Matthew E Falagas1, Georgios L Voulgaris2, Kyriaki Tryfinopoulou3, Panagiota Giakkoupi3, Margarita Kyriakidou4, Alkiviadis Vatopoulos3, Anthony Coates5, Yanmin Hu5. 1. Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Department of Medicine, Henry Dunant Hospital Center, Athens, Greece; Department of Medicine, Tufts University School of Medicine, Boston, MA, USA. Electronic address: m.falagas@aibs.gr. 2. Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Laboratory of Pharmacokinetics and Toxicology, Department of Pharmacy, 401 General Military Hospital, Athens, Greece. 3. Department of Microbiology, National School of Public Health; Central Public Health Laboratory, Hellenic Centre of Disease Control and Prevention, Vari, Greece. 4. Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece. 5. Institute for Infection and immunity, St. George's, University of London, London, UK.
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.
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.