Investigation of the in vitro antimicrobial activity of eravacycline alone and in combination with various antibiotics against MDR Acinetobacter baumanni strains.

Abstract

Background: Acinetobacter baumannii is an obligately aerobic, non-motile, non-fermenting, gram-negative, opportunistic pathogen. The fact that this pathogen, which is the leading cause of nosocomial infections, is naturally resistant to many antibiotics and quickly acquires new resistance mechanisms gradually limits the antibiotic options that can be used in treatment. So, our study aims to investigate the in vitro antibacterial effects of eravacycline, a new tetracycline-class antibiotic, and compare this antibiotic with the antibiotics used in the clinic to treat the infection caused by A. baumannii. Also, eravacycline was tested in combination with meropenem or colistin against A. baumannii strains, which are resistant to colistin and meropenem. The antibiotic susceptibility of strains was determined by the microbroth dilution method. In addition, the agar dilution method determined the mutant inhibition concentration (MPC) values of the studied antibiotics. To investigate the effects of the antibiotics mentioned in our study on biofilm formation, the biofilm-forming abilities of the strains were evaluated by the crystal violet staining method. The bactericidal and synergistic effects of the studied antibiotics alone or in combination were determined by the time-dependent killing curve (TKC) method.

Results: The present antibacterial susceptibility experiments showed that 98% of the strains were multi-drug resistant (MDR). Our results in mutant inhibition studies showed that eravacycline is an antibiotic with the potential to prevent the emergence of resistant mutants with its low MPC value. When the effects of antibiotics on biofilm formation were investigated in our thesis study, it was determined that 95% of our strains formed biofilm. In biofilm inhibition experiments, it was observed that eravacycline at minimum inhibitory concentration (MIC) inhibited biofilm formation by 84% alone, 86% combined with colistin, and 85% combined with meropenem. Our combination experiments showed that 1×MIC eravacycline-meropenem and 4×MIC eravacycline-colistin combinations were synergistic against A. baumannii strains. In addition, the combination of 4×MIC eravacycline-meropenem also showed bactericidal activity at the 24th hour. No antagonist effects were detected in our combination studies.

Conclusion: Present results reveal essential pharmacodynamic data on eravacycline, a new antibiotic for treating A. baumannii infections, which poses a global threat.

Clinical trial number: Not applicable.