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Niels Høiby - One of the best experts on this subject based on the ideXlab platform.
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development of Antibiotic resistance in pseudomonas aeruginosa during two decades of antipseudomonal treatment at the danish cf center
Apmis, 1994Co-Authors: Oana Ciofu, B Giwercman, Svend Stenvang Pedersen, Niels HøibyAbstract:At the Danish CF Center patients with chronic Pseudomonas aeruginosa lung infection were treated 3-4 times a year (from 1976) with a 2-week intravenous antipseudomonal course which included preferentially an aminoglycoside and a Beta-Lactam Antibiotic. We investigated the development of Antibiotic resistance in P. aeruginosa strains isolated from Danish CF patients over a period of 18 years by testing the in vitro efficacy of carbenicillin, piperacillin, ceftazidime, tobramycin and ciprofloxacin against P. aeruginosa strains collected in 1973 (51 strains), 1980 (80 strains), 1985 (58 strains), and 1991 (100 strains). All the strains were screened and assayed semiquantitatively for Beta-Lactamase activity by use of nitrocefin. We found a significant (p < 0.005) increase in the MIC values of the P. aeruginosa strains against piperacillin and ceftazidime. However, no significant correlation was found between the MIC and the number of antipseudomonal courses of Antibiotics. The proportion of resistant in vivo selected P. aeruginosa strains, presumed to be stably derepressed producers of chromosomal Beta-Lactamase, also increased significantly during the period studied. Our results confirm that the Beta-Lactamase production is an important mechanism of Antibiotic resistance in P. aeruginosa.
Claudia Jane Hackbarth - One of the best experts on this subject based on the ideXlab platform.
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kinetics of penicillin binding to penicillin binding proteins of staphylococcus aureus
Biochemical Journal, 1994Co-Authors: Henry F Chambers, Meena Sachdeva, Claudia Jane HackbarthAbstract:Reduced affinity of penicillin-binding proteins (PBPs) for binding penicillin has been proposed as a mechanism of Beta-Lactam Antibiotic resistance in staphylococci. Penicillin binding by PBPs of three penicillin-susceptible and two penicillin-resistant strains of Staphylococcus aureus was studied in kinetic assays to determine rate constants, drug concentrations at which PBPs were bound and the relationship between concentrations that bound PBPs and concentrations that inhibited bacterial growth. PBPs 1 and 2 of the resistant strains exhibited slower acylation and more rapid deacylation than susceptible strains. In contrast PBP 4, a naturally low-affinity PBP, was modified such that it exhibited a lower rate of deacylation. The concentrations of penicillin at which modified PBPs were bound correlated with concentrations that inhibited growth of the resistant strains. Acquisition of penicillin resistance in these strains of S. aureus results, at least in part, from structural modifications affecting binding of multiple PBPs and appears to include recruitment of a non-essential PBP, PBP 4.
Ameeta E. Singh - One of the best experts on this subject based on the ideXlab platform.
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Non-standard treatment for uncomplicated Chlamydia trachomatis urogenital infections: a systematic review.
BMJ Open, 2018Co-Authors: Jessica Krahn, Aaron Louette, Vera Caine, Tom Wong, Tim T Y Lau, Ameeta E. SinghAbstract:Objectives To review the literature for non-standard treatment options for uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults. Design Systematic review. Data sources Ovid MEDLINE/PubMed, Ovid EMBASE, Cochrane Trials & Systematic Review Databases, CINAHL Plus with Full Text, Web of Science Core Collection, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and Health Canada Trials Database were searched for studies in English or French from 1 January 2006 to 6 August 2017. Keywords included CT, anti-infective or anti-bacterial agents, therapy/pharmacotherapy/management. Review methods Included were primary research studies. Outcome measures included clinical or microbiological cure, treatment failure and adverse events. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed for risk of bias using the Revised Cochrane Risk of Bias V.2.0 tool for randomised and the Newcastle-Ottawa Quality Assessment Scale for non-randomised studies. Funding source Public Health Agency of Canada. Results Of the 6899 records identified through the database search, 11 studies were included. One randomised controlled trial reported that delayed release doxycycline was non-inferior to azithromycin. Two studies examined higher doses of azithromycin but reported no additional benefit. One study looked at a 5-day azithromycin treatment regimen and reported a high cure rate. Two studies reported efficacy of sitafloxacin, and a single study supports the use of levofloxacin. Two phase 2 studies reported efficacy of single-dose rifalazil in both men and women. Only one retrospective study was identified that examined treatment in pregnant women and reported that efficacy with single-dose azithromycin exceeded that of amoxicillin and erythromycin. A single study examining the efficacy of a Beta-Lactam Antibiotic was stopped early due to high treatment failures. Conclusions The paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections. PROSPERO registration number CRD42017073096.
Maria Victoria Moncada - One of the best experts on this subject based on the ideXlab platform.
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Emergence and spread of a new community-genotype methicillin-resistant Staphylococcus aureus clone in Colombia
BMC Infectious Diseases, 2017Co-Authors: Javier Escobar-perez, Niradiz Reyes, Ricaurte Alejandro Marquez-ortiz, Juan Rebollo, Hernando Pinzón, Catalina Tovar, Jaime Moreno-castañeda, Zayda Lorena Corredor, Betsy Esperanza Castro, Maria Victoria MoncadaAbstract:Background Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) clones are a global concern due to their resistance and increased virulence and their ability to cause infections both hospitalized patients and healthy people in the community. Here, we characterize 32 isolates of a new CG-MRSA clone. These isolates were identified in four cities in Colombia, South America. Methods The isolates were recovered from four different epidemiological and prospective studies that were conducted in several regions of Colombia. Molecular characterizations included multilocus sequence typing; pulsed-field gel electrophoresis; SCC mec, agr and spa typing; and whole-genome sequencing. Results All isolates belonged to ST923 (clonal complex 8), harbouring SCC mec IVa and a spa type t1635 and lacking an arginine catabolism mobile element. The isolates were classified as COL923, were resistant to at least one non-Beta-Lactam Antibiotic, and exhibited high frequencies (>60%) of resistance to macrolides and tetracycline. Using whole-genome sequencing, we found that this new clone harbours novel prophage 3 and beta-island structures and a slightly different pathogenicity island 5. Moreover, isolates belonging to the COL923 clone are grouped in a different clade than USA300 and USA300-LV. Conclusion Our results show the emergence and spread of the COL923 clone in different cities in Colombia. This clone is resistant to several Antibiotics and possesses new structures in its mobile genetic elements.
Jim Todd - One of the best experts on this subject based on the ideXlab platform.
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improved outcome of clindamycin compared with beta lactam Antibiotic treatment for invasive streptococcus pyogenes infection
Pediatric Infectious Disease Journal, 1999Co-Authors: Julie Zimbelman, April Palmer, Jim ToddAbstract:Context. Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment. Objective. To determine the most effective Antibiotic treatment for invasive S. pyogenes infection in humans. Design and setting. We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Children's Hospital. Patients. Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections. Main outcome measure. Lack of progression of disease (or improvement) after at least 24 h of treatment. Results. The median number of Antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting Antibiotics and Beta-Lactams predominating amongst the cell wall-inhibiting Antibiotics in 123 of 126 of the remainder. Clindamycin was often used in combination with a Beta-Lactam Antibiotic. Overall there was a 68% failure rate of cell wall-inhibiting Antibiotics when used alone. Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting Antibiotic as compared with exclusive treatment with cell wall-inhibiting Antibiotics (83% vs. 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs. 48%, P = 0.07). For those children initially treated with cell wall-inhibiting Antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs. 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs. 0%, P = 0.14). Conclusions. This retrospective study suggests that clindamycin in combination with a Beta-Lactam Antibiotic (with surgery if indicated) might be the most effective treatment for invasive S. pyogenes infection.