• 1. Schneider RK, Bramlage LR, Moore RM, et al. A retrospective study of 192 horses affected with septic arthritis/tenosynovitis. Equine Vet J 1992;24:436442.

    • Search Google Scholar
    • Export Citation
  • 2. Oreff GL, Tatz AJ, Dahan R, et al. Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses. Vet Surg 2017;46:11201125.

    • Search Google Scholar
    • Export Citation
  • 3. Rubio-Martínez LM, Elmas CR, Black B, et al. Clinical use of antimicrobial regional limb perfusion in horses: 174 cases (1999–2009). J Am Vet Med Assoc 2012;241:16501658.

    • Search Google Scholar
    • Export Citation
  • 4. Chapman AM. Acute diarrhea in hospitalized horses. Vet Clin North Am Equine Pract 2009;25:363380.

  • 5. van der Harst MR, Bull S, Laffont CM, et al. Gentamicin nephrotoxicity—a comparison of in vitro findings with in vivo experiments in equines. Vet Res Commun 2005;29:247261.

    • Search Google Scholar
    • Export Citation
  • 6. Gilbertie JM, Schnabel LV, Stefanovski D, et al. Gram-negative multi-drug resistant bacteria influence survival to discharge for horses with septic synovial structures: 206 cases (2010–2015). Vet Microbiol 2018;226:6473.

    • Search Google Scholar
    • Export Citation
  • 7. Gales AC, Jones RN, Sader HS. Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance Program (2006-09). J Antimicrob Chemother 2011;66:20702074.

    • Search Google Scholar
    • Export Citation
  • 8. Zavascki AP, Goldani LZ, Li J, et al. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 2007;60:12061215.

    • Search Google Scholar
    • Export Citation
  • 9. Barton MH, Parviainen A, Norton N. Polymyxin B protects horses against induced endotoxaemia in vivo. Equine Vet J 2004;36:397401.

  • 10. Kwa AL, Lim TP, Low JG, et al. Pharmacokinetics of polymyxin B1 in patients with multidrug-resistant gram-negative bacterial infections. Diagn Microbiol Infect Dis 2008;60:163167.

    • Search Google Scholar
    • Export Citation
  • 11. Landman D, Georgescu C, Martin DA, et al. Polymyxins revisited. Clin Microbiol Rev 2008;21:449465.

  • 12. Morresey PR, MacKay RJ. Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses. Am J Vet Res 2006;67:642647.

    • Search Google Scholar
    • Export Citation
  • 13. Morrison DC, Jacobs DM. Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides. Immunochemistry 1976;13:813818.

    • Search Google Scholar
    • Export Citation
  • 14. Parviainen AK, Barton MH, Norton NN. Evaluation of polymyxin B in an ex vivo model of endotoxemia in horses. Am J Vet Res 2001;62:7276.

    • Search Google Scholar
    • Export Citation
  • 15. Raisbeck MF, Garner HE, Osweiler GD. Effects of polymyxin B on selected features of equine carbohydrate overload. Vet Hum Toxicol 1989;31:422426.

    • Search Google Scholar
    • Export Citation
  • 16. Cheah SE, Bulitta JB, Li J, et al. Development and validation of a liquid chromatography-mass spectrometry assay for polymyxin B in bacterial growth media. J Pharm Biomed Anal 2014;92:177182.

    • Search Google Scholar
    • Export Citation
  • 17. Simar S, Sibley D, Ashcraft D, et al. Colistin and polymyxin B minimal inhibitory concentrations determined by Etest found unreliable for Gram-negative bacilli. Ochsner J 2017;17:239242.

    • Search Google Scholar
    • Export Citation
  • 18. Sanders WE Jr, Sanders CC. Toxicity of antibacterial agents: mechanism of action on mammalian cells. Annu Rev Pharmacol Toxicol 1979;19:5383.

    • Search Google Scholar
    • Export Citation
  • 19. Maddox TW, Clegg PD, Williams NJ, et al. Antimicrobial resistance in bacteria from horses: epidemiology of antimicrobial resistance. Equine Vet J 2015;47:756765.

    • Search Google Scholar
    • Export Citation
  • 20. Lin QY, Tsai YL, Liu MC, et al. Serratia marcescens arn, a PhoP-regulated locus necessary for polymyxin B resistance. Antimicrob Agents Chemother 2014;58:51815190.

    • Search Google Scholar
    • Export Citation
  • 21. Sud IJ, Feingold DS. Mechanism of polymyxin B resistance in Proteus mirabilis. J Bacteriol 1970;104:289294.

  • 22. Nation RL, Li J, Cars O, et al. Framework for optimization of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus. Lancet Infect Dis 2015;15:225234.

    • Search Google Scholar
    • Export Citation
  • 23. Storm DR, Rosenthal KS, Swanson PE. Polymyxin and related peptide antibiotics. Annu Rev Biochem 1977;46:723763.

  • 24. Tran TB, Velkov T, Nation RL, et al. Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet? Int J Antimicrob Agents 2016;48:592597.

    • Search Google Scholar
    • Export Citation
  • 25. Evans ME, Feola DJ, Rapp RP. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother 1999;33:960967.

    • Search Google Scholar
    • Export Citation
  • 26. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006;10:R27.

    • Search Google Scholar
    • Export Citation
  • 27. Hermsen ED, Sullivan CJ, Rotschafer JC. Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical applications. Infect Dis Clin North Am 2003;17:545562.

    • Search Google Scholar
    • Export Citation
  • 28. Humphries RM. Susceptibility testing of the polymyxins: where are we now? Pharmacotherapy 2015;35:2227.

  • 29. Li J, Nation RL, Turnidge JD, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis 2006;6:589601.

    • Search Google Scholar
    • Export Citation
  • 30. Phe K, Lee Y, McDaneld PM, et al. In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy. Antimicrob Agents Chemother 2014;58:27402746.

    • Search Google Scholar
    • Export Citation
  • 31. Errico JA, Trumble TN, Bueno AC, et al. Comparison of two indirect techniques for local delivery of a high dose of an antimicrobial in the distal portion of forelimbs of horses. Am J Vet Res 2008;69:334342.

    • Search Google Scholar
    • Export Citation
  • 32. Gunderson BW, Ross GH, Ibrahim KH, et al. What do we really know about antibiotic pharmacodynamics? Pharmacotherapy 2001;21:302S318S.

    • Search Google Scholar
    • Export Citation
  • 33. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987;155:9399.

    • Search Google Scholar
    • Export Citation
  • 34. Colbath AC, Wittenburg LA, Gold JR, et al. The effects of mepivacaine hydrochloride on antimicrobial activity and mechanical nociceptive threshold during amikacin sulfate regional limb perfusion in the horse. Vet Surg 2016;45:798803.

    • Search Google Scholar
    • Export Citation
  • 35. Hyde RM, Lynch TM, Clark CK, et al. The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse. Can Vet J 2013;54:363367.

    • Search Google Scholar
    • Export Citation
  • 36. Kelmer G, Bell GC, Martin-Jimenez T. Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses. J Vet Pharmacol Ther 2013;36:236240.

    • Search Google Scholar
    • Export Citation
  • 37. Parra-Sanchez A, Lugo J, Boothe DM, et al. Pharmacokinetics and pharmacodynamics of enrofloxicin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses. Am J Vet Res 2006;67:16871695.

    • Search Google Scholar
    • Export Citation
  • 38. Alkabes SB, Adams SB, Moore GE, et al. Comparison of two tourniquets and determination of amikacin sulfate concentrations after metacarpophalangeal joint lavage performed simultaneously with intravenous regional limb perfusion in horses. Am J Vet Res 2011;72:613619.

    • Search Google Scholar
    • Export Citation
  • 39. Kilcoyne I, Dechant JE, Nieto JE. Evaluation of 10-minute versus 30-minute tourniquet time for intravenous regional limb perfusion with amikacin sulfate in standing sedated horses. Vet Rec 2016;178:585588.

    • Search Google Scholar
    • Export Citation
  • 40. Levine DG, Epstein KL, Ahern BJ, et al. Efficacy of three tourniquet types for intravenous antimicrobial regional limb perfusion in standing horses. Vet Surg 2010;39:10211024.

    • Search Google Scholar
    • Export Citation
  • 41. Kelmer G. Regional limb perfusion in horses. Vet Rec 2016;178:581584.

  • 42. Beccar-Varela AM, Epstein KL, White CL. Effect of experimentally induced synovitis on amikacin concentrations after intravenous regional limb perfusion. Vet Surg 2011;40:891897.

    • Search Google Scholar
    • Export Citation

Advertisement

Tarsocrural joint polymyxin B concentrations achieved following intravenous regional limb perfusion of the drug via a saphenous vein to healthy standing horses

View More View Less
  • 1 1Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.
  • | 2 2Department of Biomedical and Diagnostic Services, University of Tennessee, Knoxville, TN 37996.
  • | 3 3College of Veterinary Medicine, and the Department of Research Computing Support, Office of Information and Technology, University of Tennessee, Knoxville, TN 37996.

Abstract

OBJECTIVE

To determine whether therapeutic concentrations (> 0.5 to 1.0 μg/mL) of polymyxin B (PB) were achieved in the tarsocrural joint of horses when the drug was administered by IV regional limb perfusion (IV-RLP) via a saphenous vein at doses of 25, 50, and 300 mg and to describe any adverse systemic or local effects associated with such administration.

ANIMALS

9 healthy adult horses.

PROCEDURES

In the first of 2 experiments, 6 horses each received 25 and 50 mg of PB by IV-RLP via a saphenous vein with at least 2 weeks between treatments. For each treatment, a tourniquet was placed at the midmetatarsus and another was placed midway between the stifle joint and tarsus. Both tourniquets were removed 30 minutes after the assigned dose was administered. Blood and tarsocrural joint fluid samples were collected for determination of PB concentration before and at predetermined times after drug administration. In experiment 2, 4 horses were administered 300 mg of PB by IV-RLP in 1 randomly selected pelvic limb in a manner identical to that used in experiment 1.

RESULTS

For all 3 doses, the mean synovial fluid PB concentration was > 10 times the therapeutic concentration and below the level of quantification at 30 and 1,440 minutes after drug administration, respectively. No adverse systemic or local effects were observed following PB administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that IV-RLP of PB might be a viable alternative for treatment of horses with synovial infections caused by gram-negative bacteria.

Abstract

OBJECTIVE

To determine whether therapeutic concentrations (> 0.5 to 1.0 μg/mL) of polymyxin B (PB) were achieved in the tarsocrural joint of horses when the drug was administered by IV regional limb perfusion (IV-RLP) via a saphenous vein at doses of 25, 50, and 300 mg and to describe any adverse systemic or local effects associated with such administration.

ANIMALS

9 healthy adult horses.

PROCEDURES

In the first of 2 experiments, 6 horses each received 25 and 50 mg of PB by IV-RLP via a saphenous vein with at least 2 weeks between treatments. For each treatment, a tourniquet was placed at the midmetatarsus and another was placed midway between the stifle joint and tarsus. Both tourniquets were removed 30 minutes after the assigned dose was administered. Blood and tarsocrural joint fluid samples were collected for determination of PB concentration before and at predetermined times after drug administration. In experiment 2, 4 horses were administered 300 mg of PB by IV-RLP in 1 randomly selected pelvic limb in a manner identical to that used in experiment 1.

RESULTS

For all 3 doses, the mean synovial fluid PB concentration was > 10 times the therapeutic concentration and below the level of quantification at 30 and 1,440 minutes after drug administration, respectively. No adverse systemic or local effects were observed following PB administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that IV-RLP of PB might be a viable alternative for treatment of horses with synovial infections caused by gram-negative bacteria.

Contributor Notes

Address correspondence to Dr. Snowden (rsnowden@utk.edu).