b Trimethoprim-sulfamethoxazole alone and combined with colistin was tested in vitro against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim-sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections.
Acinetobacter baumannii has been an important nosocomial pathogen for the past 30 years, being frequently implicated in ventilator-associated pneumonia and bloodstream, urinary tract, and soft tissue infections (1) and having a propensity to develop particular antibiotic resistance. According to the ECDC's annual epidemiological surveillance report for 2014, carbapenem-resistant A. baumannii (CRAB) is endemic in many European countries; half of the reported isolates from all over Europe were resistant to carbapenems, aminoglycosides, and fluoroquinolones, while in Greece, the respective percentages were 93%, 89%, and 95% (2).Trimethoprim-sulfamethoxazole is a combination of two antimicrobial agents that act synergistically against a wide variety of bacteria. Maximum synergistic inhibition occurs when the trimethoprim/sulfamethoxazole concentration ratio is 1:20. The drug combination is prepared at a fixed ratio of 1:5; however, the achievable serum concentration after both oral and intravenous administration is 1:20, because of the wider volume of distribution of trimethoprim than of sulfamethoxazole. The combination may be effective in a variety of infections, such as respiratory, urinary, gastrointestinal, and skin and wound infections and septicemias. ⌻trimethoprim and sulfamethoxazole exert their synergistic effect by inhibiting successive steps in the folate synthesis pathway (3). Despite the scarcity of novel antibiotics active against carbapenem-resistant Gram-negative bacteria and the existing need to rely on available old antibiotics, the in vitro killing activity of trimethoprim-sulfamethoxazole against CRAB has not been studied.During the last few years, susceptibility data for A. baumannii from our large tertiary hospital have shown high rates of resistance to carbapenems (Ͼ90% for imipenem and meropenem), while resistance to trimethoprim-sulfamethoxazole has been lower (approximately 70%) (unpublished data). The aim of our study was to test the in vitro antibacterial activity of trimethoprim-sulfamethoxazole, alone and in combination with colistin, against CRAB blood isolates. Trimethoprim-sulfamethoxazole is an old drug, and a large body of pharmacokinetic/pharmacodynamic data is available, including phase IV data on safety profiles. In that respect, the results of this study might be readily applicable by clinicians treating CRAB infections, possibly broadening their therapeutic ars...
