Carbapenems For Treatment Research Articles

Antimicrobial Resistance Conferred by OXA-48 β-Lactamases: Towards a Detailed Mechanistic Understanding.

OXA-48-type β-lactamases are now routinely encountered in bacterial infections caused by carbapenem-resistant Enterobacterales These enzymes are of high and growing clinical significance due to the importance of carbapenems in treatment of health care-associated infections by Gram-negative bacteria, the wide and increasing dissemination of OXA-48 enzymes on plasmids, and the challenges posed by their detection. OXA-48 confers resistance to penicillin (which is efficiently hydrolyzed) and carbapenem antibiotics (which is more slowly broken down). In addition to the parent enzyme, a growing array of variants of OXA-48 is now emerging. The spectrum of activity of these variants varies, with some hydrolyzing expanded-spectrum oxyimino-cephalosporins. The growth in importance and diversity of the OXA-48 group has motivated increasing numbers of studies that aim to elucidate the relationship between structure and specificity and establish the mechanistic basis for β-lactam turnover in this enzyme family. In this review, we collate recently published structural, kinetic, and mechanistic information on the interactions between clinically relevant β-lactam antibiotics and inhibitors and OXA-48 β-lactamases. Collectively, these studies are starting to form a detailed picture of the underlying bases for the differences in β-lactam specificity between OXA-48 variants and the consequent differences in resistance phenotype. We focus specifically on aspects of carbapenemase and cephalosporinase activities of OXA-48 β-lactamases and discuss β-lactamase inhibitor development in this context. Throughout the review, we also outline key open research questions for future investigation.

Bacterial biofilm dependent catheter associated urinary tract infections: Characterization, antibiotic resistance pattern and risk factors

ABSTRACT Biofilms cause recurrent and resistant device-related infections. We aimed to detect the prevalence of biofilm-dependent catheter-associated urinary tract infections (CAUTI) among catheterized patients, identify bacterial pathogens, antibiotic resistance pattern and risk factors associated with biofilm production. Adult and pediatric patients admitted to Mansoura University Urology and Nephrology Center and fulfilling the criteria of CAUTI were enrolled in this study. urine sample and a part of urinary catheter were collected for microbiological testing and assessment of biofilm formation using tube method (TM) and scanning electron microscope (SEM). The prevalence of biofilm-dependent CAUTI was 82.85%, in which Klebsiella pneuomoniae had the highest biofilm-forming potential. Biofilm producers uropathogens are more resistant to antibiotics. Extremes of age and prolonged duration of catheterization were significantly associated with biofilm formation. TM showed good correlation with SEM regarding degree of biofilm production, sensitivity (100%) and specificity (100%). Prevalence of biofilm-dependent CAUTI was high. Minimizing the duration of catheterization and usage of silicone catheter are recommended. Using carbapenems in treatment of biofilm-dependent CAUTI should be considered. TM can be implemented for biofilm detection as it is cheap, rapid, easy and showed good correlation with SEM.

Antimicrobial resistance surveillance in the South African private sector report for 2016

Aim: The relevance of surveillance for antimicrobial resistance is increasingly recognised in the light of a global action plan to combat resistance. This report presents antimicrobial susceptibility testing on ESKAPE pathogens from private sector laboratories in South Africa for 2016.Methods: Antimicrobial susceptibility testing (AST) performed on ESKAPE organisms (Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae and Escherichia coli) isolated from blood cultures at four private pathology laboratories in 2016 were analysed. Analysis and reporting of data were done via a uniform platform created by the NICD for national AST data.Results: AST were reported on 9 029 ESKAPE organisms including 58% Enterobacteriaceae, 28% Gram-positive bacteria and 14% Gram-negative bacteria and drug-bug combination was performed following the Global Antimicrobial Surveillance System (GLASS) guidelines by the World Health Organization.Conclusions: The most important resistance to address is a high level of ESBL in Enterobacteriaceae, which necessitates the use of carbapenems for treatment. Resistance to carbapenems is recorded in this report but not confirmation of genes by genotypic methods. During this period, no increase in vancomycin-resistant Enterococci was observed.

Ertapenem as treatment for ESBL producing E coli prostatitis

Background: Prostatitis presents one of the most common entities encountered in urologic practice. Treating ESBL producing enterobacteriaecea urinary tract infections is a major problem especially in prostatitis because of the absence of active transporters for antibiotics and a relatively low prostate penetration of these drugs. Thus, therapeutic options are limited in infections with such resistant bacteria and require the use of carbapenems in the majority of the cases. Ertapenem is used in acute bacterial prostatitis yet not been approved by the FDA for this indication. The goal of this study is to compare the efficacy of ertapenem as to other antibiotics in the treatment of prostatitis with ESBL producing E. Coli. Methods & Materials: It is a comparative retrospective study of the files of patients admitted in a tertiary care hospital between 1st July 2008 and 1st July 2014 treated for acute bacterial prostatitis caused by E. Coli producing ESBL with ertapenem and other antibiotics. Results: The mean age of the 110 patients of this study was 69.58 years. Ertapenem was administered without previous efficient antibiotic treatment in 34 cases. 18.18% recurred in a period of three months. 85% of recurrences were caused by ESBL producing E.Coli (15.45%). 17% and 19% of patients treated with meropenem and imipenem respectively recurred in a 3 months period. Conclusion: Ertapenem is as effective as other carbapenems in treatment of E.Coli producing ESBL and is not associated with a higher recurrence rate.

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

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.

Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae

BackgroundExtended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.MethodsAll adult patients with a BSI caused by cefotaxime non-susceptible E. coli or K. pneumoniae were included from May 2012-May 2013. We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.ResultsThere were 92 BSIs that fulfilled the microbiological inclusion criteria. 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy died (adjusted HR for survival 0.91, 95% CI 0.13 to 6.28; p = 0.92). The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97). The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed BSI (0% vs. 2%, p = 0.23).ConclusionsBLBLIs appear to have a similar efficacy to carbapenems in the treatment of cefotaxime-resistant E. coli and K. pneumoniae bloodstream infections. Directed therapy with a BLBLI, when susceptibility is proven, may represent an appropriate carbapenem-sparing option.Electronic supplementary materialThe online version of this article (doi:10.1186/s13756-015-0055-6) contains supplementary material, which is available to authorized users.

A retrospective cohort study of panipenem/betamipron for adult pneumococcal bacteremia at three teaching hospitals in Japan

Panipenem/betamipron (PAPM/BP) may be highly effective for life-threatening Streptococcus pneumoniae infection. However, the efficacy of PAPM/BP for S. pneumoniae infections has not been compared with that of other antimicrobial agents. We retrospectively compared PAPM/BP with other carbapenems for treatment of life-threatening infections in newly hospitalized adults with pneumococcal bacteremia. Clinical information for cases of pneumococcal bacteremia was collected from three teaching hospitals in Japan from January 2003 to December 2010. In total, 17 patients who received PAPM/BP therapy and 34 treated with other carbapenems (27 with meropenem, 4 with imipenem/cilastatin, and 3 with biapenem) were identified. The mean age (71 vs. 70years old), sex distribution (women, 29vs. 21%), Charlson comorbidity index (CCI) (1.5 vs. 1.6), and rates of septic shock (29vs. 38%), and meningitis (5.9vs. 8.8%) did not differ significantly between the two groups. The inpatient mortality rates were lower in the PAPM/BP group (12vs. 44%, p=0.03). Multiple logistic regression analysis adjusted for age, sex, CCI, and severe sepsis/septic shock showed that use of other carbapenems was associated with higher in-hospital mortality, with an odds ratio of 6.922 (95% CI, 1.171-40.92) compared to PAPM/BP therapy. Initial PAPM/BP therapy might have a therapeutic advantage over other carbapenems in treatment of severe Streptococcus pneumoniae infections.

Activity of Temocillin against KPC-Producing Klebsiella pneumoniae and Escherichia coli

Temocillin, a 6-α-methoxy derivative of ticarcillin, is currently approved for treatment of infections due to members of the Enterobacteriaceae in Belgium and the United Kingdom. It is stable against hydrolysis by most β-lactamases, including extended-spectrum β-lactamases (ESBLs) and AmpC-type β-lactamases, with studies reporting MICs at which 90% of bacteria are inhibited (MIC90s) between 16 and 32 μg/ml (3, 4, 8). Temocillin is thus drawing attention as a potential alternative to carbapenems in treatment of infections caused by the Enterobactericeae producing these broad-spectrum β-lactamases. Carbapenem-resistant Klebsiella pneumoniae producing KPC-type β-lactamase has emerged in recent years and caused hospital outbreaks of serious infections in the United States and other parts of the world (7). Furthermore, KPC-type β-lactamase is increasingly identified in other species of the Enterobacteriaceae as well, including Escherichia coli. One concerning recent phenomenon is the occurrence of urinary tract infections due to KPC-producing organisms at nursing homes (10). Currently, the limited treatment options for infections due to KPC-producing organisms include colistin and tigecycline. Concern over nephrotoxicity due to colistin limits its use outside closely monitored settings, whereas tigecycline does not achieve a therapeutic concentration in urine (2). Furthermore, emergence of resistance to these agents has recently been recorded for the Enterobacteriaceae (5, 6). The present study was conducted to evaluate the in vitro activities of temocillin against clinical isolates of K. pneumoniae and E. coli producing KPC-type β-lactamase. A total of 33 KPC-producing clinical isolates (30 K. pneumoniae isolates and 3 E. coli isolates) were used. KPC production was confirmed by an ertapenem resistance phenotype, a positive modified Hodge test, and positive PCR for the KPC structural gene. The isolates were collected from hospitals in three states in the United States. The MIC of temocillin was determined by the standard agar dilution method (1). Temocillin was provided by Eumedica (Brussels, Belgium). In addition, MICs of temocillin against an E. coli isogenic clone producing KPC-3 were tested to determine the direct effect of KPC production on the temocillin MIC. E. coli ATCC 25922 was used as the control strain. Table ​Table11 summarizes the results. For K. pneumoniae, the MICs ranged between 16 μg/ml and 64 μg/ml (MIC at which 50% of bacteria were inhibited = 32 μg/ml; MIC90 = 32 μg/ml). The E. coli clinical isolates had MICs between 8 and 16 μg/ml. E. coli DH10B both with and without the cloning vector pBCSK− (Stratagene, La Jolla, CA) encoding blaKPC-3 had an MIC of 8 μg/ml. An inoculum effect was not observed at 105 CFU, whereas a mild inoculum effect averaging within a twofold MIC difference was seen with K. pneumoniae when 106 CFU was inoculated (Table ​(Table1).1). This result was in line with those of a previous study documenting a modest inoculum effect of temocillin for non-KPC-producing isolates (9). The frequencies of mutants of representative clinical isolates that grew at their MICs and at 2× MICs were calculated to be approximately 1 × 10−10 and 0 for K. pneumoniae and 3 × 10−10 and 1 × 10−10 for E. coli, respectively. TABLE 1. Susceptibilities of KPC-producing K. pneumoniae and E. coli isolates to temocillin Currently, the British Society for Antimicrobial Chemotherapy (BSAC) is the only organization that defines temocillin MIC breakpoints for the Enterobacteriaceae. The BSAC defines temocillin susceptibilities at ≤8 and ≤32 μg/ml in systemic and urinary tract infections, respectively (http://www.bsac.org.uk/). One gram of temocillin is known to achieve a peak serum concentration of approximately 160 μg/ml, with serum binding of 85% and a half-life of 4 to 5 h (9). The urinary concentration after a 500-mg dose is approximately 500 μg/ml (9). These pharmacokinetic properties of temocillin make it a potential alternative treatment option for mild to moderate urinary tract infections caused by KPC-producing members of the Enterobacteriaceae.

Monobactams and carbapenems for treatment of intraabdominal infections.

During the last decade improved clinical and microbiological methods have resulted in the realization that most intraabdominal infections involve both aerobic and anaerobic bacteria. Papers on the use of different antimicrobial agents directed against the polymicrobial flora of the infected site have been published. In this paper the use of monobactams and carbapenems for treatment of intraabdominal infections is reviewed. The review is based on data published since 1990. Three hundred forty-four patients participated in three trials where aztreonam combined with clindamycin was compared with other antimicrobial agents for treatment of intraabdominal infections. Eighty-six percent of the patients receiving aztreonam plus clindamycin were cured/improved, while 83% of the patients receiving the comparative drugs had favorable outcomes. Eleven trials compared imipenem/cilastatin versus other antimicrobial combinations for therapy of intraabdominal infections. One thousand three hundred seventy-five patients were evaluated in the trials. Eighty percent of patients treated with imipenem/cilastatin had favorable outcomes, while 81% of the patients receiving the comparative drugs were cured/improved. Nine studies including 1,205 patients for evaluation of meropenem versus other antimicrobial agents in the treatment of intraabdominal infections have been published. Cure/improvement was seen in 96% of the patients treated with meropenem and in 91% receiving the comparative drugs. One trial has been published comparing biapenem with imipenem/cilastatin for treatment of intraabdominal infections. Eighty-three patients participated, 65% of the patients in the biapenem group were cured/improved and 68% in the imipenem/cilastatin group.