimiliano; Di Gioia, Sante; Casavola, Valeria; Guerra, Lorenzo; Diana, Anna; Montemurro, Pasqualina; Mariggiò, Maria Addolorata; Gallo, Crescenzio; Maffione, Angela Bruna; Carella, Massimo

    2014-01-01

    In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to “healthy” condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before

  10. Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance

    PubMed Central

    Earl, Chris S; Keong, Teh Wooi; An, Shi-qi; Murdoch, Sarah; McCarthy, Yvonne; Garmendia, Junkal; Ward, Joseph; Dow, J Maxwell; Yang, Liang; O’Toole, George A; Ryan, Robert P

    2015-01-01

    Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that corticosteroid treatment promotes H. influenzae persistence. Transcriptomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of glucocorticosteroids. Importantly, a number of these corticosteroid-responsive genes also showed elevated expression in H. influenzae within sputum from asthma patients undergoing steroid treatment. Addition of corticosteroid to H. influenzae led to alteration in biofilm formation and enhanced resistance to azithromycin, and promoted azithromycin resistance in an animal model of respiratory infection. Taken together, these data strongly suggest that H. influenzae can respond directly to corticosteroid treatment in the airway potentially influencing biofilm formation, persistence and the efficacy of antibiotic treatment. PMID:25995336

  11. Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey.

    PubMed

    Vercheval, C; Gillet, M; Maes, N; Albert, A; Frippiat, F; Damas, P; Van Hees, T

    2016-09-01

    This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 ± 10.4 % vs. 90.3 ± 6.6 %, p = 0.0013; antibiotics documented 87.9 ± 9.0 % vs. 95.6 ± 5.1 %, p < 0.0001; and duration or review date documented 31.9 ± 15.4 % vs. 67.7 ± 15.2 %, p < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators. PMID:27255220

  12. Data correction pre-processing for electronically stored blood culture results: Implications on microbial spectrum and empiric antibiotic therapy

    PubMed Central

    2009-01-01

    Background The outcome of patients with bacteraemia is influenced by the initial selection of adequate antimicrobial therapy. The objective of our study was to clarify the influence of different crude data correction methods on a) microbial spectrum and ranking of pathogens, and b) cumulative antimicrobial susceptibility pattern of blood culture isolates obtained from patients from intensive care units (ICUs) using a computer based tool, MONI. Methods Analysis of 13 ICUs over a period of 7 years yielded 1427 microorganisms from positive results. Three different data correction methods were applied. Raw data method (RDM): Data without further correction, including all positive blood culture results. Duplicate-free method (DFM): Correction of raw data for consecutive patient's results yielding same microorganism with similar antibiogram within a two-week period. Contaminant-free method (CFM): Bacteraemia caused by possible contaminants was only assumed as true bloodstream infection, if an organism of the same species was isolated from > 2 sets of blood cultures within 5 days. Results Our study demonstrates that different approaches towards raw data correction – none (RDM), duplicate-free (DFM), and a contaminant-free method (CFM) – show different results in analysis of positive blood cultures. Regarding the spectrum of microorganisms, RDM and DFM yielded almost similar results in ranking of microorganisms, whereas using the CFM resulted in a clinically and epidemiologically more plausible spectrum. Conclusion For possible skin contaminants, the proportion of microorganisms in terms of number of episodes is most influenced by the CFM, followed by the DFM. However, with exception of fusidic acid for gram-positive organisms, none of the evaluated correction methods would have changed advice for empiric therapy on the selected ICUs. PMID:19500418

  13. Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®)

    PubMed Central

    2014-01-01

    Background Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. Methods 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. Results Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram – (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. Conclusions Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. Trial registration NCT02130713 Date of trial

  14. Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair?

    PubMed

    Bassetti, Matteo; Welte, Tobias; Wunderink, Richard G

    2016-01-01

    Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs.

  15. Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair?

    PubMed

    Bassetti, Matteo; Welte, Tobias; Wunderink, Richard G

    2016-01-01

    Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs. PMID:26821535

  16. Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model.

    PubMed

    Hilliard, Jamese J; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2015-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections.

  17. Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model.

    PubMed

    Hilliard, Jamese J; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2015-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections. PMID:25348518

  18. Anti-Alpha-Toxin Monoclonal Antibody and Antibiotic Combination Therapy Improves Disease Outcome and Accelerates Healing in a Staphylococcus aureus Dermonecrosis Model

    PubMed Central

    Hilliard, Jamese J.; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J.; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C. Kendall

    2014-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections. PMID:25348518

  19. Antibiotic Resistance

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... these products really help. To Learn More about Antibiotic Resistance Get Smart About Antibiotics (Video) Fact Sheets and ...

  20. Implementation of a Computerized Decision Support System to Improve the Appropriateness of Antibiotic Therapy Using Local Microbiologic Data

    PubMed Central

    Rodriguez-Maresca, Manuel; Sorlozano, Antonio; Grau, Magnolia; Rodriguez-Castaño, Rocio; Ruiz-Valverde, Andres; Gutierrez-Fernandez, Jose

    2014-01-01

    A prospective quasi-experimental study was undertaken in 218 patients with suspicion of nosocomial infection hospitalized in a polyvalent ICU where a new electronic device (GERB) has been designed for antibiotic prescriptions. Two GERB-based applications were developed to provide local resistance maps (LRMs) and preliminary microbiological reports with therapeutic recommendation (PMRTRs). Both applications used the data in the Laboratory Information System of the Microbiology Department to report on the optimal empiric therapeutic option, based on the most likely susceptibility profile of the microorganisms potentially responsible for infection in patients and taking into account the local epidemiology of the hospital department/unit. LRMs were used for antibiotic prescription in 20.2% of the patients and PMRTRs in 78.2%, and active antibiotics against the finally identified bacteria were prescribed in 80.0% of the former group and 82.4% of the latter. When neither LMRs nor PMRTRs were considered for empiric treatment prescription, only around 40% of the antibiotics prescribed were active. Hence, the percentage appropriateness of the empiric antibiotic treatments was significantly higher when LRM or PMRTR guidelines were followed rather than other criteria. LRMs and PMRTRs applications are dynamic, highly accessible, and readily interpreted instruments that contribute to the appropriateness of empiric antibiotic treatments. PMID:25197643

  1. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

    PubMed

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-11-01

    Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17

  2. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy

    PubMed Central

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-01-01

    Abstract Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection. The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance. A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by 13C-urea breath test after at least 4 weeks when treatment was finished. Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15

  3. Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials

    PubMed Central

    Falagas, Matthew E; Karageorgopoulos, Drosos E; Grammatikos, Alexandros P; Matthaiou, Dimitrios K

    2009-01-01

    We sought to evaluate the effectiveness and safety of short-course antibiotic treatment for acute bacterial sinusitis (ABS) compared with longer duration treatment. We performed a meta-analysis of randomized controlled trials (RCTs), identified by searching PubMed and the Cochrane Central Register of Controlled Trials. We included RCTs that compared short-course (up to 7 days) vs. long-course therapy (≥2 days longer than short-course), with the same antimicrobial agent, in the same daily dosage, for patients with ABS. Twelve RCTs (10 double-blinded) involving adult patients with radiologically confirmed ABS were included. There was no difference in the comparison of short-course (3–7 days) with long-course treatment (6–10 days) regarding clinical success [12 RCTs, 4430 patients, fixed effect model (FEM), odds ratio (OR) 0.95, 95% confidence interval (CI) 0.81, 1.12]; microbiological efficacy; relapses; adverse events (10 RCTs, 4172 patients, random effects model, OR 0.88, 95% CI 0.71, 1.09); or withdrawals due to adverse events. In the sensitivity analysis comparing 5- vs. 10-day regimens, clinical success was similar, although adverse events were fewer with short-course treatment (5 RCTs, 2151 patients, FEM, OR 0.79, 95% CI 0.63, 0.98). Although antibiotics for acute sinusitis should be reserved for select patients with substantial probability of bacterial disease, accurate clinical diagnosis is often difficult to attain. Short-course antibiotic treatment had comparable effectiveness to a longer course of therapy for ABS. Shortened treatment, particularly for patients without severe disease and complicating factors, might lead to fewer adverse events, better patient compliance, lower rates of resistance development and fewer costs. PMID:19154447

  4. Evaluation of clinical and laboratory findings of pediatric and adult patients with oropharyngeal tularemia in Turkey: a combination of surgical drainage and antibiotic therapy increases treatment success.

    PubMed

    Gozel, Mustafa Gokhan; Engin, Aynur; Altuntas, Emine Elif; Salk, İsmail; Kaya, Ali; Celik, Cem; Dokmetas, Ilyas; Bakir, Mehmet; Elaldi, Nazif

    2014-01-01

    We analyzed the clinical and laboratory findings of both pediatric and adult patients with oropharyngeal tularemia. We also compared the therapeutic outcomes of patients who underwent surgical drainage of lymph nodes early or late during antibiotic therapy. A total of 68 patients with oropharyngeal tularemia, including 26 children and 42 adults, were enrolled in this study. The average duration between symptom onset and hospital admission was 20.8 days (4-60 days) in the pediatric group and 32.6 days (4-90 days) in the adult group (P = 0.009). The most frequently observed clinical symptoms were sore throat (100% and 100%), fever (96.2% and 90.5%), tonsillitis (69.2% and 78.6%), and rash (15.4% and 11.9%) in the pediatric and adult groups, respectively. However, the frequencies of erythema, tenderness, and fluctuant of enlarged lymph nodes were significantly higher in the adult group than in the pediatric group (P = 0.005, P = 0.029, and P = 0.041, respectively). Treatment failure was observed in 2 (7.7%) pediatric patients and 4 (9.5%) adult patients, for a total of 6 (8.8%) treatment failures in the study group. Similar clinical findings and treatment outcomes were observed in both groups. We concluded that a combination of surgical drainage and antibiotic therapy increases treatment success for patients diagnosed with oropharyngeal tularemia.

  5. [Antibiotics: present and future].

    PubMed

    Bérdy, János

    2013-04-14

    The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

  6. Chitosan coating to enhance the therapeutic efficacy of calcium sulfate-based antibiotic therapy in the treatment of chronic osteomyelitis

    PubMed Central

    Beenken, Karen E; Smith, James K; Skinner, Robert A; Mclaren, Sandra G; Bellamy, William; Gruenwald, M Johannes; Spencer, Horace J; Jennings, Jessica A; Haggard, Warren O; Smeltzer, Mark S

    2014-01-01

    We demonstrate that coating calcium sulfate with deacetylated chitosan enhances the elution profile of daptomycin by prolonging the period during which high concentrations of antibiotic are released. Coatings reduced initial bolus release of daptomycin by a factor of 10 to approximately 1000 μg/ml, and levels remained above 100 μg/ml for up to 10 days. Chitosan-coated and uncoated calcium sulfate implants with and without 15% daptomycin were evaluated in an experimental model of staphylococcal osteomyelitis through bacteriology scores, radiology, histopathology, and Gram staining. Significant reduction in bacteriology scores was observed for implants containing daptomycin and coated with chitosan compared with all the other groups. We confirm that the use of chitosan-coated calcium sulfate beads for local antibiotic delivery can be correlated with an improved therapeutic outcome following surgical debridement in the treatment of chronic osteomyelitis. PMID:24854984

  7. Antibiotic Safety

    MedlinePlus

    ... specific to women Antibiotics can lead to vaginal yeast infections. This happens because antibiotics kill the normal bacteria in the vagina and this causes yeast to grow rapidly. Symptoms of a yeast infection ...

  8. Antibiotic Agents

    MedlinePlus

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

  9. Chronic lung infection by Pseudomonas aeruginosa biofilm is cured by L-Methionine in combination with antibiotic therapy

    PubMed Central

    Gnanadhas, Divya Prakash; Elango, Monalisha; Datey, Akshay; Chakravortty, Dipshikha

    2015-01-01

    Bacterial biofilms are associated with 80–90% of infections. Within the biofilm, bacteria are refractile to antibiotics, requiring concentrations >1,000 times the minimum inhibitory concentration. Proteins, carbohydrates and DNA are the major components of biofilm matrix. Pseudomonas aeruginosa (PA) biofilms, which are majorly associated with chronic lung infection, contain extracellular DNA (eDNA) as a major component. Herein, we report for the first time that L-Methionine (L-Met) at 0.5 μM inhibits Pseudomonas aeruginosa (PA) biofilm formation and disassembles established PA biofilm by inducing DNase expression. Four DNase genes (sbcB, endA, eddB and recJ) were highly up-regulated upon L-Met treatment along with increased DNase activity in the culture supernatant. Since eDNA plays a major role in establishing and maintaining the PA biofilm, DNase activity is effective in disrupting the biofilm. Upon treatment with L-Met, the otherwise recalcitrant PA biofilm now shows susceptibility to ciprofloxacin. This was reflected in vivo, in the murine chronic PA lung infection model. Mice treated with L-Met responded better to antibiotic treatment, leading to enhanced survival as compared to mice treated with ciprofloxacin alone. These results clearly demonstrate that L-Met can be used along with antibiotic as an effective therapeutic against chronic PA biofilm infection. PMID:26521707

  10. Resistance-resistant antibiotics.

    PubMed

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  11. Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy.

    PubMed

    Heuberger, R; Wahl, P; Krieg, J; Gautier, E

    2014-01-01

    In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied - preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE) and cross-linked polyethylene (XLPE) against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear. PMID:25340804

  12. A Novel Murine Model of Established Staphylococcal Bone Infection in the Presence of a Fracture Fixation Plate to Study Therapies Utilizing Antibiotic-laden Spacers after Revision Surgery

    PubMed Central

    Inzana, Jason A.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

    2014-01-01

    local or systemic vancomycin did not display gross pathology at the end of the study. While localized vancomycin delivery alone tended to decrease the bacterial burden and osteolysis, these effects were only significant when combined with systemic antibiotic therapy. This novel mouse model replicates key features of implant-associated osteomyelitis that make treatment extremely difficult, such as biofilm formation and osteolysis, and imitates the clinical practice of placing an antibiotic-laden spacer after infected tissue debridement. In addition, the model demonstrates the limitations of current PMMA spacers and could be an invaluable tool for evaluating alternative antimicrobial treatments for implant-associated bone infection. PMID:25459073

  13. 34 CFR 85.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Adequate evidence. 85.900 Section 85.900 Education Office of the Secretary, Department of Education GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 85.900 Adequate evidence. Adequate evidence means information sufficient to support...

  14. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  15. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  16. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  17. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  18. A call for antibiotic alternatives research.

    PubMed

    Stanton, Thaddeus B

    2013-03-01

    The persistence and spread of antibiotic resistance, in conjunction with decreased profitability of new antibiotics, have created the dangerous prospect of ineffective therapies against bacterial diseases. National strategies aimed at discovery, development, and definition of the mechanisms of effective antibiotic alternatives, especially for agricultural applications, should be encouraged. PMID:23473628

  19. Antibiotic resistance in pediatric urology

    PubMed Central

    Copp, Hillary L.

    2014-01-01

    Antibiotics are a mainstay in the treatment of bacterial infections, though their use is a primary risk factor for the development of antibiotic resistance. Antibiotic resistance is a growing problem in pediatric urology as demonstrated by increased uropathogen resistance. Lack of urine testing, nonselective use of prophylaxis, and poor empiric prescribing practices exacerbate this problem. This article reviews antibiotic utilization in pediatric urology with emphasis on modifiable practice patterns to potentially help mitigate the growing rates of antibiotic resistance. This includes urine testing to only treat when indicated and tailor broad-spectrum therapy as able; selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis with counseling regarding the importance of compliance; and using local antiobiograms, particularly pediatric-specific antiobiograms, with inpatient versus outpatient data. PMID:24688601

  20. Helicobacter  pylori Eradication Therapies in the Era of Increasing Antibiotic Resistance: A Paradigm Shift to Improved Efficacy

    PubMed Central

    Georgopoulos, Sotirios D.; Papastergiou, Vasilios; Karatapanis, Stylianos

    2012-01-01

    With the rising prevalence of antimicrobial resistance, the eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing to unacceptable levels (i.e., ≤80%) in most countries. After these disappointing results, several authorities have proposed that infection with H. pylori should be approached and treated as any other bacterial infectious disease. This implicates that clinicians should prescribe empirical treatments yielding a per protocol eradication of at least 90%. In recent years several treatments producing ≥90% cure rates have been proposed including sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy, and bismuth-containing quadruple therapy. These treatments are likely to represent the recommended first-line treatments in the near future. In the present paper, we are considering a series of critical issues regarding currently available means and approaches for the management of H. pylori infection. Clinical needs and realistic endpoints are taken into account. Furthermore, emerging strategies for the eradication of H. pylori and the existing evidence of their clinical validation and widespread applicability are discussed. PMID:22778723

  1. Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP).

    PubMed

    Liew, Y X; Chlebicki, M P; Lee, W; Hsu, L Y; Kwa, A L

    2011-07-01

    Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 μg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

  2. “Ten Commandments” for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting

    PubMed Central

    Levy-Hara, Gabriel; Amábile-Cuevas, Carlos F.; Gould, Ian; Hutchinson, Jim; Abbo, Lilian; Saxynger, Lynora; Vlieghe, Erika; Cardoso, Fernando L. Lopes; Methar, Shaheen; Kanj, Souha; Ohmagari, Norio; Harbarth, Stephan

    2011-01-01

    A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients’ compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically – but intelligently; know local susceptibility trends, and also surveillance limitations. PMID:22164154

  3. Misuse of antibiotics reserved for hospital settings in outpatients: a prospective clinical audit in a university hospital in Southern France.

    PubMed

    Roche, Manon; Bornet, Charléric; Monges, Philippe; Stein, Andreas; Gensollen, Sophie; Seng, Piseth

    2016-07-01

    Some antibiotics are reserved essentially for hospital settings owing to cost effectiveness and in order to fight the emerging antibiotic resistance crisis. In some cases, antibiotics reserved exclusively for use in hospitals may be prescribed in outpatients for serious infections or in the absence of a therapeutic alternative. A 30-day prospective audit of outpatient prescriptions of antibiotics reserved exclusively for use in hospitals was performed. The objective of this study was to evaluate the relevance of outpatient antibiotic prescriptions by measuring appropriateness according to guidelines. During the study period, 53 prescriptions were included, only 40% of which were appropriate. Among the 32 inappropriate prescriptions, 4 cases lacked microbial arguments, 1 case was not adequate for the infection type, 1 case involved an incorrect antibiotic dosage, 1 case involved an incorrect interval of dose administration, 3 cases had a therapeutic alternative and 22 cases were not recommended. Of the 53 prescriptions, 66% were started in hospital and 34% in outpatients. Only 25% of cases were prescribed with infectious diseases specialist (IDS) advice, 64% were based on microbiological documentation and 13% had a negative bacterial culture. Inappropriate prescriptions were usually observed in antibiotic lock therapy, skin infections, Clostridium difficile colitis, intra-abdominal infections and intravascular catheter-related infections. Outpatient prescriptions of antimicrobial drugs reserved exclusively for use in hospitals are frequently inappropriate. We recommend a real-time analysis algorithm with the involvement of an IDS for monitoring prescriptions to improve the quality of these prescriptions and possibly to prevent antibiotic resistance. PMID:27234677

  4. Antibiotics Quiz

    MedlinePlus

    ... Viruses b) Bacteria c) Viruses and Bacteria 2. Bacteria are germs that cause colds and flu. a) ... The Flu c) Cold d) Strep Throat 4. Bacteria that cause infections can become resistant to antibiotics. ...

  5. Use of 16S rRNA sequencing and quantitative PCR to correlate venous leg ulcer bacterial bioburden dynamics with wound expansion, antibiotic therapy, and healing

    PubMed Central

    Sprockett, Daniel D.; Ammons, Christine G.; Tuttle, Marie S.

    2016-01-01

    Clinical diagnosis of infection in chronic wounds is currently limited to subjective clinical signs and culture-based methods that underestimate the complexity of wound microbial bioburden as revealed by DNA-based microbial identification methods. Here, we use 16S rRNA next generation sequencing and quantitative polymerase chain reaction to characterize weekly changes in bacterial load, community structure, and diversity associated with a chronic venous leg ulcer over the 15-week course of treatment and healing. Our DNA-based methods and detailed sampling scheme reveal that the bacterial bioburden of the wound is unexpectedly dynamic, including changes in the bacterial load and community structure that correlate with wound expansion, antibiotic therapy, and healing. We demonstrate that these multidimensional changes in bacterial bioburden can be summarized using swabs taken prior to debridement, and therefore, can be more easily collected serially than debridement or biopsy samples. Overall, this case illustrates the importance of detailed clinical indicators and longitudinal sampling to determine the pathogenic significance of chronic wound microbial dynamics and guide best use of antimicrobials for improvement of healing outcomes. PMID:25902876

  6. A Pilot Trial of Cognitive-Behavioral Therapy Augmentation of Antibiotic Treatment in Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome-Related Obsessive-Compulsive Disorder

    PubMed Central

    Jordan, Cary; Selles, Robert R.; Wu, Monica S.; King, Morgan A.; Patel, Priyal D.; Hanks, Camille E.; Arnold, Elysse B.; Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.

    2015-01-01

    Abstract Background: This study reports an open trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD) exhibiting an onset pattern consistent with pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Eleven primarily Caucasian youth with PANS-related OCD (range=4–14 years; 6 boys) who were incomplete responders to antibiotic treatment, received family-based CBT delivered either face-to-face or via web camera. Results: All participants completing treatment (8 of 8) were considered improved at posttreatment, and average obsessive-compulsive symptom severity was reduced by 49%. Significant reductions in obsessive-compulsive symptom severity and in clinician- and parent-rated OCD-related impairment were noted. Reductions in parent- and child-rated anxiety, child-rated OCD-related impairment, and comorbid neuropsychiatric symptoms were not statistically significant. Conclusions: Gains were maintained at follow-up, with 100% (6 of 6) of those assessed remaining improved. Implications for treatment and further research are discussed. PMID:25978743

  7. Origins and Evolution of Antibiotic Resistance

    PubMed Central

    Davies, Julian; Davies, Dorothy

    2010-01-01

    Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

  8. Antibiotic stewardship programmes and the surgeon's role.

    PubMed

    Çakmakçi, M

    2015-04-01

    Inappropriate antibiotic use is a frequent occurrence, especially in surgical units. Among the unnecessary costs of such usage are unfavourable outcomes for patients and the emergence and spread of resistant bacteria. Antibiotic stewardship programmes aim to limit the spread of antibiotic resistance by promoting thoughtful prescribing of antibiotics. Such programmes usually try to control inappropriate use of antibiotics; to optimize the choice of drug, dosing, route, and duration of therapy; to maximize clinical cure or prevention of infection; and to limit unwanted effects and excess cost. In this paper, I discuss the impact of improper use of antibiotics and outline why I believe that antibiotic stewardship is likely to be the best way of dealing with it. Engagement of surgeons in antibiotic stewardship programmes is crucial to their success.

  9. Impact of antibiotic resistance on the treatment of sepsis.

    PubMed

    Turnidge, John

    2003-01-01

    Antibiotics are essential to the treatment of bacterial sepsis as they reduce the bacterial burden. The impact of bacterial resistance has recently been studied and found to be important in a range of conditions. Resistance to antibiotics can be defined genotypically, phenotypically and clinically through pharmacokinetic/pharmacodynamic studies and their correlations with clinical outcomes. Although the kinetics of antibiotics has been shown to be favourably altered in sepsis, a range of studies in sepsis has revealed that for most pathogens resistance contributes to significant increases in mortality. This has been clearly demonstrated in bacteraemia, including community- and hospital-acquired infection, and with bacteraemia caused by vancomycin-resistant enterococci, methicillin-resistant staphylococci and extended-spectrum producing Gram-negative bacteria. Significant mortality increases have also been seen with ventilator-associated pneumonia and serious infections requiring admission to intensive care. Gentotypic and phenotypic resistance in coagulase-negative staphylococci causing bacteraemia, and in invasive pneumococcal disease has not shown differences in mortality. In the latter case, dosage regimens have to date been adequate to overcome laboratory-defined resistance. Early indications are that de-escalating therapy from broad-spectrum initial coverage after results of cultures and susceptibility tests become available does not jeopardize outcomes, and further prospective studies are warranted. There is now convincing evidence that broad-spectrum initial therapy to cover the likely pathogens and their resistances pending culture results is mandatory in sepsis to minimize adverse outcomes.

  10. [Phenomenology of craving: from differentiation to adequate therapy].

    PubMed

    Mendelevich, V D

    2010-01-01

    The author analyzes a phenomenon of addiction from the psychological/psychiatric position and differentiates it from psychopathological disorders, including parabulia, hyperbulia, paraphylia, commonly used for the definition of drive disorders. It has been concluded that addition is a specific complex of clinical symptoms which is not similar to other drive disorders. To avoid diagnostic and therapeutic errors, the author suggests to revise definitions by assigning the biological sense to the conception of addiction within psychoactive substance dependence and sexual addiction, some forms of eating dependence and to use the definition of paraaddictive drives in cases of over-valued drives (gambling, Internet dependence, fanaticism etc). PMID:21322141

  11. Review of antibiotics and indications for prophylaxis.

    PubMed

    Weiss, Adam; Dym, Harry

    2012-01-01

    Antibiotic prophylaxis to prevent infective endocarditis has been controversial through the years, with various changes made to recommendations provided to treating physicians and dentists. The dentist must always use his or her best judgment when applying any guideline. However, it is important to remember that the guidelines may be cited in any malpractice litigation as evidence of the standard of care. Early diagnosis with prompt treatment with effective antimicrobial therapy is the best way to lower the mortality and morbidity. When prescribing antibiotics, the clinician must realize that the overprescription of antibiotics has led to resistance to antibiotic regimens and the rise of antibiotic-resistant bacteria.

  12. Aerosolized Antibiotics.

    PubMed

    Restrepo, Marcos I; Keyt, Holly; Reyes, Luis F

    2015-06-01

    Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

  13. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and in some cases suggest that sensitivity to existing antibiotics may be restored, in otherwise drug resistant organisms. PMID:25458541

  14. Asbestos/NESHAP adequately wet guidance

    SciTech Connect

    Shafer, R.; Throwe, S.; Salgado, O.; Garlow, C.; Hoerath, E.

    1990-12-01

    The Asbestos NESHAP requires facility owners and/or operators involved in demolition and renovation activities to control emissions of particulate asbestos to the outside air because no safe concentration of airborne asbestos has ever been established. The primary method used to control asbestos emissions is to adequately wet the Asbestos Containing Material (ACM) with a wetting agent prior to, during and after demolition/renovation activities. The purpose of the document is to provide guidance to asbestos inspectors and the regulated community on how to determine if friable ACM is adequately wet as required by the Asbestos NESHAP.

  15. Supervision of Student Teachers: How Adequate?

    ERIC Educational Resources Information Center

    Dean, Ken

    This study attempted to ascertain how adequately student teachers are supervised by college supervisors and supervising teachers. Questions to be answered were as follows: a) How do student teachers rate the adequacy of supervision given them by college supervisors and supervising teachers? and b) Are there significant differences between ratings…

  16. Small Rural Schools CAN Have Adequate Curriculums.

    ERIC Educational Resources Information Center

    Loustaunau, Martha

    The small rural school's foremost and largest problem is providing an adequate curriculum for students in a changing world. Often the small district cannot or is not willing to pay the per-pupil cost of curriculum specialists, specialized courses using expensive equipment no more than one period a day, and remodeled rooms to accommodate new…

  17. Toward More Adequate Quantitative Instructional Research.

    ERIC Educational Resources Information Center

    VanSickle, Ronald L.

    1986-01-01

    Sets an agenda for improving instructional research conducted with classical quantitative experimental or quasi-experimental methodology. Includes guidelines regarding the role of a social perspective, adequate conceptual and operational definition, quality instrumentation, control of threats to internal and external validity, and the use of…

  18. An Adequate Education Defined. Fastback 476.

    ERIC Educational Resources Information Center

    Thomas, M. Donald; Davis, E. E. (Gene)

    Court decisions historically have dealt with educational equity; now they are helping to establish "adequacy" as a standard in education. Legislatures, however, have been slow to enact remedies. One debate over education adequacy, though, is settled: Schools are not financed at an adequate level. This fastback is divided into three sections.…

  19. Funding the Formula Adequately in Oklahoma

    ERIC Educational Resources Information Center

    Hancock, Kenneth

    2015-01-01

    This report is a longevity, simulational study that looks at how the ratio of state support to local support effects the number of school districts that breaks the common school's funding formula which in turns effects the equity of distribution to the common schools. After nearly two decades of adequately supporting the funding formula, Oklahoma…

  20. Antibiotics in dentistry: Bacteremia, antibiotic prophylaxis, and antibiotic misuse.

    PubMed

    Dinsbach, Nathan A

    2012-01-01

    What is known regarding bacteremia? How effective is antibiotic prophylaxis for distant-site infections (late prosthetic joint infections and infective endocarditis)? Antibiotic resistance poses a growing danger to mankind. The misuse of antibiotics is a main cause of antibiotic resistance in bacteria. The author undertook a Medline search and a hand search of the literature regarding bacteremia, antibiotic prophylaxis for late prosthetic joint infections and infective endocarditis, antibiotic misuse, and antibiotic resistance. The findings indicate a clearer understanding of bacteremia emerging in the past 30 years, which has led to recent changes in antibiotic prophylaxis regimens. Dentists should understand how bacteremia affects their at-risk patients, the rationale for antibiotic prophylaxis, and how antibiotic misuse poses a threat to all.

  1. Delivery of antibiotics with polymeric particles.

    PubMed

    Xiong, Meng-Hua; Bao, Yan; Yang, Xian-Zhu; Zhu, Yan-Hua; Wang, Jun

    2014-11-30

    Despite the wide use of antibiotics, bacterial infection is still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic therapy is linked with low bioavailability, poor penetration to bacterial infection sites, and the side effects of antibiotics, as well as the antibiotic resistance properties of bacteria. Antibiotics encapsulated in nanoparticles or microparticles made up of a biodegradable polymer have shown great potential in replacing the administration of antibiotics in their "free" form. Polymeric particles provide protection to antibiotics against environmental deactivation and alter antibiotic pharmacokinetics and biodistribution. Polymeric particles can overcome tissue and cellular barriers and deliver antibiotics into very dense tissues and inaccessible target cells. Polymeric particles can be modified to target or respond to particular tissues, cells, and even bacteria, and thereby facilitate the selective concentration or release of the antibiotic at infection sites, respectively. Thus, the delivery of antibiotics with polymeric particles augments the level of the bioactive drug at the site of infection while reducing the dosage and the dosing frequency. The end results are improved therapeutic effects as well as decreased "pill burden" and drug side effects in patients. The main objective of this review is to analyze recent advances and current perspectives in the use of polymeric antibiotic delivery systems in the treatment of bacterial infection.

  2. Oral trimethoprim as a third-line antibiotic in the management of acne vulgaris.

    PubMed

    Bottomley, W W; Cunliffe, W J

    1993-01-01

    Acne vulgaris usually improves with long-term oral antibiotic therapy; however, some patients fail or only partially respond to the commonly prescribed antibiotics. Only a proportion of these patients warrants treatment with isotretinoin suggesting a need for additional therapeutic options. We have therefore performed an open retrospective study of the efficacy of trimethoprim as a third-line antibiotic in the treatment of patients whose acne vulgaris failed to respond to at least 2 courses of antibiotics. A total of 56 patients were reviewed, who had all failed to respond adequately to a minimum of 2 courses of antibiotics. All patients received trimethoprim in a dosage of 300 mg twice daily for at least 4 months, unless it had been withdrawn due to side effects. Topically they were given 1% clindamycin lotion twice daily to the affected areas. The severity of the patient's acne was graded on the face, back and chest. The changes in acne grades were evaluated using non-parametric statistics (Wilcoxon matched pairs). At 4 months there were significant improvements from the grades at initiation in all three sites (p = 0.005 or less). Twenty-one patients remained on the treatment for 8 months, and a significant improvement in the changes of the acne grades remained (p = 0.02 or less). Two patients had the trimethoprim stopped due to side effects. We can therefore recommend this regime as a third-line treatment in the management of acne.

  3. Facts about Antibiotic Resistance

    MedlinePlus

    ... Trends and Cost Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance has been called one of the world’s most ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children is of particular concern ...

  4. Treatment of acne with topical antibiotics.

    PubMed

    Frank, S B

    1977-06-01

    The introduction of topical antibiotics for acne vulgaris has ushered in a new era in the treatment of this troublesome disorder. Tetracycline, erythromycin, and clindamycin can now be prepared in lotion form in vehicles that are capable of carrying the antibiotic into the follicular canal, where the primary lesion of acne occurs. Topical antibiotics are practically as effective as oral antibiotics in treating acne and are particularly useful for mild papular acne of puberty and early adolescence and papular-pustular acne of adult women. Use of topical antibiotics avoids the possibility of the adverse effects of systemic therapy; the side effects from the formulations reported here are negligible. Above all, antibiotic lotions do not produce the dryness and scaling that occur with most other topical acne preparations.

  5. Dilemmas in primary care: antibiotic treatment of acute otitis media.

    PubMed

    True, B L; Helling, D K

    1986-09-01

    Antibiotic treatment of acute otitis media (AOM) accounts for a significant number of all antibiotic prescriptions each year. In the primary care setting, initial antibiotic selection is rarely based on direct evidence, such as cultures of middle ear fluid. Initial antibiotic therapy by the primary care practitioner involves the evaluation and application of information related to prevalence of infecting organisms; in vitro antibiotic spectrum and penetration into middle ear fluid; initial cure rate, relapse and recurrence rates; and antibiotic cost, safety, and convenience. The influence of these factors on the initial antibiotic choice for AOM is reviewed. Several therapeutic dilemmas confronting the prescriber are discussed and a rational approach to initial antibiotic therapy is presented.

  6. Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

    PubMed

    Brogan, David M; Mossialos, Elias

    2016-02-01

    Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development. PMID:26808335

  7. Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

    PubMed

    Brogan, David M; Mossialos, Elias

    2016-02-01

    Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development.

  8. Preparing and administering injectable antibiotics: How to avoid playing God.

    PubMed

    Longuet, P; Lecapitaine, A L; Cassard, B; Batista, R; Gauzit, R; Lesprit, P; Haddad, R; Vanjak, D; Diamantis, S

    2016-07-01

    The emergence of bacterial resistance and the lack of new antibiotics in the pipeline represent a public health priority. Maximizing the quality of antibiotic prescriptions is therefore of major importance in terms of adequate preparation and administration modalities. Adequate preparation prevents the inactivation of antibiotics and is a prerequisite to maximizing their efficacy (taking into account the pharmacokinetic/pharmacodynamic relationship) and to minimizing their toxicity. Many antibiotic guidelines address the choice of drugs and treatment duration but none of them exclusively address preparation and administration modalities. These guidelines are based on the available literature and offer essential data for a proper antibiotic preparation and administration by physicians and nurses. They may lead to a better efficacy and to a reduced antibiotic resistance. Such guidelines also contribute to a proper use of drugs and improve the interaction between inpatient and outpatient care for a better overall management of patients.

  9. Effects of antibiotic dry-cow therapy and internal teat sealant on milk somatic cell counts and clinical and subclinical mastitis in early lactation.

    PubMed

    Golder, H M; Hodge, A; Lean, I J

    2016-09-01

    The objective of this study was to determine the efficacy of an internal teat sealant (TS; Teatseal; Zoetis Australia, Silverwater, NSW, Australia), when used in combination with antibiotic dry-cow therapy (ADCT) administered at dry-off, on milk individual somatic cell count (ISCC), milk production and components, and the incidence of clinical and subclinical mastitis in dairy cows up to 60 d after calving, when compared with ADCT only. Multiparous Holstein, Jersey, or Holstein cross cows (n=2,200) from 8 farms in southern and eastern Australia were randomly assigned to treatment of all 4 quarters with ADCT alone or with ADCT plus TS (ADCT + TS) at dry-off in this randomized, multisite clinical trial. Individual milk yield, fat and protein percentages, and ISCC were measured at intervals of 14±3 d after calving for the first 60 d of lactation. The first measurement occurred between 10 and 24 d after calving. Clinical mastitis and health events were recorded from dry-off to 60 d of lactation. Milk samples were collected from first cases of clinical mastitis and subjected to bacteriology. Treatment and the interaction of treatment by time did not affect milk yield, ISCC weighted by milk yield, or fat and protein percentages. Treatment with ADCT + TS decreased geometric mean ISCC compared with treatment with ADCT alone over the first 60 d of lactation. Geometric mean ISCC (×10(3) cells/mL) was 32.0 [95% confidence interval (CI): 26.8 to 38.3] and 43.5 (95% CI: 36.2 to 52.1) for ADCT + TS and ADCT alone, respectively. The odds of at least 1 case of subclinical mastitis (ISCC ≥250,000 cells/mL) were 1.9 times higher (95% CI: 1.4 to 2.6) with ADCT alone in the first 60 d of lactation compared with ADCT + TS. Use of ADCT + TS reduced the estimated incidence of at least 1 case of subclinical mastitis on all 8 farms, compared with use of ADCT alone. Only 4 cows that calved 40 to 100 d after dry-off had a first case of clinical mastitis in the dry period. Five percent of

  10. Effects of antibiotic dry-cow therapy and internal teat sealant on milk somatic cell counts and clinical and subclinical mastitis in early lactation.

    PubMed

    Golder, H M; Hodge, A; Lean, I J

    2016-09-01

    The objective of this study was to determine the efficacy of an internal teat sealant (TS; Teatseal; Zoetis Australia, Silverwater, NSW, Australia), when used in combination with antibiotic dry-cow therapy (ADCT) administered at dry-off, on milk individual somatic cell count (ISCC), milk production and components, and the incidence of clinical and subclinical mastitis in dairy cows up to 60 d after calving, when compared with ADCT only. Multiparous Holstein, Jersey, or Holstein cross cows (n=2,200) from 8 farms in southern and eastern Australia were randomly assigned to treatment of all 4 quarters with ADCT alone or with ADCT plus TS (ADCT + TS) at dry-off in this randomized, multisite clinical trial. Individual milk yield, fat and protein percentages, and ISCC were measured at intervals of 14±3 d after calving for the first 60 d of lactation. The first measurement occurred between 10 and 24 d after calving. Clinical mastitis and health events were recorded from dry-off to 60 d of lactation. Milk samples were collected from first cases of clinical mastitis and subjected to bacteriology. Treatment and the interaction of treatment by time did not affect milk yield, ISCC weighted by milk yield, or fat and protein percentages. Treatment with ADCT + TS decreased geometric mean ISCC compared with treatment with ADCT alone over the first 60 d of lactation. Geometric mean ISCC (×10(3) cells/mL) was 32.0 [95% confidence interval (CI): 26.8 to 38.3] and 43.5 (95% CI: 36.2 to 52.1) for ADCT + TS and ADCT alone, respectively. The odds of at least 1 case of subclinical mastitis (ISCC ≥250,000 cells/mL) were 1.9 times higher (95% CI: 1.4 to 2.6) with ADCT alone in the first 60 d of lactation compared with ADCT + TS. Use of ADCT + TS reduced the estimated incidence of at least 1 case of subclinical mastitis on all 8 farms, compared with use of ADCT alone. Only 4 cows that calved 40 to 100 d after dry-off had a first case of clinical mastitis in the dry period. Five percent of

  11. [Alliance against MDRO: safeguarding antibiotics].

    PubMed

    Carlet, J; Rambaud, C; Pulcini, C

    2012-09-01

    Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the 5 next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practitioners, and veterinarians.

  12. Is a vegetarian diet adequate for children.

    PubMed

    Hackett, A; Nathan, I; Burgess, L

    1998-01-01

    The number of people who avoid eating meat is growing, especially among young people. Benefits to health from a vegetarian diet have been reported in adults but it is not clear to what extent these benefits are due to diet or to other aspects of lifestyles. In children concern has been expressed concerning the adequacy of vegetarian diets especially with regard to growth. The risks/benefits seem to be related to the degree of restriction of he diet; anaemia is probably both the main and the most serious risk but this also applies to omnivores. Vegan diets are more likely to be associated with malnutrition, especially if the diets are the result of authoritarian dogma. Overall, lacto-ovo-vegetarian children consume diets closer to recommendations than omnivores and their pre-pubertal growth is at least as good. The simplest strategy when becoming vegetarian may involve reliance on vegetarian convenience foods which are not necessarily superior in nutritional composition. The vegetarian sector of the food industry could do more to produce foods closer to recommendations. Vegetarian diets can be, but are not necessarily, adequate for children, providing vigilance is maintained, particularly to ensure variety. Identical comments apply to omnivorous diets. Three threats to the diet of children are too much reliance on convenience foods, lack of variety and lack of exercise.

  13. Role of antibiotics in generalized aggressive periodontitis: A review of clinical trials in humans

    PubMed Central

    Ahuja, Annapurna; Baiju, C. S.; Ahuja, Vipin

    2012-01-01

    Background: It is well-recognized fact that periodontal diseases are caused by multifactorial etiologies, in which microorganisms play an important role. An essential component of therapy is to eliminate or manage these pathogens. This has been traditionally accomplished through mechanical means by scaling and root planning which is ineffective in some of the aggressive periodontal diseases. These aggressive diseases involve particular groups of microorganisms which are not eliminated by mechanical means; and they require anti-infective therapy, which includes local and systemic antimicrobials. This approach of therapy is of interest to periodontist due to the aforementioned shortcomings of conventional methods. Materials and Methods: A manual and electronic search was made for human studies up to March 2011 that presented clinical and microbiological data for the efficacy of a systemic antibiotics in generalized aggressive periodontitis along with scaling and root planning. A systematic approach was followed by two independent reviewers and included eligibility criteria for study inclusion, quality assessment, and determination of outcome measures, data extraction, data synthesis, and drawing of conclusion. Results: Only three randomized controlled human trials qualified, and they concluded that both scaling and root planing (SRP) mono-therapy and SRP with antibiotics proves beneficial in improving clinical and microbiological parameters in aggressive periodontitis. Better results were seen in SRP with antibiotic groups as compared with SRP alone. Conclusion: Because of the insufficient quantity and heterogenecity of studies, no adequate evidence could be gathered to use the beneficial effects of these antibiotics along with SRP in aggressive periodontitis compared with SRP alone. PMID:23162322

  14. Adipose Tissue - Adequate, Accessible Regenerative Material

    PubMed Central

    Kolaparthy, Lakshmi Kanth.; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-01-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  15. Adipose Tissue - Adequate, Accessible Regenerative Material.

    PubMed

    Kolaparthy, Lakshmi Kanth; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-11-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  16. Antibiotic resistance in probiotic bacteria

    PubMed Central

    Gueimonde, Miguel; Sánchez, Borja; G. de los Reyes-Gavilán, Clara; Margolles, Abelardo

    2013-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue. PMID:23882264

  17. Antibiotic treatments and microbes in the gut.

    PubMed

    Macfarlane, Sandra

    2014-04-01

    Antibiotic therapies are important in combating disease-causing microorganisms and maintaining host health. It is widely accepted that exposure of the gut microbiota to antibiotics can lead to decreased susceptibility and the development of multi-drug-resistant disease-causing organisms, which can be a major clinical problem. It is also important to consider that antibiotics not only target pathogenic bacteria in the gut, but also can have damaging effects on the ecology of commensal species. This can reduce intrinsic colonization resistance and contribute to problems with antibiotic resistance, including lateral transfer of resistance genes. Our knowledge of the impact of antibiotic treatment on the ecology of the normal microbiota has been increased by recent advances in molecular methods and use of in vitro model systems to investigate the impact of antibiotics on the biodiversity of gut populations and the spread of antibiotic resistance. These highlight the need for more detailed structural and functional information on the long-term antibiotic-associated alterations in the gut microbiome, and spread of antibiotic resistance genes. This will be crucial for the development of strategies, such as targeted therapeutics, probiotics, prebiotics and synbiotics, to prevent perturbations in the gut microbiota, the restoration of beneficial species and improvements in host health.

  18. [Documentation of Antibiotic Stewardship (ABS)-interventions during proactive audit of antibiotic use].

    PubMed

    Wilke, Katja; de With, Katja

    2015-01-01

    Proactive audit of antibiotic use ensures quality of prescribing and can improve outcome in patients with infections. A rational, individualized therapy is being defined in interdisciplinary cooperation on the basis of clinical, laboratory, radiological and microbiological examination findings. By fostering targeted antibiotic therapy proactive audit reduces adverse effects and contributes to drug therapy safety and subsequently to patient safety. A proactive audit of antibiotic use is performed weekly on four intensive care units at the University Hospital Dresden by a infectious disease specialist a pharmacist and the attending physicians. Patient-related therapy adjustments were systematically documented over a 4-month period; antibiotic use before and after audit as well as ABS strategies (de-escalation, oral switch, duration of treatment, dose and administration optimization) were analyzed. Both targeted therapy and interventions regarding the duration of treatment led to a reduction in the prescribing of broad spectrum antibiotics by 20%. Routine interdisciplinary proactive audit of antibiotic use with intervention and feedback increases guideline-adherent therapy and process quality.

  19. Novel approaches to developing new antibiotics for bacterial infections.

    PubMed

    Coates, A R M; Hu, Y

    2007-12-01

    Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new antibiotics that kill the resistant mutants. Unfortunately, after more than 50 years of success, the pharmaceutical industry is now producing too few antibiotics, particularly against Gram-negative organisms, to replace antibiotics that are no longer effective for many types of infection. This paper reviews possible new ways to discover novel antibiotics. The genomics route has proven to be target rich, but has not led to the introduction of a marketed antibiotic as yet. Non-culturable bacteria may be an alternative source of new antibiotics. Bacteriophages have been shown to be antibacterial in animals, and may find use in specific infectious diseases. Developing new antibiotics that target non-multiplying bacteria is another approach that may lead to drugs that reduce the emergence of antibiotic resistance and increase patient compliance by shortening the duration of antibiotic therapy. These new discovery routes have given rise to compounds that are in preclinical development, but, with one exception, have not yet entered clinical trials. For the time being, the majority of new antibiotics that reach the marketplace are likely to be structural analogues of existing families of antibiotics or new compounds, both natural and non-natural which are screened in a conventional way against live multiplying bacteria.

  20. Adequate mathematical modelling of environmental processes

    NASA Astrophysics Data System (ADS)

    Chashechkin, Yu. D.

    2012-04-01

    In environmental observations and laboratory visualization both large scale flow components like currents, jets, vortices, waves and a fine structure are registered (different examples are given). The conventional mathematical modeling both analytical and numerical is directed mostly on description of energetically important flow components. The role of a fine structures is still remains obscured. A variety of existing models makes it difficult to choose the most adequate and to estimate mutual assessment of their degree of correspondence. The goal of the talk is to give scrutiny analysis of kinematics and dynamics of flows. A difference between the concept of "motion" as transformation of vector space into itself with a distance conservation and the concept of "flow" as displacement and rotation of deformable "fluid particles" is underlined. Basic physical quantities of the flow that are density, momentum, energy (entropy) and admixture concentration are selected as physical parameters defined by the fundamental set which includes differential D'Alembert, Navier-Stokes, Fourier's and/or Fick's equations and closing equation of state. All of them are observable and independent. Calculations of continuous Lie groups shown that only the fundamental set is characterized by the ten-parametric Galilelian groups reflecting based principles of mechanics. Presented analysis demonstrates that conventionally used approximations dramatically change the symmetries of the governing equations sets which leads to their incompatibility or even degeneration. The fundamental set is analyzed taking into account condition of compatibility. A high order of the set indicated on complex structure of complete solutions corresponding to physical structure of real flows. Analytical solutions of a number problems including flows induced by diffusion on topography, generation of the periodic internal waves a compact sources in week-dissipative media as well as numerical solutions of the same

  1. Exposure of Prebiopsy Antibiotics Influence Bacteriological Diagnosis and Clinical Outcomes in Patients With Infectious Spondylitis

    PubMed Central

    Wang, Ying-Chih; Wong, Chak-Bor; Wang, I-Chun; Fu, Tsai-Sheng; Chen, Lih-Huei; Chen, Wen-Jer

    2016-01-01

    Abstract The benefit of prebiopsy empirical antibiotics for patients with infectious spondylitis and the effect on clinical outcome are not well known. This study assessed the impact of prebiopsy empirical antibiotics in patients with infectious spondylitis. We retrospectively reviewed 41 adult in-patients with infectious spondylitis who received percutaneous endoscopic debridement and drainage (PEDD) at a tertiary care hospital from August 2002 to August 2012. The average patient age was 55.2 years old and causative bacteria were identified in 32 out of 41 biopsy specimens (78.0%) via the PEDD procedure, which has good diagnostic efficacy comparable to open biopsy. Seventeen patients (41.5%) received prebiopsy empirical antimicrobial therapy, and these patients were less likely to have positive cultures than those who did not receive preoperative antibiotics (64.7% vs 87.5%, P = 0.04). Patients with positive cultures had a better infection control rate (78.1% vs 67.7%) and were less likely to undergo subsequent open surgery. Patients given preoperative antibiotics were more likely to need subsequent open surgery (35.3% vs 16.7%, P = 0.02). From multivariate logistic analysis showed age at diagnosis to be an independent risk factor for the need of further surgery. There were no major complications following the PEDD procedure, except 2 patients had transient paresthesia in the affected lumbar segments. Prebiopsy empirical antibiotic therapy was associated with lower positive culture rate and an increased need for subsequent open surgery. Patients with positive cultures were more likely to have initially adequate treatment, better infection control, and better clinical outcome. PMID:27082590

  2. Spread of community-acquired meticillin-resistant Staphylococcus aureus skin and soft-tissue infection within a family: implications for antibiotic therapy and prevention.

    PubMed

    Amir, N H; Rossney, A S; Veale, J; O'Connor, M; Fitzpatrick, F; Humphreys, H

    2010-04-01

    Outbreaks or clusters of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) within families have been reported. We describe a family cluster of CA-MRSA skin and soft-tissue infection where CA-MRSA was suspected because of recurrent infections which failed to respond to flucloxacillin. While the prevalence of CA-MRSA is low worldwide, CA-MRSA should be considered in certain circumstances depending on clinical presentation and risk assessment. Surveillance cultures of family contacts of patients with MRSA should be considered to help establish the prevalence of CA-MRSA and to inform the optimal choice of empiric antibiotic treatment.

  3. Targeted therapy with a novel enediyene antibiotic calicheamicin theta(I)1 effectively suppresses growth and dissemination of liver metastases in a syngeneic model of murine neuroblastoma.

    PubMed

    Lode, H N; Reisfeld, R A; Handgretinger, R; Nicolaou, K C; Gaedicke, G; Wrasidlo, W

    1998-07-15

    The suppression of metastases in malignant diseases is one of the major goals in targeted chemotherapy. This was achieved with an antibody drug conjugate between a novel, rationally designed enediyene antibiotic calicheamicin theta(I)1 of exceptionally high cytotoxic potency and an antiganglioside GD2 monoclonal antibody 14G2a. Effective suppression of hepatic metastases was demonstrated in a novel syngeneic model of murine neuroblastoma that simulates the situation in patients in terms of antigen heterogeneity and presence of the target antigen on normal tissues. Here, we describe the first successful use of calicheamicin theta(I)1 for targeted chemotherapy in a clinically relevant syngeneic metastasis model. PMID:9679947

  4. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance. PMID:25450262

  5. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.

  6. Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle.

    PubMed

    de Boer, A H; Le Brun, P P H; van der Woude, H G; Hagedoorn, P; Heijerman, H G M; Frijlink, H W

    2002-07-01

    The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization. This part of the study describes the development of a powder formulation with colistin sulfate as model substance. The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients. A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler. A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler. The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles. But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler. The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.

  7. Study of immunological aspects of aspergillosis in mice and effect of polyene macrolide antibiotic (SJA-95) and IFN-γ: a possible role of IFN-γ as an adjunct in antifungal therapy.

    PubMed

    Naik, Suresh R; Thakare, Vishnu N; Desai, Sandhya K; Rahalkar, Prabhakar R

    2011-12-30

    New polyene macrolide antibiotic SJA-95 in free as well as liposomal (lip.) forms, with and without interferon-γ (IFN-γ) was studied in mice model of aspergillosis using biological and biochemical parameters viz. colony forming units (CFU) in liver, spleen, kidney, lung and brain, and serum IgG, and interleukin-4 (IL-4). Treatment with free and lip SJA-95 along with IFN-γ prolonged the survival time, reduced CFU in vital organs, decreased serum IgG and IL-4 levels. SJA-95 lip form showed greater antifungal activity as compared to free form. The combined treatment of lip SJA-95 with IFN-γ showed further enhancement in antifungal activity of SJA-95 (lip). The present experimental findings demonstrated IFN-γ might act as a potent modulator in immune reaction during fungal infection and can be a useful adjunctive in antifungal therapy in the management of deep seated systemic mycoses.

  8. Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus.

    PubMed

    Teow, Sin-Yeang; Ali, Syed Atif

    2015-11-01

    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) <0.5 in three antibiotics i.e. Gentamicin, Amikacin, and Ciprofloxacin. Other antibiotics showed indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.

  9. Bacteria subsisting on antibiotics.

    PubMed

    Dantas, Gautam; Sommer, Morten O A; Oluwasegun, Rantimi D; Church, George M

    2008-04-01

    Antibiotics are a crucial line of defense against bacterial infections. Nevertheless, several antibiotics are natural products of microorganisms that have as yet poorly appreciated ecological roles in the wider environment. We isolated hundreds of soil bacteria with the capacity to grow on antibiotics as a sole carbon source. Of 18 antibiotics tested, representing eight major classes of natural and synthetic origin, 13 to 17 supported the growth of clonal bacteria from each of 11 diverse soils. Bacteria subsisting on antibiotics are surprisingly phylogenetically diverse, and many are closely related to human pathogens. Furthermore, each antibiotic-consuming isolate was resistant to multiple antibiotics at clinically relevant concentrations. This phenomenon suggests that this unappreciated reservoir of antibiotic-resistance determinants can contribute to the increasing levels of multiple antibiotic resistance in pathogenic bacteria. PMID:18388292

  10. [Modification of antibiotic resistance in microbial symbiosis].

    PubMed

    Aznabaeva, L M; Usviatsov, B Ia; Bukharin, O V

    2010-01-01

    In antibiotic therapy it is necessary to use drugs active against the pathogen in its association with the host normal microflora. The aim of the study was to investigate modification of antibiotic resistance under conditions of the pathogen association with the representatives of the host normal microflora and to develop the microbiological criteria for determining effectiveness of antibacterials. Modification of microbial antibiotic resistance was investigated in 408 associations. Various changes in the antibiotic resistance of the strains were revealed: synergism, antagonism and indifference. On the basis of the results it was concluded that in the choice of the antibiotic active against Staphylococcus aureus and Streptococcus pyogenes the preference should be given to oxacillin, gentamicin and levomycetin, since the resistance of the pathogens to these antibiotics under the association conditions did not increase, which could contribute to their destruction, whereas the resistance of the normoflora increased or did not change, which was important for its retention in the biocenosis. The data on changeability of the antibiotic resistance of the microbial strains under the association conditions made it possible to develop microbiological criteria for determining effectiveness of antibiotics in the treatment of inflammatory diseases of microbial etiology (RF Patent No. 2231554). PMID:21033469

  11. Multicenter randomized controlled trial on combination therapy with 0.1% adapalene gel and oral antibiotics for acne vulgaris: comparison of the efficacy of adapalene gel alone and in combination with oral faropenem.

    PubMed

    Hayashi, Nobukazu; Kawashima, Makoto

    2012-06-01

    We conducted a randomized controlled trial in patients with acne vulgaris with moderate to severe inflammatory lesions. The patients were assigned to the following three treatment groups: group A received monotherapy with 0.1% topical adapalene gel for 4 weeks; group B received combination therapy with 0.1% topical adapalene gel and 600 mg oral faropenem for 2 weeks followed by 0.1% topical adapalene gel alone for 2 weeks; and group C received combination therapy with 0.1% topical adapalene gel and 600 mg oral faropenem for 4 weeks. The result of the analysis indicated that the percentage reduction in inflammatory lesion counts after 2 weeks of treatment was significantly higher in groups B and C than in group A (P < 0.05). After 4 weeks of treatment, group C showed significantly higher percentage reduction in inflammatory lesion counts than in groups A and B (P < 0.05), whereas no significant difference was noted between the latter two groups. Adverse reactions included dryness and irritation at the adapalene application sites that were observed in 10.1% of cases (16/158 patients) and diarrhea and loose stool because of oral faropenem that were observed in 7.5% of cases (8/106 patients). Taken together, our results suggest that combination therapy with oral antibiotics and adapalene results in earlier improvement in patients with moderate to severe inflammatory acne compared to the application of adapalene alone, and that 4 weeks of the combination therapy is preferable to 2 weeks of treatment. PMID:22168326

  12. Improving antibiotic prescribing in Hai Phong Province, Viet Nam: the "antibiotic-dose" indicator.

    PubMed Central

    Chalker, J.

    2001-01-01

    OBJECTIVE: To improve the use and dosage of antibiotics prescribed at Commune Health Stations in Viet Nam, and in so doing find out whether antibiotic dosage can be easily and reliably measured as a drug-use indicator. METHODS: All commune health workers from the 217 commune health stations in Hai Phong Province, Viet Nam, were enlisted over an 18-month study period during 1994-96. The study design was a longitudinal time series, with each new district baseline acting as a rolling control. Each health station was monitored monthly by district supervisors. Two formal evaluations by doctors external to the study were compared with the supervisors' results. Basic medical equipment was provided three times over nine months, conditional on improvements in prescribing practices and adequate supervision of prescribing practices. FINDINGS: The supervisors' data showed that the percentage of encounters in which a patient was prescribed an antibiotic decreased from over 65% to around 45%. When antibiotics were given, the percentage of patients who received an adequate dose increased from under 30% to 98%. These changes were stable for 17 months after the intervention stopped. CONCLUSIONS: Such initiatives require the active collaboration of health personnel and civic leaders at every level. Conditional equipment donation was shown to be effective. A simple indicator measuring adequacy of antibiotic dose can be an effective tool to improve the use of antibiotics in a sustainable way. PMID:11357210

  13. Antibodies: an alternative for antibiotics?

    PubMed

    Berghman, L R; Abi-Ghanem, D; Waghela, S D; Ricke, S C

    2005-04-01

    In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases. PMID:15844826

  14. Antibiotics and Resistance: Glossary

    MedlinePlus

    ... induced by natural or human activity on the ecology and living organisms. Ecology The study of the relationships and interactions between ... antibiotics The Cost of Resistance Science of Resistance Ecology Antibiotics in Agriculture Antibacterial Agents Glossary References Web ...

  15. Combating Antibiotic Resistance

    MedlinePlus

    ... for infectious diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...

  16. Reversibility of antibiotic resistance

    PubMed Central

    2014-01-01

    Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

  17. Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia: A Nationwide Population-Based Cohort Study.

    PubMed

    Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

    2016-02-01

    Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics.This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups.After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77-0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92-1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30-1.62) between the 2 groups.The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted.

  18. Finding alternatives to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The spread of antibiotic-resistant pathogens requires new treatments. The availability of new antibiotics has severely declined, and so alternatives to antibiotics need to be considered in both animal agriculture and human medicine. Products for disease prevention are different than products for d...

  19. Antibiotic resistant in microorganisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial agents are necessary for use in veterinary medicine including the production of food producing animals. Antibiotic use is indicated for the treatment of bacterial target organisms and/or disease for which the antibiotic was developed. However, an unintended consequence of antibiotic ...

  20. Antibiotic Resistance Questions and Answers

    MedlinePlus

    ... on the Farm Get Smart About Antibiotics Week Antibiotic Resistance Questions and Answers Language: English Español (Spanish) Recommend ... Many ear infections Top of Page Questions about Antibiotic Resistance Examples of How Antibiotic Resistance Spreads Click for ...

  1. Antibiotic Prescription Practices Among Children with Influenza.

    PubMed

    Nitsch-Osuch, A; Gyrczuk, E; Wardyn, A; Życinska, K; Brydak, L

    2016-01-01

    The important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. The aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. A total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. The patients had influenza-like symptoms: fever > 38 °C, cough, and sore throat of less than 4 days duration. Nasal and pharyngeal swabs were tested for influenza A and B virus with a real-time PCR. Thirty six cases of influenza were diagnosed: 34 of influenza A (H3N2) and 2 of influenza B. The rate of influenza infection was 32 % in the study group. The antibiotic therapy was ordered for 58 % patients with influenza. Antibiotics were given less frequently in the outpatient setting (33 %) compared with the hospitalized patients (93 %) (p < 0.05). The most often administrated antibiotics were amoxicillin with clavulanic acid, cefuroxime, and amoxicillin. None of the patients received oseltamivir. Antibiotics were overused, while antivirals were underused among children with influenza. To improve health care quality, more efforts in the diagnosis of influenza and the appropriate use of antimicrobials and antivirals are required. PMID:26801146

  2. A Supramolecular Antibiotic Switch for Antibacterial Regulation.

    PubMed

    Bai, Haotian; Yuan, Huanxiang; Nie, Chenyao; Wang, Bing; Lv, Fengting; Liu, Libing; Wang, Shu

    2015-11-01

    A supramolecular antibiotic switch is described that can reversibly "turn-on" and "turn-off" its antibacterial activity on demand, providing a proof-of-concept for a way to regulate antibacterial activity of biotics. The switch relies on supramolecular assembly and disassembly of cationic poly(phenylene vinylene) derivative (PPV) with cucurbit[7]uril (CB[7]) to regulate their different interactions with bacteria. This simple but efficient strategy does not require any chemical modification on the active sites of the antibacterial agent, and could also regulate the antibacterial activity of classical antibiotics or photosensitizers in photodynamic therapy. This supramolecular antibiotic switch may be a successful strategy to fight bacterial infections and decrease the emergence of bacterial resistance to antibiotics from a long-term point of view.

  3. Antibiotic stewardship in the intensive care unit.

    PubMed

    Luyt, Charles-Edouard; Bréchot, Nicolas; Trouillet, Jean-Louis; Chastre, Jean

    2014-01-01

    The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root 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. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial infections in these critically ill patients, based on pharmacokinetic-pharmacodynamic characteristics, but also improving our ability to avoid administering unnecessary broad-spectrum antibiotics, shortening the duration of their administration, and reducing the numbers of patients receiving undue antibiotic therapy. Either we will be able to implement such a policy or we and our patients will face an uncontrollable surge of very difficult-to-treat pathogens.

  4. Prophylactic antibiotics prevent bacterial biofilm graft infection.

    PubMed

    Bergamini, T M; Peyton, J C; Cheadle, W G

    1992-02-01

    Bacterial biofilm graft infection is due to prostheses colonization by Staphylococcus epidermidis, a pathogen frequently recovered from perigraft tissues of man during vascular procedures despite the use of asepsis and prophylactic antibiotics. The effect of preoperative intraperitoneal cefazolin, administered at a standard (15 or 30 mg/kg) and high (120 mg/kg) dose, on the prevention of bacterial biofilm infection was studied in a rat model. Seventy-four Dacron grafts, colonized in vitro with S. epidermidis to produce an adherent biofilm (3.19 +/- 0.71 x 10(7) colony-forming units/cm2 graft), were implanted in the dorsal subcutaneous tissue at 0.5, 2, and 4 hr after antibiotic administration. The study strain was a slime-producing clinical isolate with minimum inhibitory concentration (MIC) of 15-30 micrograms/ml to cefazolin. Subcutaneous tissue antibiotic levels were determined at each time interval. One week after implantation, the concentration of bacteria in the surface biofilm by quantitative agar culture was significantly decreased (P less than 0.05) only for grafts implanted when antibiotic tissue levels were greater than or equal to the MIC of the study strain. The result of no growth by biofilm broth culture was significantly achieved (P less than 0.01) only for grafts implanted 0.5 hr after high dose cefazolin, in which the tissue antibiotic level was above the MIC of the study strain. Antibiotics can markedly reduce the bacteria concentration of a prosthetic surface biofilm. The effectiveness of prophylactic antibiotics on the prevention of graft infection is dependent upon maintaining an adequate antibiotic level in the perigraft tissues for the duration of the procedure.

  5. Study of the chemical chelates and anti-microbial effect of some metal ions in nanostructural form on the efficiency of antibiotic therapy "norfloxacin drug"

    NASA Astrophysics Data System (ADS)

    Refat, Moamen S.; El-Hawary, W. F.; Mohamed, Mahmoud A.

    2012-04-01

    This paper has reviewed the chemical and biological impact resulting from the interaction between norfloxacin (norH) antibiotic drug and two lanthanide (lanthanum(III) and cerium(III)) metal ions, which prepared in normal and nano-features. La(III) and Ce(III) complexes were synthesized with chemical formulas [La(nor)3]·3H2O and [Ce(nor)3]·2H2O. Lanthanum and cerium(III) ions coordinated toward norH with a hexadentate geometry. The norH acts as deprotonated bidentate ligand through the oxygen atom of carbonyl group and the oxygen atom of carboxylic group. Elemental analysis, FT-IR spectral, electrical conductivity, thermal analysis (TG/DTA), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) measurements have been used to characterize the mentioned isolated complexes. The Coats-Redfern and Horowitz-Metzger integral methods are used to estimate the kinetic parameters for the major successive steps detectable in the TG curve. The brightness side in this study is to take advantage for the preparation and characterization of single phases of La2O3 and CeO2 nanoparticles using urea as precursors via a solid-state decomposition procedure. The norH ligand in comparison with both cases (normal and nano-particles) of lanthanide complexes were screened against for antibacterial (Escherichia Coli, Staphylococcus Aureus, Bacillus subtilis and Pseudomonas aeruginosa) and antifungal (Aspergillus Flavus and Candida Albicans) activities. The highest antibacterial and antifungal activities data of the nano-particles complexes were observed with more potent than the free norH and normal lanthanide complexes.

  6. Experimental phage therapy of burn wound infection: difficult first steps

    PubMed Central

    Rose, Thomas; Verbeken, Gilbert; Vos, Daniel De; Merabishvili, Maya; Vaneechoutte, Mario; Lavigne, Rob; Jennes, Serge; Zizi, Martin; Pirnay, Jean-Paul

    2014-01-01

    Antibiotic resistance has become a major public health problem and the antibiotics pipeline is running dry. Bacteriophages (phages) may offer an ‘innovative’ means of infection treatment, which can be combined or alternated with antibiotic therapy and may enhance our abilities to treat bacterial infections successfully. Today, in the Queen Astrid Military Hospital, phage therapy is increasingly considered as part of a salvage therapy for patients in therapeutic dead end, particularly those with multidrug resistant infections. We describe the application of a well-defined and quality controlled phage cocktail, active against Pseudomonas aeruginosa and Staphylococcus aureus, on colonized burn wounds within a modest clinical trial (nine patients, 10 applications), which was approved by a leading Belgian Medical Ethical Committee. No adverse events, clinical abnormalities or changes in laboratory test results that could be related to the application of phages were observed. Unfortunately, this very prudent ‘clinical trial’ did not allow for an adequate evaluation of the efficacy of the phage cocktail. Nevertheless, this first ‘baby step’ revealed several pitfalls and lessons for future experimental phage therapy and helped overcome the psychological hurdles that existed to the use of viruses in the treatment of patients in our burn unit. PMID:25356373

  7. Ribosomal Antibiotics: Contemporary Challenges.

    PubMed

    Auerbach-Nevo, Tamar; Baram, David; Bashan, Anat; Belousoff, Matthew; Breiner, Elinor; Davidovich, Chen; Cimicata, Giuseppe; Eyal, Zohar; Halfon, Yehuda; Krupkin, Miri; Matzov, Donna; Metz, Markus; Rufayda, Mruwat; Peretz, Moshe; Pick, Ophir; Pyetan, Erez; Rozenberg, Haim; Shalev-Benami, Moran; Wekselman, Itai; Zarivach, Raz; Zimmerman, Ella; Assis, Nofar; Bloch, Joel; Israeli, Hadar; Kalaora, Rinat; Lim, Lisha; Sade-Falk, Ofir; Shapira, Tal; Taha-Salaime, Leena; Tang, Hua; Yonath, Ada

    2016-06-29

    Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of "pathogen-specific antibiotics," in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

  8. Ribosomal Antibiotics: Contemporary Challenges.

    PubMed

    Auerbach-Nevo, Tamar; Baram, David; Bashan, Anat; Belousoff, Matthew; Breiner, Elinor; Davidovich, Chen; Cimicata, Giuseppe; Eyal, Zohar; Halfon, Yehuda; Krupkin, Miri; Matzov, Donna; Metz, Markus; Rufayda, Mruwat; Peretz, Moshe; Pick, Ophir; Pyetan, Erez; Rozenberg, Haim; Shalev-Benami, Moran; Wekselman, Itai; Zarivach, Raz; Zimmerman, Ella; Assis, Nofar; Bloch, Joel; Israeli, Hadar; Kalaora, Rinat; Lim, Lisha; Sade-Falk, Ofir; Shapira, Tal; Taha-Salaime, Leena; Tang, Hua; Yonath, Ada

    2016-01-01

    Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of "pathogen-specific antibiotics," in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification. PMID:27367739

  9. Ribosomal Antibiotics: Contemporary Challenges

    PubMed Central

    Auerbach-Nevo, Tamar; Baram, David; Bashan, Anat; Belousoff, Matthew; Breiner, Elinor; Davidovich, Chen; Cimicata, Giuseppe; Eyal, Zohar; Halfon, Yehuda; Krupkin, Miri; Matzov, Donna; Metz, Markus; Rufayda, Mruwat; Peretz, Moshe; Pick, Ophir; Pyetan, Erez; Rozenberg, Haim; Shalev-Benami, Moran; Wekselman, Itai; Zarivach, Raz; Zimmerman, Ella; Assis, Nofar; Bloch, Joel; Israeli, Hadar; Kalaora, Rinat; Lim, Lisha; Sade-Falk, Ofir; Shapira, Tal; Taha-Salaime, Leena; Tang, Hua; Yonath, Ada

    2016-01-01

    Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification. PMID:27367739

  10. Do antibiotics clear bladder infections?

    PubMed

    Reid, G

    1994-09-01

    An examination of transitional bladder epithelial cells from 69 urine specimens from 23 spinal cord injury patients showed the presence of adherent bacterial biofilms in 66 cases (96%). All patients were receiving antimicrobial therapy, primarily trimethoprim-sulfamethoxazole (41 of 69), without any apparent effect on the bladder colonization. The large number of bacteria that emerged with highly virulent and potentially multi-drug resistant characteristics, especially Enterococcus faecalis (33% of isolates), was of concern. These findings raise questions about the proved efficacy and effectiveness of antibiotics against uropathogenic biofilms adherent to tissues.

  11. [Possibilities of bacteriophage therapy].

    PubMed

    Skurnik, Mikael; Kiljunen, Saija

    2016-01-01

    Antibiotic resistance of bacterial pathogens has increased, and new therapies are urgently needed. Bacteriophages (phages), viruses infecting and killing bacteria, are the most abundant organisms on earth. In nature there are several specific phages for every bacterium, controlling bacterial numbers and maintaining ecological balance. Phage therapy, i.e., treating bacterial infections with phages, offers an alternative complementary to antibiotics as phages infect and kill also multi-resistant bacteria. Phages possess narrow host specificity, each phage infecting only a few bacterial species or strains. Thereby phages do not harm the normal microbiota as antibiotics do. We aim to begin clinical trials of phage therapy in Finland. PMID:27244930

  12. Biotic acts of antibiotics

    PubMed Central

    Aminov, Rustam I.

    2013-01-01

    Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and β-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

  13. Methicillin-resistant Staphylococcus aureus antibiotic resistance and virulence.

    PubMed

    Xia, Jufeng; Gao, Jianjun; Kokudo, Norihiro; Hasegawa, Kiyoshi; Tang, Wei

    2013-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most critical causes of healthcare-related or community-related infections. Resistance to most β-lactam antibiotics makes MRSA a big threat to clinical treatment. Utilization of low efficiency antibiotics such as vancomycin and teicoplanin makes new choices for therapies. Recently, much researchhas shed light on relevance between genetic mutations of MRSA and clinical characteristics such as antibiotic resistance, and virulence. These findings could contribute to development of novel antibiotics and vaccines.

  14. Antibiotic resistance in Burkholderia species.

    PubMed

    Rhodes, Katherine A; Schweizer, Herbert P

    2016-09-01

    The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. PMID:27620956

  15. Antibiotics and the gut microbiota

    PubMed Central

    Modi, Sheetal R.; Collins, James J.; Relman, David A.

    2014-01-01

    Antibiotics have been a cornerstone of innovation in the fields of public health, agriculture, and medicine. However, recent studies have shed new light on the collateral damage they impart on the indigenous host-associated communities. These drugs have been found to alter the taxonomic, genomic, and functional capacity of the human gut microbiota, with effects that are rapid and sometimes persistent. Broad-spectrum antibiotics reduce bacterial diversity while expanding and collapsing membership of specific indigenous taxa. Furthermore, antibiotic treatment selects for resistant bacteria, increases opportunities for horizontal gene transfer, and enables intrusion of pathogenic organisms through depletion of occupied natural niches, with profound implications for the emergence of resistance. Because these pervasive alterations can be viewed as an uncoupling of mutualistic host-microbe relationships, it is valuable to reconsider antimicrobial therapies in the context of an ecological framework. Understanding the biology of competitive exclusion, interspecies protection, and gene flow of adaptive functions in the gut environment may inform the design of new strategies that treat infections while preserving the ecology of our beneficial constituents. PMID:25271726

  16. [Antibiotic treatment of clostridial colitis].

    PubMed

    Beneš, J; Polívková, S

    2016-01-01

    The advantages and disadvantages of various antibiotics used in the treatment of Clostridium difficile infection (CDI) are compared with respect to their pharmacokinetic and pharmacodynamic properties. Recommendations are made for their optimal use in clinical practice. Metronidazole is suitable for the treatment of mild forms of CDI which are essentially self-limiting. Vancomycin kills clostridia reliably but the treatment is encumbered with considerable risk of recurrence. This can be decreased by shortening the treatment to seven days and then switching to a (pulse, taper, chaser) regimen to prevent recurrence or by active restoration of the intestinal ecosystem (fecal transplant). Fidaxomicin works faster than vancomycin and is associated with a lower risk of recurrence. Thus, it can be profitably used in patients with impending ileus and also in those whose medical condition does not allow prolonged treatment. The duration of fidaxomicin treatment could be reduced to as few as five days. Rifaximin does not have a clear place in the treatment of CDI because no compelling data are available on its efficacy in this disease. The risk of resistance is also important. Tigecycline is a promising antibiotic for parenteral use. According to the available data, it should be more effective than intravenous metronidazole which has been considered the drug of choice.Clostridial colitis is associated with intestinal dysmicrobia which is the major cause of recurrence. Severe dysmicrobia cannot be treated by antibiotics but only by gut flora restoration; stool transplant from a healthy donor is the only proven therapy for this condition. PMID:27246640

  17. Desensitization to antibiotics in children.

    PubMed

    Cernadas, Josefina R

    2013-02-01

    Drug hypersensitivity reactions can occur to almost all drugs and antibiotics are among the most common cause for this kind of reactions. Drug hypersensitivity may affect any organ or system, and manifestations range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. In case of infection, there is usually a safe antibiotic alternative. Nonetheless, in some cases, no alternative treatment exists for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance to a drug which can only be maintained by continuous administration of the medication responsible for the hypersensitivity reaction. Desensitization is mainly performed in IgE-mediated reactions. Increasing doses of the implicated drug are administered over a short period of time, until the therapeutic dose is achieved and tolerated. Very few studies confined to children are found in literature. Most of them are case reports. In general, the proposed desensitization schemes are similar to those used in adults differing only in the final dose administered. The purpose of this study is to review desensitization to antibiotics in children presenting and discussing three clinical practical cases of desensitization in this age group.

  18. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  19. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  20. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  1. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  2. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order to... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for...

  3. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  4. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  5. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  6. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  7. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  8. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  9. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  10. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  11. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  12. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  13. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  14. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  15. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  16. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  17. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  18. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  19. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  20. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  1. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES Qualifying for an SBIC License Capitalizing An Sbic § 107.200 Adequate capital...

  2. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  3. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  4. 7 CFR 4290.200 - Adequate capital for RBICs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Adequate capital for RBICs. 4290.200 Section 4290.200 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND... Qualifications for the RBIC Program Capitalizing A Rbic § 4290.200 Adequate capital for RBICs. You must meet...

  5. "Something Adequate"? In Memoriam Seamus Heaney, Sister Quinlan, Nirbhaya

    ERIC Educational Resources Information Center

    Parker, Jan

    2014-01-01

    Seamus Heaney talked of poetry's responsibility to represent the "bloody miracle", the "terrible beauty" of atrocity; to create "something adequate". This article asks, what is adequate to the burning and eating of a nun and the murderous gang rape and evisceration of a medical student? It considers Njabulo…

  6. Infection, antibiotics, and preterm delivery.

    PubMed

    Locksmith, G; Duff, P

    2001-10-01

    The relationship between genital tract infection and preterm delivery has been established on the basis of biochemical, microbiological, and clinical evidence. In theory, pathogenic bacteria may ascend from the lower reproductive tract into the uterus, and the resulting inflammation leads to preterm labor, rupture of the membranes, and birth. A growing body of evidence suggests that preterm labor and/rupture of the membranes are triggered by micro-organisms in the genital tract and by the host response to these organisms, ie, elaboration of cytokines and proteolytic enzymes. Epidemiologic and in vitro studies do not prove a cause-and-effect relationship between infection and preterm birth. However, the preponderance of evidence indicates that treatment of asymptomatic bacteriuria and symptomatic lower genital tract infections such as bacterial vaginosis (BV), trichomoniasis, gonorrhea, and chlamydia will lower the risk of preterm delivery. Based on current evidence, pregnant women who note an abnormal vaginal discharge should be tested for BV, trichomonas, gonorrhea, and chlamydia. Those who test positive should be treated appropriately. A 3- to 7-day course of antibiotic treatment for asymptomatic bacteriuria during pregnancy is clinically indicated to reduce the risk of pyelonephritis and preterm delivery. Routine screening for chlamydia and gonorrhea should be performed for women at high risk of acquiring sexually transmitted diseases. The practice of routine screening for BV in asymptomatic women who are at low risk for preterm delivery cannot be supported based on evidence from the literature. Routine screening for asymptomatic bacteriuria during pregnancy is cost-effective, particularly in high-prevalence populations. The results of antibiotic trials for the treatment of preterm labor have been inconsistent. In the absence of reasonable evidence that antimicrobial therapy leads to significant prolongation of pregnancy in the setting of preterm labor

  7. Antibiotic dose optimization in critically ill patients.

    PubMed

    Cotta, M O; Roberts, J A; Lipman, J

    2015-12-01

    The judicious use of existing antibiotics is essential for preserving their activity against infections. In the era of multi-drug resistance, this is of particular importance in clinical areas characterized by high antibiotic use, such as the ICU. Antibiotic dose optimization in critically ill patients requires sound knowledge not only of the altered physiology in serious infections - including severe sepsis, septic shock and ventilator-associated pneumonia - but also of the pathogen-drug exposure relationship (i.e. pharmacokinetic/pharmacodynamic index). An important consideration is the fact that extreme shifts in organ function, such as those seen in hyperdynamic patients or those with multiple organ dysfunction syndrome, can have an impact upon drug exposure, and constant vigilance is required when reviewing antibiotic dosing regimens in the critically ill. The use of continuous renal replacement therapy and extracorporeal membrane oxygenation remain important interventions in these patients; however, both of these treatments can have a profound effect on antibiotic exposure. We suggest placing emphasis on the use of therapeutic drug monitoring and dose individualization when optimizing therapy in these settings.

  8. Discovery and preclinical development of new antibiotics.

    PubMed

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

  9. Pediatric acute otitis media: the case for delayed antibiotic treatment.

    PubMed

    Johnson, Nicholas C; Holger, Joel S

    2007-04-01

    Acute otitis media (AOM) is both a commonly diagnosed condition and a frequent indication for antibiotic use in children. Recent literature suggests that antibiotics are not needed in many children with AOM, as most cases resolve spontaneously without complication. However, a majority of AOM infections in children are still treated with antibiotics. The American Academy of Pediatrics and American Academy of Family Physicians released a guideline for treatment of AOM in children. We review the guideline as well as scientific evidence related to AOM treatment options. We support a set of evidence-based guidelines employing a delayed prescription option for antibiotic therapy in selected children. If used appropriately, these cost-effective guidelines will reduce the amount of antibiotics prescribed, increase parental satisfaction, and may lower rates of antibiotic resistance while producing similar rates of resolution of AOM.

  10. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies.

    PubMed

    Robinson, Jennifer G; Colhoun, Helen M; Bays, Harold E; Jones, Peter H; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

    2014-10-01

    The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20-40 mg/d) or rosuvastatin (10-20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20-40 mg) or rosuvastatin (10-20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level. PMID:25269777

  11. Efficacy and Safety of Alirocumab as Add-on Therapy in High–Cardiovascular-Risk Patients With Hypercholesterolemia Not Adequately Controlled With Atorvastatin (20 or 40 mg) or Rosuvastatin (10 or 20 mg): Design and Rationale of the ODYSSEY OPTIONS Studies

    PubMed Central

    Robinson, Jennifer G; Colhoun, Helen M; Bays, Harold E; Jones, Peter H; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

    2014-01-01

    The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20–40 mg/d) or rosuvastatin (10–20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20–40 mg) or rosuvastatin (10–20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level. PMID:25269777

  12. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies.

    PubMed

    Robinson, Jennifer G; Colhoun, Helen M; Bays, Harold E; Jones, Peter H; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

    2014-10-01

    The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20-40 mg/d) or rosuvastatin (10-20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20-40 mg) or rosuvastatin (10-20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level.

  13. Homeopathic Ear Drops as an Adjunct in Reducing Antibiotic Usage in Children With Acute Otitis Media.

    PubMed

    Taylor, James A; Jacobs, Jennifer

    2014-01-01

    Objective. To determine if use of a homeopathic ear drop preparation reduces antibiotic use in children diagnosed with acute otitis media (AOM). Methods. Children 6 months to 11 years old, diagnosed with AOM and managed with a delayed antibiotic approach, were randomized to standard therapy alone or standard therapy plus a homeopathic ear drop preparation. The primary outcome was whether or not the antibiotic prescription given at the index visit was filled during a 12- to 15-day follow-up period. Results. Among 210 enrolled children, follow-up antibiotic data were collected on 206. During the 12- to 15-day follow-up period, fewer parents of children randomized to the homeopathic ear drops group filled the antibiotic prescription compared with those of children receiving standard therapy alone (26.9% and 41.2%, respectively, P = .032). Conclusion. Homeopathic ear drops may be effective in reducing the use of antibiotics in children with AOM managed with a delayed antibiotic approach.

  14. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics.

    PubMed

    Hersh, Adam L; Jackson, Mary Anne; Hicks, Lauri A

    2013-12-01

    Most upper respiratory tract infections are caused by viruses and require no antibiotics. This clinical report focuses on antibiotic prescribing strategies for bacterial upper respiratory tract infections, including acute otitis media, acute bacterial sinusitis, and streptococcal pharyngitis. The principles for judicious antibiotic prescribing that are outlined focus on applying stringent diagnostic criteria, weighing the benefits and harms of antibiotic therapy, and understanding situations when antibiotics may not be indicated. The principles can be used to amplify messages from recent clinical guidelines for local guideline development and for patient communication; they are broadly applicable to antibiotic prescribing in general.

  15. Correlation between clinical data and antibiotic resistance in coagulase-negative Staphylococcus species isolated from 68 patients with acute post-cataract endophthalmitis.

    PubMed

    Chiquet, C; Maurin, M; Altayrac, J; Aptel, F; Boisset, S; Vandenesch, F; Cornut, P L; Romanet, J P; Gain, P; Carricajo, A

    2015-06-01

    Coagulase-negative staphylococci (CNS) cause the majority of post-cataract endophthalmitis, which can lead to anatomical and/or functional loss of the eye. This study reports the antibiotic susceptibilities of CNS isolates associated with acute post-cataract endophthalmitis cases and correlates antibiotic resistance with severity and outcome of infection in these patients. Clinical data (initial ocular examination, final prognosis, antibiotic treatment) and the antibiotic susceptibilities of the isolated CNS strains were obtained from 68 patients with post-surgical endophthalmitis recruited during a 7-year period by the FRench Institutional ENDophthalmitis Study (FRIENDS) group. The CNS strains displayed 100% susceptibility to vancomycin, 70% to fluoroquinolones, 83% to fosfomycin, 46% to imipenem and 18% to piperacillin. The most effective antibiotic combinations were fosfomycin plus a fluoroquinolone and imipenem plus a fluoroquinolone, which were considered adequate in 80% and 58% of patients, respectively. Methicillin resistance was significantly associated with older age (p 0.001), diabetes mellitus (p 0.004), absence of fundus visibility (p 0.06), and poor visual prognosis (p 0.03). Resistance to fluoroquinolones was significantly associated with absence of fundus visibility (p 0.05) and diabetes mellitus (p 0.02). This large prospective study demonstrates that methicillin resistance and, to a lesser extent, fluoroquinolone resistance in CNS strains causing postoperative endophthalmitis are both prevalent in France and associated with a poorer visual prognosis. These results emphasize the need for an effective surveillance of this antibiotic resistance and the development of new diagnostic tools for rapid detection for early optimization of antibiotic therapy in endophthalmitis patients.

  16. Setamycin, a new antibiotic.

    PubMed

    Omura, S; Otoguro, K; Nishikiori, T; Oiwa, R; Iwai, Y

    1981-10-01

    A new antibiotic, setamycin, was extracted from the mycelia of a rare actinomycete strain KM-6054. The antibiotic, the molecular formula of which was found to be C42H61NO12 (tentative), is a yellow powder showing activity against some fungi, trichomonads and weakly against Gram-positive bacteria. PMID:7309621

  17. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  18. Metagenomics and antibiotics.

    PubMed

    Garmendia, L; Hernandez, A; Sanchez, M B; Martinez, J L

    2012-07-01

    Most of the bacterial species that form part of the biosphere have never been cultivated. In this situation, a comprehensive study of bacterial communities requires the utilization of non-culture-based methods, which have been named metagenomics. In this paper we review the use of different metagenomic techniques for understanding the effect of antibiotics on microbial communities, to synthesize new antimicrobial compounds and to analyse the distribution of antibiotic resistance genes in different ecosystems. These techniques include functional metagenomics, which serves to find new antibiotics or new antibiotic resistance genes, and descriptive metagenomics, which serves to analyse changes in the composition of the microbiota and to track the presence and abundance of already known antibiotic resistance genes in different ecosystems.

  19. [Perspective applications of multi-species probiotics in the prevention of antibiotic-associated diarrhea].

    PubMed

    Uspenskiĭ, Iu P; Zakharenko, S M; Fominykh, Iu A

    2013-01-01

    The problem of antibiotic-associated conditions is one of the most actual problems of clinical practice. The antibiotic-associated diarrhea is a multidisciplinary problem. Investigations of the small intestine microecological status and assessment of microflora at the patients receiving antibiotics testifies to dysbiosis existence. In article results of open-label investigation of a multispecies probiotic RioFlora Balance using for antibiotic-associated diarrhea prophylaxis in patients used antibacterial therapy are presented.

  20. Marriage or Family Therapy.

    ERIC Educational Resources Information Center

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  1. Solving the Antibiotic Crisis.

    PubMed

    Wright, Gerard D

    2015-02-13

    Antibiotics are essential for both treating and preventing infectious diseases. Paradoxically, despite their importance as pillars of modern medicine, we are in danger of losing antibiotics because of the evolution and dissemination of resistance mechanisms throughout all pathogenic microbes. This fact, coupled with an inability to bring new drugs to market at a pace that matches resistance, has resulted in a crisis of global proportion. Solving this crisis requires the actions of many stakeholders, but chemists, chemical biologists, and microbiologists must drive the scientific innovation that is required to maintain our antibiotic arsenal. This innovation requires (1) a deep understanding of the evolution and reservoirs of resistance; (2) full knowledge of the molecular mechanisms of antibiotic action and resistance; (3) the discovery of chemical and genetic probes of antibiotic action and resistance; (4) the integration of systems biology into antibiotic discovery; and (5) the discovery of new antimicrobial chemical matter. Addressing these pressing scientific gaps will ensure that we can meet the antibiotic crisis with creativity and purpose. PMID:27622298

  2. Rediscovering the antibiotics of the hive.

    PubMed

    Boukraâ, Laïd; Sulaiman, Siti A

    2009-11-01

    Honey and other bee products were subjected to laboratory and clinical investigations during the past few decades and the most remarkable discovery was their antibacterial activity. Honey has been used since ancient times for the treatment of some diseases and for the healing of wounds but its use as an anti-infective agent was superseded by modern dressings and antibiotic therapy. However, the emergence of antibiotic resistant strains of bacteria has confounded the current use of antibiotic therapy leading to the re-examination of former remedies. Honey, propolis, royal jelly and bee venom have a strong antibacterial activity. Even antibiotic-resistant strains such as epidemic strains of methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycine resistant Enterococcus (VRE) have been found to be as sensitive to honey as the antibiotic-sensitive strains of the same species. Sensitivity of bacteria to bee products varies considerably within the product and the varieties of the same product. Botanical origin plays a major role in its antibacterial activity. Propolis has been found to have the strongest action against bacteria. This is probably due to its richness in flavonoids. The most challenging problems of using hive products for medical purposes are dosage and safety. Honey and royal jelly produced as a food often are not well filtered, and may contain various particles. Processed for use in wound care, they are passed through fine filters which remove most of the pollen and other impurities to prevent allergies. Also, although honey does not allow vegetative bacteria to survive, it does contain viable spores, including clostridia. With the increased availability of licensed medical stuffs containing bee products, clinical use is expected to increase and further evidence will become available. Their use in professional care centres should be limited to those which are safe and with certified antibacterial activities. The present article is a short review

  3. Fighting antibiotic resistance in the intensive care unit using antibiotics.

    PubMed

    Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

  4. Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.

    PubMed

    Berglund, Björn; Khan, Ghazanfar Ali; Weisner, Stefan E B; Ehde, Per Magnus; Fick, Jerker; Lindgren, Per-Eric

    2014-04-01

    Recently, there have been growing concerns about pharmaceuticals including antibiotics as environmental contaminants. Antibiotics of concentrations commonly encountered in wastewater have been suggested to affect bacterial population dynamics and to promote dissemination of antibiotic resistance. Conventional wastewater treatment processes do not always adequately remove pharmaceuticals causing environmental dissemination of low levels of these compounds. Using constructed wetlands as an additional treatment step after sewage treatment plants have been proposed as a cheap alternative to increase reduction of wastewater contaminants, however this means that the natural microbial community of the wetlands becomes exposed to elevated levels of antibiotics. In this study, experimental surface-flow wetlands in Sweden were continuously exposed to antibiotics of concentrations commonly encountered in wastewater. The aim was to assess the antibiotic removal efficiency of constructed wetlands and to evaluate the impact of low levels of antibiotics on bacterial diversity, resistance development and expression in the wetland bacterial community. Antibiotic concentrations were measured using liquid chromatography-mass spectrometry and the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing gradient gel electrophoresis. Real-time PCR was used to detect and quantify antibiotic resistance genes and integrons in the wetlands, during and after the exposure period. The results indicated that the antibiotic removal efficiency of constructed wetlands was comparable to conventional wastewater treatment schemes. Furthermore, short-term treatment of the constructed wetlands with environmentally relevant concentrations (i.e. 100-2000 ng×l(-1)) of antibiotics did not significantly affect resistance gene concentrations, suggesting that surface-flow constructed wetlands are well-suited for wastewater treatment purposes.

  5. Antibiotic prophylaxis in primary immune deficiency disorders.

    PubMed

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  6. Medical Treatment of Diverticular Disease: Antibiotics.

    PubMed

    Lué, Alberto; Laredo, Viviana; Lanas, Angel

    2016-10-01

    Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients. PMID:27622367

  7. Multiple Myeloma. Diagnostic challenges and standard therapy.

    PubMed

    Kyle, R A

    2001-04-01

    In the diagnosis of multiple myeloma (MM), the clinician must exclude other disorders in which a plasma cell reaction may occur such as rheumatoid arthritis and connective tissue disorders, or metastatic carcinoma where the patient may have osteolytic lesions associated with bone metastases. Patients with smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) have none of the complicating features of MM and do not require treatment with potentially toxic agents. The plasma cell labeling index can help make a differential diagnosis of MM from SMM. Patients with a high labeling index have a high risk of complications and should be monitored carefully. However, the labeling index can be low in active MM. In addition, SMM or MGUS patients have few or no circulating plasma cells. High-dose chemotherapy and stem cell support prolong overall survival in contrast to conventional therapy. If stem cell transplantation is considered, it is important to harvest the cells before using alkylating agents to obtain a sufficient number of cells. Supportive treatment consists of the occasional use of erythropoietin to maintain adequate hemoglobin levels and adequate hydration to protect renal function. Vaccination against pneumococcal infections and the prophylactic use of antibiotic therapy during the first 2 months of treatment can be beneficial. Recognizing the symptoms of spinal cord compression and initiating dexamethasone therapy promptly to prevent paraplegia are critical. PMID:11309703

  8. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePlus

    ... on the Farm Get Smart About Antibiotics Week File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  9. Targeting Antibiotic Resistance

    PubMed Central

    Chellat, Mathieu F.; Raguž, Luka

    2016-01-01

    Abstract Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID:27000559

  10. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    SciTech Connect

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  11. Clinical Characteristics Associated with Antibiotic Treatment Failure for Tuboovarian Abscesses

    PubMed Central

    Farid, Huma; Lau, Trevin C.; Karmon, Anatte E.; Styer, Aaron K.

    2016-01-01

    Objective. Although parenteral antibiotic treatment is a standard approach for tuboovarian abscesses, a significant proportion of patients fail therapy and require interventional radiology (IR) guided drainage. The objective of this study is to assess if specific clinical factors are associated with antibiotic treatment failure. Study Design. Retrospective medical record review of patients hospitalized for tuboovarian abscesses from 2001 through 2012 was performed. Clinical characteristics were compared for patients who underwent successful parenteral antibiotic treatment, failed antibiotic treatment necessitating subsequent IR drainage, initial drainage with concurrent antibiotics, and surgery. Results. One hundred thirteen patients admitted for inpatient treatment were identified. Sixty-one (54%) patients were treated with antibiotics alone. Within this group, 24.6% failed antibiotic treatment and required drainage. Mean white blood cell count (K/μL) (18.7 ± 5.94 versus 13.9 ± 5.12) (p = 0.003), mean maximum diameter of tuboovarian abscess (cm) (6.8 ± 2.9 versus 5.2 ± 2.0) (p = 0.03), and length of stay (days) (9.47 ± 7.43 versus 4.59 ± 2.4) (p = 0.002) were significantly greater for patients who failed antibiotic treatment. Conclusions. Admission white blood cell count greater than 16 K/μL and abscess size greater than 5.18 cm are associated with antibiotic treatment failure. These factors may provide guidance for initial selection of IR guided drainage. PMID:26989337

  12. Adaptive Landscapes of Resistance Genes Change as Antibiotic Concentrations Change.

    PubMed

    Mira, Portia M; Meza, Juan C; Nandipati, Anna; Barlow, Miriam

    2015-10-01

    Most studies on the evolution of antibiotic resistance are focused on selection for resistance at lethal antibiotic concentrations, which has allowed the detection of mutant strains that show strong phenotypic traits. However, solely focusing on lethal concentrations of antibiotics narrowly limits our perspective of antibiotic resistance evolution. New high-resolution competition assays have shown that resistant bacteria are selected at relatively low concentrations of antibiotics. This finding is important because sublethal concentrations of antibiotics are found widely in patients undergoing antibiotic therapies, and in nonmedical conditions such as wastewater treatment plants, and food and water used in agriculture and farming. To understand the impacts of sublethal concentrations on selection, we measured 30 adaptive landscapes for a set of TEM β-lactamases containing all combinations of the four amino acid substitutions that exist in TEM-50 for 15 β-lactam antibiotics at multiple concentrations. We found that there are many evolutionary pathways within this collection of landscapes that lead to nearly every TEM-genotype that we studied. While it is known that the pathways change depending on the type of β-lactam, this study demonstrates that the landscapes including fitness optima also change dramatically as the concentrations of antibiotics change. Based on these results we conclude that the presence of multiple concentrations of β-lactams in an environment result in many different adaptive landscapes through which pathways to nearly every genotype are available. Ultimately this may increase the diversity of genotypes in microbial populations.

  13. Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis.

    PubMed

    Droege, Molly E; Van Fleet, Suzanne L; Mueller, Eric W

    2016-04-01

    Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes. Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen. Time-dependent antibiotics, such as β-lactams, can be given as extended or continuous infusions. Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring. Vancomycin and fluoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration. PMID:27037336

  14. Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis.

    PubMed

    Droege, Molly E; Van Fleet, Suzanne L; Mueller, Eric W

    2016-04-01

    Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes. Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen. Time-dependent antibiotics, such as β-lactams, can be given as extended or continuous infusions. Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring. Vancomycin and fluoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration.

  15. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jørgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases. PMID:24326504

  16. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jørgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases.

  17. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

  18. [Current concepts on hemodynamic support and therapy in septic shock].

    PubMed

    Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Corrêa, Thiago Domingos; Pereira, Adriano José; de Assunção, Murillo Santucci Cesar; Silva, Eliézer

    2015-01-01

    Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

  19. Current concepts on hemodynamic support and therapy in septic shock.

    PubMed

    Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Corrêa, Thiago Domingos; Pereira, Adriano José; de Assunção, Murillo Santucci Cesar; Silva, Eliézer

    2015-01-01

    Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

  20. Infections in neurologic surgery. The intraventricular use of antibiotics.

    PubMed

    Wen, D Y; Bottini, A G; Hall, W A; Haines, S J

    1992-04-01

    Intraventricular antibiotic therapy appears to be a useful treatment modality in those CSF infections in which systemic therapy may fail. Consideration should be given to using this form of treatment when infecting organisms are only sensitive to antibiotics with poor penetration of the CSF (e.g., aminoglycosides and vancomycin) and for cases in which intravenous therapy has failed to sterilize the CSF, toxicity from systemic therapy precludes further increases in dosages, and shunts or other CSF hardware might be expected to reduce the efficacy of systemic therapy by providing a foreign body to harbor organisms. Shunts or reservoirs that are infected may be successfully sterilized with IVT therapy alone or in conjunction with systemic therapy, but this has a lower success rate than cases in which the shunt is removed. There is a wealth of clinical experience with IVT vancomycin and gentamicin that suggests that they are relatively safe. Until more data are available on other aminoglycosides and newer antibiotics, these two agents should be considered the antibiotics of choice for IVT therapy. In situations in which the organism is sensitive to both vancomycin and gentamicin, vancomycin should be used in view of the documented neurotoxicity seen with gentamicin. When gentamicin resistance occurs, amikacin and tobramycin are appropriate alternatives. The high risk of epilepsy with the penicillins and cephalosporins makes them less suited for IVT therapy, although the newer cephalosporins have some promise for IVT therapy. CNS fungal infections can be treated effectively with IVT amphotericin B but with a high risk of significant toxicity. Miconazole appears to be safer than amphotericin B but there is less clinical experience with this drug. Table 1 summarizes the dosages, indications, and toxicity of those antibiotics commonly used for intraventricular administration, which have been reported previously.

  1. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus.

    PubMed

    Lehar, Sophie M; Pillow, Thomas; Xu, Min; Staben, Leanna; Kajihara, Kimberly K; Vandlen, Richard; DePalatis, Laura; Raab, Helga; Hazenbos, Wouter L; Morisaki, J Hiroshi; Kim, Janice; Park, Summer; Darwish, Martine; Lee, Byoung-Chul; Hernandez, Hilda; Loyet, Kelly M; Lupardus, Patrick; Fong, Rina; Yan, Donghong; Chalouni, Cecile; Luis, Elizabeth; Khalfin, Yana; Plise, Emile; Cheong, Jonathan; Lyssikatos, Joseph P; Strandh, Magnus; Koefoed, Klaus; Andersen, Peter S; Flygare, John A; Wah Tan, Man; Brown, Eric J; Mariathasan, Sanjeev

    2015-11-19

    Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody-antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody-antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections. PMID:26536114

  2. Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae.

    PubMed

    Band, Victor I; Crispell, Emily K; Napier, Brooke A; Herrera, Carmen M; Tharp, Greg K; Vavikolanu, Kranthi; Pohl, Jan; Read, Timothy D; Bosinger, Steven E; Trent, M Stephen; Burd, Eileen M; Weiss, David S

    2016-01-01

    Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics. PMID:27572838

  3. Understanding Your Adequate Yearly Progress (AYP), 2011-2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation Rates.…

  4. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  5. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  6. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  7. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  8. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  9. Adequate Schools and Inadequate Education: An Anthropological Perspective.

    ERIC Educational Resources Information Center

    Wolcott, Harry F.

    To illustrate his claim that schools generally do a remarkably good job of schooling while the society makes inadequate use of other means to educate young people, the author presents a case history of a young American (identified pseudonymously as "Brad") whose schooling was adequate but whose education was not. Brad, jobless and homeless,…

  10. Comparability and Reliability Considerations of Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Maier, Kimberly S.; Maiti, Tapabrata; Dass, Sarat C.; Lim, Chae Young

    2012-01-01

    The purpose of this study is to develop an estimate of Adequate Yearly Progress (AYP) that will allow for reliable and valid comparisons among student subgroups, schools, and districts. A shrinkage-type estimator of AYP using the Bayesian framework is described. Using simulated data, the performance of the Bayes estimator will be compared to…

  11. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... operate actively in accordance with your Articles and within the context of your business plan,...

  12. Assessing Juvenile Sex Offenders to Determine Adequate Levels of Supervision.

    ERIC Educational Resources Information Center

    Gerdes, Karen E.; And Others

    1995-01-01

    This study analyzed the internal consistency of four inventories used by Utah probation officers to determine adequate and efficacious supervision levels and placement for juvenile sex offenders. Three factors accounted for 41.2 percent of variance (custodian's and juvenile's attitude toward intervention, offense characteristics, and historical…

  13. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... identifiable personal data and automated systems shall be adequately trained in the security and privacy of... records in which identifiable personal data are processed or maintained, including all reports and output... personal records or data; must minimize, to the extent practicable, the risk that skilled technicians...

  14. Do Beginning Teachers Receive Adequate Support from Their Headteachers?

    ERIC Educational Resources Information Center

    Menon, Maria Eliophotou

    2012-01-01

    The article examines the problems faced by beginning teachers in Cyprus and the extent to which headteachers are considered to provide adequate guidance and support to them. Data were collected through interviews with 25 school teachers in Cyprus, who had recently entered teaching (within 1-5 years) in public primary schools. According to the…

  15. Antibiotics and probiotics in treatment of inflammatory bowel disease.

    PubMed

    Gionchetti, Paolo; Rizzello, Fernando; Lammers, Karen-M; Morselli, Claudia; Sollazzi, Lucia; Davies, Samuel; Tambasco, Rosy; Calabrese, Carlo; Campieri, Massimo

    2006-06-01

    Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn's disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy.

  16. Prophylactic Antibiotic Guidelines in Modern Interventional Radiology Practice

    PubMed Central

    Moon, Eunice; Tam, Matthew D.B.S.; Kikano, Raghid N.; Karuppasamy, Karunakaravel

    2010-01-01

    Modern interventional radiology practice is continuously evolving. Developments include increases in the number of central venous catheter placements and tumor treatments (uterine fibroid therapy, radio- and chemoembolization of liver tumor, percutaneous radiofrequency and cryoablation), and new procedures such as abdominal aortic aneurysm stent-graft repair, vertebroplasty, kyphoplasty, and varicose vein therapies. There have also been recent advancements in standard biliary and urinary drainage procedures, percutaneous gastrointestinal feeding tube placement, and transjugular intrahepatic portosystemic shunts. Prophylactic antibiotics have become the standard of care in many departments, with little clinical data to support its wide acceptance. The rise in antibiotic-resistant strains of organisms in all hospitals worldwide have forced every department to question the use of prophylactic antibiotics. The authors review the evidence behind use of prophylactic antibiotics in standard interventional radiology procedures, as well as in newer procedures that have only recently been incorporated into interventional radiology practice. PMID:22550374

  17. Antibiotic treatment for Helicobacter pylori: Is the end coming?

    PubMed Central

    Kim, Su Young; Choi, Duck Joo; Chung, Jun-Won

    2015-01-01

    Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID:26558152

  18. Probiotics - a helpful additional therapy for bacterial vaginosis

    PubMed Central

    Bodean, O; Munteanu, O; Cirstoiu, C; Secara, D; Cirstoiu, M

    2013-01-01

    Abstract Background: Bacterial vaginosis is a condition of unknown etiology, associated with an imbalance of the normal vaginal microbiota, characterized by a high recurrence rate despite of classical therapy solutions. Probiotics are microorganisms, which taken in adequate amounts, are proven to bring health benefits in human and animal bodies, by re-establishing the normal flora at different levels. Objective: The present article studies the possibility of using probiotic treatment as an adjuvant therapy for nonspecific vaginosis and reducing its recurrence rate. Methods: We have evaluated the evolution of patients with bacterial vaginosis who received the classical antibiotic therapy and a probiotic product. The study group consisted of 173 non-pregnant, sexually active patients, 20-45 years old, with no additional health problems and no contraceptive undergoing treatment, which have been admitted to the department of Obstetrics and Gynecology of the Bucharest Emergency University Hospital between 1.01.2012-31.12.2012.The bacteriological evaluation was made on cervical and vaginal cultures. Results: From a total of 173 patients, those who used probiotics oral capsules while taking an antibiotic had lower recurrence rates. More than a half of women who did not use any probiotic product had 3 or more relapse episodes per year. Vaginal capsules with probiotics have also proven to be useful in lowering the recurrence rate, but research is still needed. Conclusion: Probiotic products are proven to be a helpful adjuvant therapy for bacterial vaginosis, with no adverse outcomes. PMID:24868256

  19. Glucocorticoids and antibiotics, how do they get together?

    PubMed

    Reidl, Joachim; Monsó, Eduard

    2015-06-15

    Antibiotic therapy in patients currently treated with corticosteroids is common in chronic respiratory diseases when exacerbation symptoms attributable to infection appear. Among them, obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major health issues affecting hundreds of million people worldwide that are frequently treated with inhaled corticosteroids. Systemic corticosteroids are also used for idiopathic pulmonary fibrosis, a less prevalent chronic respiratory disease. In this issue of EMBO Molecular Medicine, Earl et al (2015) report a potentially baleful relationship between steroid and antibiotic treatment in chronic respiratory diseases, affecting colonization persistence and antibiotic tolerance for Haemophilus influenzae, one of the leading potentially pathogenic microorganisms (PPMs) of the respiratory system.

  20. Alternatives to antibiotics-a pipeline portfolio review.

    PubMed

    Czaplewski, Lloyd; Bax, Richard; Clokie, Martha; Dawson, Mike; Fairhead, Heather; Fischetti, Vincent A; Foster, Simon; Gilmore, Brendan F; Hancock, Robert E W; Harper, David; Henderson, Ian R; Hilpert, Kai; Jones, Brian V; Kadioglu, Aras; Knowles, David; Ólafsdóttir, Sigríður; Payne, David; Projan, Steve; Shaunak, Sunil; Silverman, Jared; Thomas, Christopher M; Trust, Trevor J; Warn, Peter; Rex, John H

    2016-02-01

    Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future. PMID:26795692

  1. Acute sinusitis in children: do antibiotics have any role?

    PubMed

    Abzug, Mark J

    2014-01-01

    Bacteria can be recovered from paranasal sinuses in the majority of patients given the diagnosis of acute bacterial sinusitis (ABS), and bacteriologic cure can be achieved with appropriate antibiotic treatment. The critical question is whether bacteriologic cure correlates with meaningful clinical endpoints such as clinical improvement, reduction in recurrent disease, or prevention of complications. Of the 4 pediatric placebo-controlled randomized clinical trials (PCRCTs), 2 suggest superiority of antibiotic treatment and 2 suggest lack of superiority. PCRCTs in adults are mixed as to clinical benefit. Pediatric and adult meta-analyses demonstrate modest benefit of antibiotic therapy and rates of spontaneous recovery without antibiotics of 60-65%. Although retrospective studies indicate that some patients who develop orbital or neurologic complications of sinusitis were pre-treated with antibiotic therapy, a low rate of complications precludes determination of whether antibiotic treatment prevents complications in some proportion of patients. Like the literature evidence, expert guideline recommendations are mixed. Although the evidence base is incomplete and conflicting, the limited data suggest that antibiotics probably do have a role in the treatment of pediatric ABS. The most compelling rationale is prevention of serious complications, but proof for this rationale is lacking.

  2. Alternatives to antibiotics-a pipeline portfolio review.

    PubMed

    Czaplewski, Lloyd; Bax, Richard; Clokie, Martha; Dawson, Mike; Fairhead, Heather; Fischetti, Vincent A; Foster, Simon; Gilmore, Brendan F; Hancock, Robert E W; Harper, David; Henderson, Ian R; Hilpert, Kai; Jones, Brian V; Kadioglu, Aras; Knowles, David; Ólafsdóttir, Sigríður; Payne, David; Projan, Steve; Shaunak, Sunil; Silverman, Jared; Thomas, Christopher M; Trust, Trevor J; Warn, Peter; Rex, John H

    2016-02-01

    Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.

  3. Chronic leg ulcer: does a patient always get a correct diagnosis and adequate treatment?

    PubMed

    Mooij, Michael C; Huisman, Laurens C

    2016-03-01

    Patients with chronic leg ulcers have severely impaired quality of life and account for a high percentage of annual healthcare costs. To establish the cause of a chronic leg ulcer, referral to a center with a multidisciplinary team of professionals is often necessary. Treating the underlying cause diminishes healing time and reduces costs. In venous leg ulcers adequate compression therapy is still a problem. It can be improved by training the professionals with pressure measuring devices. A perfect fitting of elastic stockings is important to prevent venous leg ulcer recurrence. In most cases, custom-made stockings are the best choice for this purpose. PMID:26916772

  4. Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.

    PubMed

    Lewis, James D; Chen, Eric Z; Baldassano, Robert N; Otley, Anthony R; Griffiths, Anne M; Lee, Dale; Bittinger, Kyle; Bailey, Aubrey; Friedman, Elliot S; Hoffmann, Christian; Albenberg, Lindsey; Sinha, Rohini; Compher, Charlene; Gilroy, Erin; Nessel, Lisa; Grant, Amy; Chehoud, Christel; Li, Hongzhe; Wu, Gary D; Bushman, Frederic D

    2015-10-14

    Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.

  5. [Evolution in the antibiotic susceptibility and resistance].

    PubMed

    Stefani, S

    2009-07-01

    Over the last decade the proliferation of antibiotic-resistant pathogens has been a growing problem, especially in some geographic areas, making useless most of the classical antibiotic therapies. The rapid emergence of resistant bacteria is the result of different factors as the intrinsic microbial complexity, the growing attitude to travel of humans, animals and goods, the use of antibiotics outside hospitals, and the lack of precise therapeutic chooses for high risk group of patients. The antibiotic-resistance becomes certainly a serious problem when a resistant pathogen, and often multi-resistant today, is present in an infective site. In fact in a recent estimate of the Centre for Disease Control and Prevention (CDC) about 90.000 deaths per year in the USA are attributable to bacterial infections and in particular to resistant pathogens. It appears clear that the clinic relevance of this problem is the decimation of the sensible germs of the normal flora that leads to the upper hand of the only resistant bacteria. The antibiotic therapy, in fact, select the resistance and each bacteria has developed a particular strategy to survive: mutations of the genetic content or acquisition of resistance genes from the external. Among the Gram positive bacteria, besides methicillin resistant Staphyloccocus aureus, there are other pathogens such as coagulase-negative staphylococci (CoNS), Enterococcus faecium and Enterococcus faecalis, some species of streptococci and multiresistant Corynebacterium. The CoNS, eg. S. epidermidis, S. hominis and S. haemolyticus, are recognized as new important nosocomial pathogens and are not only responsible of invasive infections but have become in few years resistant to oxacillin (more than 60%) and multiresistant. The unsuspected fragility of glycopeptides, which for 40 years have been the most important treatment against infections due to Gram-positive bacteria, has posed the need for new antimicrobial molecules. Among the therapeutic

  6. The therapeutic potential of antibiotics and probiotics in the treatment of pouchitis.

    PubMed

    Gionchetti, Paolo; Calabrese, Carlo; Lauri, Adriano; Rizzello, Fernando

    2015-01-01

    Pouchitis is the most frequent long-term complication of pouch surgery for ulcerative colitis. There is consistent evidence on the implication of bacterial flora in the pathogenesis of pouchitis, and there is evidence for a therapeutic role of antibiotics and probiotics in therapy of this disease. Antibiotics, particularly ciprofloxacin and metronidazole, are the mainstay of treatment for acute pouchitis. In chronic refractory pouchitis, after having excluded other diagnoses (infections, Crohn's disease of the pouch, ischemia and irritable pouch), antibiotic combination therapy is the treatment of choice. The highly concentrated probiotic mixture VSL#3 has been shown to be effective in prevention of pouchitis onset and in maintaining antibiotic-induced remission.

  7. Concentrations of some antibiotics in synovial fluid after oral administration, with special reference to antistaphylococcal activity.

    PubMed

    Sattar, M A; Barrett, S P; Cawley, M I

    1983-02-01

    One of 4 antibiotics with antistaphylococcal activity was given in a conventional oral dose for one day to each of 20 hospitalised patients with synovial effusion of a knee joint requiring aspiration. Serial synchronous samples of serum and synovial fluid (SF) were taken over 36 hours through indwelling cannulae. No morbidity was experienced either during or after this procedure. Satisfactory antistaphylococcal concentrations in SF were achieved with sodium fusidate (500 mg 8 hourly) and amoxycillin (250 mg 8 hourly). Cephradine (500 mg 6 hourly) frequently failed to reach the minimum inhibitory concentration for Staphylococcus aureus in the SF, and flucloxacillin (250 mg 6 hourly) was unpredictable in its penetration of the synovial space. Wide interpatient variation of both serum and SF concentrations was found. Our results indicate that sodium fusidate is an appropriate early treatment for a nonresistant staphylococcal joint infection. Amoxycillin is a suitable alternative or second antistaphylococcal drug and would also be appropriate initial therapy when the infecting organism is unknown. We strongly recommend that SF antibiotic concentrations be measured, to ensure adequate penetration of the synovial cavity, in the treatment of septic arthritis.

  8. Discovery and preclinical development of new antibiotics

    PubMed Central

    Karlén, Anders

    2014-01-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted. PMID:24646082

  9. The multifaceted roles of antibiotics and antibiotic resistance in nature

    PubMed Central

    Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

    2013-01-01

    Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics

  10. Analysis of macrolide antibiotics.

    PubMed

    Kanfer, I; Skinner, M F; Walker, R B

    1998-07-01

    The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included.

  11. Antibiotic Precautions in Athletes

    PubMed Central

    Fayock, Kristopher; Voltz, Matthew; Sandella, Bradley; Close, Jeremy; Lunser, Matthew; Okon, Joshua

    2014-01-01

    Context: Antibiotics are the mainstay of treatment for bacterial infections in patients of all ages. Athletes who maximally train are at risk for illness and various infections. Routinely used antibiotics have been linked to tendon injuries, cardiac arrhythmias, diarrhea, photosensitivity, cartilage issues, and decreased performance. Evidence Acquisition: Relevant articles published from 1989 to 2012 obtained through searching MEDLINE and OVID. Also, the Food and Drug Administration website was utilized. Study Design: Clinical review. Level of Evidence: Level 3. Results: The team physician should consider alternative medications in place of the “drug of choice” when adverse drug effects are a concern for an athlete’s health or performance. If alternative medications cannot be selected, secondary preventative measures, including sunscreen or probiotics, may be needed. Conclusion: Physicians choose medications based on a variety of factors to help ensure infection resolution while limiting potential side effects. Extra precautions are indicated when treating athletes with certain antibiotics. PMID:24982704

  12. Antibiotic activity in space.

    PubMed

    Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R

    1986-01-01

    Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon.

  13. Antibiotic activity in space.

    PubMed

    Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R

    1986-01-01

    Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon. PMID:3569006

  14. Antibiotic prophylaxis in otolaryngologic surgery

    PubMed Central

    Ottoline, Ana Carolina Xavier; Tomita, Shiro; Marques, Marise da Penha Costa; Felix, Felippe; Ferraiolo, Priscila Novaes; Laurindo, Roberta Silveira Santos

    2013-01-01

    Summary Aim: Antibiotic prophylaxis aims to prevent infection of surgical sites before contamination or infection occurs. Prolonged antibiotic prophylaxis does not enhance the prevention of surgical infection and is associated with higher rates of antibiotic-resistant microorganisms. This review of the literature concerning antibiotic prophylaxis, with an emphasis on otolaryngologic surgery, aims to develop a guide for the use of antibiotic prophylaxis in otolaryngologic surgery in order to reduce the numbers of complications stemming from the indiscriminate use of antibiotics. PMID:25991999

  15. Tackling antibiotic resistance.

    PubMed

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A; Kishony, Roy; Kreiswirth, Barry N; Kutter, Elizabeth; Lerner, Stephen A; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H; Mobashery, Shahriar; Piddock, Laura J V; Projan, Steven; Thomas, Christopher M; Tomasz, Alexander; Tulkens, Paul M; Walsh, Timothy R; Watson, James D; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I

    2011-11-02

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis.

  16. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  17. Antibiotic drug discovery.

    PubMed

    Wohlleben, Wolfgang; Mast, Yvonne; Stegmann, Evi; Ziemert, Nadine

    2016-09-01

    Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years. PMID:27470984

  18. Antibiotics in Animal Products

    NASA Astrophysics Data System (ADS)

    Falcão, Amílcar C.

    The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

  19. Antibiotics and antibiotic resistance in agroecosystems: State of the science

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review article proposes a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal ...

  20. Maggot Debridement Therapy: Advancing to the Past in Wound Care.

    PubMed

    Klaus, Kelsey; Steinwedel, Cynthia

    2015-01-01

    Maggot debridement therapy (MDT) is experiencing resurgence as an effective alternative to conventional mechanical debridement in nonhealing wounds, especially those with antibiotic-resistant organisms. MDT has antibiotic, antifungal, and anti-inflammatory properties. Military use is on the rise.

  1. Microbial profiles at baseline and not the use of antibiotics determine the clinical outcome of the treatment of chronic periodontitis

    PubMed Central

    Bizzarro, S.; Laine, M. L.; Buijs, M. J.; Brandt, B. W.; Crielaard, W.; Loos, B. G.; Zaura, E.

    2016-01-01

    Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequent, microbial resistance. Here, using an open-ended technique, we report the changes in the subgingival microbiome up to one year post-treatment of patients treated with basic periodontal therapy with or without antibiotics. Antibiotics resulted in a greater influence on the microbiome 3 months after therapy, but this difference disappeared at 6 months. Greater microbial diversity, specific taxa and certain microbial co-occurrences at baseline and not the use of antibiotics predicted better clinical treatment outcomes. Our results demonstrate the predictive value of specific subgingival bacterial profiles for the decision to prescribe antibiotics in the treatment of periodontitis, but they also indicate the need for alternative therapies based on ecological approaches. PMID:26830979

  2. Review article: antibiotics and probiotics in inflammatory bowel disease.

    PubMed

    Kruis, W

    2004-10-01

    Treatment with antibiotics in inflammatory bowel disease has a long tradition and is widely used. The indications for antibiotic therapy are wide ranging, from specific situations such as abscesses or fistulae, to patients with severe disease (as an unspecific 'protective' measure), and to address the hypothesis that the enteric flora as a whole, or specific microorganisms such as mycobacteria, are involved in the pathogenesis of inflammatory bowel disease. The best-studied single antibiotic compound is metronidazole. However, overall, the scientific basis for the use of antibiotics is limited, which may reflect a lack of interest from sponsors within the pharmaceutical industry. Despite this weak evidence base, antibiotics are a globally established therapeutic tool in inflammatory bowel disease. Growing evidence from human and animal studies points towards a pivotal pathogenetic role of intestinal bacteria in inflammatory bowel disease. In view of these experimental findings, clinical trials have been undertaken to elucidate the therapeutic effects of probiotics in inflammatory bowel disease. Probiotics are viable nonpathogenic microorganisms which confer health benefits to the host by improving the microbial balance of the indigenous microflora. So far, of the many candidates, one specific strain (Escherichia coli Nissle 1917) and a mixture of eight different bacteria have demonstrated convincing therapeutic efficacy in controlled studies. Maintenance therapy in ulcerative colitis and prevention therapy, as well as the treatment of pouchitis, have emerged as areas in which probiotic therapy offers a valid therapeutic alternative to current treatments. Further investigations may detect additional clinically effective probiotics and other clinical indications.

  3. A review of the microbiology, antibiotic usage and resistance in chronic skin wounds.

    PubMed

    Howell-Jones, R S; Wilson, M J; Hill, K E; Howard, A J; Price, P E; Thomas, D W

    2005-02-01

    Chronic leg and foot wounds represent an increasing burden to healthcare systems as the age of the population increases. The deep dermal tissues of all chronic wounds harbour microorganisms, however, the precise interaction between microbes in the wounds and impaired healing is unknown. With regard to antibiotic therapy, there is a lack of evidence concerning its effectiveness, optimal regimens or clinical indications for treatment. Despite this lack of evidence, antibiotics are frequently a feature of the management of chronic wounds and these patients receive significantly more antibiotic prescriptions (both systemic and topical) than age and sex-matched patients. Current guidelines for antibiotic prescribing for such wounds are often based on expert opinion rather than scientific fact and may present difficulties in interpretation and implementation to the clinician. Although the increasing prevalence of antibiotic resistance is widely recognized, the relationships between antibiotic resistance, chronic wound microbiology and rationales for antibiotic therapy have yet to be determined. This review discusses the role of microbes in chronic wounds from a clinical perspective with particular focus on the occurrence of bacteria and their impact on such wounds. The evidence and role of antibiotics in the treatment of such wounds are outlined and current practice of antibiotic usage for chronic wounds in the primary care setting described. The implications of antibiotic usage with regard to antibiotic resistance are also considered.

  4. A review of the microbiology, antibiotic usage and resistance in chronic skin wounds.

    PubMed

    Howell-Jones, R S; Wilson, M J; Hill, K E; Howard, A J; Price, P E; Thomas, D W

    2005-02-01

    Chronic leg and foot wounds represent an increasing burden to healthcare systems as the age of the population increases. The deep dermal tissues of all chronic wounds harbour microorganisms, however, the precise interaction between microbes in the wounds and impaired healing is unknown. With regard to antibiotic therapy, there is a lack of evidence concerning its effectiveness, optimal regimens or clinical indications for treatment. Despite this lack of evidence, antibiotics are frequently a feature of the management of chronic wounds and these patients receive significantly more antibiotic prescriptions (both systemic and topical) than age and sex-matched patients. Current guidelines for antibiotic prescribing for such wounds are often based on expert opinion rather than scientific fact and may present difficulties in interpretation and implementation to the clinician. Although the increasing prevalence of antibiotic resistance is widely recognized, the relationships between antibiotic resistance, chronic wound microbiology and rationales for antibiotic therapy have yet to be determined. This review discusses the role of microbes in chronic wounds from a clinical perspective with particular focus on the occurrence of bacteria and their impact on such wounds. The evidence and role of antibiotics in the treatment of such wounds are outlined and current practice of antibiotic usage for chronic wounds in the primary care setting described. The implications of antibiotic usage with regard to antibiotic resistance are also considered. PMID:15649989

  5. Methodology in improving antibiotic implementation policies

    PubMed Central

    Özgenç, Onur

    2016-01-01

    The basic requirements of antibiotic prescribing are components of methodology; knowledge, logical reasoning, and analysis. Antimicrobial drugs are valuable but limited resources, different from other drugs and they are among the most commonly prescribed drugs all over the world. They are the only drugs which do not intentionally affect the patient. They affect the pathogens which invade the host. The emergence and spread of antibiotic-resistant pathogens are accelerated by heavy antibiotic usage. The effective antimicrobial stewardship and infection control program have been shown to limit the emergence of antimicrobial-resistant bacteria. In this respect, education for antibiotic prescribing could be designed by going through the steps of scientific methodology. A defined leadership and a coordinated multidisciplinary approach are necessary for optimizing the indication, selection, dosing, route of administration, and duration of antimicrobial therapy. In scenarios, knowledge is also as important as experience for critical decision making as is designated. In this setting, the prevalence and resistance mechanisms of antimicrobials, and their interactions with other drugs need to be observed. In this respect, infectious disease service should play an important role in improving antimicrobial use by giving advice on the appropriate use of antimicrobial agents, and implementing evidence-based guidelines. PMID:27376019

  6. Suppression of antibiotic resistance acquisition by combined use of antibiotics.

    PubMed

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2015-10-01

    We analyzed the effect of combinatorial use of antibiotics with a trade-off relationship of resistance, i.e., resistance acquisition to one drug causes susceptibility to the other drug, and vice versa, on the evolution of antibiotic resistance. We demonstrated that this combinatorial use of antibiotics significantly suppressed the acquisition of resistance.

  7. Mechanisms of Antibiotic Resistance

    PubMed Central

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  8. [Antibiotical prophylaxy in gynecology].

    PubMed

    Záhumenský, J; Menzlová, E; Zmrhal, J; Kučera, E

    2013-08-01

    Gynecological surgery is considered to be clear with possible contamination by gram-positive cocci from the skin, gram-negatives from the perineum or groins or polymicrobial biocenosis from vagina, depending on the surgical approach. Antibiotical prophylaxy enforces the natural mechanisms of immunity and helps to exclude present infection. There were presented many studies comparing useful effect of prophylaxis in gynecological surgery. The benefits of antibiotical prophylaxy before IUD insertion, before the cervical surgery and before hysteroscopies were not verified. On the other hand the prophylaxy of vaginal surgery including vaginal hysterectomy decreases the number of postoperative febrile complications. The positive influence of prophylaxis before the simple laparoscopy and laparoscopy without bowel injury or the opening of the vagina was not evidently verified. In abdominal hysterectomy the antibiotical prophylaxy decreases the incidence of postoperative complications significantly. The administration of 2 g of cefazolin can be recommended. In procedures taking more than 3 hours the repeated administration of cefazolin is suitable. New urogynecological procedures, using mesh implants, were not sufficiently evaluated as for postoperative infections and the posible antibiotical effect. The presence of implant in possibly non sterile area should be considered as high risc of postoperative complications. PMID:24040985

  9. Mechanisms of Antibiotic Resistance.

    PubMed

    Munita, Jose M; Arias, Cesar A

    2016-04-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens. PMID:27227291

  10. Antibiotics before surgery.

    PubMed

    Kaatz, B

    1996-01-01

    The antimicrobial era (along with greater surgical skill and precision) has brought us relative safety for procedures that previously were fraught with danger. Civil War amputation surgeries, for example, had an extraordinarily high incidence of infections and mortality. Staying aware of and avoiding the small, but real, risks associated with surgical antibiotic prophylaxis will help sustain the advances we enjoy today. PMID:8650524

  11. Antibiotics, pediatric dysbiosis, and disease.

    PubMed

    Vangay, Pajau; Ward, Tonya; Gerber, Jeffrey S; Knights, Dan

    2015-05-13

    Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.

  12. Bacterial cheating limits antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

    2012-02-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

  13. [Two chapters from the medical history of this century: antibacterial therapy].

    PubMed

    Bol, P

    1999-02-13

    The antibiotic era brought adequate therapies for bacterial infections and began with the introduction of sulphonamides (discovered earlier by Domagk) in 1935 and penicillins (discovered earlier by Fleming) in the course of World War II. Notwithstanding the usual description as 'discoveries', they were the fruits of systematic investigations for chemicals with antibacterial properties and little or no toxicity for the host. Despite the role of serendipity in the discovery of penicillin, the bactericidal moulds that Fleming observed had fallen on fertile soil: a laboratory where the search for antibacterial drugs had been going on for years. PMID:10221100

  14. [Abdominal cure procedures. Adequate use of Nobecutan Spray].

    PubMed

    López Soto, Rosa María

    2009-12-01

    Open abdominal wounds, complicated by infection and/or risk of eventration tend to become chronic and usually require frequent prolonged cure. Habitual changing of bandages develop into one of the clearest risk factors leading to the deterioration of perilesional cutaneous integrity. This brings with it new complications which draw out the evolution of the process, provoking an important deterioration in quality of life for the person who suffers this and a considerable increase in health costs. What is needed is a product and a procedure which control the risk of irritation, which protect the skin, which favor a patient's comfort and which shorten treatment requirements while lowering health care expenses. This report invites medical personnel to think seriously about the scientific rationale, and treatment practice, as to why and how to apply Nobecutan adequately, this reports concludes stating the benefits in the adequate use of this product. The objective of this report is to guarantee the adequate use of this product in treatment of complicated abdominal wounds. This product responds to the needs which are present in these clinical cases favoring skin care apt isolation and protection, while at the same time, facilitating the placement and stability of dressings and bandages used to cure wounds. In order for this to happen, the correct use of this product is essential; medical personnel must pay attention to precautions and recommendations for proper application. The author's experiences in habitual handling of this product during various years, included in the procedures for standardized cures for these wounds, corroborates its usefulness; the author considers use of this product to be highly effective while being simple to apply; furthermore, one succeeds in providing quality care and optimizes resources employed.

  15. Side effects of antibiotics during bacterial infection: mitochondria, the main target in host cell.

    PubMed

    Singh, Rochika; Sripada, Lakshmi; Singh, Rajesh

    2014-05-01

    Antibiotics are frontline therapy against microbial infectious diseases. Many antibiotics are known to cause several side effects in humans. Ribosomal RNA (rRNA) is the main target of antibiotics that inhibit protein synthesis. According to the endosymbiont theory, mitochondrion is of bacterial origin and their molecular and structural components of the protein expression system are almost similar. It has been observed that the rate of mutations in mitochondrial rRNA is higher as compared to that of nuclear rRNA. The presence of these mutations may mimic prokaryotic rRNA structure and bind to antibiotics targeted to ribosomes of bacteria. Mitochondrial functions are compromised hence may be one of the major causes of side effects observed during antibiotic therapy. The current review had summarized the studies on the role of antibiotics on mitochondrial functions and its relevance to the observed side effects in physiological and pathological conditions.

  16. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  17. What Can Be Done about Antibiotic Resistance?

    MedlinePlus

    ... antibiotics for treating human disease. (See Antibiotics in agriculture .) Is there any international action on the antibiotic ... and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking ...

  18. Probing minority population of antibiotic-resistant bacteria.

    PubMed

    Huang, Tianxun; Zheng, Yan; Yan, Ya; Yang, Lingling; Yao, Yihui; Zheng, Jiaxin; Wu, Lina; Wang, Xu; Chen, Yuqing; Xing, Jinchun; Yan, Xiaomei

    2016-06-15

    The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 β-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic-resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies. PMID:26852201

  19. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.

  20. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed Central

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

  1. Selection of antibiotic resistance at very low antibiotic concentrations.

    PubMed

    Sandegren, Linus

    2014-05-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  2. Quantifying dose to the reconstructed breast: Can we adequately treat?

    SciTech Connect

    Chung, Eugene; Marsh, Robin B.; Griffith, Kent A.; Moran, Jean M.; Pierce, Lori J.

    2013-04-01

    To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V{sub 20}. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

  3. The use of systemic antibiotics in the treatment of chronic wounds.

    PubMed

    Hernandez, Robert

    2006-01-01

    The role of microorganisms in the etiology and persistence of chronic wounds remains poorly understood. The chronic wound bed houses a complex microenvironment that typically includes more than one bacterial species. Difficulty lies in determining when the presence of bacteria impedes wound healing, thereby warranting intervention. Indications for antibiotic therapy and optimal treatment regimens are ill defined. The goal of this article is to describe the appropriate role of systemic antibiotics in the management of chronic wounds. A common sense approach will be offered based on six clinically pertinent questions: Is infection present? Are systemic antibiotics necessary? Should treatment be enteral or parenteral? What antibiotic or combination of antibiotics should be used? What should be the duration of therapy? What special circumstances are present (i.e., concomitant illnesses, potential drug-drug interactions) that can impact therapy?

  4. The use of systemic antibiotics in the treatment of chronic wounds.

    PubMed

    Hernandez, Robert

    2006-01-01

    The role of microorganisms in the etiology and persistence of chronic wounds remains poorly understood. The chronic wound bed houses a complex microenvironment that typically includes more than one bacterial species. Difficulty lies in determining when the presence of bacteria impedes wound healing, thereby warranting intervention. Indications for antibiotic therapy and optimal treatment regimens are ill defined. The goal of this article is to describe the appropriate role of systemic antibiotics in the management of chronic wounds. A common sense approach will be offered based on six clinically pertinent questions: Is infection present? Are systemic antibiotics necessary? Should treatment be enteral or parenteral? What antibiotic or combination of antibiotics should be used? What should be the duration of therapy? What special circumstances are present (i.e., concomitant illnesses, potential drug-drug interactions) that can impact therapy? PMID:17199675

  5. The analysis of the antibiotic resistome offers new opportunities for therapeutic intervention.

    PubMed

    Corona, Fernando; Blanco, Paula; Alcalde-Rico, Manuel; Hernando-Amado, Sara; Lira, Felipe; Bernardini, Alejandra; Sánchez, María B; Martínez, José L

    2016-06-01

    Most efforts in the development of antimicrobials have focused on the screening of lethal targets. Nevertheless, the constant expansion of antimicrobial resistance makes the antibiotic resistance determinants themselves suitable targets for finding inhibitors to be used in combination with antibiotics. Among them, inhibitors of antibiotic inactivating enzymes and of multidrug efflux pumps are suitable candidates for improving the efficacy of antibiotics. In addition, the application of systems biology tools is helping to understand the changes in bacterial physiology associated to the acquisition of resistance, including the increased susceptibility to other antibiotics displayed by some antibiotic-resistant mutants. This information is useful for implementing novel strategies based in metabolic interventions or combination of antibiotics for improving the efficacy of antibacterial therapy. PMID:27304087

  6. Combinatorial approaches with selected phytochemicals to increase antibiotic efficacy against Staphylococcus aureus biofilms.

    PubMed

    Abreu, Ana Cristina; Saavedra, Maria José; Simões, Lúcia C; Simões, Manuel

    2016-10-01

    Combinations of selected phytochemicals (reserpine, pyrrolidine, quinine, morin and quercetin) with antibiotics (ciprofloxacin, tetracycline and erythromycin) were tested on the prevention and control of Staphylococcus aureus biofilms. The phytochemicals were also studied for their ability to avoid antibiotic adaptation and to inhibit antibiotic efflux pumps. Morin, pyrrolidine and quercetin at subinhibitory concentrations had significant effects in biofilm prevention and/or control when applied alone and combined with antibiotics. Synergism between antibiotics and phytochemicals was found especially against biofilms of NorA overexpressing strain S. aureus SA1199B. This strain when growing with subinhibitory concentrations of ciprofloxacin developed increased tolerance to this antibiotic. However, this was successfully reversed by quinine and morin. In addition, reserpine and quercetin showed significant efflux pump inhibition. The overall results demonstrate the role of phytochemicals in co-therapies to promote more efficient treatments and decrease antimicrobial resistance to antibiotics, with substantial effects against S. aureus in both planktonic and biofilm states.

  7. A new strategy to fight antimicrobial resistance: the revival of old antibiotics

    PubMed Central

    Cassir, Nadim; Rolain, Jean-Marc; Brouqui, Philippe

    2014-01-01

    The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative to the treatment of MDR bacterial pathogens. It would help to optimize the armamentarium of antibiotics in the way to preserve new antibiotics and avoid the prescription of molecules known to favor the spread of resistance (i.e., quinolones). Furthermore, in a global economical perspective, this could represent a useful public health orientation knowing that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of MDR bacterial infections with the use of old antibiotics and discuss their place in current practice. PMID:25368610

  8. Combinatorial approaches with selected phytochemicals to increase antibiotic efficacy against Staphylococcus aureus biofilms.

    PubMed

    Abreu, Ana Cristina; Saavedra, Maria José; Simões, Lúcia C; Simões, Manuel

    2016-10-01

    Combinations of selected phytochemicals (reserpine, pyrrolidine, quinine, morin and quercetin) with antibiotics (ciprofloxacin, tetracycline and erythromycin) were tested on the prevention and control of Staphylococcus aureus biofilms. The phytochemicals were also studied for their ability to avoid antibiotic adaptation and to inhibit antibiotic efflux pumps. Morin, pyrrolidine and quercetin at subinhibitory concentrations had significant effects in biofilm prevention and/or control when applied alone and combined with antibiotics. Synergism between antibiotics and phytochemicals was found especially against biofilms of NorA overexpressing strain S. aureus SA1199B. This strain when growing with subinhibitory concentrations of ciprofloxacin developed increased tolerance to this antibiotic. However, this was successfully reversed by quinine and morin. In addition, reserpine and quercetin showed significant efflux pump inhibition. The overall results demonstrate the role of phytochemicals in co-therapies to promote more efficient treatments and decrease antimicrobial resistance to antibiotics, with substantial effects against S. aureus in both planktonic and biofilm states. PMID:27643487

  9. [Prophylactic antibiotics in plastic surgery].

    PubMed

    Sabovcík, R; Kyslan, K

    2006-06-01

    There is no consensus on the use of prophylactic antibiotics in plastic surgery to prevent postoperative infection. This study was performed to investigate whether the use of prophylactic antibiotics has an effect on postoperative infection rate. A total of 500 patients were classified into 3 groups based on their diagnosis. Approximately half of the cases received amoxicilin/clavulanate combination the other half had no antibiotics. Wound infection was observed in the post operative period. According to our clinical findings, antibiotic prophylaxis is not necessary in plastic surgery in all patients. We did not find significant difference between the antibiotic prophylaxis and placebo group.

  10. Antibiotics and the developing infant gut microbiota and resistome.

    PubMed

    Gibson, Molly K; Crofts, Terence S; Dantas, Gautam

    2015-10-01

    The microbial communities colonizing the human gut are tremendously diverse and highly personal. The composition and function of the microbiota play important roles in human health and disease, and considerable research has focused on understanding the ecological forces shaping these communities. While it is clear that factors such as diet, genotype of the host, and environment influence the adult gut microbiota community composition, recent work has emphasized the importance of early-life assembly dynamics in both the immediate and long-term personalized nature of the gut microbiota. While the mature adult gut microbiota is believed to be relatively stable, the developing infant gut microbiota (IGM) is highly dynamic and prone to disruption by external factors, including antibiotic exposure. Studies have revealed both transient and persistent alterations to the adult gut microbiota community resulting from antibiotic treatment later in life. As antibiotics are routinely prescribed at a greater rate in the first years of life, the impact of these interventions on the developing IGM is emerging as a key research priority. In addition to understanding the impact of these disruptions on the infant gut microbial architecture and related host diseases, we need to understand the contribution of early life antibiotics to the selection of antibiotic resistance gene reservoirs in the microbiota, and their threat to successful treatment of infectious disease. Here we review the current understanding of the developmental progression of the IGM and the impact of antibiotic therapies on its composition and encoded reservoir of antibiotic resistance genes.

  11. Antibiotics and the developing infant gut microbiota and resistome

    PubMed Central

    Gibson, Molly K.; Crofts, Terence S.; Dantas, Gautam

    2015-01-01

    The microbial communities colonizing the human gut are tremendously diverse and highly personal. The composition and function of the microbiota play important roles in human health and disease, and considerable research has focused on understanding the ecological forces shaping these communities. While it is clear that factors such as diet, genotype of the host, and environment play important roles in adult gut community composition, recent work has emphasized the importance of early-life assembly dynamics in both the immediate and long-term personalized nature of the gut microbiota. While the mature adult gut microbiota is believed to be relatively stable, the developing infant gut microbiota is highly dynamic and prone to disruption by external factors, including antibiotic exposure. Studies have revealed both transient and persistent alterations to the adult gut microbiota community resulting from antibiotic treatment later in life. As antibiotics are routinely prescribed at a greater rate in the first years of life, the impact of these interventions on the developing infant gut microbiota is emerging as a key research priority. In addition to understanding the impact of these disruptions on the infant gut microbial architecture and related host diseases, we need to understand the contribution of early life antibiotics to the selection of antibiotic resistance gene reservoirs in the microbiota, and their threat to successful treatment of infectious disease. Here we review the current understanding of the developmental progression of the infant gut microbiota and the impact of antibiotic therapies on its encoded reservoir of antibiotic resistance genes. PMID:26241507

  12. Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry.

    PubMed

    Saint-Ruf, Claude; Crussard, Steve; Franceschi, Christine; Orenga, Sylvain; Ouattara, Jasmine; Ramjeet, Mahendrasingh; Surre, Jérémy; Matic, Ivan

    2016-01-01

    Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH), which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides, and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility.

  13. Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry

    PubMed Central

    Saint-Ruf, Claude; Crussard, Steve; Franceschi, Christine; Orenga, Sylvain; Ouattara, Jasmine; Ramjeet, Mahendrasingh; Surre, Jérémy; Matic, Ivan

    2016-01-01

    Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH), which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides, and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility. PMID:27507962

  14. Antibiotic use during the intracoelomic implantation of electronic tags into fish

    USGS Publications Warehouse

    Mulcahy, D.M.

    2011-01-01

    The use of antibiotics, in particular, the use of a single dose of antibiotics during electronic tag implantation is of unproven value, and carries with it the potential for the development of antibiotic resistance in bacteria and the alteration of the immune response of the fish. Antibiotic use during electronic tag implantation must conform to relevant drug laws and regulations in the country where work is being done, including the requirements for withdrawal times before human consumption is a possibility. Currently, the choice of antibiotics (most often tetracycline or oxytetracycline) and the use of a single dose of the drug are decisions made without knowledge of the basic need for antibiotic usage and of the bacteria involved in infections that occur following electronic tag implantation. Correct perioperative use of an antibiotic is to apply the drug to the animal before surgery begins, to assure serum and tissue levels of the drug are adequate before the incision is made. However, the most common perioperative application of antibiotics during implantation of an electronic tag is to delay the administration of the drug, injecting it into the coelom after the electronic tag is inserted, just prior to closure of the incision. There is little empirical evidence that the present application of antibiotics in fish being implanted with electronic tags is of value. Improvements should first be made to surgical techniques, especially the use of aseptic techniques and sterilized instruments and electronic tags, before resorting to antibiotics. ?? 2010 Springer Science+Business Media B.V.(outside the USA).

  15. Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry.

    PubMed

    Saint-Ruf, Claude; Crussard, Steve; Franceschi, Christine; Orenga, Sylvain; Ouattara, Jasmine; Ramjeet, Mahendrasingh; Surre, Jérémy; Matic, Ivan

    2016-01-01

    Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH), which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides, and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility. PMID:27507962

  16. Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance

    PubMed Central

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

    2014-01-01

    For many years, the battle between humans and the multitudes of infection and disease causing pathogens continues. Emerging at the battlefield as some of the most significant challenges to human health are bacterial resistance and its rapid rise. These have become a major concern in global public health invigorating the need for new antimicrobial compounds. A rational approach to deal with antibiotic resistance problems requires detailed knowledge of the different biological and non-biological factors that affect the rate and extent of resistance development. Combination therapy combining conventional antibiotics and essential oils is currently blooming and represents a potential area for future investigations. This new generation of phytopharmaceuticals may shed light on the development of new pharmacological regimes in combating antibiotic resistance. This review consolidated and described the observed synergistic outcome between essential oils and antibiotics, and highlighted the possibilities of essential oils as the potential resistance modifying agent. PMID:24627729

  17. How antibiotics kill bacteria: from targets to networks

    PubMed Central

    Kohanski, Michael A; Dwyer, Daniel J; Collins, James J

    2010-01-01

    Preface Antibiotic drug-target interactions, and their respective direct effects, are generally well-characterized. In contrast, the bacterial responses to antibiotic drug treatments that contribute to cell death are not as well understood and have proven to be quite complex, involving multiple genetic and biochemical pathways. Here, we review the multi-layered effects of drug-target interactions, including the essential cellular processes inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing by bactericidal antibiotics. We also discuss new insights into these mechanisms that have been revealed through the study of biological networks, and describe how these insights, together with related developments in synthetic biology, may be exploited to create novel antibacterial therapies. PMID:20440275

  18. Reviving old antibiotics.

    PubMed

    Theuretzbacher, Ursula; Van Bambeke, Françoise; Cantón, Rafael; Giske, Christian G; Mouton, Johan W; Nation, Roger L; Paul, Mical; Turnidge, John D; Kahlmeter, Gunnar

    2015-08-01

    In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to 're-develop' these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections.

  19. When antibiotics are unnecessary.

    PubMed

    Hirschmann, J V

    2009-01-01

    Dermatologists can decrease unnecessary use of antimicrobial agents by avoiding them in situations wherein good evidence indicates that they are ineffective. Controlled trials indicate that antimicrobial agents are unhelpful in treating cutaneous abscesses, inflamed epidermal cysts, uninfected atopic eczema, and cutaneous ulcers caused by venous insufficiency or diabetes in the absence of significant contiguous soft-tissue inflammation. Prophylactic antibiotics are rarely appropriate for routine dermatologic surgery and are not indicated for patients who have prosthetic joints or vascular grafts. They are recommended only for a small group of patients who have abnormal cardiac valves, and then only with surgery involving clearly infected skin or soft-tissue. Topical antibiotics are no better than white petrolatum in covering sutured wounds, and with moist occlusive dressings, no ointment is necessary. PMID:18984370

  20. The Comprehensive Antibiotic Resistance Database

    PubMed Central

    McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

    2013-01-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  1. Choices for achieving adequate dietary calcium with a vegetarian diet.

    PubMed

    Weaver, C M; Proulx, W R; Heaney, R

    1999-09-01

    To achieve adequate dietary calcium intake, several choices are available that accommodate a variety of lifestyles and tastes. Liberal consumption of dairy products in the diet is the approach of most Americans. Some plants provide absorbable calcium, but the quantity of vegetables required to reach sufficient calcium intake make an exclusively plant-based diet impractical for most individuals unless fortified foods or supplements are included. Also, dietary constituents that decrease calcium retention, such as salt, protein, and caffeine, can be high in the vegetarian diet. Although it is possible to obtain calcium balance from a plant-based diet in a Western lifestyle, it may be more convenient to achieve calcium balance by increasing calcium consumption than by limiting other dietary factors.

  2. Genetic Modification of Preimplantation Embryos: Toward Adequate Human Research Policies

    PubMed Central

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects. PMID:15016248

  3. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  4. Surveillance of antibiotic resistance

    PubMed Central

    Johnson, Alan P.

    2015-01-01

    Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

  5. ASSOCIATION BETWEEN THE INTRODUCTION OF A NEW CYSTIC FIBROSIS INHALED ANTIBIOTIC CLASS AND CHANGE IN PREVALENCE OF PATIENTS RECEIVING MULTIPLE INHALED ANTIBIOTIC CLASSES

    PubMed Central

    Dasenbrook, Elliott C.; Konstan, Michael W.; VanDevanter, Donald R.

    2014-01-01

    Background In 2010, aztreonam for inhalation solution joined aminoglycosides and colistimethate as a new cystic fibrosis (CF) chronic inhaled antimicrobial therapy. We studied how introduction of this new inhaled antibiotic class changed management of US CF patients. Methods Use of inhaled aminoglycosides, colistimethate, and aztreonam among patients followed in the CF Foundation Patient Registry was analyzed by age group, lung disease stage, and microbiologic status both annually, and at individual visits between 2009 and 2012. Results The overall prevalence of inhaled antibiotic use did not change during the period, but the prevalence of annual and any visit treatment with >1 inhaled antibiotic class more than doubled. Adults, those with advanced lung disease, and those with >1 Pseudomonas aeruginosa respiratory culture were more likely to receive >1 antibiotic class. Conclusions Inhaled antibiotic management of US CF patients has dramatically changed in association with the introduction of a third inhaled antibiotic class. PMID:25496726

  6. Comparative evaluation of prophylactic single-dose intravenous antibiotic with postoperative antibiotics in elective urologic surgery

    PubMed Central

    Moslemi, Mohammad K; Movahed, Seyed M Moosavi; Heidari, Akram; Saghafi, Hossein; Abedinzadeh, Mehdi

    2010-01-01

    administered antibiotics decreased to approximately one quarter. Conclusion Our protocol effectively decreased the amount of antibiotics used without increasing perioperative infection rates. Thus, our protocol of prophylactic antibiotic therapy can be recommended as an appropriate method for preventing perioperative infection in urologic surgery. PMID:21151625

  7. Topical application of antibiotics in primary teeth: an overview.

    PubMed

    Kayalvizhi, Gurusamy; Subramaniyan, Balaji; Suganya, Gurusamy

    2013-01-01

    Root canal infections are polymicrobial in nature, consisting of both aerobic and anaerobic species. The successful treatment of both primary and secondary endodontic infections involves effective eradication of the causative microorganisms during root canal treatment procedures. Reduction and elimination of microorganisms from the infected root canal provides optimal opportunity for treatment success. Local application of antibiotics has been considered an effective way to deliver antibiotics. A combination of antibiotic drugs have been tried under the concept of lesion sterilization and tissue repair therapy to eliminate the target bacteria, which are possible sources of endodontic lesions. The purpose of this article is to discuss the lesion sterilization and tissue repair therapy technique in primary teeth.

  8. Strategies for appropriate antibiotic use in intensive care unit

    PubMed Central

    da Silva, Camila Delfino Ribeiro; Silva, Moacyr

    2015-01-01

    The comsumption of antibiotics is high, mainly in intensive care units. Unfortunately, most are inappropriately used leading to increased multi-resistant bacteria. It is well known that initial empirical therapy with broad-spectrum antibiotics reduce mortality rates. However the prolonged and irrational use of antimicrobials may also increase the risk of toxicity, drug interactions and diarrhea due to Clostridium difficile. Some strategies to rational use of antimicrobial agents include avoiding colonization treatment, de-escalation, monitoring serum levels of the agents, appropriate duration of therapy and use of biological markers. This review discusses the effectiveness of these strategies, the importance of microbiology knowledge, considering there are agents resistant to Staphylococcus aureus and Klebsiella pneumoniae, and reducing antibiotic use and bacterial resistance, with no impact on mortality. PMID:26132360

  9. Antibiotic resistance: an ecological imbalance.

    PubMed

    Levy, S B

    1997-01-01

    Antibiotic resistance thwarts the treatment of infectious diseases worldwide. Although a number of factors can be identified which contribute to the problem, clearly the antibiotic as a selective agent and the resistance gene as the vehicle of resistance are the two most important, making up a 'drug resistance equation'. Both are needed in order for a clinical problem to arise. Given sufficient time and quantity of antibiotic, drug resistance will eventually appear. But a public health problem is not inevitable if the two components of the drug resistance equation are kept in check. Enhancing the emergence of resistance is the case by which resistance determinants and resistant bacteria can spread locally and globally, selected by widespread use of the same antibiotics in people, animal husbandry and agriculture. Antibiotics are societal drugs. Each individual use contributes to the sum total of society's antibiotic exposure. In a broader sense, the resistance problem is ecological. In the framework of natural competition between susceptible and resistant bacteria, antibiotic use has encouraged growth of the resistant strains, leading to an imbalance in prior relationships between susceptible and resistant bacteria. To restore efficacy to earlier antibiotics and to maintain the success of new antibiotics that are introduced, we need to use antibiotics in a way which assures an ecological balance that favours the predominance of susceptible bacterial flora.

  10. Community Intervention Model to Reduce Inappropriate Antibiotic Use

    ERIC Educational Resources Information Center

    Alder, Stephen; Wuthrich, Amy; Haddadin, Bassam; Donnelly, Sharon; Hannah, Elizabeth Lyon; Stoddard, Greg; Benuzillo, Jose; Bateman, Kim; Samore, Matthew

    2010-01-01

    Background: The Inter-Mountain Project on Antibiotic Resistance and Therapy (IMPART) is an intervention that addresses emerging antimicrobial resistance and the reduction of unnecessary antimicrobial use. Purpose: This study assesses the design and implementation of the community intervention component of IMPART. Methods: The study was conducted…

  11. Antibiotics as part of the management of severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. In this randomized, double-blind, plac...

  12. Optimizing Antibiotic Use in Nursing Homes Through Antibiotic Stewardship.

    PubMed

    Sloane, Philip D; Huslage, Kirk; Kistler, Christine E; Zimmerman, Sheryl

    2016-01-01

    Antibiotic stewardship is becoming a requirement for nursing homes. Programs should be interdisciplinary and multifaceted; should have support from nursing home administrators; and should aim to promote antibiotics only when needed, not just in case. Recommended components include use of evidence-based guidelines; ongoing monitoring of antibiotic prescriptions, cultures, and study results; monitoring of health outcomes; use of nursing home-specific antibiograms; regular reporting and feedback to medical providers and nurses; and education of residents and families. PMID:27621341

  13. Rationalizing antibiotic use to limit antibiotic resistance in India+

    PubMed Central

    2011-01-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  14. Current status in outpatient parenteral antimicrobial therapy: a practical view.

    PubMed

    Candel, Francisco Javier; Julián-Jiménez, Agustin; González-Del Castillo, Juan

    2016-04-01

    Outpatient parenteral antimicrobial therapy (OPAT) programs are a current and widely spread trend in clinical practice because of it's a cost-effective option, it's associated with a greater comfort for the patient, a lower risk of nosocomial complications and an important cost saving for the health care system. OPAT is used for treating a wide range of infections, including skin and soft tissue infections, osteoarticular infections, bacteraemia, endocarditis and complex intra-abdominal and urinary tract infections, even in presence of multiresistant microorganisms. Correct choice of antimicrobial agent and adequate patient selection are crucial for reaching therapeutic success and avoiding readmissions, treatment prolongation or treatment-related toxicity. The optimal antimicrobial for OPAT must be highly effective, have a long half-life and an adequate spectrum of action. Ceftriaxone and teicoplanin are currently the most prescribed antibiotics for OPAT, though daptomycin and ertapenem are also on the rise, due to their high efficiency, safety and wide spectrum of action. Antibiotics that are stable at room temperature can be administered through a continuous perfusion, though self-administration is preferable although it requires training of the patient or the caregiver. Factors that are most frequently associated with OPAT failure include advanced age, recent hospitalization and isolation of multiresistant microorganisms. PMID:27014770

  15. Bacteriophage biosensors for antibiotic-resistant bacteria.

    PubMed

    Sorokulova, Irina; Olsen, Eric; Vodyanoy, Vitaly

    2014-03-01

    An increasing number of disease-causing bacteria are resistant to one or more anti-bacterial drugs utilized for therapy. Early and speedy detection of these pathogens is therefore very important. Traditional pathogen detection techniques, that include microbiological and biochemical assays are long and labor-intensive, while antibody or DNA-based methods require substantial sample preparation and purification. Biosensors based on bacteriophages have demonstrated remarkable potential to surmount these restrictions and to offer rapid, efficient and sensitive detection technique for antibiotic-resistant bacteria.

  16. Effects of antibiotics on acquired immunity in vivo--current state of knowledge.

    PubMed

    Pomorska-Mól, M; Pejsak, Z

    2012-01-01

    Antibiotics are widely used in the therapy of infections. Besides the respective interactions between antibiotics and pathogens it seems that antibiotics also directly interact with the immune system. Some commonly used antibiotics are currently known to have effects on the innate immune response, as shown by in vitro, ex vivo and also in vivo animal experiments and clinical studies. Most of the experimental papers published to date, as well as most reviews, relate to how antibiotics affect the innate immune response or non-specific monocyte or lymphocyte proliferation. However the effects of antibiotics on the adaptive immune response are still not well characterized. This review of the literature considering different in vivo experiments indicate the real importance of interrelations existing between acquired immune responses and antibiotics, however, the mechanism of immunomodulatory effects of antibiotics are still poorly understood. Currently, data on the immunomodulating effects of antibiotics often remain heterogeneous, contradictory or insufficient, but most results published to date revealed the immunosuppressive effect of antibiotics on the antigen-specific immune response in vivo. In pigs as well as in poultry herds, it is not uncommon practice to add antibiotics to drinking water or feed at the time of vaccination. Information on the effects of such practices on the immune system of animals is restricted and more in vivo studies are needed to investigate the effects of antimicrobial drugs on the immune system, especially in the field conditions.

  17. [Analysis of the antibiotics resistance in the patients treated in the Ternopyl university hospital].

    PubMed

    Olĭnyk, O V; Krasiĭ, N I

    2013-10-01

    The results of monitoring of the microorganisms resistance to antibiotics in departments of anesthesiology and abdominal surgery of the Ternopyl University Hospital are adduced. The data obtained permit to estimate possibilities for application of antimicrobic preparations in empiric therapy. Taking into account a large quantity of multiresistant isolates in a certain stationary, administration of empiric therapy in the treatment of intrahospital infection must be conducted, basing on the local data, concerning the microflora sensitivity to antibiotics.

  18. Dose Limits for Man do not Adequately Protect the Ecosystem

    SciTech Connect

    Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

    2004-08-01

    It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words, if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.

  19. DARHT - an `adequate` EIS: A NEPA case study

    SciTech Connect

    Webb, M.D.

    1997-08-01

    The Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility Environmental Impact Statement (EIS) provides a case study that is interesting for many reasons. The EIS was prepared quickly, in the face of a lawsuit, for a project with unforeseen environmental impacts, for a facility that was deemed urgently essential to national security. Following judicial review the EIS was deemed to be {open_quotes}adequate.{close_quotes} DARHT is a facility now being built at Los Alamos National Laboratory (LANL) as part of the Department of Energy (DOE) nuclear weapons stockpile stewardship program. DARHT will be used to evaluate the safety and reliability of nuclear weapons, evaluate conventional munitions and study high-velocity impact phenomena. DARHT will be equipped with two accelerator-driven, high-intensity X-ray machines to record images of materials driven by high explosives. DARHT will be used for a variety of hydrodynamic tests, and DOE plans to conduct some dynamic experiments using plutonium at DARHT as well.

  20. ENSURING ADEQUATE SAFETY WHEN USING HYDROGEN AS A FUEL

    SciTech Connect

    Coutts, D

    2007-01-22

    Demonstration projects using hydrogen as a fuel are becoming very common. Often these projects rely on project-specific risk evaluations to support project safety decisions. This is necessary because regulations, codes, and standards (hereafter referred to as standards) are just being developed. This paper will review some of the approaches being used in these evolving standards, and techniques which demonstration projects can implement to bridge the gap between current requirements and stakeholder desires. Many of the evolving standards for hydrogen-fuel use performance-based language, which establishes minimum performance and safety objectives, as compared with prescriptive-based language that prescribes specific design solutions. This is being done for several reasons including: (1) concern that establishing specific design solutions too early will stifle invention, (2) sparse performance data necessary to support selection of design approaches, and (3) a risk-adverse public which is unwilling to accept losses that were incurred in developing previous prescriptive design standards. The evolving standards often contain words such as: ''The manufacturer shall implement the measures and provide the information necessary to minimize the risk of endangering a person's safety or health''. This typically implies that the manufacturer or project manager must produce and document an acceptable level of risk. If accomplished using comprehensive and systematic process the demonstration project risk assessment can ease the transition to widespread commercialization. An approach to adequately evaluate and document the safety risk will be presented.

  1. Quantifying variability within water samples: the need for adequate subsampling.

    PubMed

    Donohue, Ian; Irvine, Kenneth

    2008-01-01

    Accurate and precise determination of the concentration of nutrients and other substances in waterbodies is an essential requirement for supporting effective management and legislation. Owing primarily to logistic and financial constraints, however, national and regional agencies responsible for monitoring surface waters tend to quantify chemical indicators of water quality using a single sample from each waterbody, thus largely ignoring spatial variability. We show here that total sample variability, which comprises both analytical variability and within-sample heterogeneity, of a number of important chemical indicators of water quality (chlorophyll a, total phosphorus, total nitrogen, soluble molybdate-reactive phosphorus and dissolved inorganic nitrogen) varies significantly both over time and among determinands, and can be extremely high. Within-sample heterogeneity, whose mean contribution to total sample variability ranged between 62% and 100%, was significantly higher in samples taken from rivers compared with those from lakes, and was shown to be reduced by filtration. Our results show clearly that neither a single sample, nor even two sub-samples from that sample is adequate for the reliable, and statistically robust, detection of changes in the quality of surface waters. We recommend strongly that, in situations where it is practicable to take only a single sample from a waterbody, a minimum of three sub-samples are analysed from that sample for robust quantification of both the concentrations of determinands and total sample variability. PMID:17706740

  2. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic

    PubMed Central

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents — linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2

  3. Role of antibiotics for treatment of inflammatory bowel disease

    PubMed Central

    Nitzan, Orna; Elias, Mazen; Peretz, Avi; Saliba, Walid

    2016-01-01

    Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn’s disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms

  4. Antibiotics from predatory bacteria

    PubMed Central

    Korp, Juliane; Vela Gurovic, María S

    2016-01-01

    Summary Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism. PMID:27340451

  5. Antibiotics from predatory bacteria.

    PubMed

    Korp, Juliane; Vela Gurovic, María S; Nett, Markus

    2016-01-01

    Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism. PMID:27340451

  6. Treating appendicitis with antibiotics.

    PubMed

    Brook, Itzhak

    2016-03-01

    A nonsurgical approach using antimicrobial agents has been advocated as the initial treatment of uncomplicated appendicitis. Several studies and meta-analyses explored this approach. Because many of these studies included individuals with resolving appendicitis, their results were biased. Antimicrobials, however, are warranted and needed for the management of surgical high-risk patients with perforated appendicitis and those with localized abscess or phlegmon. Randomized placebo-controlled trials that focus on early identification of complicated acute appendicitis patients needing surgery and that prospectively evaluate the optimal use of antibiotic treatment in patients with uncomplicated acute appendicitis are warranted.

  7. Ecology and evolution of antibiotic resistance.

    PubMed

    Baquero, F; Alvarez-Ortega, C; Martinez, J L

    2009-12-01

    The evolution of bacterial pathogens towards antibiotic resistance is not just a relevant problem for human health, but a fascinating example of evolution that can be studied in real time as well. Although most antibiotics are natural compounds produced by environmental microbiota, exposure of bacterial populations to high concentrations of these compounds as the consequence of their introduction for human therapy (and later on for farming) a few decades ago is a very recent situation in evolutionary terms. Resistance genes are originated in environmental bacteria, where they have evolved for millions of years to play different functions that include detoxification, signal trafficking or metabolic functions among others. However, as the consequence of the strong selective pressure exerted by antimicrobials at clinical settings, farms and antibiotic-contaminated natural ecosystems, the selective forces driving the evolution of these potential resistance determinants have changed in the last few decades. Natural ecosystems contain a large number of potential resistance genes; nevertheless, just a few of them are currently present in gene-transfer units and disseminated among pathogens. Along the review, the processes implied in this situation and the consequences for the future evolution of resistance and the environmental microbiota are discussed.

  8. Colistin: Revival of an Old Polymyxin Antibiotic.

    PubMed

    Dijkmans, Anneke C; Wilms, Erik B; Kamerling, Ingrid M C; Birkhoff, Willem; Ortiz-Zacarías, Natalia V; van Nieuwkoop, Cees; Verbrugh, Henri A; Touw, Daan J

    2015-08-01

    Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined.

  9. New Is Old, and Old Is New: Recent Advances in Antibiotic-Based, Antibiotic-Free and Ethnomedical Treatments against Methicillin-Resistant Staphylococcus aureus Wound Infections

    PubMed Central

    Dou, Jian-Lin; Jiang, Yi-Wei; Xie, Jun-Qiu; Zhang, Xiao-Gang

    2016-01-01

    Staphylococcus aureus is the most common pathogen of wound infections. Thus far, methicillin-resistant S. aureus (MRSA) has become the major causative agent in wound infections, especially for nosocomial infections. MRSA infections are seldom eradicated by routine antimicrobial therapies. More concerning, some strains have become resistant to the newest antibiotics of last resort. Furthermore, horizontal transfer of a polymyxin resistance gene, mcr-1, has been identified in Enterobacteriaceae, by which resistance to the last group of antibiotics will likely spread rapidly. The worst-case scenario, “a return to the pre-antibiotic era”, is likely in sight. A perpetual goal for antibiotic research is the discovery of an antibiotic that lacks resistance potential, such as the recent discovery of teixobactin. However, when considering the issue from an ecological and evolutionary standpoint, it is evident that it is insufficient to solve the antibiotic dilemma through the use of antibiotics themselves. In this review, we summarized recent advances in antibiotic-based, antibiotic-free and ethnomedical treatments against MRSA wound infections to identify new clues to solve the antibiotic dilemma. One potential solution is to use ethnomedical drugs topically. Some ethnomedical drugs have been demonstrated to be effective antimicrobials against MRSA. A decline in antibiotic resistance can therefore be expected, as has been demonstrated when antibiotic-free treatments were used to limit the use of antibiotics. It is also anticipated that these drugs will have low resistance potential, although there is only minimal evidence to support this claim to date. More clinical trials and animal tests should be conducted on this topic. PMID:27120596

  10. New Is Old, and Old Is New: Recent Advances in Antibiotic-Based, Antibiotic-Free and Ethnomedical Treatments against Methicillin-Resistant Staphylococcus aureus Wound Infections.

    PubMed

    Dou, Jian-Lin; Jiang, Yi-Wei; Xie, Jun-Qiu; Zhang, Xiao-Gang

    2016-01-01

    Staphylococcus aureus is the most common pathogen of wound infections. Thus far, methicillin-resistant S. aureus (MRSA) has become the major causative agent in wound infections, especially for nosocomial infections. MRSA infections are seldom eradicated by routine antimicrobial therapies. More concerning, some strains have become resistant to the newest antibiotics of last resort. Furthermore, horizontal transfer of a polymyxin resistance gene, mcr-1, has been identified in Enterobacteriaceae, by which resistance to the last group of antibiotics will likely spread rapidly. The worst-case scenario, "a return to the pre-antibiotic era", is likely in sight. A perpetual goal for antibiotic research is the discovery of an antibiotic that lacks resistance potential, such as the recent discovery of teixobactin. However, when considering the issue from an ecological and evolutionary standpoint, it is evident that it is insufficient to solve the antibiotic dilemma through the use of antibiotics themselves. In this review, we summarized recent advances in antibiotic-based, antibiotic-free and ethnomedical treatments against MRSA wound infections to identify new clues to solve the antibiotic dilemma. One potential solution is to use ethnomedical drugs topically. Some ethnomedical drugs have been demonstrated to be effective antimicrobials against MRSA. A decline in antibiotic resistance can therefore be expected, as has been demonstrated when antibiotic-free treatments were used to limit the use of antibiotics. It is also anticipated that these drugs will have low resistance potential, although there is only minimal evidence to support this claim to date. More clinical trials and animal tests should be conducted on this topic.

  11. A new antitumor antibiotic, kazusamycin.

    PubMed

    Umezawa, I; Komiyama, K; Oka, H; Okada, K; Tomisaka, S; Miyano, T; Takano, S

    1984-07-01

    A new antibiotic kazusamycin, was isolated from the culture broth of Streptomyces sp. No. 81-484, which shows antitumor activity against experimental murine tumors. This antibiotic did not possess antibacterial activity against Gram-positive and Gram-negative bacteria, but showed strong cytotoxic activity against HeLa cells in vitro. The chemical and physico-chemical properties of kazusamycin suggest that the molecular formula of this antibiotic is C33H48O7 (MW 556). PMID:6432763

  12. Prothracarcin, a novel antitumor antibiotic.

    PubMed

    Shimizu, K; Kawamoto, I; Tomita, F; Morimoto, M; Fujimoto, K

    1982-08-01

    A novel antibiotic, prothracarcin was isolated from the culture broth of Streptomyces umbrosus subsp. raffinophilus DO-62. The antibiotic has the molecular formula of C14H14N2O and belongs to the pyrrolo [1,4]benzodiazepine antibiotics. Its structure has been elucidated by mass and NMR spectra. It is active against Gram-positive and Gram-negative bacteria and experimental murine tumor sarcoma 180 and leukemia P388. PMID:7142014

  13. Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs.

    PubMed

    Hostutler, Roger A; Luria, Brian J; Johnson, Susan E; Weisbrode, Steven E; Sherding, Robert G; Jaeger, Jordan Q; Guilford, W Grant

    2004-01-01

    Canine histiocytic ulcerative colitis (HUC) is characterized by colonic inflammation with predominantly periodic acid-Schiff (PAS)-positive macrophages. The inflammation results in colonic thickening, ulcerations, and distortion of normal glandular architecture. Resultant clinical signs consist of chronic large bowel diarrhea, tenesmus, and marked weight loss, and the disease frequently results in euthanasia. Conventional therapy consists of some combination of prednisone, azathioprine, sulfasalazine, and metronidazole. Nine dogs (8 Boxers and 1 English Bulldog) with histologic confirmation of HUC were treated with antibiotic therapy (either with enrofloxacin alone or in combination with metronidazole and amoxicillin). Clinical signs, physical examination findings, laboratory abnormalities, and the histologic severity of the disease were evaluated. Four of the 9 dogs had been treated previously with conventional therapy and had failed to respond favorably; then, these dogs were placed on antibiotic therapy (enrofloxacin, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3) and had resolution of clinical signs within 3-12 days. Five dogs were treated solely with antibiotic therapy (enrofloxacin, n = 1; enrofloxacin and metronidazole, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3), and clinical signs resolved in 2-7 days. Repeated biopsy specimens were obtained from 5 dogs after treatment, and all showed marked histologic improvement. The increase in body weight after treatment was statistically significant (P = .01). Three dogs currently are not on any treatment and have had resolution of clinical signs for up to 14 months. These observations suggest that an infectious agent responsive to antibiotics plays an integral role in the clinical manifestation of canine HUC, and they support the use of antibiotics in its treatment.

  14. The role of prophylactic antibiotics in preventing perioperative infection.

    PubMed

    Setiawan, Budi

    2011-10-01

    With the increasing number of surgery or operation, perioperative infection has become one of problems that have been found more often. Surgical site infection is the most common perioperative infection causing increased hospitalization stay, high cost, morbidity and mortality rate. Infection occurs within 30 days after the operation on surgical site or within one year if implant is in place. Such infection may be prevented through several ways including some aspects of health-care provider, operating-room environment, and adequate preoperative preparation of the patients. Antibiotic prophylaxis is one of important modalities in preventing surgical site infection. Antibiotic prophylaxis administration significantly reduces the incidence of surgical site infection up to four-fold of decrease. Short-term antibiotic is given prior to incision in order to reduce the contamination of bacterial inoculums during surgery. The decision to administer antibiotic prophylaxis should be made by considering their risk and benefits. One of them includes utilization of the NNIS (National Nosocomial Infections Surveillance) score system, which considers three factors, such as wound class, ASA physical status scale, and duration of operation according to the NNIS Survey. The selection on timing and appropriately administered antibiotic prophylaxis is critical to maximize the benefits.

  15. The role of prophylactic antibiotics in preventing perioperative infection.

    PubMed

    Setiawan, Budi

    2011-10-01

    With the increasing number of surgery or operation, perioperative infection has become one of problems that have been found more often. Surgical site infection is the most common perioperative infection causing increased hospitalization stay, high cost, morbidity and mortality rate. Infection occurs within 30 days after the operation on surgical site or within one year if implant is in place. Such infection may be prevented through several ways including some aspects of health-care provider, operating-room environment, and adequate preoperative preparation of the patients. Antibiotic prophylaxis is one of important modalities in preventing surgical site infection. Antibiotic prophylaxis administration significantly reduces the incidence of surgical site infection up to four-fold of decrease. Short-term antibiotic is given prior to incision in order to reduce the contamination of bacterial inoculums during surgery. The decision to administer antibiotic prophylaxis should be made by considering their risk and benefits. One of them includes utilization of the NNIS (National Nosocomial Infections Surveillance) score system, which considers three factors, such as wound class, ASA physical status scale, and duration of operation according to the NNIS Survey. The selection on timing and appropriately administered antibiotic prophylaxis is critical to maximize the benefits. PMID:22156360

  16. Reservoirs of antibiotic resistance genes.

    PubMed

    Salyers, Abigail; Shoemaker, Nadja B

    2006-01-01

    A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating the risk of agricultural use of antibiotics are assessed critically. In addition, the potential benefits of applying new technology and using new insights from the field of microbial ecology are explained.

  17. Ionomycin, a new polyether antibiotic.

    PubMed

    Liu, W C; Slusarchyk, D S; Astle, G; Trejo, W H; Brown, W E; Meyers, E

    1978-09-01

    Ionomycin, a new polyether antibiotic with a high affinity for calcium ions, is obtained in pure form from fermentation broths of Streptomyces conglobatus sp. nov. Trejo by solvent extraction. It is unique amongst known polyether antibiotics in that it has a UV absorption maximum at 300 nm. thereby distinguishing it from other antibiotics of its class. The Ca salt has the molecular formula C41H70O9Ca. Ionomycin is a narrow spectrum antibiotic being active against Gram-positive bacteria. PMID:711623

  18. On Adequate Comparisons of Antenna Phase Center Variations

    NASA Astrophysics Data System (ADS)

    Schoen, S.; Kersten, T.

    2013-12-01

    One important part for ensuring the high quality of the International GNSS Service's (IGS) products is the collection and publication of receiver - and satellite antenna phase center variations (PCV). The PCV are crucial for global and regional networks, since they introduce a global scale factor of up to 16ppb or changes in the height component with an amount of up to 10cm, respectively. Furthermore, antenna phase center variations are also important for precise orbit determination, navigation and positioning of mobile platforms, like e.g. the GOCE and GRACE gravity missions, or for the accurate Precise Point Positioning (PPP) processing. Using the EUREF Permanent Network (EPN), Baire et al. (2012) showed that individual PCV values have a significant impact on the geodetic positioning. The statements are further supported by studies of Steigenberger et al. (2013) where the impact of PCV for local-ties are analysed. Currently, there are five calibration institutions including the Institut für Erdmessung (IfE) contributing to the IGS PCV file. Different approaches like field calibrations and anechoic chamber measurements are in use. Additionally, the computation and parameterization of the PCV are completely different within the methods. Therefore, every new approach has to pass a benchmark test in order to ensure that variations of PCV values of an identical antenna obtained from different methods are as consistent as possible. Since the number of approaches to obtain these PCV values rises with the number of calibration institutions, there is the necessity for an adequate comparison concept, taking into account not only the numerical values but also stochastic information and computational issues of the determined PCVs. This is of special importance, since the majority of calibrated receiver antennas published by the IGS origin from absolute field calibrations based on the Hannover Concept, Wübbena et al. (2000). In this contribution, a concept for the adequate

  19. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment.

  20. Are women with psychosis receiving adequate cervical cancer screening?

    PubMed Central

    Tilbrook, Devon; Polsky, Jane; Lofters, Aisha

    2010-01-01

    ABSTRACT OBJECTIVE To investigate the rates of cervical cancer screening among female patients with psychosis compared with similar patients without psychosis, as an indicator of the quality of primary preventive health care. DESIGN A retrospective cohort study using medical records between November 1, 2004, and November 1, 2007. SETTING Two urban family medicine clinics associated with an academic hospital in Toronto, Ont. PARTICIPANTS A random sample of female patients with and without psychosis between the ages of 20 and 69 years. MAIN OUTCOME MEASURES Number of Papanicolaou tests in a 3-year period. RESULTS Charts for 51 female patients with psychosis and 118 female patients without psychosis were reviewed. Of those women with psychosis, 62.7% were diagnosed with schizophrenia, 19.6% with bipolar disorder, 17.6% with schizoaffective disorder, and 29.4% with other psychotic disorders. Women in both groups were similar in age, rate of comorbidities, and number of full physical examinations. Women with psychosis were significantly more likely to smoke (P < .0001), to have more primary care appointments (P = .035), and to miss appointments (P = .0002) than women without psychosis. After adjustment for age, other psychiatric illnesses, number of physical examinations, number of missed appointments, and having a gynecologist, women with psychosis were significantly less likely to have had a Pap test in the previous 3 years compared with women without psychosis (47.1% vs 73.7%, respectively; odds ratio 0.19, 95% confidence interval 0.06 to 0.58). CONCLUSION Women with psychosis are more than 5 times less likely to receive adequate Pap screening compared with the general population despite their increased rates of smoking and increased number of primary care visits. PMID:20393098

  1. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment. PMID:26068436

  2. Infectious Spondylodiscitis by Uncommon Pathogens: A Pitfall of Empirical Antibiotics

    PubMed Central

    Yu, Seung Han; Kim, Dong Hwan; Kim, Hwan Soo; Nam, Kyoung Hyup; Choi, Byung Kwan

    2016-01-01

    Objective The goal of this study is to evaluate the prevalence of spondylodiscitis (SD) caused by uncommon pathogens and review the efficacy of the treatment strategy including the coverage by usual empirical broad-spectrum antibiotic therapy. Methods Ninety-nine consecutive patients diagnosed and treated for infectious SD between January 2007 to May 2015 were reviewed retrospectively. The prevalence of uncommon SD, predisposing factors, antibiotics sensitivity, and clinical outcome were analyzed in comparison with that of common SD. Results Among 99 patients, 68 patients were culture positive. Out of 68 patients with positive culture results, 54 of them(79.4%) were common pathogen and 14 (20.6%) were uncommon pathogen. Postoperative SDs were significantly prevalent in uncommon SD(42.9%) than common SD(27.8%). Recurrence rate was higher in uncommon pathogen SD(14.3%) than common SD group (2.3%), and it showed statistically significant difference (p=0.025). Empirical antibiotics of vancomycin and 3rd or 4th generation cephalosporin covered 100% of nontuberculous common SD and 14.3% of uncommon SD. Conclusion In our study, the prevalence of uncommon SD was relatively high uncommon (20.5% of culture positive SD and 14.1% of total cases) and the coverage rate of empirical antibiotics for them were only 14.3%. In particular, the possibility of SD with fun gal, polymicrobial, or multiple drug resistant organism should be considered in SD unresponsive to broad spectrum antibiotics therapy. PMID:27799986

  3. Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry improves appropriateness of antibiotic treatment of bacteremia.

    PubMed

    Vlek, Anne L M; Bonten, Marc J M; Boel, C H Edwin

    2012-01-01

    Matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows the identification of microorganisms directly from positive blood culture broths. Use of the MALDI-TOF MS for rapid identification of microorganisms from blood culture broths can reduce the turnaround time to identification and may lead to earlier appropriate treatment of bacteremia. During February and April 2010, direct MALDI-TOF MS was routinely performed on all positive blood cultures. During December 2009 and March 2010 no direct MALDI-TOF MS was used. Information on antibiotic therapy was collected from the hospital and intensive care units' information systems from all positive blood cultures during the study period. In total, 253 episodes of bacteremia were included of which 89 during the intervention period and 164 during the control period. Direct performance of MALDI-TOF MS on positive blood culture broths reduced the time till species identification by 28.8-h and was associated with an 11.3% increase in the proportion of patients receiving appropriate antibiotic treatment 24 hours after blood culture positivity (64.0% in the control period versus 75.3% in the intervention period (p0.01)). Routine implementation of this technique increased the proportion of patients on adequate antimicrobial treatment within 24 hours.

  4. Enhancing the utility of existing antibiotics by targeting bacterial behaviour?

    PubMed Central

    Rogers, Geraint B; Carroll, Mary P; Bruce, Kenneth D

    2012-01-01

    The discovery of novel classes of antibiotics has slowed dramatically. This has occurred during a time when the appearance of resistant strains of bacteria has shown a substantial increase. Concern is therefore mounting over our ability to continue to treat infections in an effective manner using the antibiotics that are currently available. While ongoing efforts to discover new antibiotics are important, these must be coupled with strategies that aim to maintain as far as possible the spectrum of activity of existing antibiotics. In many instances, the resistance to antibiotics exhibited by bacteria in chronic infections is mediated not by direct resistance mechanisms, but by the adoption of modes of growth that confer reduced susceptibility. These include the formation of biofilms and the occurrence of subpopulations of ‘persister’ cells. As our understanding of these processes has increased, a number of new potential drug targets have been revealed. Here, advances in our ability to disrupt these systems that confer reduced susceptibility, and in turn increase the efficacy of antibiotic therapy, are discussed. PMID:21864314

  5. The effect of past antibiotic exposure on diabetes risk

    PubMed Central

    Boursi, Ben; Mamtani, Ronac; Haynes, Kevin; Yang, Yu-Xiao

    2015-01-01

    Objective Gut microbiota influence metabolic pathways relevant to the pathogenesis of obesity, insulin-resistance and diabetes. Antibiotic therapy can alter the microbiota and is commonly used in western countries. We sought to evaluate whether past antibiotic exposure increases diabetes risk. Research design and methods We conducted a nested case-control study using a large population-based database from the United Kingdom (UK). Cases were defined as those with incident diagnosis of diabetes. For every case, 4 eligible controls matched on age, sex, practice-site, and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The risk was adjusted for body mass index (BMI), smoking, last glucose level and number of infections before index-date, as well as past medical history of coronary artery disease and hyperlipidemia. Results The study included 208,002 diabetic cases and 815,576 matched controls. Exposure to a single antibiotic prescription was not associated with higher adjusted diabetes risk. Treatment with 2–5 antibiotic courses was associated with increase in diabetic risk for penicillin, cephalosporins, macrolides and quinolones with adjusted OR ranging from 1.08 (95%CI 1.05–1.11) for penicillin to 1.15 (95%CI 1.08–1.23) for quinolones. The risk increased with the number of antibiotic courses and reached 1.37 (95%CI 1.19–1.58) for >5 courses of quinolones. There was no association between exposure to anti-virals and anti-fungals and diabetes risk. Conclusions Exposure to certain antibiotic groups increases diabetes risk. PMID:25805893

  6. Antibiotics and antibiotic resistance: a bitter fight against evolution.

    PubMed

    Rodríguez-Rojas, Alexandro; Rodríguez-Beltrán, Jerónimo; Couce, Alejandro; Blázquez, Jesús

    2013-08-01

    One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance.

  7. A window of opportunity to control the bacterial pathogen Pseudomonas aeruginosa combining antibiotics and phages.

    PubMed

    Torres-Barceló, Clara; Arias-Sánchez, Flor I; Vasse, Marie; Ramsayer, Johan; Kaltz, Oliver; Hochberg, Michael E

    2014-01-01

    The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches.

  8. A Window of Opportunity to Control the Bacterial Pathogen Pseudomonas aeruginosa Combining Antibiotics and Phages

    PubMed Central

    Torres-Barceló, Clara; Arias-Sánchez, Flor I.; Vasse, Marie; Ramsayer, Johan

    2014-01-01

    The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches. PMID:25259735

  9. Effects of therapeutical and reduced levels of antibiotics on the fraction of antibiotic-resistant strains of Escherichia coli in the chicken gut.

    PubMed

    van der Horst, Michael A; Fabri, Teun H; Schuurmans, J Merijn; Koenders, Belinda B; Brul, Stanley; ter Kuile, Benno H

    2013-01-01

    Development of antibiotic resistance in the microbiota of farm animals and spread of antibiotic-resistant bacteria in the agricultural sector not only threaten veterinary use of antibiotics, but jeopardize human health care as well. The effects of exposure to antibiotics on spread and development of antibiotic resistance in Escherichia coli from the chicken gut were studied. Groups of 15 pullets each were exposed under strictly controlled conditions to a 2-day course of amoxicillin, oxytetracycline, or enrofloxacin, added to the drinking water either at full therapeutic dose, 75% of that, or at the carry-over level of 2.5%. During treatment and for 12 days afterwards, the minimal inhibitory concentration (MIC) for the applied antibiotics of E. coli strains isolated from cloacal swabs was measured. The full therapeutic dose yielded the highest percentage of resistant strains during and immediately after exposure. After 12 days without antibiotics, only strains from chickens that were given amoxicillin were significantly more often resistant than the untreated control. Strains isolated from pullets exposed to carry-over concentrations were only for a few days more often resistant than those from the control. These results suggest that, if chickens must be treated with antibiotics, a short intensive therapy is preferable. Even short-term exposure to carry-over levels of antibiotics can be a risk for public health, as also under those circumstances some selection for resistance takes place.

  10. Antibiotic-free selection in biotherapeutics: now and forever.

    PubMed

    Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

    2015-01-01

    The continuously improving sophistication of molecular engineering techniques gives access to novel classes of bio-therapeutics and new challenges for their production in full respect of the strengthening regulations. Among these biologic agents are DNA based vaccines or gene therapy products and to a lesser extent genetically engineered live vaccines or delivery vehicles. The use of antibiotic-based selection, frequently associated with genetic manipulation of microorganism is currently undergoing a profound metamorphosis with the implementation and diversification of alternative selection means. This short review will present examples of alternatives to antibiotic selection and their context of application to highlight their ineluctable invasion of the bio-therapeutic world. PMID:25854922

  11. [Pregnancy and breast feeding: antibiotics, irrigation and pastes].

    PubMed

    Fatori Popovic, Sandra; Lübbers, Heinz-Theo; von Mandach von Mandach, Ursula

    2016-01-01

    The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix(®) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl(®) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period.

  12. [Pregnancy and lactation: antibiotics. mouthwashes and pastes or ointments.

    PubMed

    Fatori Popovic, Sandra; Lübbers, Heinz-Theo; von Mandach, Ursula

    2016-01-01

    The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix(®) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl(®) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period.

  13. [Microbiology and antibiotic treatment of diabetic foot infection].

    PubMed

    Zanella, Marie-Céline; Kressmann, Benjamin; Wuarin, Lydia; Coulin, Benoit; Maître, Sophie; Suva, Domizio; Lipsky, Benjamin A; Uçkay, Ilker

    2016-04-13

    In diabetic patients, foot ulcer is a common problem which prevalence during life is about 25%. Infection occurs as a complication in almost 50% of cases, is associated with significant morbidity and a reduced quality of life and is sometimes the trigger leading to amputation. Ulcers and infections occur among patients with predisposing factors such as peripheral neuropathy and arterial insufficiency, and require a multi-disciplinary care system. The knowledge of the microbiology of diabetic foot infection is necessary for a wise use of empirical and targeted antibiotic therapy. This article will focus on the definition and diagnosis of diabetic foot infection, on the main aspects of its microbiology and antibiotic treatment.

  14. Antibiotic-Free Selection in Biotherapeutics: Now and Forever

    PubMed Central

    Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

    2015-01-01

    The continuously improving sophistication of molecular engineering techniques gives access to novel classes of bio-therapeutics and new challenges for their production in full respect of the strengthening regulations. Among these biologic agents are DNA based vaccines or gene therapy products and to a lesser extent genetically engineered live vaccines or delivery vehicles. The use of antibiotic-based selection, frequently associated with genetic manipulation of microorganism is currently undergoing a profound metamorphosis with the implementation and diversification of alternative selection means. This short review will present examples of alternatives to antibiotic selection and their context of application to highlight their ineluctable invasion of the bio-therapeutic world. PMID:25854922

  15. [Pregnancy and breast feeding: antibiotics, irrigation and pastes].

    PubMed

    Fatori Popovic, Sandra; Lübbers, Heinz-Theo; von Mandach von Mandach, Ursula

    2016-01-01

    The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix(®) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl(®) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period. PMID:27277144

  16. Hyperbaric oxygen therapy in the treatment of diabetic foot ulcers--prudent or problematic: a case report.

    PubMed

    Mutluoglu, Mesut; Uzun, Günalp; Yildiz, Senol

    2010-06-01

    Hyperbaric oxygen (HBO) therapy is increasingly used in the management of problem wounds, notably diabetic foot ulcers. However, concerns about unnecessary, inappropriate, and prolonged use of this adjunctive treatment exist. A case report of a 52-year-old patient with diabetes mellitus, Charcot foot, and a nonhealing plantar ulcer who had received HBO treatments only illustrates these concerns. He presented with normal pedal pulses, adequate transcutaneous partial oxygen pressure levels, no offloading footwear, and a heavily contaminated ulcer (Pseudomonas spp.). Following a course of oral antibiotics, appropriate topical wound care, and offloading instructions, the wound healed within 3 months. Advanced wound therapy modalities are only indicated for use in patients when accepted standards of wound care, including identification and correction of underlying disorders and comorbidities, have failed. To prevent misuse/overuse of HBO therapy, stand-alone HBO centers should include a multidisciplinary wound care team.

  17. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  18. Do we need new antibiotics?

    PubMed

    Rolain, J-M; Abat, C; Jimeno, M-T; Fournier, P-E; Raoult, D

    2016-05-01

    For several years, alarmist articles both in mass media and in the scientific community have reported an increase in antibiotic resistance, even citing an inability to treat patients infected with multidrug-resistant bacteria (MDR) responsible for high mortality worldwide. In this review we summarize and discuss the key points associated with the reality of (i) the existence of pandrug-resistant bacteria, (ii) the increase of resistance worldwide, (iii) the link between resistance and death, and (iv) the need to develop new antibiotics. Data on antibiotic resistance in Europe for the main bacteria associated with invasive infections apparently demonstrate that apart from Klebsiella pneumoniae, which is resistant to carbapenems in three countries (Romania, Italy and Greece), the level of resistance to three or more classes of antibiotics (defined as MDR phenotype) has remained low and stable over the last 5 years and that therapeutic options exist both for reference antibiotics and for old antibiotics. The clinical outcome of patients infected by MDR bacteria remains controversial and death rates attributable to MDR bacteria versus non-MDR bacteria are still debated. The arsenal of antibiotics currently available (including 'old antibiotics') suffices for facing the waves of emergence of new bacterial resistance and should be considered as a World Heritage. This heritage should be managed in a non-profit model with international regulatory approval. PMID:27021418

  19. Antibiotic use in livestock production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic usage is a useful and commonly implemented practice in livestock and production agriculture that has progressively gained attention in recent years from consumers of animal products due to concerns about human and environmental health. Sub-therapeutic usage of antibiotics has led to a con...

  20. Emergence of a Potent Multidrug Efflux Pump Variant That Enhances Campylobacter Resistance to Multiple Antibiotics

    PubMed Central

    Yao, Hong; Shen, Zhangqi; Wang, Yang; Deng, Fengru; Liu, Dejun; Naren, Gaowa; Dai, Lei; Su, Chih-Chia; Wang, Bing; Wang, Shaolin; Wu, Congming; Yu, Edward W.

    2016-01-01

    ABSTRACT Bacterial antibiotic efflux pumps are key players in antibiotic resistance. Although their role in conferring multidrug resistance is well documented, the emergence of “super” efflux pump variants that enhance bacterial resistance to multiple drugs has not been reported. Here, we describe the emergence of a resistance-enhancing variant (named RE-CmeABC) of the predominant efflux pump CmeABC in Campylobacter, a major zoonotic pathogen whose resistance to antibiotics is considered a serious antibiotic resistance threat in the United States. Compared to the previously characterized CmeABC transporters, RE-CmeABC is much more potent in conferring Campylobacter resistance to antibiotics, which was shown by increased MICs and reduced intracellular accumulation of antibiotics. Structural modeling suggests that sequence variations in the drug-binding pocket of CmeB possibly contribute to the enhanced efflux function. Additionally, RE-CmeABC expands the mutant selection window of ciprofloxacin, enhances the emergence of antibiotic-resistant mutants, and confers exceedingly high-level resistance to fluoroquinolones, an important class of antibiotics for clinical therapy of campylobacteriosis. Furthermore, RE-CmeABC is horizontally transferable, shifts antibiotic MIC distribution among clinical isolates, and is increasingly prevalent in Campylobacter jejuni isolates, suggesting that it confers a fitness advantage under antimicrobial selection. These findings reveal a new mechanism for enhanced multidrug resistance and an effective strategy utilized by bacteria for adaptation to selection from multiple antibiotics. PMID:27651364

  1. Experimental gram-negative bacterial sepsis: prevention of mortality not preventable by antibiotics alone.

    PubMed Central

    Greisman, S E; DuBuy, J B; Woodward, C L

    1979-01-01

    Outbred Swiss mice were inoculated intraperitoneally or intravenously with one 90 to 100% lethal dose of Escherichia coli O:18, Proteus mirabilis, or Klebsiella pneumoniae. After carefully timed intervals, aminoglycoside antibiotics were begun at dosages nnd intervals predetermined to constitute optimal therapy. With progressive increases in delay of antibiotic therapy, mortality rates increased progressively from 0% to 90 to 100%. Standardized models of infection were developed by selecting delay periods before initiating antibiotic therapy such that 50 to 70% mortalities resulted. Utilizing these models, agents with reputed anti-endotoxin activity were administered concomitantly with the delayed antibiotic therapy to determine if any could prevent gram-negative septic mortality no longer preventable by the antibiotics alone. The following were observed: (i) adrenal corticosteroids prevented mortality that was no longer preventable by optimal aminoglycoside antibiotics alone. The following were preventable by optimal aminoglycoside antibiotic therapy alone; (ii) specific antisera also did so, provided anaphylaxis was circumvented; (iii) in one model (P. mirabilis), such protection by adrenal corticosteroids and specific antiserum could be additive; (iv) adrenal corticosteroids and specific antiserum acted synergistically with the aminoglycoside antibiotics--no protection was achieved by delayed administration of the steroids or antiserum alone; (v) timing was crucial--the synergistic protective activity of adrenal corticosteroids and of specific antiserum with aminoglycosides declined rapidly as infection progressed; (vi) cyclophosphamide pretreatment markedly impaired the synergistic protective activity of specific antiserum and of adrenal corticosteroids with aminoglycosides; (vii) no reputed anti-endotoxin agents other than adrenal corticosteroids and specific antiserum proved capable of preventing mortality not preventable by aminoglycoside antibiotics alone

  2. [Antibiotic resistance: A global crisis].

    PubMed

    Alós, Juan-Ignacio

    2015-12-01

    The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics.

  3. Antibiotics, microbiota, and immune defense.

    PubMed

    Ubeda, Carles; Pamer, Eric G

    2012-09-01

    The gastrointestinal tract microbiota contributes to the development and differentiation of the mammalian immune system. The composition of the microbiota affects immune responses and affects susceptibility to infection by intestinal pathogens and development of allergic and inflammatory bowel diseases. Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities and decreases host resistance to antibiotic-resistant microbes. Here, we review recent advances that begin to define the interactions between complex intestinal microbial populations and the mammalian immune system and how this relation is perturbed by antibiotic administration. We further discuss how antibiotic-induced disruption of the microbiota and immune homeostasis can lead to disease and we review strategies to restore immune defenses during antibiotic administration.

  4. The Prehistory of Antibiotic Resistance.

    PubMed

    Perry, Julie; Waglechner, Nicholas; Wright, Gerard

    2016-01-01

    Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. PMID:27252395

  5. Comparison of knowledge and attitudes about antibiotics and resistance, and antibiotics self-practicing between Bachelor of Pharmacy and Doctor of Pharmacy students in Southern India

    PubMed Central

    Ahmad, Akram; Khan, Muhammad U.; Moorthy, Jagadeesan; Jamshed, Shazia Q.; Patel, Isha

    2014-01-01

    Background: There is limited research on pharmacy specialization based differences with regards to usage of antibiotics. Objective: To compare the knowledge, attitude and practice of Bachelor of Pharmacy (BPharm) and Doctor of Pharmacy (PharmD) students about usage and resistance of antibiotics in Southern India. Methods: This was a cross sectional study involving final year BPharm and PharmD students studying in two private institutions located in Andra Pradesh, India. The study was conducted for the period of 3 months. The questionnaire was divided into 5 components: demographics, knowledge about antibiotic use, attitude towards antibiotic use and resistance, self-antibiotic usage, and possible causes of antibiotic resistance. The study questionnaire was assessed for reliability. Data were analysed by employing Mann Whitney and chi square tests using SPSS version 19. Results: The sample size comprised of 137 students. The response rate was 76.11% for the study. There was a significant difference in the knowledge of antibiotic use in BPharm and PharmD students (Mean score: 5.09 vs 6.18, p<0.001). The overall attitude of PharmD students about antibiotic use and resistance was positive compared to BPharm students (Mean score: 3.05 vs 2.23, p<0.05). The self-antibiotic practices was higher in BPharm students than PharmD students (36.4% vs 20%, p<0.05). A significantly high number of PharmD students believed that empirical antibiotic therapy led to antibiotic resistance (19.5% versus 48%, P<0.05). Conclusion: PharmD students were more knowledgeable about antibiotic usage and resistance compared to BPharm students who did not have accurate and the much needed information about the same. Future interventions should be targeted towards educating the BPharm students so that they can implement the acquired knowledge in their practice. PMID:25883690

  6. Adequate iron stores and the 'Nil nocere' principle.

    PubMed

    Hollán, S; Johansen, K S

    1993-01-01

    There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial pathogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron

  7. Efficacy of medical therapy in treatment of chronic rhinosinusitis.

    PubMed

    Young, Lee C; Stow, Nicholas W; Zhou, Lifeng; Douglas, Richard G

    2012-01-01

    Uncomplicated chronic rhinosinusitis (CRS) is generally treated with medical therapy initially and surgery is contemplated only after medical therapy has failed. However, there is considerable variation in the medical treatment regimens used and studies defining their efficacy are few. The aim of this study was to determine the proportion of patients treated medically who responded sufficiently well so that surgery was not required. Subgroup analysis to identify clinical features that predicted a favorable response to medical therapy was also performed. Eighty patients referred to the Otorhinolaryngology Clinic at North Shore Hospital were treated with a standardized medical therapy protocol (oral prednisone for 3 weeks, oral antibiotics and ongoing saline lavage and intranasal budesonide spray). Symptom scores were collected before and after medical therapy. Clinical features such as presence of polyps, asthma, and aspirin hypersensitivity were recorded. Failure of medical therapy was defined as the persistence of significant CRS symptoms, and those patients who failed medical therapy were offered surgery. Follow-up data were available for 72 (90%) patients. Of this group, 52.5%, (95% CI, 42.7%, 62.2%) failed to respond adequately to medical therapy and were offered surgery. The remaining patients (37.5%) were successfully treated with medical therapy and did not require surgery at the time of follow-up. The premedical therapy symptom scores were significantly higher than the postmedical therapy symptom scores (p < 0.01). The symptom scores of those patients postmedical therapy who proceeded to have surgery were significantly higher than the group who responded well to maximum medical therapy (MMT) and did not require surgery (p < 0.0001). There were no significant differences in the proportion of patients with asthma, aspirin sensitivity, or polyps between the groups failing or not failing MMT. In approximately one-third of patients with CRS, medical therapy

  8. Curing bacteria of antibiotic resistance: reverse antibiotics, a novel class of antibiotics in nature.

    PubMed

    Hiramatsu, Keiichi; Igarashi, Masayuki; Morimoto, Yuh; Baba, Tadashi; Umekita, Maya; Akamatsu, Yuzuru

    2012-06-01

    By screening cultures of soil bacteria, we re-discovered an old antibiotic (nybomycin) as an antibiotic with a novel feature. Nybomycin is active against quinolone-resistant Staphylococcus aureus strains with mutated gyrA genes but not against those with intact gyrA genes against which quinolone antibiotics are effective. Nybomycin-resistant mutant strains were generated from a quinolone-resistant, nybomycin-susceptible, vancomycin-intermediate S. aureus (VISA) strain Mu 50. The mutants, occurring at an extremely low rate (<1 × 10(-11)/generation), were found to have their gyrA genes back-mutated and to have lost quinolone resistance. Here we describe nybomycin as the first member of a novel class of antibiotics designated 'reverse antibiotics'. PMID:22534508

  9. A New Approach for the Discovery of Antibiotics by Targeting Non-Multiplying Bacteria: A Novel Topical Antibiotic for Staphylococcal Infections

    PubMed Central

    Hu, Yanmin; Shamaei-Tousi, Alireza; Liu, Yingjun; Coates, Anthony

    2010-01-01

    In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates. PMID:20676403

  10. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes.

    PubMed

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I

    2013-01-01

    Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the "perfect microbial storm". Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

  11. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    PubMed Central

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

    2013-01-01

    Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water. PMID:27029309

  12. Antibiotic resistance: challenges and successes in respiratory infection.

    PubMed

    Sethi, Sanjay; Bryan, Jenny

    2016-01-01

    European Respiratory Society Congress, Amsterdam, 26-30 September 2015, and CHEST 2015, Montréal, Canada, 24-28 October 2015 With approximately 50,000 deaths in the US and EU attributed to antibacterial resistance each year, together with several million days of hospital care [1], the need to address resistance mechanisms and find new targets for novel antibiotics has never been greater. At the annual congresses of the European Respiratory Society and the American College of Chest Physicians, presenters reported advances in understanding of the mechanisms of antibiotic resistance and how these may be overcome. The latest clinical trial data on antibiotic treatment for hospital- and community-acquired pneumonia, including the potential for novel nebulized forms of therapy, were also discussed. PMID:27081910

  13. Mycobacteriophage putative GTPase-activating protein can potentiate antibiotics.

    PubMed

    Yan, Shuangquan; Xu, Mengmeng; Duan, Xiangke; Yu, Zhaoxiao; Li, Qiming; Xie, Longxiang; Fan, Xiangyu; Xie, Jianping

    2016-09-01

    The soaring incidences of infection by antimicrobial resistant (AR) pathogens and shortage of effective antibiotics with new mechanisms of action have renewed interest in phage therapy. This scenario is exemplified by resistant tuberculosis (TB), caused by resistant Mycobacterium tuberculosis. Mycobacteriophage SWU1 A321_gp67 encodes a putative GTPase-activating protein. Mycobacterium smegmatis with gp67 overexpression showed changed colony formation and biofilm morphology and supports the efficacy of streptomycin and capreomycin against Mycobacterium. gp67 down-regulated the transcription of genes involved in cell wall and biofilm development. To our knowledge, this is the first report to show that phage protein in addition to lysin or recombination components can synergize with existing antibiotics. Phage components might represent a promising new clue for better antibiotic potentiators. PMID:27345061

  14. The role of probiotics in the prevention and treatment of antibiotic-associated diarrhea and Clostridium difficile colitis.

    PubMed

    Friedman, Gerald

    2012-12-01

    Clostridium difficile colitis is the most common gastrointestinal infection, exceeding all other gastrointestinal infections combined. There has been a dramatic increase in Clostridium difficile infection (CDI) worldwide during the past decade. Antibiotic therapy is a trigger precipitating antibiotic-associated diarrhea (AAD), which may lead to CDI. The antibiotic alters the protective, diverse bacteria allowing pathogenic bacteria to cause disease. Probiotics have been effective in reducing AAD and preventing CDI.

  15. Homeopathic Ear Drops as an Adjunct in Reducing Antibiotic Usage in Children With Acute Otitis Media.

    PubMed

    Taylor, James A; Jacobs, Jennifer

    2014-01-01

    Objective. To determine if use of a homeopathic ear drop preparation reduces antibiotic use in children diagnosed with acute otitis media (AOM). Methods. Children 6 months to 11 years old, diagnosed with AOM and managed with a delayed antibiotic approach, were randomized to standard therapy alone or standard therapy plus a homeopathic ear drop preparation. The primary outcome was whether or not the antibiotic prescription given at the index visit was filled during a 12- to 15-day follow-up period. Results. Among 210 enrolled children, follow-up antibiotic data were collected on 206. During the 12- to 15-day follow-up period, fewer parents of children randomized to the homeopathic ear drops group filled the antibiotic prescription compared with those of children receiving standard therapy alone (26.9% and 41.2%, respectively, P = .032). Conclusion. Homeopathic ear drops may be effective in reducing the use of antibiotics in children with AOM managed with a delayed antibiotic approach. PMID:27335917

  16. Antibiotic resistance in wild birds

    PubMed Central

    Bonnedahl, Jonas

    2014-01-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

  17. Antibiotic Treatment of Hidradenitis Suppurativa.

    PubMed

    Bettoli, Vincenzo; Join-Lambert, Olivier; Nassif, Aude

    2016-01-01

    Although hidradenitis suppurativa (HS) is not primarily an infectious disease, antibiotics are widely used to treat HS. Recent microbiological data show that HS suppurating lesions are associated with a polymorphous anaerobic flora, including actinomycetes and milleri group streptococci, and can therefore be considered as polymicrobial soft tissue and skin infections. Analysis of the literature provides little information on the efficacy of antibiotics in HS but suggests a beneficial effect of certain antimicrobial treatments, depending on the clinical severity of the disease. Patients must be informed and should agree with the treatment strategy before starting antibiotic treatments.

  18. Antibiotic resistance in wild birds.

    PubMed

    Bonnedahl, Jonas; Järhult, Josef D

    2014-05-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

  19. Optimal Treatment for Complicated Intra-abdominal Infections in the Era of Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Therapy With Metronidazole

    PubMed Central

    Mikamo, Hiroshige; Yuasa, Akira; Wada, Keiko; Crawford, Bruce; Sugimoto, Naomi

    2016-01-01

    Background. Carbapenem-resistant Enterobacteriaceae has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. A combination of metronidazole with an antimicrobial agent active against aerobes is an alternative effective treatment for patients with complicated intra-abdominal infections (cIAIs). This study aimed to compare efficacy and safety of metronidazole combination therapies and carbapenem and to provide clinical evidence regarding the optimal treatment of cIAI. Methods. A systematic review and a meta-analysis of randomized clinical trials in the treatment of cIAI were conducted. The systematic review with PubMed, Embase, and the Cochrane Database of Systematic Reviews followed the Cochrane Handbook's recommended methodology, and the meta-analysis used a Mantel-Haenszel random-effects model with RevMan, version 5.3. Primary endpoints were clinical success and bacteriological eradication, and secondary endpoints were all-cause mortality and drug-related adverse events. Results. Eight studies comparing metronidazole combination therapies and carbapenem were included in the meta-analysis. No difference was found between combined therapy with metronidazole and carbapenem regarding clinical success (odds ratio [OR] = 1.31; 95% confidence interval [CI], .75–2.31), bacteriological eradication (OR = 1.27; 95% CI, .84–1.91), all-cause mortality (OR = 0.61; 95% CI, .37–1.00), or drug-related adverse events (OR = 0.58; 95% CI, .18–1.88). Sensitivity analyses found similar results. Conclusions. Combined therapy with metronidazole is as effective and safe as carbapenem in treatment of cIAI. Therefore, combined therapy with metronidazole offers an effective alternative to carbapenem with low risk of drug resistance. PMID:27704002

  20. Trust, reciprocity and collective action to fight antibiotic resistance. An experimental approach.

    PubMed

    Rönnerstrand, Björn; Andersson Sundell, Karolina

    2015-10-01

    Antibiotic resistance is a collective action dilemma. Individuals may request antibiotics, but an overall reduction in use is necessary to limit resistance. A reoccurring theoretical claim is that social capital increase cooperation in social dilemmas. The aim of this paper is to investigate the link between generalized trust and reciprocity and the willingness to postpone antibiotic treatment in order to limit overuse in a scenario-based study. A between-subject scenario experimental approach with hypothetical scenarios was utilized. Participants were asked to imagine that they were seeing a doctor for a respiratory infection. The doctor prescribes antibiotics, but advise postponing therapy to see if the disease resolves by itself, for the sake of limiting overuse. Respondents were asked to answer how long they could accept postponing antibiotic treatment, from 0 to 7 days. The number of days that most people would be able to accept postponing treatment was considered the between-subject factor. In total, the study sample included 981 respondents with a mean age of 51 years. A majority of respondents were men (65.7%). The mean number of days that the respondents stated they were willing to postpone antibiotic treatment was positively associated with the number of days the respondents were told that most people were willing to postpone antibiotic treatment, p < 0.001. There was a positive association between number of days they were willing to postpone antibiotic treatment and generalized trust, p = 0.001. In conclusion, the results showed that the proclaimed public willingness to postpone therapy influenced a respondent's willingness to postpone antibiotic therapy in different scenarios. Also, generalized trust was positively associated with the willingness to postpone therapy.