Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 2011

Objectives: The aim of this study was to determine the antimicrobial activities of the combination between colistin and rifampicin against carbapenems-resistant Acinetobacter baumannii. Methods: Thirty carbapenems-resistant A. baumannii isolates from Bumratnaradoon Hospital between April 2007 and May 2009 were included in this study. Antimicrobial susceptibility tests were performed by both Kirby-Bauer disk diffusion and Agar dilution methods. Synergy effect of the combination of colistin and rifampicin was determined by checkerboard method. In addition, the time-kill study was used to determine the bactericidal activity at 0.5×MIC and 1×MIC of either colistin or rifampicin alone and the combination of both agents. Morphological cell changes of the bacteria after growth in the media plus antimicrobials were observed by using scanning electron microscopy. Results: Susceptibility testing of 12 antimicrobial agents against carbapenems-resistant A. baumannii showed that all 30 isolates were resistant to meropenem, imipenem and rifampicin, while 96.7% of these isolates were resistant to cefepime, ceftazidime, piperacillin/tazobactam and ciprofloxacin. Ninety percent of tested isolates were resistant to amikacin, gentamicin, netilmicin and tobramycin, but 80% were still susceptible to colistin. The MIC ranges for colistin and rifampicin were 1-4 µg/ml and 8-16 µg/ml, respectively. MIC₅₀ and MIC₉₀ of colistin were 1, 2 µg/ml, respectively and MIC₅₀ and MIC₉₀ of rifampicin were 8 µg/ml. The synergy study showed the partial synergy effect of colistin when combined with rifampicin in 26.7% of the isolates. Bactericidal activity of the combination was observed at all incubation times by time-kill study. The more damaging effect of the bacterial cell lysis was clearly observed when the bacteria were grown in the combined antimicrobials as compared with the growth in each antimicrobial agent. Conclusion: The in vitro bactericidal activity of the combination between colistin and rifampicin was superior to the single agent. The combination could be a promising alternative for the treatment of infections due to carbapenems-resistant A. baumannii.