Pharmacokinetics and pharmacological target attainment of standard temocillin dosing in non-critically ill patients with complicated urinary tract infections.
J Antimicrob Chemother
; 2024 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-38985543
ABSTRACT
OBJECTIVES:
Temocillin, a carbapenem-sparing ß-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 nâ=â5, mild RI nâ=â8, moderate RI nâ=â9). 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% fTâ>âMIC (minimal inhibitory concentration).RESULTS:
Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC0-12h = 1143 h.mg/L and %fTâ>âMICâ=â68%), followed by mild RI patients (median AUC0-12hâ=â918 h.mg/L and %fTâ>âMICâ=â34%), and the lowest in those with healthy kidney function (median AUC0-12hâ=â692 h.mg/L and %fTâ>âMICâ=â26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rateâ<â60 mL/min and MICâ≤â8 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.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Bélgica