In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates.
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.
Owen
Roxanne J
RJ
Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Li
Jian
J
Nation
Roger L
RL
Spelman
Denis
D
D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D003091:Colistin