Synergy between induction heating, antibiotics, and N-acetylcysteine eradicates Staphylococcus aureus from biofilm

Int J Hyperthermia. 2020;37(1):130-136. doi: 10.1080/02656736.2019.1710269.

Abstract

Background: Non-contact induction heating (NCIH) is a noninvasive treatment modality that can be used to cause thermal damage to bacterial biofilms on a metal implant surface in the context of a prosthetic joint infection. The purpose of this study was (1) to determine the effectiveness of NCIH on killing Staphylococcus aureus from biofilm and (2) to determine the possible synergistic effect of NCIH and cocktails of antibiotics and N-acetylcysteine (NAC).Methods:Staphylococcus aureus biofilms were grown on titanium alloy (Ti6Al4V) coupons. These coupons were heated to 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C for 3.5 min and subsequently exposed to cocktails of vancomycin, rifampicin and NAC at clinically relevant concentrations over 24 h.Results: In the control group without induction heating, 2.2*107 colony forming units (CFU)/cm2 were observed. At 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C, a reduction of 0.3-log, 3.9-log, 4.2-log, 4.3-log, and 6.6-log CFU/cm2 were observed, respectively. There was synergy between antibiotics and induction heating that resulted in less than 100 CFU/cm2 remaining after 3.5 min at 60 °C, and exposure to vancomycin and rifampicin. Total eradication was observed at 80 °C. Total eradication was also observed at 60 °C and a cocktail of antibiotics with NAC.Conclusion: Induction heating of titanium alloy coupons is effective for the reduction of bacterial load in vitro in S. aureus biofilms. Induction heating and cocktails of antibiotics and NAC have a synergistic effect that results in the total eradication of the biofilm at 60 °C and higher for clinically relevant concentrations of vancomycin, rifampicin and NAC.

Keywords: Infection; antibiotics; induction heating; prosthetic joint infection (PJI); total joint replacement.

MeSH terms

  • Acetylcysteine / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Biofilms / drug effects*
  • Heating / methods*
  • Humans
  • Staphylococcus aureus / drug effects*

Substances

  • Anti-Bacterial Agents
  • Acetylcysteine