Synergistic activity of colistin with azidothymidine against colistin-resistant Klebsiella pneumoniae clinical isolates collected from inpatients in Greek hospitals

Abstract

Background: New antibiotics are urgently needed to treat multi-drug resistant infections; however, production of novel antibiotics is diminishing. Synergistic combination drug therapy to enhance the activity of available antibiotics may improve management of patients with resistant infections.

Methods: Colistin-resistant Klebsiella pneumoniae isolates were collected from inpatients in 10 Greek hospitals and used to study combination activity of colistin plus azidothymidine. Combination activity was evaluated with the sum of fractional inhibitory concentrations (ΣFIC) using the mini checkerboard broth microdilution method.

Results: A hundred individual strains were tested. Synergistic activity was noted in 79% (79/100) of isolates and additive activity in the remaining 21% (21/100). ΣFIC₅₀ and ΣFIC₉₀ were 0.28 and 0.56, respectively.

Conclusion: Colistin with azidothymidine exhibited promising synergistic activity against colistin-resistant Klebsiella pneumoniae isolates warranting further investigation of the combination.

Keywords: Azidothymidine; Colistin; Enterobacteriaceae; Gram-negative; Repurposing; Synergism.