David J Minich, Anthony J Cerreta, Alexis Nix, Daniel Thompson, Lilyvette Barajas, Ashley Portala, Dania Gamez, Allison Sacerdote-Velat, Matthew R O'Connor, Jennifer M Reinhart, Sherry Cox, Laura Adamovicz, Karisa N Tang, Matthew C Allender
Multdose treatment at 30 mg/kg with orally administered, bioencapsulated terbinafine every 48 hours for 12 months failed to achieve molecular resolution of natural E testavorans infection in Blanding's turtles and failed to consistently achieve appropriate plasma concentrations.
OBJECTIVE: Evaluate multidose bioencapsulated terbinafine for the treatment of Emydomyces testavorans in naturally infected Blanding's turtles (Emydoidea blandingii) and determine if this protocol resulted in therapeutic drug concentrations.
METHODS: Blanding's turtles housed within a quarantine facility were treated with oral terbinafine (30 mg/kg) bioencapsulated within earthworms delivered every 48 hours for 12 months in this experimental study. For all turtles, plasma terbinafine concentrations were quantified, and turtles were routinely tested for of E testavorans through quantitative PCR of combined oral, cloacal, and carapace/plastron swabs.
RESULTS: 13 Blanding's turtles were enrolled, and no turtle consistently tested negative via quantitative PCR for E testavorans after 12 months of treatment. The median plasma terbinafine concentrations at months 3 and 6 (trough concentrations) were 18 ng/mL (11 to 78 ng/mL) and 36 ng/mL (10 to 76 ng/mL), respectively. The median plasma terbinafine concentrations at months 9 and 12 (peak concentrations) were 163 ng/mL (61 to 575 ng/mL) and 100 ng/mL (13 to 247 ng/mL), respectively. Plasma terbinafine concentrations inconsistently measured above the MIC for E testavorans. No correlation was observed between plasma terbinafine concentrations and E testavorans target copy number by quantitative PCR.
CONCLUSIONS: Multdose treatment at 30 mg/kg with orally administered, bioencapsulated terbinafine every 48 hours for 12 months failed to achieve molecular resolution of natural E testavorans infection in Blanding's turtles and failed to consistently achieve appropriate plasma concentrations.
CLINICAL RELEVANCE: Emydomyces testavorans is associated with a challenging disease process and is of increasing concern for the health, welfare, and conservation of chelonian species. Further investigation of alternative dosing regimens and/or the use of oral terbinafine as part of multimodal treatment protocols is warranted.