Too much of a good thing: a retrospective study of β-lactam concentration–toxicity relationships
| Autor: | Indy Sandaradura, Sahand Imani, Deborah Marriott, Hergen Buscher, Sheridan Gentili |
|---|---|
| Přispěvatelé: | Imani, Sahand, Buscher, Hergen, Marriott, Debbie, Gentili, Sheridan, Sandaradura, Indy |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Gastroenterology antibiotics Cohort Studies 0302 clinical medicine meropenem piperacillin polycyclic compounds Pharmacology (medical) lactams 030212 general & internal medicine toxic effect medicine.diagnostic_test nephrotoxicity Incidence Bacterial Infections Middle Aged Anti-Bacterial Agents Infectious Diseases Toxicity neurotoxicity syndromes Female Neurotoxicity Syndromes Drug Monitoring medicine.drug Adult Microbiology (medical) hepatotoxicity medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions floxacillin 030106 microbiology Microbial Sensitivity Tests beta-Lactams Meropenem Floxacillin Nephrotoxicity 03 medical and health sciences Cmin Internal medicine medicine Humans Adverse effect Aged Retrospective Studies Piperacillin Pharmacology business.industry Therapeutic drug monitoring Clostridium Infections Thienamycins Flucloxacillin business |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 72:2891-2897 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkx209 |
| Popis: | Objectives To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Patients and methods: 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. Results: 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 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. Conclusions: 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. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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