Challenges and potential solutions for cycloserine dosing in patients with sepsis undergoing continuous renal replacement therapy

Abstract

Continuous kidney replacement therapy (CRRT) is a special form of dialysis, which has more significant advantages than traditional intermittent hemodialysis in treating critically ill patients. The impact of CRRT and disease complexity on drug clearance in critically ill patients has been reported in several studies, nevertheless, the pharmacokinetic changes of cycloserine in patients with sepsis undergoing CRRT have not been reported. Here, we report a case of a 52-year-old man with septic shock and severe multidrug-resistant tuberculosis who underwent anti-TB therapy. The patient's anti-TB regimen included linezolid, clofazimine, cycloserine, and bedaquiline. Following continuous administration for 14 days, the patient was treated with CRRT due to acid-base imbalance and acute renal failure. Blood samples were collected at 0, 2, 4, 6, 10, and 12 hours following cycloserine administration (CRRT was initiated two hours after administration). Changes in plasma concentration of cycloserine before and after the CRRT were measured. The peak concentration of cycloserine was 39.93 mg/L with a trough concentration of 7.90 mg/L, and the AUC0-12h was 294.36 mg•h/L. These findings firstly suggested that the pharmacokinetics of cycloserine may be influenced by sepsis and CRRT therapy, and cycloserine doses may need to be increased during CRRT therapy in patients with sepsis.