Penicillin G Treatment in Infective Endocarditis Patients – Does Standard Dosing Result in Therapeutic Plasma Concentrations?

Penicillin G is frequently used to treat infective endocarditis (IE) caused by streptococci, penicillin-susceptible staphylococci and enterococci. Appropriate antibiotic exposure is essential for survival and reduces the risk of complications and drug resistance development. We determined Penicillin G plasma concentrations [p-penicillin] once weekly in 46 IE patients. The aim was to evaluate if Penicillin G 3g every 6 hr (q6h) resulted in therapeutic concentrations and to analyse potential factors that influence inter- and intra-individual variability, using linear regression and a random coefficient model. [P-penicillin] at 3 hr and at 6 hr was compared with the minimal inhibitory concentration (MIC) of the bacteria isolated from blood cultures to evaluate the following PK/PD targets: 50% fT>MIC and 100% fT>MIC. [P-penicillin] varied notably between patients and was associated with age, weight, p-creatinine and estimated creatinine clearance (eCLcr). Additionally, an increase in [p-penicillin] during the treatment period showed strong correlation with age, a low eCLcr, a low weight and a low p-albumin. Of the 46 patients, 96% had [p-penicillin] that resulted in 50% fT>MIC, while 71% had [p-penicillin] resulting in 100% fT>MIC. The majority of patients not achieving the 100% fT>MIC target were infected with enterococci. Streptococci and staphylococci isolated from blood cultures were highly susceptible to Penicillin G. Our results suggest that Penicillin G 3g q6h is suitable to treat IE caused by streptococci and penicillin-susceptible staphylococci, but caution must be taken when the infection is caused by enterococci. When treating enterococci, therapeutic drug monitoring should be applied to optimize Penicillin G dosing and exposure. This article is protected by copyright. All rights reserved.