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

Research output: Contribution to journalJournal articleResearchpeer-review


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  • Kristina Öbrink-Hansen
  • Henrik Wiggers
  • Bo Martin Bibby
  • Tore Forsingdal Hardlei
  • Kaare Troels Jensen
  • Marianne Kragh Thomsen
  • Birgitte Brock
  • Eskild Petersen
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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.

Original languageEnglish
JournalBasic & clinical pharmacology & toxicology
Issue number2
Pages (from-to)179-186
Number of pages8
Publication statusPublished - Feb 2017
Externally publishedYes

    Research areas

  • Aged, Anti-Bacterial Agents, Drug Administration Schedule, Drug Dosage Calculations, Drug Monitoring, Endocarditis, Bacterial, Female, Humans, Linear Models, Male, Microbial Sensitivity Tests, Middle Aged, Penicillin G, Prospective Studies, Recurrence, Staphylococcal Infections, Streptococcal Infections, Treatment Outcome, Journal Article, Observational Study

ID: 51418979