Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis.
Konstantinos Z. Vardakas1,2, Giannoula S. Tansarli1, Petros I. Rafailidis1,2 and Matthew E. Falagas1,2,3,*
– Author Affiliations
1Alfa Institute of Biomedical Sciences, 9 Neapoleos St. 151 23 Marousi, Athens, Greece
2Department of Medicine, Henry Dunant Hospital, 107 Mesogion Avenue, 115 26 Athens, Greece
3Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA
↵*Corresponding author. Tel: +30-694-611-0000; Fax: +30-210-683-9605; E-mail: firstname.lastname@example.org
Received April 5, 2012.
Revision requested April 21, 2012.
Revision received June 28, 2012.
Accepted July 7, 2012.
Objectives 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.
ESBLs Klebsiella Escherichia Proteus Enterobacter mortality Gram-negative
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