Objectives: To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients. Patients and methods: Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay. Results: A two-compartment model was required to characterize linezolid pharmacokinetics (n=28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 ±0.016 L/h/kg (±s.e.m. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4 mg/L for 10.88 h (95% CI 10.09–11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% CI 57.2–127.7). Teicoplanin was best described by a two-compartment model (n=26). The clearance was 4.97±1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% CI 329.6–469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died. Conclusions: Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level.

Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD.