Increased antimicrobial susceptibility profiles among polymyxin-resistant Acinetobacter baumannii clinical isolates.

Objective: Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become a major treatment challenge, requiring the re-introduction of polymyxins into clinical practice. Given this situation, the emergence of polymyxin B resistance is expected. Recently, increased antimicrobial susceptibility among in vitro passaging of colistin-resistant A. baumannii isolates was observed when compared with the parent colistin-susceptible strains. The aim of this study was to compare the susceptibility profile between polymyxin B-resistant and -susceptible A. baumannii patient isolates submitted to the SENTRY Antimicrobial Surveillance Program. Methods: A collection of 3,707 A. baumannii clinical isolates was susceptibility tested by the CLSI broth microdilution method and the susceptibility rates of epidemiologically unrelated polymyxin B-resistant isolates were compared to those of polymyxin B-susceptible isolates. Susceptibility rates were analyzed by χ test using the Epi InfoTM Version 3.4.1 software package. P values <0.05 were considered to be statistically significant. Results: The majority of the antimicrobials tested showed limited spectrums of activity (susceptibility rates, ≤55.4%) against the polymyxin B-susceptible A. baumannii group, except for imipenem (73.2%), meropenem (76.5%) and some tetracyclines. Doxycycline, minocycline and tigecycline showed the highest susceptibility rates 74.7, 91.7 and 97.0%, respectively. Overall, the polymyxin Bresistant group showed a higher susceptibility rate for the vast majority of antimicrobials tested. This shift was not observed among those antimicrobial agents with higher activity against the polymyxin B-susceptible group (i.e. carbapenems and tetracyclines). Statistically significant differences were observed among most drugs showing lower activity, including ampicillin/sulbactam (susceptibility rate 3x higher), aztreonam (4x), cefoxitin (20x), ceftriaxone (2x) and cefuroxime (8x). Tigecycline was highly active regardless the susceptibility to polymyxin B. Conclusions: Polymyxin B-resistant A. baumannii clinical isolates showed higher susceptibility rates when compared to polymyxin B-susceptible isolates for the majority of antimicrobials tested. These findings suggest that possible lipopolysaccharide modifications among polymyxin B-resistant bacterial cells may increase permeability to the antimicrobial agents. These data may provide additional insights for combination therapeutic options and also for possible novel antimicrobial agents in drug development.