title: Staphylococcus aureus osteo-articular infection: usefulness of the determination of daptomycin serum concentration to explain a treatment failure.
abstract: We report two cases of treatment failure in patients with osteoarticular infection associated withStaphylococcus aureusbacteremia and receiving daptomycin. Using a published population-pharmacokinetic model and daptomycin blood level in these patients, area under the curve (AUC) was calculated and compared to the pharmacological target. For the first patient, treated with 6 mg/kg every 48 hours due to acute renal failure and then every 24 hours, the AUC was 820 mg×h×L-1, with a minimal concentration of 23.5 mg/L confirming the right dose adjustment and the absence of underdosing. The methicillin-resistantStaphylococcus aureus(MRSA) strain was still susceptible to daptomycin, but it was not sufficient to observe a favorable outcome. For the second patient, treated with 10 mg/kg/d, the steady state residual concentration was 10.4 mg/L, and the calculated AUC value was 550 mg×h×L-1. AUC/MIC values evolved during treatment to be under the cut-off for bactericidal effects (> 800 hours), and theStaphylococcus aureus(SA) strain became daptomycin resistant. This study highlights the inter-individual pharmacokinetic variation leading sometimes to drug underdosing. Drug monitoring should be encouraged in order to avoid treatment failure.
authors: Sylvain
authors: S
authors: Barreau
authors: Sihem
authors: S
authors: Benaboud
authors: Solen
authors: S
authors: Kernéis
authors: Laurence
authors: L
authors: Moachon
authors: Philippe
authors: P
authors: Blanche
authors: Matthieu
authors: M
authors: Groh
authors: Laurent
authors: L
authors: Massias
authors: Jean-Marc
authors: JM
authors: Treluyer
authors: Claire
authors: C
authors: Poyart
authors: Josette
authors: J
authors: Raymond
mesh_terms: D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001850:Bone Diseases, Infectious / Q000188:drug therapy* / Q000382:microbiology*; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000382:microbiology*; D002358:Cartilage, Articular; D017576:Daptomycin / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D010019:Osteomyelitis / Q000188:drug therapy / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D017211:Treatment Failure; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin