Infectious Diseases - Research Publications

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    Access, knowledge and experience with fluorodeoxyglucose positron emission tomography/computed tomography in infection management: a survey of Australia and New Zealand infectious diseases physicians and microbiologists
    Douglas, AP ; Thursky, KA ; Worth, LJ ; Harrison, SJ ; Hicks, RJ ; Slavin, MA (WILEY, 2019-05-01)
    BACKGROUND: Despite fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) being funded only for staging and restaging of some malignancies in Australia, there is evidence of benefit of FDG-PET/CT for infection indications such as pyrexia of unknown origin (PUO), prolonged neutropenic fever (NF) and prosthetic device infection. AIM: To evaluate the current knowledge, utilisation of and gaps in access to FDG-PET/CT for infectious indications by Australasian infectious diseases (ID) physicians and microbiologists. METHODS: An online survey was administered to ID and microbiology doctors practising in adult medicine in Australia and New Zealand through two established email networks. Using targeted questions and case-based examples, multiple themes were explored, including access to FDG-PET/CT, use and perceived benefit of FDG-PET/CT in diagnosis and monitoring of non-malignant conditions such as NF and PUO, and barriers to clinical use of FDG-PET/CT. RESULTS: A response was received from 120 participants across all states and territories. Onsite and offsite FDG-PET/CT access was 63% and 31% respectively. Eighty-six percent reported using FDG-PET/CT for one or more infection indications and all had found it clinically useful, with common indications being PUO, prosthetic device infections and use in the immunocompromised host for prolonged NF and invasive fungal infection. Thirty-eight percent reported barriers in accessing FDG-PET/CT for infection indications and 76% would utilise FDG-PET/CT more frequently if funding existed for infection indications. CONCLUSION: Access to FDG-PET/CT in Australia and New Zealand is modest and is limited by lack of reimbursement for infection indications. There is discrepancy between recognised ID indications for FDG-PET/CT and funded indications.
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    Impact of a hospital-wide sepsis pathway on improved quality of care and clinical outcomes in surgical patients at a comprehensive cancer centre
    Hiong, A ; Thursky, KA ; Venn, G ; Teh, BW ; Haeusler, GM ; Crane, M ; Slavin, MA ; Worth, LJ (WILEY, 2019-05-01)
    PURPOSE: Sepsis is a significant complication following cancer surgery. Although standardised care bundles improve sepsis outcomes in other populations, the benefits in cancer patients are unclear. The objectives of this study were to describe the epidemiology of sepsis in cancer patients post-surgery, and to evaluate the impact of a clinical sepsis pathway on management and clinical outcomes. METHODS: A standardised hospital-wide sepsis pathway was developed in 2013, and all cases of sepsis at the Peter MacCallum Cancer Centre in 2014 were retrospectively evaluated. Inclusion criteria were sepsis onset during the 100-day period following a surgical procedure for cancer diagnosis. Patients were identified using ICD-10-AM sepsis discharge codes, audit documentation and the hospital's antimicrobial approval system. Sepsis episodes were classified as managed on- or off-pathway. RESULTS: A total of 119 sepsis episodes were identified. Of these, 71 (59.7%) were managed on the sepsis pathway. Episodes managed on-pathway resulted more frequently in administration of appropriate antibiotics compared to those off-pathway (94.4% vs. 66.7%, p < 0.001), and had shorter time to first-dose antibiotics (median 85 vs. 315 min, p < 0.001). Pathway utilisation was associated with significant reductions in need for inotropes (7% vs. 13%, p = 0.023), ventilation (3% vs. 10%, p = 0.006) and length of hospitalisation (median 15 vs. 30 days, p = 0.008). The most frequent source of infection was organ-space surgical site infection (24.4% of instances). CONCLUSIONS: A dedicated hospital-wide sepsis pathway had significant impact on the quality of care and clinical outcomes of sepsis in cancer surgery patients. Cost-benefit analysis of sepsis pathways for cancer patients is required.
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    Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital
    Teh, BW ; Worth, LJ ; Harrison, SJ ; Thursky, KA ; Slavin, MA (SPRINGER, 2015-07-01)
    INTRODUCTION: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. METHODS: Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. RESULTS: Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. CONCLUSION: Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.
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    Oseltamivir Resistance in Adult Oncology and Hematology Patients Infected with Pandemic (H1N1) 2009 Virus, Australia
    Tramontana, AR ; George, B ; Hurt, AC ; Doyle, JS ; Langan, K ; Reid, AB ; Harper, JM ; Thursky, K ; Worth, LJ ; Dwyer, DE ; Morrissey, CO ; Johnson, PDR ; Buising, KL ; Harrison, SJ ; Seymour, JF ; Ferguson, PE ; Wang, B ; Denholm, JT ; Cheng, AC ; Slavin, M (CENTERS DISEASE CONTROL, 2010-07-01)
    We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after > or = 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.
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    Facilitating Surveillance of Pulmonary Invasive Mold Diseases in Patients with Haematological Malignancies by Screening Computed Tomography Reports Using Natural Language Processing
    Ananda-Rajah, MR ; Martinez, D ; Slavin, MA ; Cavedon, L ; Dooley, M ; Cheng, A ; Thursky, KA ; Rota, R (PUBLIC LIBRARY SCIENCE, 2014-09-24)
    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. The classifier was trained and tested on a reference standard of 449 physician annotated reports including a development subset (n = 366), from a total of 1880 reports, using 10-fold cross validation, comparing binary and probabilistic predictions to the reference standard to generate sensitivity, specificity and area under the receiver-operating-curve (ROC). RESULTS: For the development subset, sensitivity/specificity was 91% (95%CI 86% to 94%)/79% (95%CI 71% to 84%) and ROC area was 0.92 (95%CI 89% to 94%). Of 25 (5.6%) missed notifications, only 4 (0.9%) reports were regarded as clinically significant. CONCLUSION: CT reports are a readily available and timely resource that may be exploited by NLP to facilitate continuous prospective IMD surveillance with translational benefits beyond surveillance alone.
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    The impact of antimicrobial allergy labels on antimicrobial usage in cancer patients
    Trubiano, JA ; Leung, VK ; Chu, MY ; Worth, LJ ; Slavin, MA ; Thursky, KA (BMC, 2015-06-01)
    BACKGROUND: Antibiotic allergy labels are associated with sub-optimal prescribing patterns and poorer clinical outcomes in non-cancer populations, but the effect of labelling on antimicrobial usage in patients with cancer is unknown. FINDINGS: A retrospective review of hospitalized patients admitted to the Peter MacCallum Cancer Centre (2010-2012) identified 23 % of cancer patients (n = 198) with an antimicrobial allergy label (AA). Comparison of those with an antimicrobial allergy label to those without demonstrated increased antibiotic use per admission (3 vs. 2, p = 0.01), increased fluoroquinolone use (11 % vs. 6 %, p < 0.05), increased antibiotic course duration (15 vs. 13 days, p = 0.09), higher readmission rates (53 % vs. 28 %, p < 0.001) and poorer concordance with prescribing guidelines (47 % vs. 91 %, p < 0.001). Patients in the AA group on multivariate analysis had a higher number of antibiotics employed, longer duration of antibiotic therapy and higher rate of readmission. CONCLUSIONS: Antimicrobial usage, including the use of restricted antibiotics, is higher in patients with cancer. Antibiotic de-labelling strategies in cancer patients must be evaluated to aid antimicrobial stewardship initiatives.
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    Improving Antimicrobial Stewardship by Antibiotic Allergy Delabeling: Evaluation of Knowledge, Attitude, and Practices Throughout the Emerging Infections Network
    Trubiano, JA ; Beekmann, SE ; Worth, LJ ; Polgreen, PM ; Thursky, KA ; Slavin, MA ; Grayson, ML ; Phillips, EJ (OXFORD UNIV PRESS INC, 2016-06-01)
    Antibiotic allergy testing (AAT) practices of Emerging Infections Network infectious disease physicians were surveyed. Although AAT was perceived to be necessary for removal of inappropriate or unnecessary allergy labels, there was limited access to any form of testing. In this study, we discuss current antibiotic allergy knowledge gaps and the development of AAT practices within antimicrobial stewardship programs, which will potentially improve antimicrobial prescribing.
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    Predicting Infectious ComplicatioNs in Children with Cancer: an external validation study
    Haeusler, GM ; Thursky, KA ; Mechinaud, F ; Babl, FE ; Lourenco, RDA ; Slavin, MA ; Phillips, R (NATURE PUBLISHING GROUP, 2017-07-11)
    BACKGROUND: The aim of this study was to validate the 'Predicting Infectious ComplicatioNs in Children with Cancer' (PICNICC) clinical decision rule (CDR) that predicts microbiologically documented infection (MDI) in children with cancer and fever and neutropenia (FN). We also investigated costs associated with current FN management strategies in Australia. METHODS: Demographic, episode, outcome and cost data were retrospectively collected on 650 episodes of FN. We assessed the discrimination, calibration, sensitivity and specificity of the PICNICC CDR in our cohort compared with the derivation data set. RESULTS: Using the original variable coefficients, the CDR performed poorly. After recalibration the PICNICC CDR had an area under the receiver operating characteristic (AUC-ROC) curve of 0.638 (95% CI 0.590-0.685) and calibration slope of 0.24. The sensitivity, specificity, positive predictive value and negative predictive value of the PICNICC CDR at presentation was 78.4%, 39.8%, 28.6% and 85.7%, respectively. For bacteraemia, the sensitivity improved to 85.2% and AUC-ROC to 0.71. Application at day 2, taking into consideration the proportion of MDI known (43%), further improved the sensitivity to 87.7%. Length of stay is the main contributor to cost of FN treatment, with an average cost per day of AUD 2183 in the low-risk group. CONCLUSIONS: For prediction of any MDI, the PICNICC rule did not perform as well at presentation in our cohort as compared with the derivation study. However, for bacteraemia, the predictive ability was similar to that of the derivation study, highlighting the importance of recalibration using local data. Performance also improved after an overnight period of observation. Implementation of a low-risk pathway, using the PICNICC CDR after a short period of inpatient observation, is likely to be safe and has the potential to reduce health-care expenditure.
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    Predicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma: Utility of Immune Profiling
    Teh, BW ; Harrison, SJ ; Allison, CC ; Slavin, MA ; Spelman, T ; Worth, LJ ; Thursky, KA ; Ritchie, D ; Pellegrini, M (FRONTIERS MEDIA SA, 2017-10-05)
    BACKGROUND: A translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted. METHODS: Baseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 × 106 cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05) and refined with multivariable analysis to define a predictive immune profile. RESULTS: 525 stimulant samples with 19,950 stimulant-cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection. CONCLUSION: Profiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy.
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    Microbiome transplantation and modulation of immune related adverse events
    Smibert, OC ; Guo, CW ; Khoo, C ; Thursky, KA ; Sandhu, S ; Slavin, MA (ELSEVIER, 2019-02-01)