Comparative time-kill study of doxycycline, tigecycline, sulbactam, and imipenem against several clones of Acinetobacter baumannii

To assess potential alternative options for the treatment of infections caused by Acinetobacter baumannii, we performed time-kill studies of doxycycline and tigecycline using several isolates recovered from patients residing in 10 different cities in Argentina. Imipenem and sulbactam were also included for comparison purposes. Eleven isolates representing 5 distinctive clones, or isolates with different susceptibility patterns within the same clone, were selected. Tubes containing cation-supplemented Mueller-Hinton broth with and without antibiotics were seeded with a log-phase inoculum of roughly 5 x 10(5) CFU/mL. By using the viable counts determined at 2-, 4-, 6-, 8-, and 24-h intervals after inoculation, a 24-h time-kill curve was constructed for each isolate. No bactericidal activity (defined as a >= 3-log(10) CFU/mL decrease in the viable cell counts with respect to the original inoculum) was observed at any time with sulbactam (4 mu g/mL) or tigecycline (1 mu g/mL), whereas low bactericidal rate (IS% of the isolates) was shown for doxycycline (1 mu g/mL) and sulbactam (16 mu g/mL) after 24 h of incubation. Doxycycline (4 mu g/mL) and tigecycline (8 mu g/mL) displayed bactericidal activity at 24 h of incubation against 36% and 54% of the isolates, respectively, including the carbapenem-resistant isolate. Corresponding values for imipenem (1 and 4 mu g/mL) against the 10 carbapenem-susceptible isolates were 60% and 90%, respectively. The present study confirms the in vitro efficacy of imipenem against A. baumannii, suggests that doxycycline could be a suitable, cost-effective, alternative option in some instances, and sheds light on the potential role of tigecycline in the treatment of infections with this organism. (C) 2008 Elsevier Inc. All rights reserved.