SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Imipenem

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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

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Carbapenems resistance among multidrug resistant (CR-MDR) P. aeruginosa were isolated from tertiary hospitals in Thailand. Decreased expression of oprD mRNA (93.65%) was predominant followed by increased expression of mexAB-oprM mRNA (92.06%) and mexXY mRNA (63.49%). Interestingly, there were 23 out of 126 (18.25%) isolates which were susceptible to imipenem with down-regulated oprD expression and non-up-regulated mexCD-oprJ mRNA expression. Metallo-β-lactamases production was clearly positive in 24 isolates (18.46%) and weakly positive in 12 isolates (9.23%). Among both of them, imp-1, imp-14, and vim-2 were identified. Hyperproduction of AmpC β-lactamase was the lowest prevalence rate (3.97%). It could be concluded that CR-MDR P. aeruginosa clinical isolates in Thailand seemed to possess multifactorial resistance mechanisms.

Concepts: Bacteria, Medical statistics, Antibiotic resistance, Messenger RNA, Pseudomonas aeruginosa, Pseudomonas, Pseudomonadales, Imipenem

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Carbapenems are among the most powerful antipseudomonal agents. Limited data is available on drug susceptibility testing by routine methods (disc diffusion and Etest) for meropenem and doripenem. We aimed to compare the in vitro activity of imipenem, meropenem, and doripenem against Pseudomonas aeruginosa.

Concepts: Pseudomonas aeruginosa, Beta-lactam antibiotic, Doripenem, Carbapenem, Carbapenem antibiotics, Ertapenem, Imipenem, Imipenem/cilastatin

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Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an endemic problem in certain countries including Greece. CRPA and multidrug-resistant P. aeruginosa (MDRPA) firstly emerged in our region during the 80s, right after the launch of imipenem and meropenem as therapeutic agents against P. aeruginosa infections. The role of outer membrane protein (Opr) inactivation has been known to contribute to imipenem resistance since many years, while efflux overexpression systems have been mainly associated with meropenem resistance. Among carbapenemases, metallo-β-lactamases (MBL) and mostly Verona integron-mediated (VIM) MBL’s have played the most crucial role in CRPA emergence. VIM-2 and VIM-4 producing CRPA, usually belonging to clonal complexes (CC) 111 and 235 respectively, have most frequently been isolated. BlaVIM-2 and blaVIM-4 are usually associated with a class 1 integron. VIM-17 also has appeared in Greece. On the other hand, other VIM subtypes detected in a global level, such as VIM-3, VIM-5, VIM-6, VIM-7, VIM-11, VIM-14, VIM-15, VIM-16 and VIM-18 have not yet emerged in Greece. However, new VIM subtypes will probably emerge in the future. In addition, MBL carbapenemases other than VIM, detected worldwide have not yet appeared. A single CRPA isolate producing KPC has emerged in our region several years ago. The study of the molecular basis of Opr deficiency and efflux overexpression remains a challenge for the future. In this article, we review the molecular epidemiology of CRPA in an endemic area, compared to global data.

Concepts: Epidemiology, Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Pseudomonas, Pseudomonadales, Ertapenem, Imipenem

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This study aimed to analyse the prevalence, antibiotic resistance and genetic relatedness of P. aeruginosa isolates obtained from potable and recreational water samples (n. 8,351) collected from different settings (swimming pools, n. 207; healthcare facilities, n 1,684; accommodation facilities, n. 1,518; municipal waterworks, n. 4,500; residential buildings, n. 235). Possible mechanisms underlying resistance to imipenem, with particular focus on those involving oprD-based uptake, were also explored.

Concepts: Bacteria, Nosocomial infection, Antibiotic resistance, Pseudomonas aeruginosa, Phage therapy, Pseudomonas, Pseudomonadales, Imipenem

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Heteroresistance is not rare in a variety of microbes, but carbapenem heteroresistace (CHR) among invasive P. aeruginosa infections has not been thoroughly characterized to date. The objective of this study was to investigate the mechanisms, molecular epidemiology, and risk factors for invasive carbapenem heteroresistant P. aeruginosa (CHPA) infections between 2011 and 2015 in Chongqing, China. We observed a significant increase in rates of heteroresistance to IPM (IPM-HR) and MEM (MEM-HR) during the study period. Mechanistic analysis revealed that the overexpression of efflux systems and decreased OprD could have contributed to the carbapenem heteroresistance in P. aeruginosa. We also observed that all of the subpopulations produced enhanced levels of biofilm compared to their native strains. Moreover, previous carbapenem exposure was identified as the common independent risk factor for IPM-HR and MEM-HR, but patients infected with MEM-HR were at higher risk of poor outcomes than were those with IPM-HR. Most importantly, there was a remarkable increase in the prescription of carbapenems during the study period, which was demonstrated to correlate significantly with the quarter increasing prevalence of IPM-HR and MEM-HR, respectively. These findings show the necessity of routine detection of CHR strains and that strict control of carbapenem use is critical to reduce CHPA infections in hospitalized patients.

Concepts: Epidemiology, Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Biofilm, Pseudomonas, Ertapenem, Imipenem

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The variability of carbapenem-resistant Pseudomonas aeruginosa strains (CRPA) isolated from urine and respiratory samples in a large microbiological laboratory, serving several health care settings, and from effluents of two wastewater treatment plants (WWTP) from the same region was assessed by PFGE typing and by resistance to 10 antibiotics. During the 12-month period altogether 213 carbapenem-resistant P. aeruginosa isolates were cultured and distributed into 65 pulsotypes and ten resistance profiles. For representatives of all 65 pulsotypes 49 different MLSTs were determined. Variability of clinical and environmental strains was comparable, 130 carbapenem-resistant P. aeruginosa obtained from 109 patients were distributed into 38 pulsotypes, while 83 isolates from WWTPs were classified into 31 pulsotypes. Only 9 pulsotypes were shared between two or more settings (hospital or WWTP). Ten MLST were determined for those prevalent pulsotypes, two of them (ST111 and ST235) are among most successful CRPA types worldwide. Clinical and environmental carbapenem-resistant P. aeruginosa strains differed in antibiotic resistance. The highest proportion of clinical isolates was resistant to piperacillin/tazobactam (52.3%) and ceftazidime (42.3%). The highest proportion of environmental isolates was resistant to ceftazidime (37.1%) and ciprofloxacin (35.5%). The majority of isolates was resistant only to imipenem and/or meropenem. Strains with additional resistances were distributed into nine different patterns. All of them included clinically relevant strains, while environmental strains showed only four additional different patterns.

Concepts: Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Sewage treatment, Biofilm, Pseudomonas, Ertapenem, Imipenem

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This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of Pseudomonas aeruginosa.

Concepts: Pseudomonas aeruginosa, Ertapenem, Imipenem

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This study aimed to systematically identify the aminoglycoside concentrations required for synergy with a carbapenem and characterize the permeabilizing effect of aminoglycosides on the outer membrane of Pseudomonas aeruginosa Monotherapies and combinations of four aminoglycosides and three carbapenems were studied against P. aeruginosa strain AH298-GFP in 48 h static-concentration time-kill studies (SCTK) (inoculum; 10(7.6) CFU/mL). The outer membrane permeabilizing effect of tobramycin alone and in combination with imipenem was characterized via electron micrographs, confocal imaging and the nitrocefin assay. A mechanism-based model (MBM) was developed to simultaneously describe the time-course of bacterial killing and prevention of regrowth by imipenem combined with each of the four aminoglycosides. Notably, 0.25 mg/liter tobramycin, which was inactive in monotherapy, achieved synergy (i.e ≥2 log10 more killing than the most active monotherapy at 24 h) combined with imipenem. Electron micrographs, confocal image analyses, and the nitrocefin hydrolysis data showed distinct outer membrane damage by tobramycin, which was more extensive for the combination with imipenem. The MBM indicated that aminoglycosides enhanced the imipenem target site concentration up to 4.27-fold. Tobramycin was the most potent aminoglycoside to permeabilize the outer membrane; tobramycin (0.216 mg/liter), gentamicin (0.739 mg/liter), amikacin (1.70 mg/liter) or streptomycin (5.19 mg/liter) were required for half-maximal permeabilization. In summary, our SCTK, mechanistic studies and MBM indicated tobramycin was highly synergistic and displayed the maximum outer membrane disruption potential among the tested aminoglycosides. These findings support the optimization of highly promising antibiotic combination dosage regimens for critically ill patients.

Concepts: Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Cystic fibrosis, Aminoglycoside, Tobramycin, Imipenem, Amikacin