title: Penicillin G Treatment in Infective Endocarditis Patients - Does Standard Dosing Result in Therapeutic Plasma Concentrations?
abstract: 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 concentration [p-penicillin] once weekly in 46 IE patients. The aim was to evaluate whether penicillin G 3 g every 6 hr (q6 h) 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 3 g q6 h 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.
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Kristina
authors: K
authors: Öbrink-Hansen
authors: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Henrik
authors: H
authors: Wiggers
authors: Department of Biostatistics, University of Aarhus, Aarhus, Denmark.
authors: Bo Martin
authors: BM
authors: Bibby
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors: Tore Forsingdal
authors: TF
authors: Hardlei
authors: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Kaare
authors: K
authors: Jensen
authors: Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
authors: Marianne
authors: M
authors: Kragh Thomsen
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors: Birgitte
authors: B
authors: Brock
authors: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
authors: Eskild
authors: E
authors: Petersen
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D004697:Endocarditis, Bacterial / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010400:Penicillin G / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D011446:Prospective Studies; D012008:Recurrence; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D013290:Streptococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D010400:Penicillin G