Linezolid Injection and Rifampin: Interaction Details

a) In a pharmacokinetic study, concomitant administration of linezolid and rifampin resulted in decreased linezolid concentrations. Healthy adult males (n=16) were administered oral linezolid 600 mg twice daily for 5 doses with and without rifampin 600 mg once daily for 8 days. Concomitant administration led to a 21% decrease in linezolid Cmax (90% CI 15% to 27%) and a 32% decrease in linezolid AUC (90% CI 27% to 37%). The exact mechanism for this is not known but may be related to induction of hepatic enzymes ¹.

b) In a small study in healthy males (n=8), concurrent administration of linezolid and rifampin led to reduced linezolid plasma levels compared with administration of linezolid alone. Subjects received a one-time dose of IV linezolid 600 mg. A day later, they were given concurrent doses of IV linezolid 600 mg and IV rifampin 600 mg. Six hours after the initial dose of linezolid and rifampin, linezolid serum levels were at 90%, and dropped to 80% and 65% after 9 hours and 12 hours, respectively. Up-regulation of linezolid intestinal secretion was proposed as a possible explanation for the increased linezolid clearance ³.

c) Concomitant administration of linezolid and rifampin led to decreased linezolid serum levels in a 31-year-old female. Within 24 hours of admission, this critically ill patient presented with community-acquired methicillin-resistant staphylococcus aureus (MRSA). She was treated with intravenous drotrecogin alfa, norepinephrine, vasopressin, piperacillin-tazobactam, vancomycin, and clindamycin. Based on culture results, piperacillin-tazobactam and clindamycin were discontinued. On day 6, blood cultures still showed positive for MRSA. Vancomycin was discontinued, and intravenous linezolid 600 mg every 12 hours with rifampin 300 mg every 8 hours were initiated. Three days after linezolid and rifampin initiation, blood cultures were negative for MRSA growth. During treatment with linezolid and rifampin (19 days; day 6 to 25 of admission), the patient developed daily fevers and nosocomial candidemia. Caspofungin was started and later changed to fluconazole. Escherichia coli bacteremia was initially treated with meropenem and later, therapy was changed to levofloxacin. The patient was also restarted on sertraline which she had been taking at home for depression. Additionally, hydroxychloroquine was initiated to treat systemic lupus erythematosus which was diagnosed around day 40 of admission. On day 35 (ie, 10 days after stopping rifampin), linezolid trough levels were reported as trace. Linezolid dose was increased to 600 mg every 8 hours, and rifampin was restarted on day 36. On day 37, linezolid peak (7.29 mcg/mL) and trough levels (2.04 mcg/mL) were obtained. Rifampin was discontinued on day 44, and linezolid peak and trough levels on day 52 had increased to 12.46 mcg/mL and 5.03 mcg/mL. Subsequently, the patient made steady progress and was discharged on day 86 ².