<i>In Vitro</i> Activity of Colistin and Vancomycin or Azithromycin Combinations on Extensively Drug Resistant <i>Acinetobacter baumannii</i> Clinical Isolates

Abstract

Background: Extensively drug resistant Acinetobacter baumannii (XDR-AB) presents an increasing challenge to health care in Egypt as they are among the most common bacteria isolated in hospital setting. Treatment of such infections usually involves the use of antimicrobial agents in combination. Various combinations have been proposed, with colistin serving as the backbone in many of them even for colistin resistant isolates. Aim: The study was conducted in order to test the in vitro combined effects of colistin and vancomycin or azithromycin against (XDR-AB) causing infections at Alexandria Main University Hospital in Egypt, in an attempt to detect the possibility of a beneficial combination therapy. Material/Methods: Thirty XDR-AB clinical isolates were included in the study. Antibiotic susceptibility testing was performed using automated Vitek 2 compact system and disc diffusion method. Colistin antibiotic disc diffusion test was compared with broth microdilution method. Organisms were also tested against colistin and vancomycin or azithromycin in combination using checkerboard synergy test and FICI (Fractional Inhibitory Concentration Index) was calculated. Synergy was defined as a FICI of ≤0.5. Results: On comparing the two methods used to detect susceptibility to colistin to broth microdilution for MIC (minimum inhibitory concentration) determination, as a reference method, the Vitek showed 100% categorical agreement (CA), on the other hand, the disc diffusion showed CA of 93% with very major errors. Synergy was detected for all isolates (100%) when combining colistin with vancomycin (FICI mean = 0.08). As for azithromycin, 21 strains had FICI range from 0.7 to 1.001, denoting indifference; the remaining 9 strains showed synergy with FICI range from 0.06 to 0.241. The mean colistin/azithromycin FICI was 0.71 for the 30 isolates. Conclusion: These findings suggest that regimens containing vancomycin may confer therapeutic benefit for infection due to XDR-AB; however, other methods (time-kill assay) should be used to confirm such synergy. Furthermore, the optimal combination treatment for serious XDR-AB infection should be addressed in a prospective clinical trial.

Exploring anti-quorum sensing potential and biofilm inhibitory effect of azithromycin against urinary Escherichia coli isolated from a teaching hospital in Alexandria

“…Azithromycin enhanced the effect of colistin in AZ/colistin combination, and this was in accordance with previous results reporting the synergistic effect of this combination in resistant isolates of K. pneumoniae and E. coli (60,61) . The obtained values of FICI corresponding to AZ/colistin were in accordance as well with another study investigating the effect of the combination in A. baumannii (62) . Saini et al (63) detected synergy upon combining AZ with ciprofloxacin when tested in P. aeruginosa.…”

Colistin-daptomycin, colistin-linezolid, colistin-vancomycin combination effects on colistin in multi-resistant acinetobacter baumannii strains

“…These findings indicate that vancomycin-containing regimens may provide therapeutic benefit for MDRAB-associated infections; However, other methods should be used to confirm such a synergy. Also optimal combination therapy in severe infections should be considered in a prospective clinical trial (14). In a study, conducted in 2013 they found that combinations of colistin resistant A. baumannii strains isolated from patients previously treated with colistin were synergistic with vancomycin-colistin containing combinations in an in vivo study and in vivo larval experiments have reported that the combination regimen containing colistin-vancomycin-doripenem increases survival compared to monotherapy (15).…”