Pharmacokinetics and pharmacological target attainment of standard temocillin dosing in non-critically ill patients with complicated urinary tract infections

Objectives: Temocillin, a carbapenem-sparing β-lactam antibiotic, is commonly used at the standard 4 g/day dosage for treating complicated urinary tract infections (cUTIs). However, pharmacokinetic/pharmacodynamic (PK/PD) data supporting this regimen is limited. This study evaluated the plasma pharmacokinetics (PK) and PTA of temocillin in non-critically ill cUTI patients with varying degrees of renal insufficiency (RI). Methods: In this single-centre clinical study, 22 cUTI patients received a fixed 4 g/day (2 g q12h, intravenously) temocillin dose, irrespective of renal function (no RI: n=5, mild RI: n=8, moderate RI: n=9). Plasma samples were collected post-dosing for LC-MS analysis of total and unbound temocillin levels. Monte Carlo simulations were performed based on the established PK/PD target of ≥35% fT>MIC (minimal inhibitory concentration). Results: Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC_0-12h = 1143 h.mg/L and %fT>MIC=68%), followed by mild RI patients (median AUC_0-12h=918 h.mg/L and %fT>MIC=34%), and the lowest in those with healthy kidney function (median AUC_0-12h=692 h.mg/L and %fT>MIC=26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rate<60 mL/min and MIC≤8 mg/L. Conclusion: The standard temocillin dose may need to be increased from 4 to 6 g/day to treat non-critically ill cUTI patients, in line with recent EUCAST recommendations. For patients with moderate RI, who experience higher exposure due to reduced renal drug clearance, 4 g/day temocillin remains appropriate.