In Vitro Activities of Colistin and Sitafloxacin Combinations against Multidrug-, Carbapenem-, and Colistin-Resistant Acinetobacter baumannii Using the Broth Microdilution Checkerboard and Time-Kill Methods

Abstract

Drug-resistant Acinetobacter baumannii (A. baumannii) infections are a critical global problem, with limited treatment choices. This study aims to determine the in vitro activities of colistin–sitafloxacin combinations against multidrug-, carbapenem- and colistin-resistant A. baumannii (MDR-AB, CRAB, CoR-AB, respectively) clinical isolates from tertiary care hospitals. We used the broth microdilution checkerboard and time-kill methods in this study. Synergy was found using both methods. The colistin–sitafloxacin combination showed synergy in MDR-AB, CRAB, and CoR-AB isolates (3.4%, 3.1%, and 20.9%, respectively). No antagonism was found in any type of drug-resistant isolate. The majority of CoR-AB isolates became susceptible to colistin (95.4%). The time-kill method also showed that this combination could suppress regrowth back to the initial inocula of all representative isolates. Our results demonstrated that the colistin–sitafloxacin combination might be an interesting option for the treatment of drug-resistant A. baumannii. However, further in vivo and clinical studies are required.

In Vitro Activity of KBP-7072 against 536 Acinetobacter baumannii Complex Isolates Collected in China

“…Currently, polymyxins (colistin and polymyxin B) and tigecycline are the last-resort antibiotics for the treatment of infection caused by CRAB isolates. Although colistin has shown well in vitro antibacterial activity against CRAB isolates with 99.4% susceptibility in this study and other reports (84.6% to 92.8% susceptibility), ( 10 , 24 – 26 ), clinical and PK/PD data demonstrate colistin and polymyxin B have limited clinical efficacy and combination with one or more active antimicrobial agents should be used. Several studies have demonstrated that colistin monotherapy against A. baumannii isolates is not inferior to colistin-based or meropenem combination therapy but has greater nephrotoxicity.…”

Colistin Monotherapy versus Colistin plus Sitafloxacin for Therapy of Carbapenem-Resistant Acinetobacter baumannii Infections: A Preliminary Study

“…Using a cut-off minimal inhibitory concentration (MIC) of sitafloxacin ≤2 mg/L, the rate of susceptibility of CR A. baumannii to sitafloxacin was 91.4% [ 13 ]. The combination of colistin and sitafloxacin demonstrated an in vitro synergistic effect against A. baumannii in previous studies [ 19 , 20 ].…”

“…However, a reduction in mortality when using colistin combined with other agents was not clearly observed when compared with colistin alone [ 7 , 8 , 9 , 22 , 23 , 24 ]. The present study selected sitafloxacin to combine with colistin because sitafloxacin was found to be active against most isolates of CR A. baumannii , and colistin combined with sitafloxacin demonstrated an in vitro synergistic effect against CR A. baumannii [ 19 , 20 ]. However, the results of our randomized controlled study in 56 patients with CR A. baumannii infection showed the combination therapy not to be superior to monotherapy relative to 28-day mortality.…”

Overcoming addition of phosphoethanolamine to lipid A mediated colistin resistance in Acinetobacter baumannii clinical isolates with colistin–sulbactam combination therapy

“…Colistin-resistant Acinetobacter baumannii (CoR-AB) strains have now been detected worldwide including Thailand, primarily due to the increasing use of colistin against carbapenem-resistant A. baumannii (CRAB) 1 – 4 . The prevalence of CoR-AB was recently reported to be 14.3% in Thailand 5 and 13% in a recent global surveillance study 6 .…”