THE RATIONALE AND REQUIREMENTS OF ROBUST DATA FOR INFECTION SURVEILLANCE IN PATIENTS WITH CANCER AND IMPLICATIONS FOR HEALTHCARE FUNDING

Name: Jake Valentine

Description: Modernisation of data management and investment in infrastructure could help the health industry keep pace with enormous and growing volumes of administrative and clinical data. Yet, limited and convoluted data linkage infrastructure in Australia remains a laggard in our efforts to develop technological solutions to streamline infection surveillance processes in vulnerable patients. This PhD will evaluate a constellation of data to estimate the burden of infectious complications in patients with cancer and will critically appraise novel health policy regarding modifications to Australia’s hospital pricing arrangements using administrative data in a cancer casemix. In addition, this PhD considers the requirements for customised and targeted prospective surveillance of key opportunistic and healthcare-associated infections in patients with haematological malignancy by linking readily available hospital-level data to streamline and expedite case ascertainment methods.

Publications:

  1. Valentine JC, Worth LJ, Verspoor KM, Hall L, Yeoh D, Thursky KA, Clark JE, Haeusler GM. Classification performance of administrative coding data for detection of invasive fungal infection in paediatric cancer patients. PLoS ONE. 2020;15(9):e0238889. Check Access

  2. Valentine JC, Hall L, Spelman T, Verspoor KM, Seymour JF, Rischin D, Thursky KA, Slavin MA, Worth LJ. Burden and clinical outcomes of hospital-coded infections in patients with cancer: an 11-year longitudinal cohort study at an Australian cancer centre. Support Care Cancer. 2020; [epub ahead of print]. Check Access

  3. Valentine JC, Hall L, Verspoor KM, Spelman T, Worth LJ. Hospital-coded infections in patients with cancer: Evaluating disease burden and outcomes in Australian cancer patients. Infect Dis Health. 2019;24(Supp_1):S2. Check Access

  4. Valentine JC, Hall L, Verspoor KM, Worth LJ. The current scope of healthcare-associated infection surveillance activities in hospitalized immunocompromised patients: a systematic review. Int J Epidemiol. 2019;48(6):1768-1782. Check Access

PREVENTING INFECTION IN HAEMATOLOGICAL MALIGNANCY AND BONE MARROW TRANSPLANTATION

Name: Julian Lindsay

Description: Infection in haematological malignancy and bone marrow transplantation is a major cause of morbidity and mortality due to a reduced immune function in patients who are at high risk of bacterial, fungal, viral, and/or parasitic infections. Preventing infections in this population can involve assessing risk factors, selection of donors, infection control measures and, using the best practice of prophylactic and pre-emptive antimicrobial therapies. This PhD will address critical knowledge gaps related to the optimisation of antimicrobial therapies; including pharmacokinetic optimisation of novel agents such as SUBA-itraconazole antifungal prophylaxis, optimisation of infection monitoring strategies including CMV and EBV pre-emptive therapies, as well as investigating incidence of opportunistic infections and associated patient risk factors in patients receiving Hematopoietic Stem Cell Transplantation (HSCT).

Publications:

  1. Lindsay J, Yong MK, Greenwood M, Kong DCM, Chen SCA, Rawlinson W, Slavin M. Epstein‐Barr virus related post‐transplant lymphoproliferative disorder prevention strategies in allogeneic hematopoietic stem cell transplantation. Rev Med Virol 2020;30(4):e2108. Check Access

  2. Lindsay J, Teh BW, Micklethwaite K, Slavin M. Azole antifungals and new targeted therapies for hematological malignancy. Curr Opin Infect Dis. 2019;32(6):538-545. Check Access

  3. Lindsay J, Mudge S, Thompson III GR. Effects of Food and Omeprazole on a Novel Formulation of Super Bioavailability Itraconazole in Healthy Subjects. Antimicrob Agents Chemother. 2018;62(12):e01723-18. Check Access

EPIDEMIOLOGY AND RISKS OF INFECTIONS IN PATIENTS WITH MULTIPLE MYELOMA MANAGED WITH NEXT IMMUNE-BASED GENERATION THERAPIES

Name: Chhay Lim

Description: Infection is a leading cause of morbidity and mortality in patients with multiple myeloma (MM), with an estimated of 45% of early deaths (within six months) due to infection. Treatment for MM has continued to evolve, resulting in new incidence and patterns of infection. Current standard-of-care for frontline therapy consists of first generation of immunomodulatory drugs (IMiDs) and proteasome inhibitor (PI), in both haematopoietic stem cell transplantation (HSCT) eligible and ineligible patients. The improved survival afforded by these novel agents alongside HSCT have transformed MM into a disease characterised by relapses requiring salvage therapies to achieve disease control. Newer agents such as second generation IMiD, PI and monoclonal antibodies have been introduced into clinical practice for relapse and refractory disease. However, the epidemiology and risks of infection remain poorly defined with the use of these agents. This study was conducted to determine patterns, risks and outcomes of infections in patients managed with second generation therapies and monoclonal antibodies.

Publications:

  1. Lim C, Sinha P, Harrison SJ, Quach H, Slavin MA, Teh BW. Low rates of invasive fungal disease in patients with multiple myeloma managed with new generation therapies: Results from a multi-centre cohort study. Mycoses. 2020; [epub ahead of print]. Check Access

EARLY DIAGNOSIS AND TREATMENT OF INFECTIONS IN PATIENTS WITH HAEMATOLOGIC MALIGNANCIES: DEVELOPMENT OF A DIAGNOSTIC PATHWAY INCORPORATING FUNGAL MULTIPLEX PCR AND FDG-PET IMAGING

Name: Abby Douglas

Description: Infections are one of the leading causes of morbidity and mortality in acute leukaemia and haemaetopoietic stem cell transplant (HSCT) patients. The aetiology of neutropenic fever in these patients is frequently not known leading to prolonged and costly empiric antimicrobial therapies and adverse outcomes. This thesis aims to improve the detection of infectious causes of neutropenic fever in those with acute leukaemia and HSCT recipients through employing the novel techniques of positron emission tomography (PET) and multiplexed tandem polymerase chain reaction (PCR) direct on blood samples. The conventional and novel diagnostic techniques will be compared with regards to change in patient management including antimicrobial prescribing and targeted secondary diagnostic techniques, as well as key patient outcomes such as length of stay, intensive care admission and mortality. 

Publications:

  1. Douglas A, Lau E, Thursky K, Slavin M. What, where and why: exploring fluorodeoxyglucose-PET’s ability to localize and differentiate infection from cancer. Curr Opin Infect Dis. 2017;30:552-564. Check Access 

  2. Ginn AN, Halliday CL, Douglas AP, Shen SCA. FDG-PET/CT imaging in detecting and guiding management of invasive fungal infections: A retrospective comparison to conventional CT imaging. Eur J Nucl Med Mol I. 2019;46(1):166-173. Check Access

  3. Douglas AP, Thursky KA, Worth LJ, Harrison SJ, Hicks RJ, Slavin MA. Access, knowledge and experience with FDG-PET/CT in infection management: a survey of Australia and New Zealand infectious diseases physicians and microbiologists. Intern Med J. 2019;49(5):615-621. Check Access 

  4. Douglas AP, Thursky KA, Worth LJ, Harrison SJ, Hicks RJ, Slavin MA. FDG-PET/CT in managing infection in patients with hematological malignancy: clinician knowledge and experience in Australia. Leuk Lymphoma. 2019;60(10):2471-2476. Check Access

PICCNIC

The Predicting Infectious ComplicatioNs In Children with Cancer (PICCNIC) study.

Lead Investigator: Dr Gabrielle Haeusler

Fever and neutropenia (FN), is the most common complication of the treatment of childhood cancer and the leading cause of unplanned hospital admissions. Of those children diagnosed with FN a severe infection, such as bacteraemia or pneumonia, is documented in fewer than half of all episodes. A number of paediatric clinical decision rules exist identify children at low-risk for severe infection who may qualify for reduced intensity treatment. However, due to a paucity of validation and implementation studies many centres continue to admit all children with FN for intravenous antibiotics, irrespective of underlying risk-status.  This approach contributes to the over-treatment of up to half of all children with FN and has the potential to negatively impact patient and family quality of life and increase health care expenditures. The Predicting Infectious ComplicatioNs In Children with Cancer (PICCNIC) study evaluates the utility of a clinical decision rule for early oral antibiotic switch and discharge in patients who would traditionally remain in hospital for the duration of their antibiotic treatment. A sub-study in collaboration with Prof Pellegrini (WEHI) will determine potential biomarkers for inclusion into a risk prediction model.

Low risk febrile neutropenia program

Lead Investigator: Dr Gabrielle Haeusler

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.

PIPA

Predictors, Immunopathogenesis and Prescribing in Antibiotic allergy

Lead Investigator: 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.