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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Alfa Institute of Biomedical Sciences, 9 Neapoleos St. 151 23 Marousi, Athens,  Greece.
Konstantinos Z
KZ
Vardakas
Giannoula S
GS
Tansarli
Petros I
PI
Rafailidis
Matthew E
ME
Falagas
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D006801:Humans; D016019:Survival Analysis; D016896:Treatment Outcome; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D001618:beta-Lactamases