PMID- 33869238
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210421
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 8
DP  - 2021
TI  - Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive 
      Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With 
      Prosthetic Joint Infection.
PG  - 583086
LID - 10.3389/fmed.2021.583086 [doi]
LID - 583086
AB  - Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in 
      patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug 
      administration can facilitate this therapy in outpatient setting, but there is 
      limited information about this practice. We have developed an original approach 
      for drug dosing in this context, based on therapeutic drug monitoring (TDM) and 
      pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study 
      was to describe our approach and its first results in a case series. We analyzed 
      data from patients who received suppressive antibiotic therapy by subcutaneous 
      (SC) route with beta-lactams as salvage therapy for prosthetic joint infection 
      (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and 
      four men with a mean age of 77 years) were included from January 2017 to May 
      2020. The drugs administered by SC route were ceftazidime (n = 4), ertapenem (n = 
      4), and ceftriaxone (n = 2). In each patient, PK/PD-guided dosage 
      individualization was performed based on TDM and minimum inhibitory concentration 
      (MIC) measurements. The dose interval could be prolonged from twice daily to 
      thrice weekly in some patients, while preserving the achievement of PK/PD 
      targets. The infection was totally controlled by the strategy in nine out the 10 
      patients during a median follow-up of 1,035 days (~3 years). No patient acquired 
      carbapenem-resistant Gram-negative bacteria during the follow-up. One patient 
      presented treatment failure with acquired drug resistance under therapy, which 
      could be explained by late MIC determination and insufficient exposure, 
      retrospectively. To conclude, our innovative approach, based on model-based TDM, 
      MIC determination, and individualized PK/PD goals, facilitates, and optimizes 
      suppressive outpatient beta-lactam therapy administered by SC route for PJI. 
      These encouraging results advocate for larger clinical evaluation.
CI  - Copyright (c) 2021 Goutelle, Conrad, Pouderoux, Braun, Laurent, Gagnieu, Cohen, 
      Guitton, Valour and Ferry.
FAU - Goutelle, Sylvain
AU  - Goutelle S
AD  - Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, 
      France.
AD  - Univ Lyon, Universite Lyon 1, ISPB, Faculte de Pharmacie de Lyon, Lyon, France.
AD  - Univ Lyon, Universite Lyon 1, UMR CNRS 5558, Laboratoire de Biometrie et Biologie 
      Evolutive, Villeurbanne, France.
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
FAU - Conrad, Anne
AU  - Conrad A
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
AD  - Service des maladies infectieuses et tropicales, Hopital de la Croix-Rousse, 
      Hospices Civils de Lyon, Lyon, France.
AD  - Universite Claude Bernard Lyon 1, Lyon, France.
AD  - CIRI-Centre International de Recherche en Infectiologie, Inserm U1111, Universite 
      Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ 
      Lyon, Lyon, France.
FAU - Pouderoux, Cecile
AU  - Pouderoux C
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
AD  - Service des maladies infectieuses et tropicales, Hopital de la Croix-Rousse, 
      Hospices Civils de Lyon, Lyon, France.
FAU - Braun, Evelyne
AU  - Braun E
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
AD  - Service des maladies infectieuses et tropicales, Hopital de la Croix-Rousse, 
      Hospices Civils de Lyon, Lyon, France.
FAU - Laurent, Frederic
AU  - Laurent F
AD  - Univ Lyon, Universite Lyon 1, ISPB, Faculte de Pharmacie de Lyon, Lyon, France.
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
AD  - CIRI-Centre International de Recherche en Infectiologie, Inserm U1111, Universite 
      Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ 
      Lyon, Lyon, France.
AD  - Institut des Agents Infectieux, Laboratoire de bacteriologie, Centre National de 
      reference des staphylocoques, Hopital de la Croix-Rousse, Hospices Civils de 
      Lyon, Lyon, France.
FAU - Gagnieu, Marie-Claude
AU  - Gagnieu MC
AD  - Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et 
      Biologie Moleculaire, UM Pharmacologie-Toxicologie, Lyon, France.
FAU - Cohen, Sabine
AU  - Cohen S
AD  - Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et 
      Biologie Moleculaire, UM Pharmacologie-Toxicologie, Lyon, France.
FAU - Guitton, Jerome
AU  - Guitton J
AD  - Univ Lyon, Universite Lyon 1, ISPB, Faculte de Pharmacie de Lyon, Lyon, France.
AD  - Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et 
      Biologie Moleculaire, UM Pharmacologie-Toxicologie, Lyon, France.
FAU - Valour, Florent
AU  - Valour F
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
AD  - Service des maladies infectieuses et tropicales, Hopital de la Croix-Rousse, 
      Hospices Civils de Lyon, Lyon, France.
AD  - Universite Claude Bernard Lyon 1, Lyon, France.
AD  - CIRI-Centre International de Recherche en Infectiologie, Inserm U1111, Universite 
      Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ 
      Lyon, Lyon, France.
FAU - Ferry, Tristan
AU  - Ferry T
AD  - Centre interregional de reference pour la prise en charge des infections 
      osteo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, 
      France.
AD  - Service des maladies infectieuses et tropicales, Hopital de la Croix-Rousse, 
      Hospices Civils de Lyon, Lyon, France.
AD  - Universite Claude Bernard Lyon 1, Lyon, France.
AD  - CIRI-Centre International de Recherche en Infectiologie, Inserm U1111, Universite 
      Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Superieure de Lyon, Univ 
      Lyon, Lyon, France.
LA  - eng
PT  - Journal Article
DEP - 20210331
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC8044368
OTO - NOTNLM
OT  - antimicrobial therapy
OT  - beta-lactam
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - prosthetic-joint infection
OT  - subcutaneous administration
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/20 06:00
MHDA- 2021/04/20 06:01
PMCR- 2021/03/31
CRDT- 2021/04/19 06:33
PHST- 2020/07/14 00:00 [received]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/04/19 06:33 [entrez]
PHST- 2021/04/20 06:00 [pubmed]
PHST- 2021/04/20 06:01 [medline]
PHST- 2021/03/31 00:00 [pmc-release]
AID - 10.3389/fmed.2021.583086 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2021 Mar 31;8:583086. doi: 10.3389/fmed.2021.583086. 
      eCollection 2021.