Safety Profile of Meropenem : An Updated Review of Over 6000 Patients Treated with Meropenem

Clostridium difficile is a frequent cause of serious nosocomial infection. Earlier reports have suggested that treatment with metronidazole cured nearly 90% of patients, with only a modest rate of recurrence of infection. In recent years, the rate of response to treatment with this drug has appeared to be much lower. We undertook a prospective, observational study of 207 patients who were treated with metronidazole for C. difficile colitis. A total of 103 patients (50%) were cured by the initial course of therapy and had no recurrence of disease. Forty-six patients (22%) continued to have symptoms of colitis for > or = 10 days despite treatment, and 58 (28%) responded initially but had a recurrence within the ensuing 90 days. The mortality rate among patients who developed C. difficile colitis was 27%, and it was higher among patients who did not respond fully to an initial course of therapy, compared with those who did (33% vs. 21%; P < .05). Because of the relatively poor response to therapy, additional approaches to prevention and/or treatment of C. difficile colitis appear to be warranted.

A systematic review of studies that investigated the association of antibiotics with hospital-acquired Clostridium difficile-associated diarrhoea (CDAD) was undertaken to summarize the strength of the evidence for this relationship. The results from the studies identified were considered after critically reviewing the design and conduct of each study. Although the majority of studies found an association with various antibiotics, antibiotic classes or components of antibiotic administration, most were limited in their ability to establish a causal relationship by the use of incorrect control groups, the presence of bias, inadequate control of confounding and small sample sizes. The limitations identified in this review prevented the pooling of results in a meta-analysis. Two studies of reasonable quality suggested an association between clindamycin, cephalosporins, penicillins and CDAD. Well-designed studies grounded in epidemiological principles are needed to identify true risk factors for CDAD and to provide reliable estimates of the strength of association.

Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam. Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality. Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality. The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.