1. Evaluation of intraosteoblastic activity of dalbavancin against Staphylococcus aureus in an ex vivo model of bone cell infection
- Author
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Pierre Chauvelot, Lelia Abad, Tristan Ferry, Céline Dupieux-Chabert, Jérôme Josse, Frédéric Laurent, Aubin Souche, and Florent Valour
- Subjects
Microbiology (medical) ,Staphylococcus aureus ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,Bone cell ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,biology ,business.industry ,Significant difference ,Dalbavancin ,Staphylococcal Infections ,biology.organism_classification ,Anti-Bacterial Agents ,Infectious Diseases ,Vancomycin ,Teicoplanin ,business ,Rifampicin ,Ex vivo ,Bacteria ,medicine.drug - Abstract
Objectives Long-acting lipoglycopeptides are promising therapeutic options in Staphylococcus aureus bone and joint infections (BJIs). This study evaluated the ability of dalbavancin to eradicate the intraosteoblastic reservoir of S. aureus, associated with BJI chronicity. Methods Osteoblastic cells were infected with a standardized inoculum of the S. aureus reference strain HG001 and incubated for 24 h with dalbavancin, vancomycin or rifampicin using the MIC, 10×MIC, 100×MIC and/or the intraosseous concentrations reached using standard therapeutic doses (i.e. vancomycin, 10 mg/L; rifampicin, 2 mg/L; and dalbavancin, 6 mg/L). The remaining intracellular bacteria were quantified by plating cell lysates. Results MICs of dalbavancin, vancomycin and rifampicin were 0.125, 1 and 0.004 mg/L, respectively. Dalbavancin significantly reduced the intracellular inoculum of S. aureus starting at a concentration equal to the MIC, with a significant dose effect, ranging from a reduction of 31.4% (95% CI = 17.6%–45.2%) at MIC to 51.6% (95% CI = 39.8%–63.4%) at 100×MIC compared with untreated cells. Of note, dalbavancin was the only molecule to significantly reduce the intraosteoblastic inoculum at low concentration (MIC). At intraosseous concentrations, dalbavancin reduced the intracellular inoculum by 49.6% (95% CI = 45.1%–54.1%) compared with untreated cells (P Conclusions Dalbavancin was able to decrease the intraosteoblastic S. aureus inoculum by 50% at intraosseous concentrations reached during standard human therapeutic dosing, with no difference compared with vancomycin, and remained less efficient than rifampicin. However, it was the only molecule significantly active at low concentration.
- Published
- 2021
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