• María Ángeles Meléndez-Carmona, Irene Muñoz-Gallego, Esther Viedma, Jaime Lora-Tamayo, and Fernando Chaves.
• Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain.
• Int. J. Antimicrob. Agents. 2019 Sep 1; 54 (3): 356-360.

BackgroundStaphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the intracellular reservoir may lead to infection relapse. This study assessed the intracellular activity of levofloxacin and rifampin in an in-vitro model of human osteoblastic infection.MethodsTen meticillin-susceptible S. aureus strains were used to infect osteoblastic MG63 cells. Osteoblasts were challenged with rifampin and levofloxacin at cortical and cancellous bone concentrations. Efficacy was measured as the intracellular counts of colony-forming units (log10CFU) compared with untreated controls. The emergence of small colony variants (SCVs) was determined, and the results were stratified according to the patient's prognosis (six cured and four with persistence/relapse).ResultsAll regimes led to a significant decrease in CFU count compared with controls (1-2 log10CFU). Levofloxacin was the most effective treatment at both cortical and cancellous bone concentrations (-2.4 to -1.9 log10CFU, respectively). The addition of rifampin to levofloxacin did not improve performance (-1.9 log10CFU for cortical concentration and -1.8 log10 CFU for cancellous concentration). An increase in SCVs was observed in the presence of rifampin. The efficacy of antimicrobials was higher and the formation of SCVs was lower against strains belonging to PJIs with a favourable outcome.ConclusionsLevofloxacin plus rifampin had good intracellular activity against S. aureus. However, from the intracellular perspective, the addition of rifampin to levofloxacin showed no benefit but could account for an increased number of SCVs.Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

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