Evaluation of omadacycline regimens for community-acquired bacterial pneumonia patients infected with Staphylococcus Aureus by pharmacokinetic/pharmacodynamic analysis

Abstract

Omadacycline is an FDA-approved agent for community-acquired bacterial pneumonia (CABP). The purpose of this study is to evaluate the effectiveness of omadacycline for treating CABP patients infected with Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA), using pharmacokinetic/pharmacodynamic (PK/PD) analysis. Monte Carlo simulations (MCSs) were performed by utilizing omadacycline pharmacokinetic (PK) parameters, minimum inhibitory concentration (MIC) data, and in vivo PK/PD targets to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) values for different dose regimens against MRSA and MSSA in CABP patients. A dosage regimen with a PTA or CFR expectation value greater than 90% was considered optimal. For all recommended dose regimens, PTA values for MRSA MIC ≤1 and MSSA MIC ≤4 on days 1, 4, and 7 were greater than 90%. Based on the MIC distribution of Staphylococcus aureus, all dose regimens had CFR values greater than 90% for both MRSA and MSSA. CFR values for different bacterial strains were still greater than 90% within the range of PK/PD target values less than 40, although they gradually decreased with increasing PK/PD target values. PK/PD modeling demonstrated that all recommended dose regimens of omadacycline are highly effective against CABP patients infected with MRSA and MSSA. The study provides theoretical support for the efficacy of omadacycline in different dose regimens.

Keywords:

• Omadacycline
• pharmacokinetics/pharmacodynamics
• Monte Carlo simulations
• community-acquired bacterial pneumonia
• methicillin-resistant Staphylococcus aureus
• methicillin-susceptible Staphylococcus aureus

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by the Zhejiang Provincial Medical Health Science and Technology Project under [Grant No. 2022KY107], and the Hospital Pharmacy Special Project of Zhejiang Pharmaceutical Association under [Grant No. 2021ZYY19].