The efficacy of combination therapy in MDR, XDR and PDR acinetobacter baumannii

Abstract

Background: Antimicrobial resistance has been emerging into alerting levels in the last few decades resulting in multi-drug resistance (MDR), extensive-drug resistance (XDR), and lately pan-drug resistance (PDR) in Gram negative bacteria such as Acinetobacter baumannii. Resistance to β-lactams, cephalosporins, and carbapenems has led to the re-emergence of polymyxin E (colistin) as a sole and last line solution to treat MDR and XDR cases. However, A. baumannii has acquired multiple resistance mechanisms to colistin, which in turn directed clinicians towards prescribing combination therapies as alternative options to improve the antibacterial activity of colistin. In Lebanon, no study addressed the in vitro combination of colistin with different antimicrobial agents against A. baumannii clinical isolates. Methods: A total of 73 A. baumannii clinical isolates collected from AUBMC Clinical Microbiology Laboratory were screened for their susceptibility to colistin using the Broth Micro-dilution assay (BMD). Pulsed Field Gel Electrophoresis (PFGE) was performed to assess the genomic relatedness among the isolates. Checkerboard assays were performed on 7 colistin-resistant A. baumannii isolates to evaluate the effect of combining each of Tigecycline (TGC), Teicoplanin (TEC), Zerbaxa (ceftolozane-tazobactam; C_T), Meropenem (MEM), Levofloxacin (LVX) and Amikacin (AMK) with colistin (COL) and determine the possible synergistic effects between antibiotics. Induction of resistance was conducted on the reference strain (DSM30008) to generate various mutants, using a panel of antimicrobial agents (colistin, tigecycline, teicoplanin, zerbaxa, meropenem, levofloxacin and amikacin) to elucidate the resistance mechanisms that developed and establish a reference strain for Whole Genome Sequence (WGS) analysis. Results: Our results revealed that n=8 (10.95 percent) of isolates were resistant to colistin by the BMD and their MICs varied between 128 and 4096 μg-mL. PFGE analysis demonstrated that A. baumanni isolates were div