PMID- 35533793
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20220608
IS  - 1872-7913 (Electronic)
IS  - 0924-8579 (Linking)
VI  - 59
IP  - 6
DP  - 2022 Jun
TI  - Therapeutic drug monitoring and clinical outcomes in severely ill patients 
      receiving amoxicillin: a single-centre prospective cohort study.
PG  - 106601
LID - S0924-8579(22)00110-8 [pii]
LID - 10.1016/j.ijantimicag.2022.106601 [doi]
AB  - Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is increasingly used to 
      overcome rising antimicrobial resistance and improve antibiotic exposure. 
      However, there is little guidance on target amoxicillin plasma concentrations. We 
      aimed to define these by evaluating associations between amoxicillin 
      concentrations and clinical outcomes. This single-centre prospective cohort study 
      enrolled severely ill and/or immunosuppressed adult patients receiving 
      amoxicillin for suspected or confirmed bacterial infection. TDM with >/=1 
      intermediate and >/=1 trough level was performed 24 h after therapy initiation. 
      Primary and secondary outcomes were incidence of adverse events (AEs) and 
      clinical failure through Day 30, respectively. A total of 156 patients were 
      included. Important variations were observed both for intermediate (mean 13 mg/L, 
      S.D. 13) and trough (mean 7 mg/L, S.D. 9) amoxicillin levels. Of 111 patients, 33 
      (30%) had trough levels below the non-species-related breakpoint (2 mg/L). AEs 
      occurred in 27/156 patients (17%); no intermediate- or trough-level threshold 
      predicting toxicity could be established. Patients with the highest-quartile 
      trough levels (9.07-51.5 mg/L) did not experience significantly increased AEs 
      [6/28 (21%) vs. 13/83 (16%); P = 0.6]. Nearly one-third (48/156; 31%) experienced 
      clinical failure; low trough levels did not correlate with failure. There were 
      few amoxicillin AEs yet a relatively high incidence of clinical failure. While no 
      toxicity threshold could be established, the absence of increased AEs among 
      patients with the highest trough concentrations suggests that trough levels up to 
      40 mg/L may be safe, at least for limited durations. Larger trials must further 
      define optimal amoxicillin concentrations. [ClinicalTrials.gov ID: NCT03790631].
CI  - Copyright (c) 2022 Elsevier Ltd and International Society of Antimicrobial 
      Chemotherapy. All rights reserved.
FAU - Marti, Christophe
AU  - Marti C
AD  - Division of General Internal Medicine, Geneva University Hospitals, Rue Gabrielle 
      Perret-Gentil 4, 1205, Geneva, Switzerland. Electronic address: 
      Christophe.marti@hcuge.ch.
FAU - Stirnemann, Jerome
AU  - Stirnemann J
AD  - Division of General Internal Medicine, Geneva University Hospitals, Rue Gabrielle 
      Perret-Gentil 4, 1205, Geneva, Switzerland.
FAU - Lescuyer, Pierre
AU  - Lescuyer P
AD  - Division of Laboratory Medicine, Geneva University Hospitals, Rue Gabrielle 
      Perret-Gentil 4, 1205, Geneva, Switzerland.
FAU - Tonoli, David
AU  - Tonoli D
AD  - Division of Laboratory Medicine, Geneva University Hospitals, Rue Gabrielle 
      Perret-Gentil 4, 1205, Geneva, Switzerland.
FAU - von Dach, Elodie
AU  - von Dach E
AD  - Center for Clinical Research, Clinical Trials Unit, Geneva University Hospitals, 
      Rue Gabrielle Perret-Gentil 4, 1205, Geneva, Switzerland; Division of Infectious 
      Diseases, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, Geneva, 
      Switzerland.
CN  - OPTIMAL TDM Study Group
FAU - Huttner, Angela
AU  - Huttner A
AD  - Center for Clinical Research, Clinical Trials Unit, Geneva University Hospitals, 
      Rue Gabrielle Perret-Gentil 4, 1205, Geneva, Switzerland; Division of Infectious 
      Diseases, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, Geneva, 
      Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT03790631
PT  - Clinical Study
PT  - Journal Article
DEP - 20220506
PL  - Netherlands
TA  - Int J Antimicrob Agents
JT  - International journal of antimicrobial agents
JID - 9111860
RN  - 0 (Anti-Bacterial Agents)
RN  - 804826J2HU (Amoxicillin)
SB  - IM
MH  - Adult
MH  - *Amoxicillin/adverse effects
MH  - Anti-Bacterial Agents/adverse effects
MH  - *Bacterial Infections/drug therapy
MH  - *Drug Monitoring
MH  - Humans
MH  - Prospective Studies
MH  - Severity of Illness Index
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Amoxicillin
OT  - Clinical outcomes
OT  - Efficacy
OT  - Therapeutic drug monitoring
OT  - Toxicity
EDAT- 2022/05/10 06:00
MHDA- 2022/06/07 06:00
CRDT- 2022/05/09 19:25
PHST- 2022/02/28 00:00 [received]
PHST- 2022/04/07 00:00 [revised]
PHST- 2022/04/28 00:00 [accepted]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/05/09 19:25 [entrez]
AID - S0924-8579(22)00110-8 [pii]
AID - 10.1016/j.ijantimicag.2022.106601 [doi]
PST - ppublish
SO  - Int J Antimicrob Agents. 2022 Jun;59(6):106601. doi: 
      10.1016/j.ijantimicag.2022.106601. Epub 2022 May 6.