P267 Candida in the biliary tract: extrapolative PK PD considerations

Abstract

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Objective Candida norvegensis is an uncommon Candida species causing infection in immunocompromised hosts. It is intrinsically resistant to Fluconazole, which is commonly the empiric choice for therapy. A strong association with post-liver transplant status, as in this case and near-100% mortality, likely due to inappropriate antifungal therapy and lack of source control has been reported in the literature.Methods and ResultsMr. AK, a 32-year-old gentleman, 10 months post-liver transplant recipient, had stenting done for biliary stricture. A month later, he developed ESBL E. coli cholangitis and bacteremia for which he was treated with Meropenem. Flaky pus was seen during stent exchange which grew Candida norvegensis on culture with 97% probability of identification (Fig. 1). Suspecting cholangitic abscesses, patient would require at least 3 weeks of antifungals and Meropenem.Since there is limited data about antifungal susceptibilities of C. norvegensis, MICs were generated on VITEK by using names of other Candida species. Micafungin was found to show an MIC of 0.12 and voriconazole of 0.25. EUCAST breakpoints are only provided for certain species and for others treatment is based on PK/PD considerations. The PK PD indices for efficacy of voriconazole is AUC/MIC of 30 and of Echinocandins is Cmax/MIC of 1R, which prompted extrapolation in this case.The extrapolative PK PD considerations were as follows (Table 1).Micafungin dose of 150 mg generates a biliary trough level of 1.9 mcg/mlR, which will lead to Cmax/MIC (1.9/0.12) of 15.83, exceeding the required target Cmax/MIC for cidal therapy of echinocandins which is 1R. Micafungin and Meropenem were administered for 3 weeks and the patient responded well to treatment.ConclusionThis case highlights the importance of speciation of Candida spp, extrapolating MICs and breakpoints for species where data are not available, early source control and use of PK/PD considerations in choosing the appropriate antifungal agent on a case-by-case basis.