Journal of Equine Veterinary Science
Volume 27, Issue 8 , Pages 341-345 , August 2007

Chemoprophylactic Antimicrobial Activity of Gallium Maltolate against Intracellular Rhodococcus equi

  • Ronald J. Martens, DVM

      Affiliations

    • From the Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
    • Corresponding Author InformationReprint requests: Ronald J. Martens, 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.
    • ,
  • Nicole A. Miller

      Affiliations

    • From the Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
    • ,
  • Noah D. Cohen, VMD, MPH, PhD, DACVIM

      Affiliations

    • From the Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
    • ,
  • Jessica R. Harrington, BS

      Affiliations

    • From the Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
    • ,
  • Lawrence R. Bernstein, PhD

      Affiliations

    • Terrametrix, Menlo Park, California

References 

  1. Cohen ND, Martens RJ. Rhodococcus equi foal pneumonia. In:  McGorum BC,  Dixon PM,  Robinson NE,  Schumacher J editor. Equine respiratory medicine and surgery. Philadelphia: Saunders Elsevier; 2007;p. 355–366
  2. Weinstock DM, Brown AE. Rhodococcus equi: an emerging pathogen. Clin Infect Dis. 2002;34:1379–1385
  3. Horowitz ML, Cohen ND, Takai S, Becu T, Chaffin MK, Chu KK, 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 Int Med. 2001;15:171–175
  4. Martens JG, Martens RJ, Renshaw HW. Rhodococcus (Corynebacterium) equi: Bactericidal capacity of neonatal and adult equine neutrophils. Am J Vet Res. 1988;49:295–299
  5. Boyd NK, Cohen ND, Lim WS, Martens RJ, Chaffin MK, Ball JM. Temporal changes in cytokine expression of foals during the first month of life. Vet Immunol Immunopathol. 2003;92:75–85
  6. Chaffin MK, Cohen ND, Martens RJ, Edwards RF, Nevill M, Smith R. 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;100:33–48
  7. Breathnach CC, Sturgill-Wright T, Stiltner JL, Adams AA, Lunn DP, Horohov DW. Foals are interferon gamma-deficient at birth. Vet Immunol Immunopathol. 2006;112:199–209
  8. Martens RJ, Martens JG, Fiske RA. Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally infected foals. Equine Vet J. 1989;21:249–255
  9. 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;44:571–578
  10. Caston SS, McClure SR, Martens RJ, Chaffin MK, Griffith RW, Cohen ND. Effects of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus equi in experimentally infected foals. Vet Ther. 2006;7:361–375
  11. Jordan MC, Harrington JR, Cohen ND, Tsolis RM, Dangott LJ, Weinberg ED, et al. Effects of iron modulation on growth and viability of Rhodococcus equi and expression of virulence-associated protein A. Am J Vet Res. 2003;64:1337–1346
  12. Bernstein LR. Mechanisms of therapeutic activity for gallium. Pharmacol Rev. 1998;50:665–682
  13. Olakanmi O, Britigan BE, Schlesinger LS. Gallium disrupts iron metabolism of mycobacteria residing within human macrophages. Infect Immun. 2000;68:5619–5627
  14. Harrington JR, Martens RJ, Cohen ND, Bernstein LR. Antimicrobial activity of gallium against virulent Rhodococcus equi in vitro and in vivo. J Vet Pharmacol Therap. 2006;29:121–127
  15. Kaneko Y, Thoendel M, Olakanmi O, Britigen BE, Singh PK. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J Clin Invest. 2007;117:877–888
  16. Martens RJ, Mealey K, Cohen ND, Harrington JR, Chaffin MK, Taylor RJ, et al. Pharmacokinetics of enteral gallium maltolate in neonatal foals. Am J Vet Res (in press).
  17. Bernstein LR, Tanner T, Godfrey C, Noll B. Chemistry and pharmacokinetics of gallium maltolate, a compound with high oral gallium bioavailability. Met Based Drugs. 2000;7:33–47
  18. Hondalus MK, Mosser DM. Survival and replication of Rhodococcus equi in macrophages. Infect Immun. 1994;62:4167–4175
  19. Pinhero JC, Bates DM. Mixed-effects models in S and S-PLUS. New York: Springer-Verlag; 2000;1–197
  20. Sidak A. Rectangular confidence regions for the means of multivariate normal distributions. J Am Stat Assoc. 1967;62:626–633
  21. Toyooka K, Takai S, Kirikae T. Rhodococcus equi can survive a phagolysomal environment in macrophages by suppressing acidification of the phagolysosome. J Med Microbiol. 2005;54:1007–1015
  22. Martens RJ, Harrington JR, Cohen ND, Chaffin MK, Mealey K, Taylor RJ, et al. Gallium therapy: a novel metal-based antimicrobial strategy for potential control of Rhodococcus equi foal pneumonia. Proc Am Assoc Equine Pract. 2006;52:219–221
  23. Tsan MF. Mechansim of gallium-67 accumulation in inflammatory lesions. J Nucl Med. 1986;26:88–92
  24. Lührmann A, Mauder N, Sydor T, Fernandez-Mora E, Schulze-Lüehrmann J, Takai S, et al. Necrotic death of Rhodococcus equi-infected macrophages is regulated by virulence-associated plasmids. Infect Immun. 2004;72:853–862

 Refereed

PII: S0737-0806(07)00243-2

doi: 10.1016/j.jevs.2007.06.007

Journal of Equine Veterinary Science
Volume 27, Issue 8 , Pages 341-345 , August 2007

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