Pharmacokinetics and Pharmacodynamic Target Attainment of Benzylpenicillin in an Adult Severely ill Sub-Saharan African Patient Population

Jeannet C. Bos, Reinier M. van Hest, Mabor C. Mistício, Ginto Nunguiane, Cláudia N. Lang, José C. Beirão, Ron A. A. Mathôt, Jan M. Prins

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3 Citations (Scopus)

Abstract

In intensive care (ICU) patients, systemic exposure of β-lactam antibiotics can be altered, and positive clinical outcome is associated with increasing fT>MIC ratios. In sub-Saharan African (SSA) hospitals, benzylpenicillin (PEN) is frequently used for the empirical treatment of severe pneumococcal infections. Pharmacokinetic data for non-ICU hospitalized populations are lacking. We performed a population pharmacokinetic (PPK) study in an adult Mozambican hospital population treated intravenously with PEN from October 2014-November 2015. Four blood samples/patient were collected for total PEN (PENt) and unbound PEN (PENu) concentration measurement. We developed a PPK model through non-linear mixed effect analysis and performed simulations for different patient variable, dosing, and pharmacodynamic target scenarios. 112 participants yielded 387 PENt and 53 PENu concentrations. The median (range) body mass index was 18.3 (10.5-31.3) and the median albumin concentration and creatinine clearance (CLCR) were 29 (12-44) g/L and 80 (3-195) mL/min, respectively. In a one-compartment model, CLCR was positively correlated with PENt CL. For infections with a microorganism with an MIC of 1 mg/L, simulations demonstrated that with 3 million IU (1.8 g) q6h, 74.1% would have a PENu concentration >MIC during half of the dosing interval (fT>MIC=50%), while this was 24.8% for the fT>MIC=100% target. For pathogens with an MIC of 0.06 mg/L, these percentages were 98.2% and 72.3%. Severely ill adult non-ICU SSA patients may be at high risk for underexposure to PENu during routine intermittent bolus dosing, especially when their renal function is intact and when infected with pathogens with intermediate susceptibility
Original languageEnglish
Pages (from-to)1261–1269
JournalClinical Infectious Diseases
Volume66
Issue number8
Early online date2017
DOIs
Publication statusPublished - 2018

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