Isobolographic analysis of the ciprofloxacin-gentamicin combination against beta-lactamase-producing Staphylococcus aureus

Fundam Clin Pharmacol. 2023 Dec;37(6):1198-1204. doi: 10.1111/fcp.12933. Epub 2023 Jun 23.

Abstract

Background: Bacterial multi-resistance is a serious global problem that continues to worsen over time due to multiple factors. Among these factors, it is important to highlight the clinical misuse of antibiotics and the mechanisms that microorganisms have developed to protect themselves from these drugs. In this sense, Staphylococcus aureus (S. aureus) is a pathogen that has found a way to resist many of the drugs currently in use, so infections by this bacterium represent a serious clinical problem.

Objectives: The purpose of this study was to determine the type of interaction between ciprofloxacin and gentamicin against beta-lactamase-producing S. aureus using isobolographic analysis.

Methods: Ciprofloxacin (0.5-0.05 mg/mL) and gentamicin (10-1 mg/mL) were used to make concentration-dependent curves for each individual drug. Thereafter, the 50 inhibitory concentration (IC50 ) of each drug was obtained, and different proportions of the ciprofloxacin-gentamicin combination-0.5:0.5, 0.8:0.2, 0.2:0.8, 0.9:0.1, 0.1:0.9, 0.95:0.05, and 0.05:0.95-were evaluated. The isobolographic analysis and the interaction index were used to analyze the data.

Results: The isobolographic evaluation of the combination showed that the ratios 0.5:0.5, 0.8:0.2, 0.2:0.8, and 0.9:0.1 produced a synergistic anti-staphylococcal effect, and the 0.95:0.05 ratio induced an additive antibacterial effect. Finally, the 0.1:0.9 and 0.05:0.95 ratios of the combination presented antagonistic effects against S. aureus. On the other hand, the interaction index showed similar results to the isobolographic analysis.

Conclusion: The isobolographic results of this in vitro assay show that the ciprofloxacin-gentamicin combination induces synergistic, additive, and antagonistic antimicrobial effects against S. aureus.

Keywords: S. aureus; ciprofloxacin; drug interaction; gentamicin.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Ciprofloxacin* / pharmacology
  • Drug Synergism
  • Gentamicins / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Staphylococcal Infections* / drug therapy
  • Staphylococcal Infections* / microbiology
  • Staphylococcus aureus
  • beta-Lactamases / pharmacology

Substances

  • Ciprofloxacin
  • Gentamicins
  • beta-Lactamases
  • Anti-Bacterial Agents