Evaluation of intraosteoblastic activity of dalbavancin against Staphylococcus aureus in an ex vivo model of bone cell infection

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 Osteoblast...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2021-11, Vol.76 (11), p.2863-2866
Main Authors: Chauvelot, Pierre, Dupieux-Chabert, Céline, Abad, Lélia, Souche, Aubin, Ferry, Tristan, Josse, Jérôme, Laurent, Frédéric, Valour, Florent
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Humans
Life Sciences
Microbial Sensitivity Tests
Staphylococcal Infections - drug therapy
Staphylococcus aureus
Teicoplanin - analogs & derivatives
Teicoplanin - pharmacology
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Summary: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 
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkab299