Correlation of β-lactam resistance with over expression of efflux pumps among neonatal septicaemic isolates of Acinetobacter baumannii from India.

Background: The emergence of multidrug-resistant Acinetobacter baumannii has created severe challenges for neonates hospitalized in NICU. A. baumannii strains have the propensity for developing antimicrobial resistances extremely rapidly. Neonatal sepsis is a common diseases caused by A. baumannii in a developing country like India. Emergence of β-lactam resistance makes the scenario more critical for neonates for whom treatment options are limited. Now-a-days efflux pumps are getting importance because of their wide substrate profile. Although their presence were scarcely reported but often work in concert to produce high antibiotic resistance. Our aim was to assess the role of efflux pumps in β-lactam resistance among neonatal septicaemic A. baumannii isolates. Methods & Materials: MIC values of carbapenems (meropenem, imipenem) and cephalosporins (cefotaxime, ceftazidime) for neonatal septicaemic A. baumannii isolates were determined using broth dilution method with and without efflux pump inhibitor PAβN. Efflux pump genes of RND families (AdeABC, AdeIJK, AbeXYZ), and SMR family (AbeS) were confirmed by PCR followed by sequencing. Over expression of the genes was carried out by real time PCR. The regulatory components (adeR and adeS) of AdeABC pump was investigated for the isolates, over expressing adeB gene. Results: Carbapenems and cephalosporins resistance was found among 61% and 90% of total A. baumannii isolates (n=49). Exposure of the isolates to PAβN resulted in =4-fold MIC decreases for carbapenem and cephalosporins among 25% and 35% of the isolates which indicated the existence of multidrug efflux pumps. Overall, 55% of these isolates had shown over expression of adeB gene followed by adeY, abeS, and adeJ (Figure 1). The relative expression level for adeB was highest in comparison to the other pump genes. The presence and over expression of AdeXYZ efflux pump had never previously been reported among A. baumannii isolates. Specific mutations had been detected within adeR (V136A) and adeS (K121E) which might have positive effect on over expression of the pump. Conclusion: This is probably the first study that showed the active efflux pumps appeared to play important roles in the lactam resistance of A. baumannii isolated from neonates. Therefore, efflux pump inhibitors may be useful as adjunct therapy for treatment of these multidrug-resistant strains. [ABSTRACT FROM AUTHOR]

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