Susceptibility profile of blaOXA-23 and metallo-β-lactamases co-harbouring isolates of carbapenem resistant Acinetobacter baumannii (CRAB) against standard drugs and combinations

Abstract

BackgroundThe rapid emergence of carbapenem resistant Acinetobacter baumannii (CRAB) has resulted in an alarming situation worldwide. Realizing the dearth of literature on susceptibility of CRAB in genetic context in the developing region, this study was performed to determine the susceptibility profile against standard drugs/combinations and the association of in-vitro drug synergy with the prevalent molecular determinants.Methods and findingsA total of 356 clinical isolates of A. baumannii were studied. Confirmation of the isolates was done by amplifying recA and ITS region genes. Susceptibility against standard drugs was tested by Kirby Bauer disc diffusion. Minimum inhibitory concentration (MIC), MIC50 and MIC90 values against imipenem, meropenem, doripenem, ampicillin/sulbactam, minocycline, amikacin, polymyxin B, colistin and tigecycline was tested as per guidelines. Genes encoding enzymes classes A (blaGES, blaIMI/NMC-A, blaSME, blaKPC), B (blaIMP, blaVIM, blaNDM) and D (blaOXA-51,blaOXA-23 and blaOXA-58) were detected by multiplex polymerase chain reaction. Synergy against meropenem-sulbactam and meropenem-colistin combinations was done by checkerboard MIC method. Correlation of drug synergy and carbapenemase encoding genes was statistically analyzed.ResultsOf the total, resistance above 90% was noted against gentamicin, ciprofloxacin, levofloxacin, ceftazidime, cefepime, ceftriaxone, cotrimoxazole and piperacillin/tazobactam. By MIC, resistance rates from highest to lowest was seen against imipenem 89.04% (n=317), amikacin 80.33% (n=286), meropenem 79.49% (n=283), doripenem 77.80% (n=277), ampicillin/sulbactam 71.62% (n=255), tigecycline 55.61% (n=198), minocycline 14.04% (n=50), polymyxin B 10.11% (n=36), and colistin 2.52% (n=9). CRAB was 317 (89.04%), 81.46% (n=290) were multidrug resistant and 13.48% (n=48) were extensively drug resistant. All the CRAB isolates harboured blaOXA-51 gene (100%) and 94% (n=298) blaOXA-23 gene. The blaIMP gene was most prevalent 70.03% (n=222) followed by blaNDM, 59.62% (n=189). Majority (87.69%, 278) were co-producers of classes D and B carbapenemases, blaOXA-23 with blaIMP and blaNDM being the commonest. Synergy with meropenem-sulbactam and meropenem-colistin was 47% and 57% respectively. Reduced synergy (p= <0.0001) was noted for those harbouring blaOXA-51+blaOXA-23with blaNDM gene alone or co-producers.ConclusionPresence of blaNDM gene was a significant cause of synergy loss in meropenem-sulbactam and meropenem-colistin. In blaNDM endemic regions, tigecycline, minocycline and polymyxins could be viable options against CRAB isolates with more than one carbapenemase encoding genes.

The Prevalence of Antibiotic Resistance Phenotypes and Genotypes in Multidrug-Resistant Bacterial Isolates from the Academic Hospital of Jaén, Spain

“…Moreover, carbapenem-resistant A. baumannii (CRAB) have been classified by the World Health Organization (WHO) as one of the "Priority 1: Critical group" organisms for which new antimicrobials are urgently needed. In this way, the emergence of A. baumannii that are resistant to carbapenem has been very significant, not only because of the resistance acquired but also because of the dissemination of the bacteria in the population [23].…”

Antimicrobial combination effects against multidrug‐resistant Acinetobacter baumannii and Pseudomonas aeruginosa strains: A cross‐sectional study

“…New combinations are increasingly suggested as a choice of therapeutic with the increasing approval of new drugs. In a world where new antibiotics discovery and production are far slower than the development of antibiotic resistance in human pathogens, although temporarily, combination therapy could be an opportunity to overcome the threat of MDR and XDR nosocomial infection 7 …”

“… 8 Simultaneous exposure of drug‐resistant bacteria to antibiotics in combination therapy improves the efficacy of antibiotics by several mechanisms. 7 For instance, cell membrane damaging antibiotics like colistin result in the higher entrance of β‐lactams or tetracycline antibiotics inside the cells or blocking destructive enzyme functions such as β‐lactamases recover the activity of β‐lactam antibiotics. 9 In the current study, we tried to assess the efficacy of different antibiotic combinations and introduce potential combinations for the treatment of antibiotic‐resistant strains.…”

“…In a world where new antibiotics discovery and production are far slower than the development of antibiotic resistance in human pathogens, although temporarily, combination therapy could be an opportunity to overcome the threat of MDR and XDR nosocomial infection. 7 Potential benefits with combinations as compared with monotherapy include synergistic effects, a broader antibacterial spectrum, and reduced risk for developing drug resistance. In the absence of evidence-based treatment choices, combinations are employed to increase the antibacterial effects of available antibiotics against MDR bacterial isolates.…”

“…In the absence of evidence‐based treatment choices, combinations are employed to increase the antibacterial effects of available antibiotics against MDR bacterial isolates 8 . Simultaneous exposure of drug‐resistant bacteria to antibiotics in combination therapy improves the efficacy of antibiotics by several mechanisms 7 . For instance, cell membrane damaging antibiotics like colistin result in the higher entrance of β‐lactams or tetracycline antibiotics inside the cells or blocking destructive enzyme functions such as β‐lactamases recover the activity of β‐lactam antibiotics 9 .…”