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Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships

Journal of antimicrobial chemotherapy, 2017-10, Vol.72 (10), p.2891-2897 [Peer Reviewed Journal]

The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. ;ISSN: 0305-7453 ;EISSN: 1460-2091 ;DOI: 10.1093/jac/dkx209 ;PMID: 29091190

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Title:
Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships
Author: Imani, Sahand ; Buscher, Hergen ; Marriott, Debbie ; Gentili, Sheridan ; Sandaradura, Indy
Subjects: Adult ; Aged ; Anti-Bacterial Agents - adverse effects ; Anti-Bacterial Agents - blood ; Anti-Bacterial Agents - therapeutic use ; Bacterial Infections - drug therapy ; beta-Lactams - adverse effects ; beta-Lactams - blood ; beta-Lactams - therapeutic use ; Clostridium Infections - etiology ; Cohort Studies ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; Female ; Floxacillin - adverse effects ; Floxacillin - blood ; Floxacillin - therapeutic use ; Humans ; Incidence ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Neurotoxicity Syndromes - diagnosis ; Neurotoxicity Syndromes - etiology ; Piperacillin - adverse effects ; Piperacillin - blood ; Piperacillin - therapeutic use ; Retrospective Studies ; Thienamycins - adverse effects ; Thienamycins - blood ; Thienamycins - therapeutic use
Is Part Of: Journal of antimicrobial chemotherapy, 2017-10, Vol.72 (10), p.2891-2897
Description: To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01; meropenem, P = 0.04; flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P < 0.01). Incidence of hepatotoxicity and C. difficile was not related to Cmin. Threshold concentrations for which there is 50% risk of developing a neurotoxicity event (piperacillin, Cmin >361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics. Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.
Publisher: England
Language: English
Identifier: ISSN: 0305-7453
EISSN: 1460-2091
DOI: 10.1093/jac/dkx209
PMID: 29091190
Source: Freely Accessible Journals
MEDLINE
Alma/SFX Local Collection

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Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships

The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. ;ISSN: 0305-7453 ;EISSN: 1460-2091 ;DOI: 10.1093/jac/dkx209 ;PMID: 29091190

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