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JAC Advance Access published online on February 8, 2007

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl512
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates

Roxanne J. Owen1, Jian Li1,*, Roger L. Nation1 and Denis Spelman2

1 Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia 2 Department of Microbiology and Infectious Diseases Unit, Alfred Hospital, Australia

Received 31 July 2006; returned 6 September 2006; accepted 20 November 2006


* Corresponding author. Tel: + 61-3-9903-9702; Fax: + 61-3-9903-9629; E-mail: Jian.Li{at}vcp.monash.edu.au

BACKGROUND: Colistin is being increasingly used for treatment of infections caused by multidrug-resistant Gram-negative bacteria, including Acinetobacter baumannii.

METHODS: The in vitro pharmacodynamic properties of colistin (sulphate) were investigated by studying the time–kill kinetics and the post-antibiotic effect (PAE) against multidrug-resistant, including colistin heteroresistant, A. baumannii. Time–kill was studied with four multidrug-resistant clinical isolates at concentrations ranging from 0.5 to 64 x MIC. The PAE was examined after 20 min exposure with five clinical isolates, including the four in the time–kill study, plus ATCC 19606.

RESULTS: Colistin showed extremely rapid killing in a concentration-dependent manner; but re-growth was observed as early as 3 h and substantial re-growth at 24 h even at concentrations up to 32 x MIC or 64 x MIC for some isolates. Colistin exhibited modest PAE of 1.0, 2.3 and 3.5 h at 16, 32 and 64 x MIC, respectively, against ATCC 19606. Surprisingly, negative PAE (range: –0.8 to –8.15 h) was observed for all of the five clinical isolates.

CONCLUSIONS: These findings suggest that monotherapy with colistin methanesulphonate, the parenteral form of colistin, and long dosage intervals (e.g. 24 h) may be problematic for treatment of infections caused by colistin heteroresistant A. baumannii.

Key Words: killing kinetics , heteroresistance , post-antibiotic effect


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