A practical thrice weekly ertapenem dosage regime for chronic hemodialysis patients

Background: Ertapenem is a parenteral carbapenem. In patients undergoing hemodialysis a dosage reduction of 50%, as a dose of 0.5 gram once daily, is advised. Hospital admission or specialised home care is needed to administer ertapenem. As these patients are already visiting the hospital 3 times a week a more patient friendly dosage regime would be favorable. This study is to determine whether this regime is a viable alternative to current daily administration. Methods: The study enrolled chronic hemodialysis patients with a proven infection caused by ertapenem-susceptible bacteria. The minimal inhibitory concentration (MIC) was determined. Patients received a dose of 1 g ertapenem 3 times a week, administerd immediately after hemodialysis. Ertapenem peak an trough levels, before and after dialysis, were measured at 2 consecutive dialysis sessions. Total ertapenem concentrations were measured using a validated LC-MS-MS method. Treatment efficacy was evaluated, based on a decrease of CRP-levels. The data were analyzed (MW/Pharm). Results: Ten patients were included, 5 female and 5 male, with an average age of 68 years. The ertapenem trough level at 68 hours was 3.7 mg/L (range, 0.5-9.6 mg/L) and exceeded the individual MIC values during the 68 hour dosing interval, and are well above the known MIC90 for most gram-negative bacteria. The overall clinical success rate was 8 out of 10. Treatment failure in patient 3 could be explained by a decreased tissue perfusion at the infection site. The treatment was well tolerated; no severe adverse reports were reported. The pharmacokinetic parameters were calculated for the investigated population. The half life (t1/2) of ertapenem was 19.9 ± 5.1 hours and the volume of distribution (Vd) 0.16 L/kg. The increased Vd and t1/2 compared to literature values could be explained by the infectious state and a severe renal insufficiency in our population. Conclusions: Ertapenem administered to chronic hemodialysis patients as a thrice weekly dosage gives adequate serum levels during the 68 hours interdialytic interval. This dosage regime is a practical, patient-friendly and effective alternative to current daily administration of ertapenem.