SciCombinator

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Concept: Ertapenem

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Direct plating of simulated stool specimens on MacConkey agar (MCA) with 10-μg of ertapenem, meropenem and imipenem disks, allowed to established the optimal zone diameters for screening of carbapenem-resistant gram negative rods (CRGNR) to: ≤ 24 mm (ertapenem), ≤ 34 mm (meropenem) and ≤ 32 mm (imipenem).

Concepts: Escherichia coli, Beta-lactamase, Carbapenem, Carbapenem antibiotics, Stool, Ertapenem, Meropenem

27

Clinical isolates of Pseudomonas aeruginosa exhibiting high-level resistance to carbapenems were recovered from a French patient with cystic fibrosis (CF) who had not received carbapenem therapy. This study was conducted to investigate the molecular mechanism conferring the carbapenem-resistant phenotype in clinical isolates of P. aeruginosa recovered from the same CF patient chronically colonised since 2005. Investigation of imipenem resistance of P. aeruginosa strain_02 isolated in May 2011 showed no carbapenemase activity. However, amplification and sequencing of the oprD porin gene revealed disruption of this gene by an insertion sequence (IS) element of 1337bp that contained a novel transposase of 1227bp (ISPa46) bordered by two terminal imperfect inverted repeats of 28bp, which was associated with carbapenem resistance. Retrospective analysis of five additional strains of P. aeruginosa isolated before May 2011 from the same patient revealed that all isolates were likely to be the same clone by multilocus sequence typing analysis (ST540/551), but one of the five isolates was imipenem-susceptible. Although it was possible to demonstrate the presence of ISPa46 in all strains by PCR, this IS was transposed in the oprD gene only for imipenem-resistant isolates. Therefore, this study reports a novel IS element (ISPa46) in P. aeruginosa clinical isolates of a CF patient in Marseille, France, that was associated with carbapenem resistance and was selected in the absence of carbapenem treatment.

Concepts: Genetics, Bacteria, Molecular biology, Antibiotic resistance, Pseudomonas aeruginosa, Cystic fibrosis, Ertapenem, Imipenem

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PURPOSE: In Japan, a national surveillance study of antimicrobial consumption has never been undertaken. This study aimed to describe antimicrobial consumption and resistance to Pseudomonas aeruginosa in 203 Japanese hospitals, to identify targets for quality improvement. METHODS: We conducted an ecological study using retrospective data (2010). Antimicrobial consumption was collected in the World Health Organization (WHO) anatomical therapeutic chemical/defined daily dose (ATC/DDD) format. Rates of imipenem (IPM), meropenem (MEPM), ciprofloxacin (CPFX), or amikacin (AMK) resistance were expressed as the incidence of non-susceptible isolates. Additionally, hospitals were asked to provide data concerning hospital characteristics and infection control policies. Hospitals were classified according to functional categories of the Medical Services Act in Japan. RESULTS: Data were collected from 203 Japanese hospitals (a total of 91,147 beds). The total antimicrobial consumption was 15.49 DDDs/100 bed-days (median), with consumptions for penicillins, carbapenems, quinolones, and glycopeptides being 4.27, 1.60, 0.41, and 0.49, respectively. The median incidences of IPM, MEPM, CPFX, and AMK resistance were 0.15, 0.10, 0.13, and 0.03 isolates per 1,000 patient-days, respectively. Antimicrobial notification and/or approval systems were present in 183 hospitals (90.1 %). In the multivariate analysis, the piperacillin/tazobactam, quinolones, and/or total consumptions and the advanced treatment hospitals showed a significant association with the incidence of P. aeruginosa resistant to IPM, MEPM, CPFX, and AMK [adjusted R 2 (aR 2) values of 0.23, 0.30, 0.22, and 0.35, respectively). CONCLUSION: This is the first national surveillance study of antimicrobial consumption in Japan. A continuous surveillance program in Japan is necessary in order to evaluate the association among resistance, antimicrobial restriction, and consumption.

Concepts: Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Pseudomonas, Pseudomonadales, World Health Organization, Ertapenem, Imipenem

8

The effect of high NAC concentrations (10 and 50 mM) on antibiotic activity against 40 strains of respiratory pathogens was investigated. NAC compromised carbapenem activity (mostly imipenem and, to a lesser extent, meropenem and ertapenem) in a dose-dependent fashion. Chemical instability of carbapenems in the presence of NAC was demonstrated. With other antibiotics, 10 mM NAC had no major effects, while 50 mM NAC sporadically decreased (ceftriaxone and aminoglycosides) or increased (penicillins) antibiotic activity.

Concepts: Bacteria, Penicillin, Beta-lactam antibiotic, Beta-lactamase, Carbapenem, Carbapenem antibiotics, Ertapenem, Meropenem

4

ESBL (Extended spectrum beta-lactamase) producing enterobacteriaceae are challenging organisms with little treatment options. Carbapenems are frequently used, but the emergence of carbapenem resistant enterobacteriaceae is a concerning issue, which may hinder the use of carbapenems. Although cephamycins such as cefoxitin, cefmetazole or cefotetan are effective against ESBL-producers in vitro, there are few clinical data demonstrating effects against bacteremia caused by these organisms.

Concepts: Effectiveness, Beta-lactam antibiotic, Beta-lactamase, Cephalosporin, Carbapenem, Ertapenem, Cephalosporin antibiotics, Cephamycin

3

The emergence of carbapenem resistance has had a significant impact on both clinical and economic outcomes.

Concepts: Carbapenem, Ertapenem, Meropenem

2

Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae.

Concepts: Randomized controlled trial, Escherichia coli, Penicillin, Beta-lactam antibiotic, Beta-lactamase, Carbapenem, Ertapenem, Meropenem

1

Pseudomonas endocarditis is exceedingly rare, especially in patients without predisposing risks. We present such a case that included unexpected switches in antibacterial resistance profiles in two Pseudomonas aeruginosa (PA) strains with the same whole-genome sequence. The case also involved diagnostic and treatment challenges, such as issues with automated testing platforms, choosing the optimal aminoglycoside, minimizing unnecessary carbapenem exposure, and the need for faster, more informative laboratory tests.

Concepts: Bacteria, Antibiotic resistance, Chemistry, Pseudomonas aeruginosa, Fiction, Pseudomonas, Software testing, Ertapenem

1

We used meropenem to successfully treat a patient with bacteremia due to ceftazidime-avibactam-resistant, meropenem- susceptible Klebsiella pneumoniae that carried mutant blaKPC-3. Meropenem was bactericidal against ceftazidime-avibactam- resistant K pneumoniae isolates in vitro. Nevertheless, the role of carbapenems in treating such infections remains uncertain, because meropenem resistance is selected readily during passage experiments.

Concepts: In vitro, Beta-lactamase, Carbapenem, Carbapenem antibiotics, Klebsiella, Ertapenem, Meropenem

1

Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem.

Concepts: Beta-lactamase, Carbapenem, Carbapenem antibiotics, Ertapenem, Meropenem