Evidence of amphotericin B resistance in Macrorhabdus ornithogaster in Australian cage-birds

Med Mycol. 2019 Jun 1;57(4):421-428. doi: 10.1093/mmy/myy062.

Abstract

Amphotericin B is widely used for the treatment of Macrorhabdus ornithogaster infections. To date, however, there have been no randomized controlled trials confirming its efficacy where cure was confirmed by postmortem examination. To determine the efficacy of amphotericin B against M. ornithogaster, a three-part study was undertaken. Treatment outcomes of M. ornithogaster infected birds treated amphotericin B were reviewed. A pilot treatment trial with two naturally infected birds (Melopsittacus undulatus and Agapornis roseicollis) was undertaken, administering amphotericin B at 100 mg/kg twice daily for 30 days. Finally, a randomized controlled trial using experimentally infected chickens treated with amphotericin B at 25 mg/kg and 100 mg/kg twice daily for 10 days was performed. Retrospective analysis indicated treatment failure in 80.4% of 36 cases that met the inclusion criteria. The pilot study showed that amphotericin B did not clear, but significantly decreased Macrorhabdus ornithogaster burden, followed by profound rebound effect of the number of organisms shed in the feces. Finally, the randomized controlled trial found that amphotericin B given at 100 mg/kg did not clear, but significantly decreased the burden of M. ornithogaster compared with both the 25 mg/kg group (P = .037) and the no treatment control group (P = .001). A strong curvilinear correlation between body weight and M. ornithogaster infection burden was present in the infected chickens. These findings represent treatment failure in three scenarios and indicate that treatment with amphotericin B has poor efficacy against Macrorhabdus ornithogaster.

Keywords: Amphotericin B, Macrorhabdus ornithogaster; resistance; treatment.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Amphotericin B / administration & dosage*
  • Amphotericin B / pharmacology
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacology
  • Australia
  • Bird Diseases / microbiology*
  • Birds*
  • Chickens
  • Colony Count, Microbial
  • Disease Models, Animal
  • Drug Resistance, Fungal*
  • Female
  • Male
  • Mycoses / microbiology
  • Mycoses / veterinary*
  • Random Allocation
  • Saccharomycetales / drug effects*
  • Saccharomycetales / isolation & purification
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Amphotericin B