Clinical relevance of in vitro synergistic activity of antibiotics for multidrug-resistant Gram-negative infections: A systematic review.

Abstract

The aim of this review was to investigate the outcomes of patients infected with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Gram-negative bacteria following synergy-guided antibiotic combination therapy (SGACT). A systematic review of PubMed and Scopus databases was performed. Published studies of any design reporting outcomes of patients with MDR Gram-negative bacteria treated with SGACT were included. Two reviewers independently assessed the relevancy and quality of the retrieved articles and extracted the available data. Nineteen reports (530 patients) were included. Eleven case reports/series described 26 cases of systemic infection due to MDR Gram-negative bacteria treated with SGACT. Five deaths were reported, two of which were attributed to the infection. Six studies (including one randomised controlled trial) provided comparative data for patients treated with SGACT and those treated with unguided combination therapy (UCT) or active monotherapy. In the pooled analysis of unadjusted data from these studies (504 patients), there was no difference between SGACT and UCT or monotherapy (OR=0.47, 95% CI 0.21-1.04; I2=52%). Analysis of adjusted data showed that SGACT was significantly associated with survival (OR=0.44, 95% CI 0.20-0.98; I2=54%). These limited but promising findings warrant further investigation of SGACT in the outcome of patients with MDR Gram-negative infections in well-designed trials.