TREATMENT AND MANAGEMENT
The triazoles are a useful class of drugs for managing cryptococcosis, especially in animals with subclinical or early clinical disease of restricted extent. Their limitation is that they are fungistatic rather than fungicidal.
Amphotericin B is a far more useful drug for symptomatic disease because it is fungicidal. The nephrotoxicity of amphotericin B can be mitigated either by using liposomal formulations of the drug IV (expensive and disruptive) or by administering amphotericin deoxycholate SC with a large fluid bolus twice weekly (Malik et al. 1996). If there is evidence of extensive disease or disseminated disease, then amphotericin B must be given as part of the treatment regimen. In the future, encochleated amphotericin B, a novel formulation which can be given orally might be a useful advance, while new polyene agents devoid of nephrotoxicity are being developed (Aigner and Lass-Florl 2020; Maji et al. 2023). Flucytosine is a very useful drug for treating cryptococcosis in domestic species but its use in Australian native mammals is yet to be explored. In localised disease, fluconazole use can be challenging because of substantial variability in bioavailability between koalas, necessitating therapeutic drug monitoring and high initial dosages of 20-25 mg/kg bid (Govendir et al. 2016); itraconazole is also useful anecdotally, including newer formulations that have improved bioavailability in other species, although currently the pharmacokinetics are unresolved. Posaconazole may be useful but is very expensive, absorption remains highly variable between individuals and is untested in diseased animals (Gharibi et al. 2017). Voriconazole and isavuconazole are untested in Australian mammals. The highly erratic absorption of most xenobiotics in the koala, which might be related to the bulk of leaf material in their stomach, remains poorly understood (see Chapter 11) and it may be that parenteral therapy, particularly amphotericin B, is far more predictable. Therapeutic drug level monitoring is vital for monitoring azole therapeutics. Just as in other species, surgical debulking can be considered as an adjunct to therapy in individual cases (Wynne et al. 2012). It must be acknowledged that cryptococcosis is extremely challenging to manage by the time signs are present. Disseminated disease and the presence of neurological signs, particularly seizures, are extremely poor prognostic indicators. Despite this, there have been good outcomes when cases are managed aggressively.Early diagnosis of subclinical disease is essential for effective management and reliably successful outcomes. This usually occurs in the setting of zoo colonies in which one or more cases of disease have occurred and a screening program is introduced to systematically examine all animals in the facility, or in pre-shipment screening programs. Management decisions in response to low positive cryptococcal serology titres may include monthly monitoring without antifungal therapy or monthly monitoring with azole therapy (ideally, combined with therapeutic monitoring), plus implementation of various environmental decontamination strategies such as substrate change, furniture decontamination or furniture replacement. Transport is not recommended for koalas with evidence of subclinical disease because of the increased likelihood of rapid progression of disease.
ACKNOWLEDGEMENTS
We thank Tim Portas for updating this chapter on our behalf.