Determine the effect of non-thermal plasma-treated antimicrobial solution on resistance of Carbapenem-resistant Acinetobacter baumannii (CRAB) Isolates

Rubina Narang

doi:10.17918/etd-6839

Acinetobacter baumannii is a third most common, Gram-negative, opportunistic pathogen responsible for nosocomial (hospital-acquired) infections in healthcare units world-wide. Carbapenems are considered to be the last resort to treat such infections but a recent increased in resistance of A. baumannii against carbapenem group of antimicrobial agents is posing great threat in control of this pathogen and leading to almost no therapeutic options available for clinicians to treat such infections. Joshi Laboratory recently isolated multidrug-resistant, carbapenem-resistant A. baumannii (CRAB) bacterial pathogens from Drexel University College of Medicine's Hahnemann University Hospital, which exhibits multiple mechanisms of carbapenem resistance. The membrane-associated drug-efflux pump is one of the major mechanisms of carbapenem resistance, which works by effluxing carbapenem and other classes of antibiotics in A. baumannii. The current pump inhibitors used in clinical set up are non-effective due to the increased resistance against them or confer high toxicity. Joshi Laboratory reported novel antimicrobial non-thermal plasma-activated antibacterial solutions which are broad-spectrum in nature. These antibacterial solutions are being explored for their exact mechanisms of action on prototype pathogen, clinical isolate #22 which is CRAB. The specific aim of present study is to re-confirm the findings of antimicrobial effect of non-thermal plasma-activated novel antibacterial solution, and determine the effect of commonly used efflux-pump inhibitor, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and non-thermal plasma-activated antibacterial solution on locally isolated CRAB # 22, and correlate with inhibition of drug-efflux pump. This research work is complementary to past and current research being carried out in Joshi Laboratory at Drexel University (1, 2). In the present study, we re-confirmed that non-thermal plasma activated methionine solution at 3 minutes of plasma treatment and 15 minutes of holding time results in complete inactivation of Acinetobacter baumannii. We found that pump inhibitor CCCP didn't decrease the MIC of amikacin and tetracycline susceptibility of CRAB isolate #22 and also didn't have significant effect on the susceptibility of meropenem. As many of the efflux pumps share the same structural homology, therefore there might be other efflux pumps that are able to affect the susceptibility of given strain. Till now no current pump inhibitors are licensed to use in clinical set ups because of the difference between concentrations being used in clinical set up and effective concentration of pump inhibitor. Therefore this area needs further research so that new efflux pump inhibitors can be developed to control the mortality rate of infections associated with MDR pathogens. In order to investigate the effect of plasma-treated antibacterial solution on inhibition of drug-efflux pumps, other efflux pump inhibitors may be tested for the given isolate that may have significant effects in inhibition of efflux pump.

Determine the effect of non-thermal plasma-treated antimicrobial solution on resistance of Carbapenem-resistant Acinetobacter baumannii (CRAB) Isolates

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Determine the effect of non-thermal plasma-treated antimicrobial solution on resistance of Carbapenem-resistant Acinetobacter baumannii (CRAB) Isolates

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