Cotrimoxazole in the intensive care unit: an impossible task for the fixed association in real life?

Cotrimoxazole (trimethoprim/sulfamethoxazole) is a widely used antibiotic in ICU for the treatment of infections such as nosocomial or Pneumocystis jirovecii pneumonia. However, dosing in ICU patients is complicated by fluctuations in renal function, particularly acute kidney injury and augmented renal clearance, which affect drug elimination. This study investigated how renal function and body weight influence trimethoprim and sulfamethoxazole concentrations.

This retrospective bicentre observational study involved 116 ICU patients receiving cotrimoxazole therapy with routine therapeutic drug monitoring. The study focused on effects of estimated glomerular filtration rate (eGFR) and weight on concentrations and dosing.

Dosing of sulfamethoxazole and trimethoprim was significantly lower in patients with eGFR <30 mL/min/1.73 m2, as recommended. In these patients, sulfamethoxazole concentrations were reduced, suggesting underdosing, while trimethoprim increased with worsening renal function, indicating overdose risk when eGFR <60 mL/min/1.73 m2. Patients on renal replacement therapy (RRT) had lower sulfamethoxazole concentrations and a reduced dose-normalized C/D ratio, raising underdosing risk during RRT. trimethoprim was less affected by RRT, supporting dose reduction regardless of RRT status. No C/D ratio difference was seen between obese and non-obese patients. Weight influenced sulfamethoxazole but not trimethoprim.

These findings underscore the need for individualized dosing in ICU patients, especially in patients with renal impairment or RRT. Current fixed-dose combination may not adequately reflect cotrimoxazole's complex pharmacokinetics in critical illness, stressing the importance of tailored strategies.