Antifungal prophylaxis in haematology patients: the role of voriconazole

Abstract Background Patients unable to take azoles are a neglected group lacking a standardized approach to antifungal prophylaxis. We evaluated the effectiveness and safety of intermittent liposomal amphotericin (L-AMB) prophylaxis in a heterogenous group of haematology patients. Methods A retrospective cohort of all haematology patients who received a course of intravenous L-AMB defined as 1mg/kg thrice weekly, from 1 July 2013-30 June 2018 were identified from pharmacy records. Outcomes included breakthrough-invasive fungal disease (BIFD), reasons for premature discontinuation and acute kidney injury. Results There were 198 patients who received 273 courses of L-AMB prophylaxis. Using a conservative definition, the BIFD rate was 9.6% (n=19/198) occurring either during L-AMB prophylaxis or up to 7 days from cessation in patients who received a course. Probable/proven-BIFD occurred in 13 patients (6.6%, 13/198), including molds in 54% (n=7) and non-albicans Candidaemia in 46% (n=6). Cumulative incidence of BIFD was highest in patients with acute myeloid leukaemia (6.8%) followed by acute lymphoblastic leukaemia (2.7%) and allogeneic stem cell transplantation (2.5%). The most common indication for L-AMB was chemotherapy or anticancer drug-azole interactions (75% of courses) dominated by vincristine or acute myeloid leukaemia clinical trials, followed by gut absorption concerns (13%) and liver function abnormalities (8.8%). Acute kidney injury using a modified international definition, complicated 27% of courses but was not clinically significant accounting for only 3.3% (9/273) of discontinuations. Conclusions Our findings demonstrate a high rate of BIFD among patients receiving L-AMB prophylaxis. Pragmatic trials will help find the optimal regimen of L-AMB prophylaxis for the many clinical scenarios where azoles are unsuitable, especially as targeted anticancer drugs increase in use.

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European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dky286 ◽

2018 ◽

Cited By ~ 20

Author(s):

Johan A Maertens ◽

Corrado Girmenia ◽

Roger J Brüggemann ◽

Rafael F Duarte ◽

Christopher C Kibbler ◽

...

Keyword(s):

Antifungal Prophylaxis ◽

European Conference ◽

European Guidelines ◽

Haematology Patients

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1129. Targeted Voriconazole Prophylaxis in Heart Transplantation Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.962 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S338-S338

Author(s):

Michael Lin ◽

Ignacio Echenique ◽

Michael Angarone ◽

Allen Anderson ◽

Valentina Stosor

Keyword(s):

Heart Transplantation ◽

Fungal Infections ◽

Single Case ◽

Statistical Significance ◽

Antifungal Prophylaxis ◽

Observational Cohort Study ◽

Observational Cohort ◽

Univariate Analyses

Abstract Background The use of antifungal prophylaxis, targeted or universal, remains controversial and unstudied. The goal of this study is to determine the role of targeted voriconazole prophylaxis (VORI) in prevention of invasive fungal infections (IFI) after heart transplantation (HT). Methods We conducted a single-center, prospective, observational cohort study of 276 HT recipients from June 2005 to April 2017 to characterize the incidence and outcome of IFI following targeted VORI. Starting in June 2013, HT recipients with thymoglobulin (ATG) treatment received VORI for 3 months. Probable/proven IFI were defined by EORTC/MSG criteria. Descriptive frequencies and univariate analyses were performed. Results Mean duration of follow-up post-HT was 1,165 days (0–3,152 days). 149 (54%) and 70 (25%) received basiliximab and thymoglobulin induction, respectively. Thirty-one (11%) received VORI, following use of ATG in the setting of induction (68%) or rejection (32%). VORI was started at median of 6 days (0–1,008 days) post-HT for a mean duration of 97 days (5–251 days). Overall, 23 IFIs occurred in 23 recipients (8%) at mean 283 days post-HT (range 2–1,579 days), including seven Aspergillus (one occurring after VORI completion), seven invasive Candida (five with candidemia), two Rhizopus, one Cunninghamella, two histoplasma, two blastomyces, one Cryptococcus, and one multifocal cutaneous Alternaria. Conclusion Targeted VORI resulted in reduced incidences of both early and overall IFI after HT although this did not reach statistical significance. Since instituting this strategy, we have observed a single case of aspergillosis following VORI discontinuation. Overall and 1-year mortality were not impacted. The use of antifungal prophylaxis following HT requires continued investigation both to determine efficacy and toxicity in this patient population. Disclosures All authors: No reported disclosures.

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