PMID- 37467019 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240329 IS - 1537-6591 (Electronic) IS - 1058-4838 (Linking) VI - 77 IP - 10 DP - 2023 Nov 17 TI - Daptomycin Exposure as a Risk Factor for Daptomycin-Induced Eosinophilic Pneumonia and Muscular Toxicity. PG - 1372-1380 LID - 10.1093/cid/ciad386 [doi] AB - BACKGROUND: High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin. METHODS: All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model. RESULTS: From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L. CONCLUSIONS: We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Garreau, Romain AU - Garreau R AUID- ORCID: 0000-0002-6605-4808 AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France. AD - LBBE-Laboratoire de Biometrie et Biologie Evolutive, CNRS, UMR 5558, Universite Lyon 1, Villeurbanne, France. FAU - Pham, Truong-Thanh AU - Pham TT AUID- ORCID: 0000-0003-0284-7080 AD - Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland. AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Hopital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre de Reference pour la prise en charge des Infections Osteo-Articulaires complexes (CRIOAc Lyon), Lyon, France. FAU - Bourguignon, Laurent AU - Bourguignon L AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France. AD - LBBE-Laboratoire de Biometrie et Biologie Evolutive, CNRS, UMR 5558, Universite Lyon 1, Villeurbanne, France. AD - Facultes de Medecine et de Pharmacie de Lyon, Univ Lyon, Universite Lyon 1, ISPB, Lyon, France. FAU - Millet, Aurelien AU - Millet A AD - Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moleculaire, UM Pharmacologie -Toxicologie, Lyon, France. FAU - Parant, Francois AU - Parant F AD - Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moleculaire, UM Pharmacologie -Toxicologie, Lyon, France. FAU - Bussy, David AU - Bussy D AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Hopital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre de Reference pour la prise en charge des Infections Osteo-Articulaires complexes (CRIOAc Lyon), Lyon, France. FAU - Desevre, Marine AU - Desevre M AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Hopital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre de Reference pour la prise en charge des Infections Osteo-Articulaires complexes (CRIOAc Lyon), Lyon, France. FAU - Franchi, Victor AU - Franchi V AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Hopital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre de Reference pour la prise en charge des Infections Osteo-Articulaires complexes (CRIOAc Lyon), Lyon, France. FAU - Ferry, Tristan AU - Ferry T AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Hopital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre de Reference pour la prise en charge des Infections Osteo-Articulaires complexes (CRIOAc Lyon), Lyon, France. AD - Facultes de Medecine et de Pharmacie de Lyon, Univ Lyon, Universite Lyon 1, ISPB, Lyon, France. AD - CIRI-Centre International de Recherche en Infectiologie, Inserm, U1111, UniversiteĢ Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ Lyon, Lyon, France. FAU - Goutelle, Sylvain AU - Goutelle S AUID- ORCID: 0000-0002-1853-2932 AD - Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France. AD - LBBE-Laboratoire de Biometrie et Biologie Evolutive, CNRS, UMR 5558, Universite Lyon 1, Villeurbanne, France. AD - Facultes de Medecine et de Pharmacie de Lyon, Univ Lyon, Universite Lyon 1, ISPB, Lyon, France. LA - eng PT - Journal Article PL - United States TA - Clin Infect Dis JT - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JID - 9203213 RN - NWQ5N31VKK (Daptomycin) RN - 0 (Anti-Bacterial Agents) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Humans MH - *Daptomycin/therapeutic use MH - Anti-Bacterial Agents/therapeutic use MH - *Pulmonary Eosinophilia/chemically induced/drug therapy MH - Myotoxicity/drug therapy MH - Prospective Studies MH - Bayes Theorem MH - C-Reactive Protein MH - Risk Factors OTO - NOTNLM OT - daptomycin OT - eosinophilic pneumonia OT - myopathy OT - pharmacokinetics OT - therapeutic drug monitoring COIS- Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. EDAT- 2023/07/19 13:06 MHDA- 2024/02/12 18:42 CRDT- 2023/07/19 11:53 PHST- 2023/02/15 00:00 [received] PHST- 2024/02/12 18:42 [medline] PHST- 2023/07/19 13:06 [pubmed] PHST- 2023/07/19 11:53 [entrez] AID - 7226491 [pii] AID - 10.1093/cid/ciad386 [doi] PST - ppublish SO - Clin Infect Dis. 2023 Nov 17;77(10):1372-1380. doi: 10.1093/cid/ciad386.