JAC Advance Access originally published online on July 26, 2006
Journal of Antimicrobial Chemotherapy 2006 58(3):689-692; doi:10.1093/jac/dkl303
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Prevention of rifampicin resistance in Acinetobacter baumannii in an experimental pneumonia murine model, using rifampicin associated with imipenem or sulbactam
1 Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío Avda. Manuel Siurot s/n, 41013, Sevilla, Spain 2 Service of Microbiology, Hospital Universitario Virgen Macarena Avda. Dr Fedriani s/n, 41009, Sevilla, Spain 3 Department of Medicine, University of Sevilla Avda. Dr Fedriani s/n, 41009, Sevilla, Spain 4 Department of Microbiology, University of Sevilla Avda. Sánchez Pizjuan s/n, 41009, Sevilla, Spain
Received 21 April 2006; returned 29 June 2006; revised 29 June 2006; accepted 5 July 2006
*Correspondence address. Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain. Tel/Fax: +34-955012376; E-mail: jeronimopachon{at}telefonica.net
Objectives: 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 
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 (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.
Keywords: resistant mutant , combined treatment , in vivo resistance
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