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Journal of veterinary pharmacology and therapeutics2025; doi: 10.1111/jvp.70007

Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin.

Abstract: Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a "moving target" along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of Rhodococcus equi infection in foals, for nearly 40 years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above R. equi minimum inhibitory concentrations (MICs), as well as better efficacy, compared with other approaches, and limiting the rate of antimicrobial resistance to either single agent. However, rifampin acts as a perpetrator drug for many co-administered drugs. This critical review evaluates the available evidence for rifampin use in foals with R. equi, concerning pharmacokinetic/pharmacodynamic characteristics of rifampin in foals, in vitro microbiological studies and selection of antimicrobial resistance, as well as an analysis of randomized clinical trials. Rifampin is a nuclear pregnane X receptor activator, which results in strong negative drug interactions towards itself and other drugs, for drug-absorption routes either by upregulation of presystemic elimination mechanisms (e.g., intestinal and hepatic CYP3A4), or functional drug-absorption carriers (e.g., intestinal P-glycoprotein) and/or inhibition of intestinal and/or hepatic drug-uptake carriers (e.g., OATP1B1, OATP2B1, MRP2). Chronic rifampin administration results in decreases in the serum and target site/s concentrations of many parent drugs, including itself. Rifampin concomitant therapies do not demonstrate a significant advantage over monotherapy with macrolides, in randomized controlled blinded and double-blinded clinical trials for subclinical, and mild-to-moderate bronchopneumonia in foals with pulmonary abscesses, regardless of initial pulmonary abscess score. Efficacy of rifampin concomitant therapies for severe Rhodococcus equi pneumonia has not been fully investigated, but there is sufficient accumulated evidence in foals to raise major concerns about the incorrect use of rifampin in equine medicine. These concerns include rifampin as a bacteriostatic antibiotic against R. equi, with changing pharmacokinetics during treatment that decreases parent/coparent concentrations as well as the risk of selecting for multi-resistant R. equi.
© 2025 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
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Publication Date: 2025-06-24 PubMed ID: 40552784DOI: 10.1111/jvp.70007Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the efficacy of the antibiotic Rifampin in treating Rhodococcus equi infections in foals, focusing on its pharmacodynamics and potential drug interactions. The authors express concern about it being widely and potentially wrongly used in equine medicine due to its complex behavior within the body and the lack of significant advantage over monotherapy with macrolides.

Understanding Rifampin’s Role and Performance

  • Rifampin has been used for treating R. equi infections in foals over four decades. Its therapeutic role depends on the belief that it can penetrate better into pulmonary abscesses and intracellular compartments, providing a superior efficacy rate to prevent and treat infections. The medication is also seen as a way of limiting antibiotic resistance when used with other drugs, such as macrolides.
  • However, Rifampin’s pharmacodynamic behavior poses a challenge as it acts as a perpetrator drug for many medicines given alongside it. This means the amount of Rifampin that effectively reaches the bloodstream can vary over the treatment course, raising concerns about its application in equine medicine.

Rifampin’s Pharmacokinetic/Pharmacodynamic Characteristics

  • Rifampin activates the nuclear pregnane X receptor, resulting in strong negative drug interactions. This interaction can lead to an increase in elimination mechanisms or functional drug-absorption carriers such as hepatic CYP3A4 and intestinal P-glycoprotein, or inhibition of uptake carriers like OATP1B1, OATP2B1, and MRP2.
  • Chronic administration of Rifampin tends to decrease the concentration of many drugs, including itself, in the serum and target sites.

Efficacy in Randomized Clinical Trials

  • When comparing the effectiveness of Rifampin with monotherapy using macrolides, the trials showed that monotherapies did not demonstrate significant disadvantage. This observation held true for foals suffering from subclinical and moderate bronchopneumonia with pulmonary abscesses, regardless of the initial pulmonary abscess score.
  • The efficacy of Rifampin for severe R. equi pneumonia has not been entirely evaluated, but existing evidence raises concerns about the drug’s incorrect usage in equine medicine.

Concerns Regarding the Use of Rifampin

  • Rifampin acts as a bacteriostatic antibiotic against R. equi, meaning it inhibits bacterial growth rather than killing it outright. This property, coupled with its changing pharmacokinetics, results in a decrease in the concentrations of the drugs it is administered with over a treatment period.
  • Further concerns lie in the potential of Rifampin usage leading to the development of multi-resistant R. equi due to the antibiotic’s resistance-selecting properties.

Cite This Article

APA
Baptiste KE, Kyvsgaard NC, Ahmed MO, Damborg P, Dowling PM. (2025). Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin. J Vet Pharmacol Ther. https://doi.org/10.1111/jvp.70007

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English

Researcher Affiliations

Baptiste, Keith Edward
  • Danish Medicines Agency, Copenhagen, Denmark.
Kyvsgaard, Niels Christian
  • Danish Medicines Agency, Copenhagen, Denmark.
Ahmed, Mohamed Omar
  • Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, Tripoli, Libya.
Damborg, Peter
  • Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Dowling, Patricia M
  • Western College of Veterinary Medicine, Saskatoon, Saskatchewan, Canada.

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