PMID- 30602511
OWN - NLM
STAT- MEDLINE
DCOM- 20200218
LR  - 20200309
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 63
IP  - 3
DP  - 2019 Mar
TI  - Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients 
      with Augmented Creatinine Clearance?
LID - 10.1128/AAC.02134-18 [doi]
LID - e02134-18
AB  - The objective of the present study was to determine whether augmented renal 
      clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic 
      (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 
      9-month period, all critically ill patients treated with ceftriaxone were 
      eligible. During the first 3 days of antimicrobial therapy, every patient 
      underwent 24-h creatinine clearance (CL(CR)) measurements and therapeutic drug 
      monitoring of unbound ceftriaxone. ARC was defined by a CL(CR) of >/=150 ml/min. 
      Empirical underdosing was defined by a trough unbound ceftriaxone concentration 
      under 2 mg/liter (percentage of the time that the concentration of the free 
      fraction of drug remained greater than the MIC [fT(>MIC)], 100%). Monte Carlo 
      simulation (MCS) was performed to determine the probability of target attainment 
      (PTA) of different dosing regimens for various MICs and three groups of CL(CR) 
      (<150, 150 to 200, and >200 ml/min). Twenty-one patients were included. The rate 
      of empirical ceftriaxone underdosing was 62% (39/63). A CL(CR) of >/=150 ml/min was 
      associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% 
      confidence interval [CI] = 2.5 to 30.7; P < 0.01). Ceftriaxone PK concentrations 
      were best described by a two-compartment model. CL(CR) was associated with 
      unbound ceftriaxone clearance (P = 0.02). In the MCS, the proportion of patients 
      who would have failed to achieve a 100% fT(>MIC) was significantly higher in ARC 
      patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P < 0.01). A 
      dose of 2 g twice a day was best suited to achieve a 100% fT(>MIC) When targeting 
      a 100% fT(>MIC) for the less susceptible pathogens, patients with a CL(CR) of 
      >/=150 ml/min remained at risk of empirical ceftriaxone underdosing. These data 
      emphasize the need for therapeutic drug monitoring in ARC patients.
CI  - Copyright (c) 2019 American Society for Microbiology.
FAU - Ollivier, Julien
AU  - Ollivier J
AD  - Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.
FAU - Carrie, Cedric
AU  - Carrie C
AD  - Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France 
      cedric.carrie@chu-bordeaux.fr.
FAU - d'Houdain, Nicolas
AU  - d'Houdain N
AD  - Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.
FAU - Djabarouti, Sarah
AU  - Djabarouti S
AD  - Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.
AD  - Pharmacokinetics and PK/PD Group, INSERM 1034, Universite Bordeaux, Bordeaux, 
      France.
FAU - Petit, Laurent
AU  - Petit L
AD  - Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France.
FAU - Xuereb, Fabien
AU  - Xuereb F
AD  - Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.
AD  - Pharmacokinetics and PK/PD Group, INSERM 1034, Universite Bordeaux, Bordeaux, 
      France.
AD  - Universite Bordeaux Segalen, Bordeaux, France.
FAU - Legeron, Rachel
AU  - Legeron R
AD  - Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.
AD  - Pharmacokinetics and PK/PD Group, INSERM 1034, Universite Bordeaux, Bordeaux, 
      France.
AD  - Universite Bordeaux Segalen, Bordeaux, France.
FAU - Biais, Matthieu
AU  - Biais M
AD  - Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France.
AD  - Universite Bordeaux Segalen, Bordeaux, France.
FAU - Breilh, Dominique
AU  - Breilh D
AD  - Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.
AD  - Pharmacokinetics and PK/PD Group, INSERM 1034, Universite Bordeaux, Bordeaux, 
      France.
AD  - Universite Bordeaux Segalen, Bordeaux, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190226
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 75J73V1629 (Ceftriaxone)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Adult
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacokinetics/therapeutic use
MH  - Ceftriaxone/administration & dosage/*pharmacokinetics/therapeutic use
MH  - Creatinine/*urine
MH  - Critical Care
MH  - Critical Illness
MH  - Drug Monitoring/*methods
MH  - Female
MH  - Humans
MH  - Intensive Care Units
MH  - Male
MH  - Metabolic Clearance Rate/*physiology
MH  - Microbial Sensitivity Tests
MH  - Middle Aged
PMC - PMC6395919
OTO - NOTNLM
OT  - augmented renal clearance
OT  - ceftriaxone
OT  - intensive care
OT  - pharmacokinetics
EDAT- 2019/01/04 06:00
MHDA- 2020/02/19 06:00
PMCR- 2019/08/26
CRDT- 2019/01/04 06:00
PHST- 2018/10/08 00:00 [received]
PHST- 2018/12/11 00:00 [accepted]
PHST- 2019/01/04 06:00 [pubmed]
PHST- 2020/02/19 06:00 [medline]
PHST- 2019/01/04 06:00 [entrez]
PHST- 2019/08/26 00:00 [pmc-release]
AID - AAC.02134-18 [pii]
AID - 02134-18 [pii]
AID - 10.1128/AAC.02134-18 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02134-18. doi: 
      10.1128/AAC.02134-18. Print 2019 Mar.