Penicillin Concentrations in Oropharyngeal and Frontal Sinus Tissue Following Intravenous Bolus and Continuous Infusion - An Experimental Porcine Study

Abstract

Background and Purpose Studies have documented that continuous infusion is superior to bolus infusion in providing longer time with drug concentration above the minimal inhibitory concentration (T > MIC). This porcine study compared steady-state penicillin concentrations in oropharyngeal and frontal sinus tissues following intravenous bolus and continuous administration. Experimental Approach Twelve pigs were randomized to receive either intravenous bolus (Group BI) or continuous (Group CI) infusion of penicillin (1.2 g). Doses were administered at 0, 6, and 12 h, with sampling from 12 to 18 h. Microdialysis was used for sampling in oropharyngeal and frontal sinus tissues, with simultaneous plasma sampling. The primary endpoints were T > MIC for two MIC targets (0.125 (low target) and 0.5 (high target) μg/mL) and attainment of ≥ 50%T > MIC treatment target. Key Results No statistically significant differences were found between Group BI and CI for either MIC target. The ≥ 50%T > MIC target was achieved in all compartments except for the high MIC target in oropharyngeal tissue in Group CI (46%). although no statistical significance, T > MIC in oropharyngeal tissue tended to be longer in Group BI (low target: 98%; high target: 74%) compared with Group CI (low target: 68%; high target: 46%) ( p = 0.07 and p = 0.19, respectively). Conclusion and Implication Penicillin bolus and continuous infusion resulted in comparable T > MIC in oropharyngeal and frontal sinus tissues. However, bolus infusion showed a higher likelihood of attaining ≥ 50%T > MIC in oropharyngeal tissue. These findings are specific to the porcine model and dosing regimens used and cannot be directly extrapolated to humans.

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