Synergistic Effect of Tazobactam on Amikacin MIC in Acinetobacter baumannii Isolated from Burn Patients in Tehran, Iran

Curr Pharm Biotechnol. 2020;21(10):997-1004. doi: 10.2174/1389201021666200220121122.

Abstract

Background: Burn is still an important global public health challenge. Wound colonization of antibiotic resistant bacteria such as Acinetobacter baumannii can lead to high morbidity and mortality in burn patients. The aim of this study was to evaluate the inhibitory effect of tazobactam on efflux pump, which can cause aminoglycoside resistant in A. baumannii isolated from burn patients.

Methods: In this study, 47 aminoglycoside resistant A. baumannii spp. were obtained from burn patients, admitted to the Shahid Motahari Burns Hospital in Tehran, Iran, during June-August 2018. The inhibitory effect of tazobactam against adeB such as efflux pump was evaluated by Minimum Inhibitory Concentration (MIC) determination of amikacin alone and in combination with tazobactam. Fractional Inhibitory Concentration index (FIC) was used to determine the efficacy of tazobactam/ amikacin combination. Further, semi-quantitative Real- Time PCR was performed to quantify the expression rates of the adeB gene before and after addition of tazobactam/amikacin.

Results: The MIC values were significantly reduced when a combined amikacin and tazobactam was utilized. The most common interaction observed was synergistic (78.2%), followed by.additive effects (21.8%), as per FIC results. The adeB mRNA expression levels were found to be downregulated in 60.7% of isolates treated with tazobactam.

Conclusion: Tazobactam can have impact on resistance to aminoglycoside by inhibiting efflux pump. Thus, the combination of tazobactam with amikacin can be used as an alternative treatment approach in multidrug resistant A. baumannii infections.

Keywords: Acinetobacter baumannii; aminoglycoside; antibiotic resistant; minimum inhibition concentration; synergism effect; tazobactam.

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / isolation & purification
  • Amikacin / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Burns / drug therapy
  • Burns / microbiology*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Synergism
  • Genes, Bacterial
  • Humans
  • Iran
  • Microbial Sensitivity Tests
  • Tazobactam / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Amikacin
  • Tazobactam