Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis

• Published in: Journal of antimicrobial chemotherapy 2012-12, Vol.67 (12), p.2793-2803
• Main Authors: VARDAKAS, Konstantinos Z, TANSARLI, Giannoula S, RAFAILIDIS, Petros I, FALAGAS, Matthew E
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Bacterial sepsis; beta-Lactam Resistance; beta-Lactamases - secretion; Biological and medical sciences; Carbapenems - therapeutic use; Enterobacteriaceae - drug effects; Enterobacteriaceae - enzymology; Enterobacteriaceae - isolation & purification; Enterobacteriaceae Infections - drug therapy; Enterobacteriaceae Infections - microbiology; Enterobacteriaceae Infections - mortality; Human bacterial diseases; Humans; Infectious diseases; Medical sciences; Pharmacology. Drug treatments; Survival Analysis; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dks301

To study the comparative mortality associated with carbapenems and alternative antibiotics for the treatment of patients with extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae bacteraemia. We searched systematically PubMed and Scopus databases for studies providing data for mortality among patients treated with carbapenems, β-lactam/β-lactamase inhibitor combinations (BL/BLIs) or non-BL/BLIs (mainly cephalosporins and fluoroquinolones), preferably as monotherapy. Studies focusing on patients of all ages with community- and healthcare-associated bacteraemia were eligible. Data were pooled using the technique of meta-analysis. Twenty-one articles, studying 1584 patients, were included. Escherichia coli and Klebsiella pneumoniae were the most commonly studied bacteria. Delay in appropriate treatment up to 6 days was reported. Carbapenems were used mainly as definitive therapy. Carbapenems were associated with lower mortality than non- BL/BLIs for definitive [risk ratio (RR) 0.65, 95% CI 0.47-0.91] and empirical (RR 0.50, 95% CI 0.33-0.77) treatment. No statistically significant differences in mortality were found between carbapenems and BL/BLIs administered as definitive (RR 0.52, 95% 0.23-1.13) or empirical (RR 0.91, 95% CI 0.66-1.25) treatment. BL/BLIs were not associated with lower mortality than non-BL/BLIs administered either definitively (RR 1.59, 95% 0.83-3.06) or empirically (RR 0.82, 95% 0.48-1.41). Data regarding subgroups according to the setting, comorbidity and bacterial species could not be extracted. Based on data from non-randomized studies, carbapenems may be considered the treatment of choice for empirical treatment of patients with ESBL-producing Enterobacteriaceae bacteraemia. The role of BL/BLIs should be further evaluated for definitive treatment. Further research should focus on faster identification of ESBL-positive pathogens and potential differences in the treatment of each bacterial species.