Michelle Ananda-Rajah

The case for antifungal stewardship.

Purpose of review Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescribing behaviour. In this review, we outline not only the elements of antifungal stewardship (AFS) in common with AMS but also features specific to antifungal drugs, combined with insights from our experience in AFS. Recent findings Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria, but their health and economic burden are substantial. Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost. High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue. The high mortality/morbidity associated with IFDs, including adverse impact on curative chemotherapy, combined with suboptimal diagnostic tools, has driven the overuse of antifungal drugs. De-escalation of empiric therapy is one of the most challenging aspects of AFS to implement. Nonculture-based tests may enhance AFS, but refinement of both target populations and clinical pathways incorporating their use is required. Performance indicators including structural, process and outcome measures are integral for demonstrating the value of AFS programmes. Summary Practice guidelines adapted to the local context are the cornerstone of AFS. Local epidemiology informs the choice of antifungal agents for the prevention and management of IFDs, underscoring the need for surveillance. Adherence to minimum standards of prescribing ensures that clinical outcomes are optimized and drug toxicities minimized, thus meeting healthcare quality and safety goals.

Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period

Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs. 8%, P=0.011), premature discontinuations (46% vs. 22% P<0.001) and empiric antifungal treatment (31% vs. 8.5%, P<0.001). Microbiologically confirmed infections were molds. Posaconazole compared to other drugs was associated with fewer courses requiring computed-tomography (43% vs. 26%, P<0.001). Adoption of voriconazole/posaconazole has decreased invasive fungal disease incidence, empiric antifungal treatment and for posaconazole, computed-tomography demand, with effectiveness of posaconazole comparable to clinical trial experience.

Attributable Hospital Cost and Antifungal Treatment of Invasive Fungal Diseases in High-Risk Hematology Patients: an Economic Modeling Approach

ABSTRACT Studies using patient-level data to determine the attributable cost of invasive fungal diseases (IFDs) are few. Using a case-control study with activity-based costing of patients admitted to a quaternary hospital from 2002 to 2007, we determined attributable hospitalization cost (and 12 weeks thereafter), length of stay (LOS), and costly antifungal treatment (C-AT; liposomal amphotericin B, voriconazole, posaconazole, caspofungin), expressed as defined daily doses (DDDs) per IFD episode, in patients with hematological malignancies and hematopoietic stem cell recipients. Matching criteria and median regression modeling controlled for confounding variables, including LOS prior to IFD onset. Multiple mycoses were identified in 43 matched case-control pairs (n = 86). A separate sensitivity analysis included 22 unmatched patients. IFD status was associated with a median excess cost of AU

Making sense of posaconazole therapeutic drug monitoring: a practical approach.

30,957 (95% confidence interval [CI] = AU

Breakthrough Disseminated Scedosporium prolificans Infection in a Patient with Relapsed Leukaemia on Prolonged Voriconazole Followed by Posaconazole Prophylaxis

2,368 to AU

Mucormycosis in Australia: contemporary epidemiology and outcomes

59,546; P = 0.034), approximating at purchasing power parity US

Isavuconazole: a new extended spectrum triazole for invasive mold diseases

21,203 (95% CI = US

Consensus guidelines for the use of empiric and diagnostic-driven antifungal treatment strategies in haematological malignancy, 2014

1,622 to US

Diagnostic and therapeutic approach to persistent or recurrent fevers of unknown origin in adult stem cell transplantation and haematological malignancy

40,784) and €15,788 (95% CI = €1,208 to €30,368), increasing to AU

Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit

80,291 (95% CI = AU