• 1.

    Prescott JF. Rhodococcus equi: an animal and human pathogen. Clin Microbiol Rev 1991;4:2034.

  • 2.

    Giguere S, Prescott JF. Clinical manifestations, diagnosis, treatment, and prevention of Rhodococcus equi infections in foals. Vet Microbiol 1997;56:313334.

    • Search Google Scholar
    • Export Citation
  • 3.

    Prescott JF. Epidemiology of Rhodococcus equi infection in horses. Vet Microbiol 1987;14:211214.

  • 4.

    Ainsworth DM, Eicker SW, Yeagar AE, et al. Associations between physical examination, laboratory, and radiographic findings and outcome and subsequent racing performance of foals with Rhodococcus equi infection: 115 cases (1984–1992). J Am Vet Med Assoc 1998;213:510515.

    • Search Google Scholar
    • Export Citation
  • 5.

    Cohen ND, Chaffin MK, Martens RJ. Control and prevention of pneumonia in foals caused by Rhodococcus equi. Compend Contin Educ Pract Vet 2000;22:10621070.

    • Search Google Scholar
    • Export Citation
  • 6.

    Chaffin MK, Martens RJ. Extrapulmonary disorders associated with Rhodococcus equi pneumonia in foals: retrospective study of 61 cases (1988–1996), in Proceedings. 43rd Annu Meet Am Assoc Equine Pract 1997;79:80.

    • Search Google Scholar
    • Export Citation
  • 7.

    Martens RJ, Martens JG, Fiske RA. Rhodococcus equi foal pneumonia: pathogenesis and immunoprophylaxis, in Proceedings. 35th Annu Meet Am Assoc Equine Pract 1989;199213.

    • Search Google Scholar
    • Export Citation
  • 8.

    Horowitz ML, Cohen ND, Takai S, et al. Application of Sartwell's model (logarithmic-normal distribution of incubation periods) to age at onset and age at death of foals with Rhodococcus equi pneumonia as evidence of perinatal infection. J Vet Intern Med 2001;15:171175.

    • Search Google Scholar
    • Export Citation
  • 9.

    Chaffin MK, Cohen ND, Martens RJ, et al. Hematologic and immunophenotypic factors associated with the development of Rhodococcus equi pneumonia of foals at equine breeding farms with endemic infection. Vet Immunol Immunopathol 2004;100:3348.

    • Search Google Scholar
    • Export Citation
  • 10.

    Breathnach CC, Sturgill-Wright T, Stiltner JL, et al. Foals are interferon gamma–deficient at birth. Vet Immunol Immunopathol 2006;112:199209.

    • Search Google Scholar
    • Export Citation
  • 11.

    Boyd NK, Cohen ND, Lim WS, et al. Temporal changes in cytokine expression of foals during the first month of life. Vet Immunol Immunopathol 2003;92:7585.

    • Search Google Scholar
    • Export Citation
  • 12.

    Hines SA, Stone DM, Hines MT, et al. Clearance of virulent but not avirulent Rhodococcus equi from the lungs of adult horses is associated with intracytoplasmic gamma interferon production by CD4+ and CD8+ T lymphocytes. Clin Diagn Lab Immunol 2003;10:208215.

    • Search Google Scholar
    • Export Citation
  • 13.

    Martens RJ, Martens JG, Fiske RA. Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally infected foals. Equine Vet J 1989;21:249255.

    • Search Google Scholar
    • Export Citation
  • 14.

    Madigan JE, Hietala S, Muller N. Protection against naturally acquired Rhodococcus equi pneumonia in foals by administration of hyperimmune plasma. J Reprod Fertil Suppl 1991;44:571578.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hurley JR, Begg AP. Failure of hyperimmune plasma to prevent pneumonia caused by Rhodococcus equi in foals. Aust Vet J 1995;72:418420.

  • 16.

    Becu T, Polledo G, Gaskin JM. Immunoprophylaxis of Rhodococcus equi pneumonia in foals. Vet Microbiol 1997;56:193204.

  • 17.

    Higuchi T, Arakawa T, Hashikura S, et al. Effect of prophylactic administration of hyperimmune plasma to prevent Rhodococcus equi infections on foals from endemically affected farms. Zentralbl Veterinarmed [B] 1999;46:641648.

    • Search Google Scholar
    • Export Citation
  • 18.

    Giguere S, Gaskin JM, Miller C, et al. Evaluation of a commercially available hyperimmune plasma product for prevention of naturally acquired pneumonia caused by Rhodococcus equi in foals. J Am Vet Med Assoc 2002;220:5963.

    • Search Google Scholar
    • Export Citation
  • 19.

    Caston SS, McClure SR, Martens RJ, et al. Effect of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus equi in experimentally infected foals. Vet Ther 2006;7:361375.

    • Search Google Scholar
    • Export Citation
  • 20.

    Peters DH, Friedel HA, McTavish D. Azithromycin. A review of its antimicrobial activity, antimicrobial activity, pharmacokinetic properties and clinical efficacy. Drugs 1992;44:750799.

    • Search Google Scholar
    • Export Citation
  • 21.

    Jacks S, Giguere S, Gronwall RR, et al. Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals. Am J Vet Res 2001;62:18701875.

    • Search Google Scholar
    • Export Citation
  • 22.

    Davis JL, Gardner SY, Jones SL, et al. Pharmacokinetics of azithromycin in foals after IV and oral dose and disposition into phagocytes. J Vet Pharmacol Ther 2002;25:99104.

    • Search Google Scholar
    • Export Citation
  • 23.

    Suarez-Mier G, Giguère S, Lee EA. Pulmonary disposition of erythromycin, azithromycin, and clarithromycin in foals. J Vet Pharmacol Ther 2007;30:109115.

    • Search Google Scholar
    • Export Citation
  • 24.

    Chaffin MK, Cohen ND, Martens RJ. Evaluation of equine breeding farm characteristics as risk factors for development of Rhodococcus equi pneumonia in foals. J Am Vet Med Assoc 2003;222:467475.

    • Search Google Scholar
    • Export Citation
  • 25.

    Chaffin MK, Cohen ND, Martens RJ. Evaluation of equine breeding farm management and preventative health practices as risk factors for development of Rhodococcus equi pneumonia in foals. J Am Vet Med Assoc 2003;222:476485.

    • Search Google Scholar
    • Export Citation
  • 26.

    Chaffin MK, Cohen ND, Edwards RF, et al. Foal-related risk factors associated with development of Rhodococcus equi pneumonia on farms with endemic infection. J Am Vet Med Assoc 2003;223:17911799.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cohen ND, O'Conor MS, Chaffin MK, et al. Farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals. J Am Vet Med Assoc 2005;226:404413.

    • Search Google Scholar
    • Export Citation
  • 28.

    Grimm MB, Cohen ND, Slovis NM, et al. Evaluation of fecal samples from mares as a source of Rhodococcus equi for their foals by use of quantitative bacteriologic culture and colony immunoblot analyses. Am J Vet Res 2007;68:6371.

    • Search Google Scholar
    • Export Citation
  • 29.

    Prescott JF, Lastra M, Barksdale L. Equi factors in the identification of Corynebacterium equi Magnusson. J Clin Microbiol 1982;16:988990.

    • Search Google Scholar
    • Export Citation
  • 30.

    Brown DF, Brown L. Evaluation of the E test, a novel method of quantifying antimicrobial activity. J Antimicrob Chemother 1991;27:185190.

    • Search Google Scholar
    • Export Citation
  • 31.

    Rosner BA. Nonparametric methods. In: Fundamentals of biostatistics. 2nd ed. Boston: Duxbury Press, 1986;278293.

  • 32.

    Rosner BA. Hypothesis testing: categorical data. Nonparametric methods. In: Fundamentals of biostatistics. 2nd ed. Boston: Duxbury Press, 1986;302357.

    • Search Google Scholar
    • Export Citation
  • 33.

    Hosmer DW, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons, 1989;187215.

  • 34.

    Breslow N, Clayton DG. Approximate inference in generalized linear mixed models. J Am Stat Assoc 1993;88:925.

  • 35.

    Pinheiro JC, Chao EC. Efficient Laplacian and adaptive Gaussian quadrature algorithms for multilevel generalized linear mixed models. J Comput Graph Stat 2006;15:5881.

    • Search Google Scholar
    • Export Citation
  • 36.

    Morley PS, Apley MD, Besser E, et al. Antimicrobial drug use in veterinary medicine. J Vet Intern Med 2005;19:617629.

  • 37.

    Stratton-Phelps M, Wilson WD, Gardner IA. Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986–1996). J Am Vet Med Assoc 2000;217:6873.

    • Search Google Scholar
    • Export Citation
  • 38.

    Lakritz J, Wilson WD. Erythromycin and other macrolide antibiotics for treating Rhodococcus equi pneumonia in foals. Compend Contin Educ Pract Vet 2002;3:256261.

    • Search Google Scholar
    • Export Citation
  • 39.

    Magdesian KG. Neonatal foal diarrhea. Vet Clin North Am Equine Pract 2005;21:295312.

  • 40.

    Martens JR, Harrington JR, Cohen ND, et al. Gallium therapy: a novel metal-based antimicrobial strategy for potential control of Rhodococcus equi foal pneumonia, in Proceedings. 52nd Annu Meet Am Assoc Equine Pract 2006;219221.

    • Search Google Scholar
    • Export Citation
  • 41.

    Harrington JR, Martens RJ, Cohen ND, et al. Antimicrobial activity of gallium against virulent Rhodococcus equi in vitro and in vivo. J Vet Pharmacol Ther 2006;29:121127.

    • Search Google Scholar
    • Export Citation
  • 42.

    Takai S, Ohbushi S, Koike K, et al. Prevalence of virulent Rhodococcus equi in isolates from soil and feces of horses from horse-breeding farms with and without endemic infections. J Clin Microbiol 1991;29:28872889.

    • Search Google Scholar
    • Export Citation
  • 43.

    Takai S, Takahagi J, Sato Y, et al. Molecular epidemiology of virulent Rhodococcus equi in horses and their environment. In: Nakajima H, Rossdale PD, eds. Equine infectious diseases VII. Newmarket, England: R & W Publications Ltd, 1997;183187.

    • Search Google Scholar
    • Export Citation
  • 44.

    Takai S, Anzai T, Yamaguchi K, et al. Prevalence of virulence plasmids in environmental isolates of Rhodococcus equi from horse-breeding farms in Hokkaido. J Equine Sci 1994;5:2125.

    • Search Google Scholar
    • Export Citation
  • 45.

    Slovis NM, McCracken JL, Mundy G. How to use thoracic ultrasound to screen foals for Rhodococcus equi at affected farms, in Proceedings. 51st Annu Meet Am Assoc Equine Pract 2005;274278.

    • Search Google Scholar
    • Export Citation
  • 46.

    Lavoie JP, Fiset L, Laverty S. Review of 40 cases of lung abscesses in foals and adult horses. Equine Vet J 1994;26:348352.

  • 47.

    Higuchi T, Hashikura S, Hagiwara S, et al. Isolation of virulent Rhodococcus equi from transtracheal aspirates of foals serodiagnosed by enzyme-linked immunosorbent assay. J Vet Med Sci 1997;59:10971101.

    • Search Google Scholar
    • Export Citation
  • 48.

    Hillidge CJ. Use of erythromycin-rifampin combination in treatment of Rhodococcus equi pneumonia. Vet Microbiol 1987;14:337342.

  • 49.

    Mueller NS, Madigan JE. Methods of implementation of an immunoprophylaxis program for the prevention of Rhodococcus equi pneumonia: results of a 5-year field study, in Proceedings. 39th Annu Meet Am Assoc Equine Pract 1992;193201.

    • Search Google Scholar
    • Export Citation
  • 50.

    Anzai T, Wada R, Nakanishi A, et al. Comparison of tracheal aspiration with other tests for diagnosis of Rhodococcus equi pneumonia in foals. Vet Microbiol 1997;56:335345.

    • Search Google Scholar
    • Export Citation
  • 51.

    Ardans AA, Hietala SK, Spensley MS, et al. Studies of naturally occurring and experimental Rhodococcus equi, in Proceedings. 32nd Annu Meet Am Assoc Equine Pract 1986;129144.

    • Search Google Scholar
    • Export Citation
  • 52.

    Sellon DC, Besser TE, Vivrette SL, et al. Comparison of nucleic acid amplification, serology, and microbiologic culture for diagnosis of Rhodococcus equi pneumonia in foals. J Clin Microbiol 2001;39:12891293.

    • Search Google Scholar
    • Export Citation
  • 53.

    Martens RJ, Fiske RA, Renshaw HW. Experimental subacute foal pneumonia induced by aerosol administration of Corynebacterium equi. Equine Vet J 1982;14:111116.

    • Search Google Scholar
    • Export Citation

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Chemoprophylactic effects of azithromycin against Rhodococcus equi–induced pneumonia among foals at equine breeding farms with endemic infections

M. Keith Chaffin DVM, MS, DACVIM1, Noah D. Cohen VMD, MPH, PhD, DACVIM2, and Ronald J. Martens DVM3
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  • 1 Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4475.
  • | 2 Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4475.
  • | 3 Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4475.

Abstract

Objective—To determine the effect of azithromycin chemoprophylaxis on the cumulative incidence of pneumonia caused by Rhodococcus equi, age at onset of pneumonia, and minimum inhibitory concentration (MIC) of azithromycin for R equi isolates cultured from fecal and clinical samples.

Design—Controlled, randomized clinical trial.

Animals—338 foals born and raised at 10 equine breeding farms; each farm had a history of endemic R equi infections.

Procedures—Group 1 foals were control foals, and group 2 foals were treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 48 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of azithromycin. Isolates of R equi were tested for susceptibility to azithromycin.

Results—The proportion of R equi–affected foals was significantly higher for control foals (20.8%) than for azithromycin-treated foals (5.3%). Adverse effects of azithromycin treatment were not detected, and there were no significant differences between groups for the MICs of azithromycin for R equi isolates cultured from fecal or clinical samples.

Conclusions and Clinical Relevance—Azithromycin chemoprophylaxis effectively reduced the cumulative incidence of pneumonia attributable to R equi among foals at breeding farms with endemic R equi infections. There was no evidence of resistance to azithromycin. Nonetheless, caution must be used because it is possible that resistance could develop with widespread use of azithromycin as a preventative treatment. Further investigation is needed before azithromycin chemoprophylaxis can be recommended for control of R equi infections.

Abstract

Objective—To determine the effect of azithromycin chemoprophylaxis on the cumulative incidence of pneumonia caused by Rhodococcus equi, age at onset of pneumonia, and minimum inhibitory concentration (MIC) of azithromycin for R equi isolates cultured from fecal and clinical samples.

Design—Controlled, randomized clinical trial.

Animals—338 foals born and raised at 10 equine breeding farms; each farm had a history of endemic R equi infections.

Procedures—Group 1 foals were control foals, and group 2 foals were treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 48 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of azithromycin. Isolates of R equi were tested for susceptibility to azithromycin.

Results—The proportion of R equi–affected foals was significantly higher for control foals (20.8%) than for azithromycin-treated foals (5.3%). Adverse effects of azithromycin treatment were not detected, and there were no significant differences between groups for the MICs of azithromycin for R equi isolates cultured from fecal or clinical samples.

Conclusions and Clinical Relevance—Azithromycin chemoprophylaxis effectively reduced the cumulative incidence of pneumonia attributable to R equi among foals at breeding farms with endemic R equi infections. There was no evidence of resistance to azithromycin. Nonetheless, caution must be used because it is possible that resistance could develop with widespread use of azithromycin as a preventative treatment. Further investigation is needed before azithromycin chemoprophylaxis can be recommended for control of R equi infections.

Contributor Notes

Supported by the Morris Animal Foundation and the Link Equine Research Endowment, Texas A&M University.

The authors thank Dr. Jeane Mounce for technical assistance.

Address correspondence to Dr. Chaffin.