title: Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept.
abstract: The extreme pharmacokinetic behaviour of drugs sometimes observed in critically ill patients poses a significant threat to the achievement of optimal antibiotic treatment outcomes. Scant information on beta-lactam antibiotic therapeutic drug monitoring (TDM) is available. The objective of this prospective study was to evaluate the practicality and utility of a beta-lactam TDM programme in critically ill patients. TDM was performed twice weekly on all eligible patients at a 30-bed tertiary referral critical care unit. Blood concentrations were determined by fast-throughput high-performance liquid chromatography (HPLC) assays and were available within 12h of sampling. Dose adjustment was instituted if the trough or steady-state blood concentration was below 4-5x the minimum inhibitory concentration (MIC) or above 10x MIC. A total of 236 patients were subject to TDM over an 11-month period. The mean+/-standard deviation age was 53.5+/-18.3 years. Dose adjustment was required in 175 (74.2%) of the patients, with 119 of these patients (50.4%) requiring dose increases after the first TDM. For outcome of therapy, 206 (87.3%) courses resulted in a positive treatment outcome and there were 30 (12.7%) treatment failures observed including 14 deaths and 15 courses requiring escalation to broader-spectrum agents; 1 course was ceased due to an adverse drug reaction. Using binomial logistic regression, only an elevated Acute Physiology and Chronic Health Evaluation (APACHE) II score (P<0.01) and elevated plasma creatinine concentration (P=0.05) were found to be predictive of mortality. In conclusion, further research is required to determine definitively whether achievement of optimal beta-lactam pharmacodynamic targets improves clinical outcomes.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia. j.roberts2@uq.edu.au
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Marta
authors.initials: M
authors.lastname: Ulldemolins
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.forename: Brett
authors.initials: B
authors.lastname: McWhinney
authors.forename: Jacobus
authors.initials: J
authors.lastname: Ungerer
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D016903:Drug Monitoring; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016896:Treatment Outcome; D047090:beta-Lactams / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams