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Antimicrobial Agents and Chemotherapy, August 2005, p. 3136-3146, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3136-3146.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Combination Therapy with Intravenous Colistin for Management of Infections Due to Multidrug-Resistant Gram-Negative Bacteria in Patients without Cystic Fibrosis

Sofia K. Kasiakou,1 Argyris Michalopoulos,1,2 Elpidoforos S. Soteriades,1,3 George Samonis,4 George J. Sermaides,5 and Matthew E. Falagas1,6,7*

Alfa Institute of Biomedical Sciences, Athens, Greece,1 Intensive Care Unit, "Henry Dunant" Hospital, Athens, Greece ,2 Harvard School of Public Health, Boston, Massachusetts,3 Department of Medicine, University of Crete, School of Medicine, Heraklion, Greece,4 Alfa HealthCare, Athens, Greece,5 Department of Medicine, "Henry Dunant" Hospital, Athens, Greece,6 Tufts University School of Medicine, Boston, Massachusetts7

Received 15 March 2005/ Returned for modification 5 April 2005/ Accepted 10 May 2005

Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 ± 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.

* Corresponding author. Mailing address: Alfa HealthCare, 9 Neapoleos Street, Marousi, Athens 151 23, Greece. Phone: 30-694-61.10.000. Fax: 30-210-68.39.605. E-mail: matthew.falagas{at}tufts.edu.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3136-3146, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3136-3146.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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