Consensus guidelines for antifungal stewardship, surveillance and infection prevention, 2021.

Invasive fungal diseases (IFD) are serious infections associated with high mortality, particularly in immunocompromised patients. The prescribing of antifungal agents to prevent and treat IFD is associated with substantial economic burden on the health system, high rates of adverse drug reactions, significant drug-drug interactions and the emergence of antifungal resistance. As the population at risk of IFD continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ antifungal stewardship (AFS) programmes and measures to monitor and prevent infection has become increasingly important.

Fluoroquinolone antibiotics and adverse events.

Fluoroquinolones are broad-spectrum antibiotics with good oral bioavailability. They are used for the treatment of a wide variety of infections, but there are restrictions on prescribing these drugs. Epidemiological studies have reported an increased risk of rare adverse effects.

Ushering in Antifungal Stewardship: Perspectives of the Hematology Multidisciplinary Team Navigating Competing Demands, Constraints, and Uncertainty.

Background: The social, contextual, and behavioral determinants that influence care in patients at risk for invasive fungal diseases (IFD) are poorly understood. This knowledge gap is a barrier to the implementation of emerging antifungal stewardship (AFS) programs. We aimed to understand the barriers and enablers to AFS, opportunities for improvement, and perspectives of AFS for hematology patients at a major medical center in Australia.

'Cold and lonely': emergency presentations of patients with hypothermia to a large Australian health network.

Background: Extreme heat is a public health priority in Australia with the health effects of cold poorly studied. A record-breaking cold winter prompted an institutional investigation into the epidemiology and outcomes of hypothermic presentations.

Aims: To describe the clinical and epidemiological characteristics of hypothermic emergency presentations including patient outcomes as well as gaps in practice.

A population-based analysis of invasive fungal disease in haematology-oncology patients using data linkage of state-wide registries and administrative databases: 2005 - 2016.

Background: Little is known about the morbidity and mortality of invasive fungal disease (IFD) at a population level. The aim of this study was to determine the incidence, trends and outcomes of IFD in all haematology-oncology patients by linking Victorian hospital data to state-based registries.

Methods: Episodes of IFD complicating adult haematological malignancy (HM) and haematopoietic stem cell transplantation (HSCT) patients admitted to Victorian hospitals from 1 July 2005 to 30 June 2016 were extracted from the Victorian Admitted Episodes Dataset and linked to the date of HM diagnosis from the Victorian Cancer Registry and mortality from the Victorian Death Index.

Renal safety of short-term empiric gentamicin therapy in aged patients.

Objective: To determine the incidence of acute kidney injury (AKI) in aged patients receiving empiric gentamicin therapy.

Methods: Patients aged ≥65 years receiving gentamicin upon admission between 2013 and 2015 at two Australian hospitals were retrospectively studied. AKI was defined as a rise in creatinine by ≥50% and/or ≥26.

Toward Electronic Surveillance of Invasive Mold Diseases in Hematology-Oncology Patients: An Expert System Combining Natural Language Processing of Chest Computed Tomography Reports, Microbiology, and Antifungal Drug Data.

Purpose: Prospective epidemiologic surveillance of invasive mold disease (IMD) in hematology patients is hampered by the absence of a reliable laboratory prompt. This study develops an expert system for electronic surveillance of IMD that combines probabilities using natural language processing (NLP) of computed tomography (CT) reports with microbiology and antifungal drug data to improve prediction of IMD.

Methods: Microbiology indicators and antifungal drug-dispensing data were extracted from hospital information systems at three tertiary hospitals for 123 hematology-oncology patients.

Safety, clinical effectiveness and trough plasma concentrations of intravenous posaconazole in patients with haematological malignancies and/or undergoing allogeneic haematopoietic stem cell transplantation: off-trial experience.

Objectives: This study describes the safety, clinical effectiveness and trough plasma concentration (C) of intravenous (iv) posaconazole, provided as part of Merck Sharp and Dohme Australia's Named Patient Programme (NPP) in non-clinical trial settings.

Methods: A multicentre, retrospective study on the NPP use of iv posaconazole between July 2014 and March 2015 across seven Australian hospitals.

Results: Seventy courses of iv posaconazole were prescribed and evaluated in 61 patients receiving treatment for haematological malignancy.

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

Objectives: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD.

Methods: A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia.

Isavuconazole: a new extended spectrum triazole for invasive mold diseases.

Isavuconazole is the first broad spectrum prodrug triazole with efficacy against invasive fungal diseases including aspergillosis and mucormycosis. Characteristics include linear dose-proportional pharmacokinetics, intravenous and oral formulations allowing therapeutic streamlining, once daily dosing, absence of nephrotoxic solubilizing agents and excellent oral bioavailability independent of prandial status and gastric acidity. An open label noncomparator study demonstrated encouraging results for isavuconazole as primary or salvage therapy for a range of fungi including mucormycosis.

Automatic detection of patients with invasive fungal disease from free-text computed tomography (CT) scans.

Background: Invasive fungal diseases (IFDs) are associated with considerable health and economic costs. Surveillance of the more diagnostically challenging invasive fungal diseases, specifically of the sino-pulmonary system, is not feasible for many hospitals because case finding is a costly and labour intensive exercise. We developed text classifiers for detecting such IFDs from free-text radiology (CT) reports, using machine-learning techniques.

Facilitating surveillance of pulmonary invasive mold diseases in patients with haematological malignancies by screening computed tomography reports using natural language processing.

Purpose: Prospective surveillance of invasive mold diseases (IMDs) in haematology patients should be standard of care but is hampered by the absence of a reliable laboratory prompt and the difficulty of manual surveillance. We used a high throughput technology, natural language processing (NLP), to develop a classifier based on machine learning techniques to screen computed tomography (CT) reports supportive for IMDs.

Patients And Methods: We conducted a retrospective case-control study of CT reports from the clinical encounter and up to 12-weeks after, from a random subset of 79 of 270 case patients with 33 probable/proven IMDs by international definitions, and 68 of 257 uninfected-control patients identified from 3 tertiary haematology centres.

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

Purpose Of Review: Therapeutic drug monitoring (TDM) may be an important adjunct to optimizing the use of posaconazole.

Recent Findings: Limited clinical studies suggest that an exposure-response relationship for posaconazole exists for the treatment of established invasive fungal diseases (IFDs), with emerging but less compelling data supporting its role in prophylaxis. The high prevalence of subtherapeutic levels has not translated to high prophylactic failure rates perhaps because of preferential uptake by effector cells important in the front-line defence against Aspergillus species.

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.

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.

Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach.

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.

The role of general quality improvement measures in decreasing the burden of endemic MRSA in a medical-surgical intensive care unit.

Purpose: To determine whether any of several quality improvement interventions with none specifically targeting methicillin-resistant Staphylococcus aureus (MRSA) were associated with a decline in endemic MRSA prevalence in an intensive care unit (ICU) where active screening and contact isolation precautions for known MRSA colonised patients are not practised.

Setting: Medical-surgical ICU with 2,000 admissions/year.

Design: 8.

Comparing the pneumonia severity index with CURB-65 in patients admitted with community acquired pneumonia.

Pneumonia severity assessment systems such as the pneumonia severity index (PSI) and CURB-65 were designed to direct appropriate site of care based on 30-d mortality. Increasingly they are being used to guide empirical antibiotic therapy and also possibly to detect patients who will require admission to the intensive care unit (ICU). We retrospectively reviewed the records of all patients admitted to our institution with confirmed community acquired pneumonia (CAP) for the 12 months from January 2002.