Prevention of rifampicin resistance in Acinetobacter baumannii in an experimental pneumonia murine model, using rifampicin associated with imipenem or sulbactam.
OBJECTIVE
To examine the development of rifampicin resistance in multidrug-resistant Acinetobacter baumannii exposed to rifampicin and the prevention of the appearance of rifampicin-resistant mutants when rifampicin is used in association with imipenem or sulbactam.


METHODS
A clinical strain of multidrug-resistant A. baumannii was used to examine the frequency of resistance to rifampicin in vivo, in a pneumonia model in immunocompetent C57BL/6 mice. The in vitro and in vivo prevention of the development of resistance to rifampicin was analysed using rifampicin alone or in association with imipenem or sulbactam, in time-kill studies and in the experimental murine pneumonia, respectively.


RESULTS
Rifampicin-resistant mutants were found at 48 and 72 h, both in vitro and in vivo, when rifampicin was used alone, with the MIC increasing from 4 to > or =128 mg/L. The in vivo frequency of rifampicin-resistant mutants was 3 x 10(-6). On the contrary, no resistant mutants appeared after 72 h, in vitro or in vivo, when rifampicin was employed in association with imipenem or sulbactam. After six daily passages in rifampicin-free agar plates the resistant mutants maintained the high resistance to rifampicin (> or =128 mg/L).


CONCLUSIONS
These results suggest that rifampicin must not be used alone in the treatment of infections caused by multidrug-resistant A. baumannii. In these cases, rifampicin may be used in combination with imipenem or sulbactam, which prevent the development of resistance to rifampicin.
Pachón-Ibáñez
María E
ME
Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío Avda, Manuel Siurot s/n, 41013, Sevilla, Spain.
Fernández-Cuenca
Felipe
F
Docobo-Pérez
Fernando
F
Pachón
Jerónimo
J
Pascual
Alvaro
A
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015378:Imipenem / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013407:Sulbactam / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D015378:Imipenem; D013407:Sulbactam; D012293:Rifampin