The effect of elevated physiological temperatures on bacterial survival and antibiotic susceptibility in an in vitro infection prevention model

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Aims Prosthetic joint infection (PJI) is a devastating adverse outcome of total joint arthroplasty surgery, and is often accompanied by treatment failure. Due to a rise in the number of orthopaedic implants and global antimicrobial resistance, non-antibiotic strategies for preventing and treating orthopaedic infections are needed. This study investigates the effect of temperature in the physiological range on bacterial killing, bacterial adhesion and the antibiotic susceptibility of bacteria. Methods Planktonic phase clinical isolates of methicillin-sensitive Staphylococcus aureus , methicillin-sensitive Staphylococcus epidermidis and Escherichia coli at 103 colony forming units (CFU)/mL were exposed for 24 h to 32 °C, 37 °C, 40 °C, and 42 °C with and without cefazolin or gentamicin in the subtherapeutic to therapeutic range. Thereafter, the bacterial load in the planktonic and adhered fractions was enumerated in CFU/mL. Dose–response curves were fitted into the data to find the effect of temperature on the antibiotic dose needed for bacterial eradication. Results Increasing the temperature from 32 to 42 °C reduced the minimum concentration required to kill Staphylococcus aureus from 0.5 to 0.05 μg/mL for both gentamicin and cefazolin. Almost full eradication of Staphylococcus aureus was achieved at 42 °C without antibiotics. Staphylococcus epidermidis demonstrated enhanced susceptibility to cefazolin at increased temperatures, with a 6-log reduction in CFU/mL upon exposure to 0.1 μg/mL cefazolin at 42 °C compared to lower temperatures. Notably, antibiotic efficacy at 32 °C was impaired compared to 37 °C. Escherichia coli did not exhibit significant changes in CFU/mL at any temperature. Conclusion These in vitro data strongly indicates that elevated temperatures within the physiological range effectively reduce the bacterial load and increase antibiotic susceptibility of the most common Gram-positive pathogens found in PJI. Conversely, hypothermic conditions reduced the bacterial susceptibility to antibiotics. Since the risks involved within the tested temperature range are minimal, applying elevated temperatures to prevent orthopaedic infections may have clinical benefits.

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