Documentation of In Vivo and In Vitro Aerobic Resistance of Feline Tritrichomonas foetus Isolates to Ronidazole

Abstract

Background: The mainstays of treatment for clinically important trichomonad infections are the 5-nitroimidazoles. Metronidazole resistance of feline Tritrichomonas foetus is presumed because of common treatment failure, and tinidazole does not consistently eradicate infection. To date, ronidazole is the only drug demonstrated as effective for treatment of cats infected with T. foetus.Objective: To document in vivo treatment failure and identify underlying causes and in vitro conditions of resistance of feline T. foetus to ronidazole.Animals: Two intact male Abyssinians failing !5 courses of treatment with increasing doses of 5-nitroimidazole drugs. An intact male Abyssinian documented to clear infection after treatment with a single course of ronidazole.Methods: T. foetus isolates were cultured from feces and tested in vitro for susceptibility to ronidazole under aerobic and anaerobic culture conditions. A urogenital nidus of T. foetus infection was investigated by culture, polymerase chain reaction, or immunohistochemical testing of urogenital specimens.Results: Resistance to ronidazole under aerobic conditions was uniquely identified in T. foetus isolated from cats with welldocumented treatment failure. Treatment failure could not be attributed to reinfection, inappropriate treatment protocol, or presence of a urogenital nidus of infection.Conclusions and Clinical Importance: Clinical resistance to metronidazole, low efficacy of tinidazole, and present documentation of in vivo and in vitro resistance to ronidazole in some cats are consistent with a high level of cross resistance of feline T. foetus to 5-nitroimidazole drugs. Current lack of alternative drugs with clinical efficacy against feline T. foetus suggests that active investigation of other treatment approaches is warranted.

Trichomonosis in cats with diarrhoea in Hong Kong, China, between 2009 and 2014

“…The cause of treatment failure in the remaining three cats was unknown; owner or patient compliance was not documented, but resistance of the Tritrichomonas species organism, which has been reported previously, could also be considered. 28 …”

Cysteine Protease Activity of Feline Tritrichomonas foetus Promotes Adhesion-Dependent Cytotoxicity to Intestinal Epithelial Cells

“…Despite a high prevalence, worldwide distribution of infection, and lack of consistently effective drugs for treatment, the cellular mechanisms of feline T. foetus intestinal epithelial pathogenicity have never been studied before (6,9,11,14). In these studies, we have identified a central role for cysteine proteases in promoting adhesion-dependent cytotoxicity of feline T. foetus to the intestinal epithelium.…”

“…Such studies are needed to better understand the pathological significance of these infections and to enable the development of novel treatment strategies to prevent or ameliorate their clinical effects. This is particularly true for feline intestinal T. foetus, where infection causes a lifelong recurrent diarrhea that is difficult to treat (5,6,(9)(10)(11)(12)(13)(14).…”

Feline Tritrichomonas foetus adhere to intestinal epithelium by receptor–ligand-dependent mechanisms

“…The nitroimidazole antibiotic, ronidazole, is currently the only effective antimicrobial treatment for feline trichomonosis. However, ronidazole has a narrow safety margin in cats and resistant strains have been recognized both clinically and in vitro (Gookin et al, 2010). In addition to a need for safer and more consistently effective drugs for killing TF, little is understood regarding how TF actually causes diarrhea.…”