In vitro synergy, pharmacodynamics, and postantibiotic effect of 11 antimicrobial agents against Rhodococcus equi.
Abstract: There are no studies investigating interactions between clarithromycin or azithromycin and rifampin or other commonly used antimicrobial agents against virulent isolates of Rhodococcus equi. In addition, there is no published data on the postantibiotic effects (PAEs) and pharmacodynamics properties of antimicrobial agents against R. equi. The objectives were to assess in vitro interactions, pharmacodynamics, and PAEs of 11 antimicrobial agents belonging to various antimicrobial classes against R. equi. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, ceftiofur, and doxycycline) were selected based on in vitro activity against large numbers of isolates of R. equi and frequency of use in foals or humans infected with R. equi. Three virulent strains of R. equi were evaluated by time-kill curves and checkerboard assays, and the postantibiotic effect was measured at 5×MIC. Only amikacin, gentamicin, enrofloxacin, and vancomycin were bactericidal against R. equi. Combinations including a macrolide (erythromycin, clarithromycin, azithromycin) and either rifampin or doxycycline, and the combination doxycycline-rifampin were synergistic. Combinations containing amikacin and erythromycin, clarithromycin, azithromycin, or rifampin and the combination gentamicin-rifampin were antagonistic. The PAEs of rifampin, erythromycin, clarithromycin, vancomycin, and doxycycline were relatively long with median values ranging between 4.5 and 6.5h. Azithromycin, gentamicin, and imipenem had intermediate PAEs ranging between 3.3 and 3.5h. Amikacin, enrofloxacin, and ceftiofur had shorter PAEs ranging between 1.3 and 2.1h. Gentamicin, amikacin, enrofloxacin, and doxycycline exhibited concentration-dependent activity whereas erythromycin, clarithromycin, azithromycin, rifampin, ceftiofur, imipenem, and vancomycin exhibited time-dependent activity against R. equi.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication Date: 2012-05-29 PubMed ID: 22704561DOI: 10.1016/j.vetmic.2012.05.031Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the effectiveness of 11 different antimicrobial agents against Rhodococcus equi, a bacterium responsible for infections in horses and humans. The authors also study the interactions between these agents and reveal insights on the postantibiotic effects of these drugs.
Objectives and Methodology of the Study
- The study aims to evaluate the synergies, pharmacodynamics, and postantibiotic effects (the period of inhibited bacterial regrowth following removal of the antibiotic agent) of 11 antimicrobial agents – namely erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, ceftiofur, and doxycycline – against Rhodococcus equi.
- These agents are chosen based on their known activity against many isolates of R. equi and frequency of use in treating infections in horses or humans.
- Three strains of the bacterium, R. equi are analyzed using time-kill curves (a graphical representation of how the concentration of an antimicrobial agent eliminates a known bacterial population over time) and checkerboard assays (a method used to study the interaction of two drugs).
Findings from the Study
- The study finds that only amikacin, gentamicin, enrofloxacin, and vancomycin are truly bactericidal against R. equi, meaning they have the ability to kill the bacteria instead of merely inhibiting its growth.
- Positive synergistic effects are observed in combinations of a macrolide type of antibiotic (erythromycin, clarithromycin, azithromycin) with either rifampin or doxycycline, as well as with the combination of doxycycline-rifampin. This means these combinations led to better results than the individual drugs.
- However, combinations including amikacin with erythromycin, clarithromycin, azithromycin, rifampin, or gentamicin-rifampin were found to be antagonistic, or counteractive, showing decreased effectiveness when used together.
Postantibiotic Effect
- In evaluating postantibiotic effects, rifampin, erythromycin, clarithromycin, vancomycin, and doxycycline exhibited long-lasting PAEs, with median values between 4.5 and 6.5 hours.
- Azithromycin, gentamicin, and imipenem showed intermediate PAEs ranging from 3.3 to 3.5 hours, whereas amikacin, enrofloxacin, and ceftiofur exhibited shorter PAEs, ranging between 1.3 and 2.1 hours.
Pharmacodynamics of the Antimicrobial Agents
- In terms of how drug concentration and time affect the efficacy, gentamicin, amikacin, enrofloxacin, and doxycycline demonstrated a concentration-dependent activity. This means they were more effective at higher concentrations.
- On the other hand, erythromycin, clarithromycin, azithromycin, rifampin, ceftiofur, imipenem, and vancomycin showed a time-dependent action against R. equi, meaning the longer the drug stays in the system, the more effective it is.
Cite This Article
APA
Giguère S, Lee EA, Guldbech KM, Berghaus LJ.
(2012).
In vitro synergy, pharmacodynamics, and postantibiotic effect of 11 antimicrobial agents against Rhodococcus equi.
Vet Microbiol, 160(1-2), 207-213.
https://doi.org/10.1016/j.vetmic.2012.05.031 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States. gigueres@uga.edu
MeSH Terms
- Actinomycetales Infections / veterinary
- Animals
- Anti-Bacterial Agents / pharmacology
- Drug Synergism
- Horse Diseases / microbiology
- Horses
- Humans
- Rhodococcus equi / drug effects
- Rhodococcus equi / isolation & purification
- Rhodococcus equi / pathogenicity
Citations
This article has been cited 15 times.- Hao Y, Teng D, Mao R, Yang N, Wang J. Site Mutation Improves the Expression and Antimicrobial Properties of Fungal Defense.. Antibiotics (Basel) 2023 Aug 3;12(8).
- Zúñiga MP, Badillo E, Abalos P, Valencia ED, Marín P, Escudero E, Galecio JS. Antimicrobial susceptibility of Rhodococcus equi strains isolated from foals in Chile.. World J Microbiol Biotechnol 2023 Jun 22;39(9):231.
- Jin Y, Yang N, Teng D, Hao Y, Mao R, Wang J. Molecular Modification of Kex2 P1' Site Enhances Expression and Druggability of Fungal Defensin.. Antibiotics (Basel) 2023 Apr 20;12(4).
- Wu Y, Yang N, Mao R, Hao Y, Teng D, Wang J. In Vitro Pharmacodynamics and Bactericidal Mechanism of Fungal Defensin-Derived Peptides NZX and P2 against Streptococcus agalactiae.. Microorganisms 2022 Apr 22;10(5).
- Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA. Antimicrobial Resistance Spectrum Conferred by pRErm46 of Emerging Macrolide (Multidrug)-Resistant Rhodococcus equi.. J Clin Microbiol 2021 Sep 20;59(10):e0114921.
- Li T, Wang Z, Han H, Teng D, Mao R, Hao Y, Yang N, Wang X, Wang J. Dual Antibacterial Activities and Biofilm Eradication of a Marine Peptide-N6NH(2) and Its Analogs against Multidrug-Resistant Aeromonas veronii.. Int J Mol Sci 2020 Dec 17;21(24).
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- Burton AJ, Giguère S, Berghaus LJ, Hondalus MK. Activity of clarithromycin or rifampin alone or in combination against experimental Rhodococcus equi infection in mice.. Antimicrob Agents Chemother 2015;59(6):3633-6.
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