- María E Pachón-Ibáñez: Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío Avda, Manuel Siurot s/n, 41013, Sevilla, Spain.
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 > 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.