Abstract
BackgroundEven if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.MethodsWe performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves.ResultsForty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6–303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulase-negative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE.ConclusionsProlonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded.
Highlights
Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection
In line with the definition given by the Health-care Supply Office (Direction Générale de l’Offre de Soins, DGOS) of the French Health Ministry (Ministère des Affaires Sociales et de la Santé), BJI was considered complex in the following circumstances: (i) relapsing BJI; and/or (ii) intolerance to first-line antimicrobial therapy; and/or (iii) requirement of large bone resection and/or reconstruction; and/or (iv) multi-drug resistant pathogen limiting therapeutic opportunities, such as a glycopeptide-resistant Grampositive isolate
Susceptibility to glycopeptides and daptomycin was assessed in methicillin-resistant staphylococci based on the criteria of the European Committee on Antimicrobial Susceptibility Testing (EUCAST: Breakpoint tables for interpretation of minimum inhibitory concentrations [MICs] and zone diameters, version 4.0), if the strain was available at the time of daptomycin prescription
Summary
Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. Daptomycin is a cyclic lipopeptide with rapid bactericidal action against Gram-positive bacteria, and is approved for complicated skin and skin-structure infection (4 mg/kg/day intravenously) and Staphylococcus aureus bacteraemia and/or right-side endocarditis (6 mg/kg/d) Beyond these FDA and European-approved indications, daptomycin is increasingly used in BJI, as: (i) Grampositive cocci are the most frequent pathogens in BJI; (ii) staphylococci exhibit growing resistance to betalactams and glycopeptides; (iii) a randomized controlled trial supported the use of daptomycin in these patients [4]. As bone penetration of daptomycin is limited, some authors proposed higher doses in BJI: i.e., 8 mg/kg/d [6] This attitude is supported by the retrospective post-marketing Eu-CORE® study, but prospective data are lacking, especially in patients at high risk of relapse receiving prolonged daptomycin therapy [7]
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