"In the expanding group of patients with haematological, solid tumour malignancies or bone marrow transplant recipients, there is currently no standardised strategy for monitoring of infections, despite the fact that these patients have been identified as a nidus for threats from difficult-to-treat infections."

The objective of this stream is to implement a hospital-wide approach to recognition and management of febrile neutropenia (FN), invasive fungal infection and sepsis for patients being treated for cancer.


Cancer Sepsis Pathways

We have led a sepsis program for cancer patients across Western Central Melbourne Integrated Cancer Service (WCMICS) hospitals since 2012. It is currently in place as a whole-of hospital clinical pathway at Peter MacCallum Cancer Centre, in cancer services at St Vincent’s and Royal Melbourne and has been adapted for use at the Women’s (obstetrics) and Werribee Mercy (community) Hospitals.

Incidence etiology and timing of infections following azacitidine therapy for myelodysplastic syndromes.jpg

We have led a sepsis program for cancer patients across Western Central Melbourne Integrated Cancer Service (WCMICS) hospitals since 2012. It is currently in place as a whole-of hospital clinical pathway at Peter MacCallum Cancer Centre, in cancer services at St Vincent’s and Royal Melbourne and has been adapted for use at the Women’s (obstetrics) and Werribee Mercy (community) Hospitals.

Low risk febrile neutropenia program

Febrile neutropenia is the most common complication of the treatment of cancer and the leading cause of unplanned hospital admissions, with over 2600 adult admissions in Victoria in 2008 and 180 paediatric admissions in 2014. FN is defined as the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes  in the blood.

The current standard of treatment for febrile neutropenia is admission of all patients, irrespective of the underlying risk, for intravenous antibiotics until fever is resolved and neutrophil count recovers. This approach over-treats up to 50% of patients. National and international guidelines support the safe management of patients deemed low-risk for medical complications outside of the inpatient setting. On a background of increasing demand for cancer services as the population ages, implementation of outpatient management for febrile neutropenia allows patients to be managed more comfortably at home with resultant increase in access to inpatient beds and associated indirect cost savings to manage other more seriously unwell patients.

This program is responsible for the identification and management of low-risk febrile neutropenia patients in an outpatient setting.  Possible outcomes include: improved patient quality of life through outpatient versus inpatient management, a reduction in the patients’ risk of hospital acquired infections by minimising interventions, increased bed capacity from early hospital discharge of low-risk FN patients, reduced hospital length of stay for patients with FN resulting in indirect cost benefits from improved bed turnover, and utilization and development of specialist staff for consistency and quality of cancer care.

Electronic Fungal Management system

Invasive fungal disease (IFD) is a lethal and costly complication of modern cancer treatments and occurs in up to 30% of acute leukemia and 10% of stem cell transplant recipients. Mortality is 50-68% (1) and delays in treatment increase mortality (2, 3). Further, these infections impact on cancer-specific treatments resulting in delayed delivery and poorer outcomes (4). Notably we have shown in the Australian health care setting IFD’s result in a mean excess cost of $79,000 and length of hospital stay of 15 days (5). If ICU admission was required costs doubled (5). Antifungal drugs are in the top 10 pharmacy budget items for haematology patients. Despite these alarming metrics, interventions such as introduction of rapid diagnostic tests are lacking. Surveillance is rarely performed as it is costly, time consuming and not sustainable (6, 7). Building on an existing antimicrobial stewardship platform, Guidance MS (successfully implemented in 62 hospitals Australia-wide) and a prototype text-mining module we have developed a real-time electronic fungal management system providing a single data source relating to fungal infection history, risk and guidelines as well as collecting data. In conjunction with the National Centre for Antimicrobial Stewardship we will also develop metrics and approaches for antifungal stewardship in transplant recipients.  The role of diagnostics and TDM in stewardship will also be evaluated. 

1. Thursky et al., Bone Marrow Transplant, 2004, 2. Slavin et al., J Antimicrob Chemother, 2010, 3. Marr et al., Ann Intern Med, 2015, 4. Even et al., Haematologica, 2011, 5. Ananda-Rajah et al., Antimicrob Agents Chemother, 2011, 6. Ananda-Rajah et al.,PLoS One ,2014 and 7.Ananda-Rajah et al., Curr Opin Infect Dis, 2012.

PIPA Study

Dr Jason Trubiano

Antibiotic allergy effects 1 in 4 cancer patients hospitalized with an infection in Australia. This antibiotic allergy often causes inappropriate antibiotics to be prescribed, affecting patient and hospital outcomes. Antibiotics are also associated with the most severe forms of reactions (e.g. Stevens-Johnson Syndrome), and as such determining the causative antibiotics and safe antimicrobials to use in the future is currently limited by an absence of reliable testing services in Australia. This frequently leads to this group of cancer patients having limited antibiotic options, resulting in increased broad spectrum antibiotic usage that drives the development of 'superbugs'.

Predictors, Immunopathogenesis and Prescribing in Antibiotic allergy – A prospective multicenter cohort study aims to translate promising pilot data utilizing laboratory tools (in vitro T-cell assays) and skin testing into a combined approach that can be used to identify the causative antibiotics in these severe drug reactions. This work was piloted in 19 patients with severe antibiotic allergies and 16 controls, identifying the causative antibiotic in 79% of cases with high specificity (100%). This proposed research project also utilizes a well characterized DNA biobank of patients with antibiotic allergies to determine the genetic causes of these reactions.

The ability to identify genetic predictors of severe antibiotic allergies in cancer patients would allow the personilization of antibiotic therapy in our must vulnerable patients to avoid serious adverse events that result in treatment delays of life saving chemotherapy. At present, there are no commercially available diagnostics to determine the cause of severe antibiotic reactions and no screening tests for prevention, in a disease with an associated mortality of up to 21%. This work will provide this vulnerable group of patients that frequently require life saving antibiotic therapy, the ability to have their clinicians more accurately chose the safest and most appropriate antibiotic given their severe antibiotic allergy history.