Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an In Vitro Pharmacokinetic/Pharmacodynamic Biofilm Model

Taylor Morrisette, Kyle C. Stamper, Katherine L. Lev, Razieh Kebriaei, Dana J. Holger, Jacinda C. Abdul-Mutakabbir, Ashlan J. Kunz Coyne, Michael J. Rybak

Research output: Contribution to journalArticlepeer-review

Abstract

Biofilm-associated infections lead to substantial morbidity. Omadacycline (OMC) is a novel aminomethylcycline with potent in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis, but data surrounding its use in biofilm-associated infections are lacking. We investigated the activity of OMC alone and in combination with rifampin (RIF) against 20 clinical strains of staphylococci in multiple in vitro biofilm analyses, including an in vitro pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor (CBR) model (simulating human exposures). The observed MICs for OMC demonstrated potent activity against the evaluated strains (0.125 to 1 mg/L), with an increase of MICs generally observed in the presence of biofilm (0.25 to.64 mg/L). Furthermore, RIF was shown to reduce OMC biofilm MICs (bMICs) in 90% of strains, and OMC plus RIF combination in biofilm time-kill analyses (TKAs) exhibited synergistic activity in most of the strains. Within the PK/PD CBR model, OMC monotherapy primarily displayed bacteriostatic activity, while RIF monotherapy generally exhibited initial bacterial eradication, followed by rapid regrowth likely due to the emergence of RIF resistance (RIF bMIC, .64 mg/L). However, the combination of OMC plus RIF produced rapid and sustained bactericidal activity in nearly all the strains (3.76 to 4.03 log10 CFU/cm2 reductions from starting inoculum in strains in which bactericidal activity was reached). Furthermore, OMC was shown to prevent the emergence of RIF resistance. Our data provide preliminary evidence that OMC in combination with RIF could be a viable option for biofilm-associated infections with S. aureus and S. epidermidis. Further research involving OMC in biofilm-associated infections is warranted.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Volume67
Issue number6
DOIs
StatePublished - Jun 2023

Bibliographical note

Funding Information:
This work was supported by an investigator-initiated grant from Paratek Pharmaceuticals (M.J.R.). M.J.R. is partially supported by NIAID R01-AI121400 and R21-AI163726-01. T.M., K.C.S., K.L.L., R.K., D.J.H., J.C.A.-M., and A.J.K.C. have no funding to disclose.

Publisher Copyright:
Copyright © 2023 American Society for Microbiology. All Rights Reserved.

Keywords

  • biofilm
  • omadacycline
  • rifampin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an In Vitro Pharmacokinetic/Pharmacodynamic Biofilm Model'. Together they form a unique fingerprint.

Cite this