title: Antimicrobial activity against intraosteoblastic Staphylococcus aureus.
abstract: Although Staphylococcus aureus persistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in an ex vivo osteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001 S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of -2.5, -3.1, -3.9, -4.2, -4.9, -4.9, and -5.2 log10 CFU/100,000 cells, respectively (P < 10(-4)). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin.
authors.affiliation: Infectious Diseases Department, Hospices Civils de Lyon, Lyon, France INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France florent.valour@chu-lyon.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Valour
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Trouillet-Assant
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Riffard
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Jason
authors.initials: J
authors.lastname: Tasse
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Flammier
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Infectious Diseases Department, Hospices Civils de Lyon, Lyon, France INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chidiac
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France French National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Infectious Diseases Department, Hospices Civils de Lyon, Lyon, France INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.affiliation: INSERM U1111, International Centre for Research in Infectiology, Université Claude Bernard Lyon 1, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France French National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001850:Bone Diseases, Infectious / Q000188:drug therapy / Q000382:microbiology; D002460:Cell Line; D003114:Colony-Forming Units Assay; D006801:Humans; D008826:Microbial Sensitivity Tests; D010006:Osteoblasts / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents