Sub-therapeutic trimethoprim and sulfamethoxazole plasma concentrations during continuous venovenous hemofiltration in a patient with COVID-19 and pulmonary Pneumocystis jirovecii co-infection: A case report

Objective: To investigate drug concentration of trimethoprim-sulfa-methoxazole (TMP-SMX) using therapeutic drug monitoring (TDM) for severe Pneumo-cystis jirovecii (PJP) infection in a critically ill patient with COVID-19 receiving continu-ous venovenous hemofiltration treatment and regional citrate anticoagulation (RCA-CCVH). Materials and methods: A 72-year -old man with hypoxemic respiratory failure due to COVID-19 infection was admitted to the intensive care unit for invasive me-chanical ventilation. The patient developed acute renal failure that required RCA-CVVH. Pulmonary co-infection with PJP was diag-nosed, and a high TMP-SMX dose was initi-ated according to (inter)national guidelines with dose reduction after 3 days because of renal failure. Population pharmacokinetics were assessed for TMP and SMX as well as clearance by RCA-CVVH, volume of distri-bution, and time above threshold levels for measured plasma concentrations. Results: During renal failure requiring RCA-CVVH, a corresponding dose reduction of TMP-SMX to 320/1,600 mg twice a day, according to current Dutch SWAB and Dutch Association of Hospital Pharmacists guidelines, resulted in unintended under-dosing with sub-ther-apeutic TMP-SMX concentrations. Pharma-cokinetic modeling and dose adjustment of TMP-SMX to 640/3,200 mg 3 times daily resulted in steady-state TMP-SMX peak con-centrations associated with efficacy against PJP. Hence, the patient was successfully weaned from the ventilator and discharged. Conclusion: We hypothesize that our new dose recommendation of 640/3,200 mg TMP-SMX 3 times daily is associated with an increased probability of critical patients being successfully liberated from mechani-cal weaning following PJP pneumonia and COVID-19 infection.