Publications by authors named "Karin Thursky"

151 Publications

Cytomegalovirus DNAemia and disease: current-era epidemiology, clinical characteristics and outcomes in cancer patients other than allogeneic hematopoietic transplantation.

Intern Med J 2021 Aug 26. Epub 2021 Aug 26.

Department of Infectious Diseases, Peter MacCallum Cancer Centre.

Background And Objectives: High-intensity chemotherapy and advances in novel immunotherapies have seen the emergence of cytomegalovirus (CMV) infections in cancer patients other than allogeneic haematopoietic cell transplantation (HCT). We therefore aimed to evaluate the epidemiology, clinical characteristics, and outcomes of CMV infection in this population.

Method: A retrospective review of cancer patients other than allogeneic HCT who had CMV DNAemia and/or disease from July 2013 till May 2020 at a quaternary cancer center was performed.

Results: Of 11,485 cancer patients who underwent treatment during this period, 953 patients had CMV DNA testing performed and 238 of them had CMV DNAemia. After excluding patients with allogeneic HCT, 62 patients with CMV DNAemia were identified of which 10 had concurrent CMV disease. The most frequent underlying malignancies were B-cell lymphoproliferative disease (LPD) (31%, 19/62), T-cell LPD (21%, 13/62), chronic lymphocytic leukemia (11%, 7/62), and multiple myeloma (10%, 6/62). Most patients had lymphopenia (77%, 48/62), multiple cancer therapies (63%, 39/62 received ≥2 previous therapies), co-infection (56%, 35/62 had ≥1 co-infection) and corticosteroid therapy (48%, 30/62) within one month before CMV diagnosis. CMV DNAemia and disease were observed in patients receiving novel immunotherapies including bispecific antibody therapy, chimeric-antigen receptor T-cell therapy and immune checkpoint inhibitors.

Conclusion: Patients with haematological malignancy, particularly B-cell LPD, T-cell LPD, chronic lymphocytic leukemia and multiple myeloma were frequently identified to have CMV DNAemia and disease. Lymphopenia, multiple cancer therapies, co-infection, and recent receipt of systemic corticosteroids were also commonly observed. Future studies are necessary to determine optimal identification and management of CMV in these patients. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15496DOI Listing
August 2021

Excess cost of care associated with sepsis in cancer patients: Results from a population-based case-control matched cohort.

PLoS One 2021 11;16(8):e0255107. Epub 2021 Aug 11.

Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.

Background: Cancer patients are at significant risk of developing sepsis due to underlying malignancy and necessary treatments. Little is known about the economic burden of sepsis in this high-risk population. We estimate the short- and long-term healthcare costs of care of cancer patients with and without sepsis using individual-level linked-administrative data.

Methods: We conducted a population-based matched cohort study of cancer patients aged ≥18, diagnosed between 2010 and 2017. Cases were identified if diagnosed with sepsis during the study period, and were matched 1:1 by age, sex, cancer type and other variables to controls without sepsis. Mean costs (2018 Canadian dollars) for patients with and without sepsis up to 5 years were estimated adjusted using survival probabilities at partitioned intervals. We estimated excess cost associated with sepsis presented as a cost difference between the two cohorts. Haematological and solid cancers were analysed separately.

Results: 77,483 cancer patients with sepsis were identified and matched. 64.3% of the cohort were aged ≥65, 46.3% female and 17.8% with haematological malignancies. Among solid tumour patients, the excess cost of care among patients who developed sepsis was $29,081 (95%CI, $28,404-$29,757) in the first year, rising to $60,714 (95%CI, $59,729-$61,698) over 5 years. This was higher for haematology patients; $46,154 (95%CI, $45,505-$46,804) in year 1, increasing to $75,931 (95%CI, $74,895-$76,968).

Conclusions: Sepsis imposes substantial economic burden and can result in a doubling of cancer care costs, particularly during the first year of cancer diagnosis. These estimates are helpful in improving our understanding of burden of sepsis along the cancer pathway and to deploy targeted strategies to alleviate this burden.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255107PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357157PMC
August 2021

Invasive fungal disease in children with acute myeloid leukaemia: An Australian multicentre 10-year review.

Pediatr Blood Cancer 2021 Aug 6:e29275. Epub 2021 Aug 6.

Infection Management Service, Queensland Children's Hospital, Brisbane, Queensland, Australia.

Background: Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML.

Methods: As part of the retrospective multicentre cohort TERIFIC (The Epidemiology and Risk factors for Invasive Fungal Infections in immunocompromised Children) study, proven/probable/possible IFD episodes occurring in children with primary or relapsed/refractory AML from 2003 to 2014 were analysed. Crude IFD prevalence, clinical characteristics, microbiology and treatment were assessed. Kaplan-Meier survival analysis was used to estimate 6-month survival.

Results: There were 66 IFD episodes diagnosed in 63 children with AML. The majority (75.8%) of episodes occurred in the context of primary AML therapy. During primary AML therapy, the overall prevalence was 20.7% (95% CI 15.7%-26.5%) for proven/probable/possible IFD and 10.3% (95% CI 6.7%-15.0%) for proven/probable IFD. Of primary AML patients, 8.2% had IFD diagnosed during the first cycle of chemotherapy. Amongst pathogens implicated in proven/probable IFD episodes, 74.4% were moulds, over a third (37.9%) of which were non-Aspergillus spp. Antifungal prophylaxis preceded 89.4% of IFD episodes, most commonly using fluconazole (50% of IFD episodes). All-cause mortality at 6 months from IFD diagnosis was 16.7% with IFD-related mortality of 7.6% (all in cases of proven IFD).

Conclusions: IFD is a common and serious complication during paediatric AML therapy. Mould infections, including non-Aspergillus spp. predominated in this cohort. A systematic approach to the identification of patients at risk, and a targeted prevention strategy for IFD is needed.
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http://dx.doi.org/10.1002/pbc.29275DOI Listing
August 2021

Evaluating the Implementation of a Pilot Quality Improvement Program to Support Appropriate Antimicrobial Prescribing in General Practice.

Antibiotics (Basel) 2021 Jul 16;10(7). Epub 2021 Jul 16.

Department of General Practice, The University of Melbourne, Melbourne 3004, Australia.

Inappropriate antimicrobial prescribing contributes to increasing antimicrobial resistance. An antimicrobial stewardship (AMS) program in the form of quality improvement activities that included audit and feedback, clinical decision support and education was developed to help optimise prescribing in general practice. The aim of this study was to evaluate the implementation of this program (Guidance GP) in three general practices in Melbourne, Australia, between November 2019 and August 2020. Thirty-one general practitioners (GPs) participated in the program, with 11 GPs and three practice managers participating in follow-up focus groups and interviews to explore the acceptability and feasibility of the program. Our findings showed that the quality improvement activities were acceptable to GPs, if they accurately fit GPs' decision-making process and workflow. It was also important that they provided clinically meaningful information in the form of audit and feedback to GPs. The time needed to coordinate the program, and costs to implement the program were some of the potential barriers identified. Facilitators of success were a "whole of practice" approach with enthusiastic GPs and practice staff, and an identified practice champion. The findings of this research will inform implementation strategies for both the Guidance GP program and AMS programs more broadly in Australian general practice, which will be critical for general practice participation and engagement.
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http://dx.doi.org/10.3390/antibiotics10070867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300821PMC
July 2021

Factors associated with antimicrobial choice for surgical prophylaxis in Australia.

JAC Antimicrob Resist 2020 Sep 18;2(3):dlaa036. Epub 2020 Jul 18.

National Health and Medical Research Council Centre of Research Excellence: National Centre for Antimicrobial Stewardship (NCAS), Peter Doherty Research Institute for Infection and Immunity Melbourne, Melbourne, VIC 3000, Australia.

Background: Cefazolin is the most commonly recommended antimicrobial for surgical antimicrobial prophylaxis (SAP). However, the Australian Surgical National Antimicrobial Prescribing Survey revealed a wide range of antimicrobials prescribed for SAP. Inappropriate use of broad-spectrum antimicrobials is associated with increased patient harm and is a posited driver for antimicrobial resistance.

Objectives: To describe patient, hospital and surgical factors that are associated with appropriateness of the top five prescribed antimicrobials/antimicrobial classes for procedural SAP.

Methods: All procedures audited from 18 April 2016 to 15 April 2019 in the Surgical National Antimicrobial Prescribing Survey were included in the analysis. Estimated marginal means analyses accounted for a range of variables and calculated a rate of adjusted appropriateness (AA). Subanalyses of the top five audited antimicrobials/antimicrobial classes identified associations between variables and appropriateness.

Results: A total of 12 419 surgical episodes with 14 150 prescribed initial procedural doses were included for analysis. When procedural SAP was prescribed, appropriateness was low (57.7%). Allergy status, surgical procedure group and the presence of prosthetic material were positively associated with cefazolin and aminoglycoside appropriateness (0.05). There were no significant positive associations with glycopeptides and third/fourth-generation cephalosporins. The use of broad-spectrum antimicrobials was the most common reason for inappropriate choice (67.9% of metronidazole to 83.3% of third/fourth-generation cephalosporin prescriptions).

Conclusions: Various factors influence appropriateness of procedural SAP choice. Identification of these factors provides targets for antimicrobial stewardship interventions, e.g. procedures where surgeons are regularly prescribing broad-spectrum SAP. These can be tailored to address local hospital prescribing practices.
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http://dx.doi.org/10.1093/jacamr/dlaa036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210066PMC
September 2020

Antifungal prescribing in neonates: using national point prevalence survey data from Australia.

Med Mycol 2021 Jun 25. Epub 2021 Jun 25.

Department of Infectious Diseases, Immunology & Sexual Health, St George Hospital, Sydney, Australia.

We describe contemporary antifungal use in neonates, with point-prevalence survey data from the National Antimicrobial Prescribing Survey across Australian hospitals from 2014-2018. There were 247 antifungal prescriptions in 243 neonates in 20 hospitals, median age six days (range 0-27 days). In 219/247 prescriptions (89%) antifungals were prescribed as prophylaxis. Topical (oral) nystatin was the most frequently prescribed in 233/247 prescriptions (94%), followed by fluconazole 11/247 (4%), with substantial variation in dosing for both. Two of 243 neonates (0.8%) had invasive fungal infection. Nystatin use dominates current antifungal prescribing for Australian neonates, in contrast to other countries, and invasive fungal infection is rare.

Lay Abstract: Novel nationwide surveillance found newborn infants in Australian hospitals commonly receive antifungal medications, mostly oral nystatin. This is given to prevent rather than treat infection, which is rare. There is substantial unexplained variation in dosing of antifungal drugs nationally.
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http://dx.doi.org/10.1093/mmy/myab037DOI Listing
June 2021

Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia.

Front Immunol 2021 20;12:641879. Epub 2021 May 20.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Objectives: Febrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia.

Methods: Thirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8-24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed.

Results: The median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8-100%) and specificity of 89% (95% CI 80.0-95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes.

Conclusion: Elevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.
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http://dx.doi.org/10.3389/fimmu.2021.641879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173204PMC
May 2021

Point Prevalence Survey of Antimicrobial Use in a Malaysian Tertiary Care University Hospital.

Antibiotics (Basel) 2021 May 4;10(5). Epub 2021 May 4.

Pharmacoepidemiology and Drug Safety Unit, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.

Antimicrobial resistance remains a significant public health issue, and to a greater extent, caused by the misuse of antimicrobials. Monitoring and benchmarking antimicrobial use is critical for the antimicrobial stewardship team to enhance prudent use of antimicrobial and curb antimicrobial resistance in healthcare settings. Employing a comprehensive and established tool, this study investigated the trends and compliance of antimicrobial prescribing in a tertiary care teaching hospital in Malaysia to identify potential target areas for quality improvement. A point prevalence survey method following the National Antimicrobial Prescribing Survey (NAPS) was used to collect detailed data on antimicrobial prescribing and assessed a set of quality indicators associated with antimicrobial use. The paper-based survey was conducted across 37 adult wards, which included all adult in-patients on the day of the survey to form the study population. Of 478 patients surveyed, 234 (49%) patients received at least one antimicrobial agent, with 357 antimicrobial prescriptions. The highest prevalence of antimicrobial use was within the ICU (80%). Agents used were mainly amoxicillin/β-lactamase inhibitor (14.8%), piperacillin/β-lactamase inhibitor (10.6%) and third-generation cephalosporin (ceftriaxone, 9.5%). Intravenous administration was ordered in 62.7% of prescriptions. Many antimicrobials were prescribed empirically (65.5%) and commonly prescribed for pneumonia (19.6%). The indications for antimicrobials were documented in the patients' notes for 80% of the prescriptions; however, the rate of review/stop date recorded must be improved (33.3%). One-half of surgical antimicrobial prophylaxis was administered for more than 24 h. From 280 assessable prescriptions, 141 (50.4%) were compliant with guidelines. Treating specialties, administration route, class of antimicrobial, and the number of prescriptions per patient were contributing factors associated with compliance. On multivariate analysis, administering non-oral routes of antimicrobial administration, and single antimicrobial prescription prescribed per patient was independently associated with non-compliance. NAPS can produce robust baseline information and identifying targets for improvement in antimicrobial prescribing in reference to current AMS initiatives within the tertiary care teaching hospital. The findings underscore the necessity to expand the AMS efforts towards reinforcing compliance, documentation, improving surgical prophylaxis prescribing practices, and updating local antibiotic guidelines.
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http://dx.doi.org/10.3390/antibiotics10050531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148015PMC
May 2021

Topical antimicrobial prescribing patterns in residents of Australian aged-care facilities: use of a national point prevalence survey to identify opportunities for quality improvement.

Am J Infect Control 2021 09 1;49(9):1113-1117. Epub 2021 Apr 1.

Victorian Healthcare Associated Infection Surveillance System (VICNISS) Coordinating Centre, Melbourne, Victoria, Australia; The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia.

Background: Australian residential aged care facilities (RACFs) are encouraged to participate in an annual Aged Care National Antimicrobial Prescribing Survey. This data source was analysed to describe patterns of topical antimicrobial prescribing and thereby provide insight into antimicrobial stewardship (AMS) changes that might be required.

Methods: 2018 and 2019 survey data was analysed.

Results: The overall prevalence of the 52,431 audited residents (629 facilities) who were prescribed 1 or more topical antimicrobials was 2.9%. Of all prescribed antimicrobials (n=4899), 33.0% were for topical application. Most frequently prescribed topical antifungals were clotrimazole (85.3%) and miconazole (9.1%), and antibacterials chloramphenicol (64.1%) and mupirocin (21.8%). Tinea (38.3%) and conjunctivitis (23.8%) were the 2 most common indications. Topical antimicrobials were sometimes prescribed for pro re nata administration (38.8%) and greater than 6 months (11.3%). The review or stop date was not always documented (38.7%).

Conclusions: To reduce the possibility of adverse consequences associated with antimicrobial use, antimicrobial stewardship programs in Australian residential aged care facilities should at least ensure mupirocin is appropriately used, first line antimicrobial therapy is prescribed for tinea, chloramphenicol is prescribed for conjunctivitis only if necessary, pro re nata orders for prescriptions are discouraged and to avoid prolonged duration of prescriptions, review or stop dates are always documented.
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http://dx.doi.org/10.1016/j.ajic.2021.03.019DOI Listing
September 2021

Latent infection screening and prevalence in cancer patients born outside of Australia: a universal versus risk-based approach?

Support Care Cancer 2021 Mar 24. Epub 2021 Mar 24.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, 3000, Australia.

Purpose: Contention surrounds how best to screen patients for latent and undiagnosed infection prior to cancer treatment. Early treatment and prophylaxis against reactivation may improve infection-associated morbidity. This study sought to examine rates of screening and prevalence of latent infection in overseas-born patients receiving cancer therapies.

Methods: A single-centre retrospective audit of 952 overseas-born patients receiving chemotherapy, targeted agents and immunotherapy between January 1 and December 31 2019 was undertaken at Peter MacCallum Cancer Centre. Pre-treatment screening for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), latent tuberculosis (LTBI), toxoplasmosis and strongyloidiasis was audited.

Results: Approximately half of our overseas-born patients were screened for HBV (58.9%) and HCV (50.7%). Fewer patients were screened for HIV (30.5%), LTBI (18.3%), strongyloidiasis (8.6%) or toxoplasmosis (8.1%). Although 59.7% of our patients were born in countries with high epidemiological risk for latent infection, according to World Health Organization data, 35% were not screened for any infection prior to commencement of therapy.

Conclusion: The prevalence of latent infections amongst overseas-born patients with cancer, and complexities associated with risk-based screening, likely supports universal latent infection screening amongst this higher-risk cohort.
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http://dx.doi.org/10.1007/s00520-021-06116-wDOI Listing
March 2021

An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams.

J Antimicrob Chemother 2021 05;76(6):1633-1640

University of Tasmania, Hobart, Australia.

Background: Healthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training.

Objectives: Little is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians' awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation.

Methods: AMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September-October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme.

Results: A total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes.

Conclusions: The development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.
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http://dx.doi.org/10.1093/jac/dkab053DOI Listing
May 2021

Improving intravenous-to-oral antibiotic switch in children: a team-based audit and implementation approach.

BMJ Open Qual 2021 03;10(1)

Medication Safety, Clinical Excellence Commission, Sydney, New South Wales, Australia.

Children in hospital are frequently prescribed intravenous antibiotics for longer than needed. Programmes to optimise timely intravenous-to-oral antibiotic switch may limit excessive in-hospital antibiotic use, minimise complications of intravenous therapy and allow children to go home faster. Here, we describe a quality improvement approach to implement a guideline, with team-based education, audit and feedback, for timely, safe switch from intravenous-to-oral antibiotics in hospitalised children. Eligibility for switch was based on evidence-based guidelines and supported by education and feedback. The project was conducted over 12 months in a tertiary paediatric hospital. Primary outcomes assessed were the proportion of eligible children admitted under paediatric and surgical teams switched within 24 hours, and switch timing prior to and after guideline launch. Secondary outcomes were hospital length of stay, recommencement of intravenous therapy or readmission. The percentage of children switched within 24 hours of eligibility significantly increased from 32/50 (64%) at baseline to 203/249 (82%) post-implementation (p=0.006). The median time to switch fell from 15 hours 42 min to 4 hours 20 min (p=0.0006). In addition, there was a 14-hour median reduction in hospital length of stay (p=0.008). Readmission to hospital and recommencement of intravenous therapy did not significantly change postimplementation. This education, audit and feedback approach improved timely intravenous-to-oral switch in children and also allowed for more timely discharge from hospital. The study demonstrates proof of concept for this implementation with a methodology that can be readily adapted to other paediatric inpatient settings.
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http://dx.doi.org/10.1136/bmjoq-2020-001120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978100PMC
March 2021

Managing low-risk febrile neutropenia in children in the time of COVID-19: What matters to parents and clinicians.

J Paediatr Child Health 2021 06 3;57(6):826-834. Epub 2021 Feb 3.

NHMRC National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.

Aim: The Australian 'There is no place like home' project is implementing a paediatric low-risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID-19) pandemic on programme implementation.

Methods: Paediatric oncology, infectious diseases and emergency medicine health-care workers and parent/carers were surveyed to explore the impact of the COVID-19 pandemic on home-based FN care. Online surveys were distributed nationally to health-care workers involved in care of children with FN and to parents or carers of children with cancer.

Results: Surveys were completed by 78 health-care workers and 32 parents/carers. Overall, 95% of health-care workers had confidence in the safety of home-based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre-pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home-based FN care. Among both groups, increased telehealth access and acceptance of home-based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re-direction of resources due to COVID-19 and challenges in implementing change during a crisis were potential barriers.

Conclusion: There is strong clinician and parent/carer support for home-based management of low-risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home-based treatments and opportunities exist to leverage these to refine the low-risk FN programme.
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http://dx.doi.org/10.1111/jpc.15330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013774PMC
June 2021

Quality of inpatient antimicrobial use in hematology and oncology patients.

Infect Control Hosp Epidemiol 2021 Feb 1:1-10. Epub 2021 Feb 1.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Objectives: To compare antimicrobial prescribing practices in Australian hematology and oncology patients to noncancer acute inpatients and to identify targets for stewardship interventions.

Design: Retrospective comparative analysis of a national prospectively collected database.

Methods: Using data from the 2014-2018 annual Australian point-prevalence surveys of antimicrobial prescribing in hospitalized patients (ie, Hospital National Antimicrobial Prescribing Survey called Hospital NAPS), the most frequently used antimicrobials, their appropriateness, and guideline concordance were compared among hematology/bone marrow transplant (hemBMT), oncology, and noncancer inpatients in the setting of treatment of neutropenic fever and antibacterial and antifungal prophylaxis.

Results: In 454 facilities, 94,226 antibiotic prescriptions for 62,607 adult inpatients (2,230 hemBMT, 1,824 oncology, and 58,553 noncancer) were analyzed. Appropriateness was high for neutropenic fever management across groups (83.4%-90.4%); however, hemBMT patients had high rates of carbapenem use (111 of 746 prescriptions, 14.9%), and 20.2% of these prescriptions were deemed inappropriate. Logistic regression demonstrated that hemBMT patients were more likely to receive appropriate antifungal prophylaxis compared to oncology and noncancer patients (adjusted OR, 5.3; P < .001 for hemBMT compared to noncancer patients). Oncology had a low rate of antifungal prophylaxis guideline compliance (67.2%), and incorrect dosage and frequency were key factors. Compared to oncology patients, hemBMT patients were more likely to receive appropriate nonsurgical antibacterial prophylaxis (aOR, 8.4; 95% CI, 5.3-13.3; P < .001). HemBMT patients were also more likely to receive appropriate nonsurgical antibacterial prophylaxis compared to noncancer patients (OR, 3.1; 95% CI, 1.9-5.0; P < .001). However, in the Australian context, the hemBMT group had higher than expected use of fluoroquinolone prophylaxis (66 of 831 prescriptions, 8%).

Conclusions: This study demonstrates why separate analysis of hemBMT and oncology populations is necessary to identify specific opportunities for quality improvement in each patient group.
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http://dx.doi.org/10.1017/ice.2020.1398DOI Listing
February 2021

Development of an antimicrobial stewardship implementation model involving collaboration between general practitioners and pharmacists: GPPAS study in Australian primary care.

Prim Health Care Res Dev 2021 01 28;22:e2. Epub 2021 Jan 28.

Department of General Practice, Monash University, Notting Hill, Victoria, Australia.

Background: Rising antimicrobial resistance (AMR) in primary care is a growing concern and a threat to community health. The rise of AMR can be slowed down if general practitioners (GPs) and community pharmacists (CPs) could work as a team to implement antimicrobial stewardship (AMS) programs for optimal use of antimicrobial(s). However, the evidence supporting a GP pharmacist collaborative AMS implementation model (GPPAS) in primary care remains limited.

Aim: With an aim to design a GPPAS model in Australia, this paper outlines how this model will be developed.

Methods: This exploratory study undertakes a systematic review, a scoping review, nationwide surveys, and qualitative interviews to design the model. Medical Research Council (MRC) framework and Normalization Process Theory are utilized as guides. Reviews will identify the list of effective GPPAS interventions. Two AMS surveys and paired interviews of GPs and CPs across Australia will explore their convergent and divergent views about the GPPAS interventions, attitudes towards collaboration in AMS and the perceived challenges of implementing GPPAS interventions. Systems Engineering Initiative for Patient Safety (SEIPS 2.0) model and factor analyses will guide the structure of GPPAS model through identifying the determinants of GPPAS uptake. The implementable GPPAS strategies will be selected based on empirical feasibility assessment by AMS stakeholders using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria.

Discussion: The GPPAS model might have potential implications to inform how to better involve GPs and CPs in AMS, and, to improve collaborative services to optimize antimicrobial use and reduce AMR in primary care.
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http://dx.doi.org/10.1017/S1463423620000687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057431PMC
January 2021

Divergent and Convergent Attitudes and Views of General Practitioners and Community Pharmacists to Collaboratively Implement Antimicrobial Stewardship Programs in Australia: A Nationwide Study.

Antibiotics (Basel) 2021 Jan 5;10(1). Epub 2021 Jan 5.

Department of General Practice, Monash University, Building 1, 270 Ferntree Gully Road, Notting Hill, VIC 3168, Australia.

Setting up an interprofessional team for antimicrobial stewardship (AMS) to improve the quality and safety of antimicrobial use in primary care is essential but challenging. This study aimed to investigate the convergent and divergent attitudes and views of general practitioners (GPs) and community pharmacists (CPs) about AMS implementation and their perceived challenges of collaboration to design a GP-pharmacist collaborative AMS (GPPAS) model. Nationwide surveys of GPs and CPs across Australia were conducted January-October 2019. Chi square statistics and a theoretical framework were used for comparative analyses of quantitative and qualitative data, respectively. In total, 999 participants responded to the surveys with 15.4% ( = 386) response rates for GPs and 30.7% ( = 613) for CPs. GPs and CPs were aware about AMS however their interprofessional perceptions varied to the benefits of AMS programs. CPs indicated that they would need AMS training; significantly higher than GPs (GP vs. CP; 46.4% vs. 76.5%; < 0.0001). GPs' use of the Therapeutic Guideline Antibiotic was much higher than CPs (83.2% vs. 45.5%; < 0.0001). No interprofessional difference was found in the very-limited use of patient information leaflets ( < 0.1162) and point-of-care tests ( < 0.7848). While CPs were more willing ( < 0.0001) to collaborate with GPs, both groups were convergent in views that policies that support GP-CP collaboration are needed to implement GPPAS strategies. GP-pharmacist collaborative group meetings (54.9% vs. 82.5%) and antimicrobial audit (46.1% vs. 86.5%) models were inter-professionally supported to optimise antimicrobial therapy, but an attitudinal divergence was significant ( < 0.001). The challenges towards GP-CP collaboration in AMS were identified by both at personal, logistical and organisational environment level. There are opportunities for GP-CP collaboration to improve AMS in Australian primary care. However, strengthening GP-pharmacy collaborative system structure and practice agreements is a priority to improve interprofessional trust, competencies, and communications for AMS and to establish a GPPAS model in future.
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http://dx.doi.org/10.3390/antibiotics10010047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824809PMC
January 2021

The role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in assessment of complex invasive fungal disease and opportunistic co-infections in patients with acute leukemia prior to allogeneic hematopoietic cell transplant.

Transpl Infect Dis 2021 Jun 28;23(3):e13547. Epub 2020 Dec 28.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.

Introduction: Individuals diagnosed with acute lymphoid and myeloid malignancies are at significant risk of invasive fungal and bacterial infections secondary to their marked immunocompromised states with a significant high risk of mortality. The role of metabolic imaging with 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly recognized in optimizing the diagnosis of invasive infection, monitoring the response to therapy and guiding the duration of antimicrobial therapy or need to escalate to surgical intervention.

Methods: Two distinct cases of pulmonary co-infection of rare fungal and bacterial pathogens are explored in severely immunocompromised individuals where FDG PET/CT aided both patients to make a full recovery and transition to HCT. The first case explores mixed Scedosporium apiospermum and Rhizomucor pulmonary infection on a background of T cell/myeloid mixed phenotype acute leukemia ultimately warranting long-term antifungal therapy and lobectomy prior to HCT. The second case explores Fusarium and Nocardia pulmonary infection on a background of relapsed AML also warranting surgical resection with lobectomy and long-term antimicrobials prior to transition to HCT.

Discussion: The cases highlight the utility of FDG PET/CT to support the diagnosis of infections, including the presence or absence of disseminated infection, and to provide highly sensitive monitoring of the infection over time. FDG PET/CT played a key role in directing therapy duration decisions and prompted the necessity for surgical intervention. Ultimately, the use of FDG PET/CT allowed for a successful transition to HCT highlighting its value in this clinical setting.

Conclusion: FDG PET/CT has an emerging role in the diagnostic and monitoring pathway for complex infections in high-risk immunocompromised patients.
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http://dx.doi.org/10.1111/tid.13547DOI Listing
June 2021

CAR-T cell therapy and infection: a review.

Expert Rev Anti Infect Ther 2021 Jun 31;19(6):749-758. Epub 2020 Dec 31.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia.

: Chimeric antigen receptor T-cell therapy (CAR-T cell therapy) is a novel immunotherapy with promising results in the treatment of relapsed or refractory B cell malignancies. Patients undergoing CAR-T cell therapy are at increased risk of infection due to prior immunosuppression, lymphodepleting chemotherapy, treatment of unique toxicities with tocilizumab and/or steroids, on-target effects of hypogammaglobulinaemia, and prolonged cytopenias.: A narrative review of infections (PubMed, August 2020) occurring in patients undergoing CAR-T cell therapy is described, and the evidence for infection prevention strategies is presented.: The rapid adoption of CAR-T cell therapy into clinical practice presents many challenges for the diagnosis, management, and prevention of infection. Ongoing surveillance of the spectrum of infectious complications and effectiveness of prophylaxis is required to support safe and effective patient care.
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http://dx.doi.org/10.1080/14787210.2021.1855143DOI Listing
June 2021

Case for antimicrobial stewardship pharmacy technicians in Australian hospitals.

Aust Health Rev 2020 Dec;44(6):941-943

National Centre for Antimicrobial Stewardship, Doherty Institute, Melbourne, Vic. 3000, Australia. Email: and University of Melbourne, Department of Medicine, Melbourne, Vic. 3010, Australia. Email: and Royal Melbourne Hospital, Victorian Infectious Diseases Service, Melbourne, Vic. 3050, Australia.

The pharmacist's role in hospital antimicrobial stewardship (AMS) programs is known to improve patient safety and the quality of care. Despite this, many Australian hospitals struggle to provide adequate pharmacy AMS program resourcing and need to explore newer models of care. The Pharmacy Board of Australia's Guidelines for Dispensing Medicines permit suitably qualified, competent and experienced pharmacy technicians to assist pharmacists in 'tasks in a pharmacy department'. The pharmacy technician workforce is expanding, and there is growing interest in career advancement and expansion of the pharmacy technician role. We propose that the pharmacy technician, a well-integrated member of many Australian hospital pharmacy departments, can play an important role in hospital AMS programs. To bolster AMS initiatives in Australian hospitals, this paper explores the existing evidence for pharmacy technicians in AMS programs and describes how this role may be better supported in Australia.
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http://dx.doi.org/10.1071/AH19236DOI Listing
December 2020

Antimicrobial stewardship by Australian community pharmacists: Uptake, collaboration, challenges, and needs.

J Am Pharm Assoc (2003) 2021 Mar-Apr;61(2):158-168.e7. Epub 2020 Nov 10.

Objective: To assess community pharmacists' (CPs') awareness and uptake of evidence-based antimicrobial stewardship (AMS) strategies, attitudes toward collaboration with general practitioners (GPs), and needs to improve AMS practices.

Methods: A nationwide survey of randomly sampled community pharmacies across Australia was conducted in April-October 2019.

Results: The response rate of CPs was 30.7% (613 of 2000) and 592 participating CPs (96.5%) described the key barriers to and facilitators of improving AMS. CPs (447 of 613, 72.9%) were familiar with AMS but felt that they would require training (468 of 612, 76.5%) and access to AMS practice guidelines (566 of 605, 93.6%). Respondents perceived that AMS programs could reduce the inappropriate use of antimicrobials (409 of 612, 66.8%) and the costs of treating infection (508 of 612, 83.0%). CPs often counseled patients (591 of 609, 97.0%) and reviewed drug interactions or allergies (569 of 607, 93.8%) before dispensing antimicrobials. Respondents less often used the national Therapeutic Guidelines: Antibiotic (274 of 602, 45.5%) or assessed guideline-compliance of prescribed antimicrobials (231 of 609, 37.9%). CPs were less likely to communicate with GPs (254 of 609, 41.8%) when an antimicrobial prescription was believed to be suboptimal and perceived that GPs are not receptive to their intervention regarding the antimicrobial choice (500 of 606, 82.6%) and dosage (416 of 606, 68.6%). Point-of-care tests (114 of 596, 19.1%) and patient information leaflets (149 of 608, 24.5%) were used uncommonly. Most respondents supported policies that could foster GP-pharmacist collaboration (560 of 606, 92.4%), limit accessibility of selected antimicrobials (420 of 604, 74.4%), and reduce repeat-dispensing of antimicrobial prescriptions (448 of 604, 74.2%). CPs faced interpersonal, interactional, structural, and resource-level barriers to collaborate with GPs for practicing AMS.

Conclusions: CPs are aware of the importance of sensible use of antimicrobials but have had limited training and resources to conduct AMS activities. Improving GPs' receptiveness and system structures for increased GP-CP collaboration seem to be a priority to accelerate CP-led AMS implementation. Further study is required to understand the views of stakeholders about the feasibility of implementing evidence-based GP-CP collaborative AMS approaches.
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http://dx.doi.org/10.1016/j.japh.2020.10.014DOI Listing
August 2021

Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study.

PLoS One 2020 16;15(9):e0238787. Epub 2020 Sep 16.

NHMRC National Centre for Infections in Cancer, University of Melbourne, Melbourne, Victoria, Australia.

Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5-10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren't (95% confidence interval, 1.89-7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238787PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494114PMC
November 2020

Electronic health record data for antimicrobial prescribing.

Lancet Infect Dis 2021 02 8;21(2):155-157. Epub 2020 Sep 8.

National Health and Medical Research Council National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia; Department of Medicine, University of Melbourne, Parkville, VIC, Australia; National Health and Medical Research Council National Centre for Antimicrobial Stewardship, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30453-9DOI Listing
February 2021

Classification performance of administrative coding data for detection of invasive fungal infection in paediatric cancer patients.

PLoS One 2020 9;15(9):e0238889. Epub 2020 Sep 9.

National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Background: Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown.

Objective: To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children's Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013.

Methods: ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated.

Results: Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58-90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61-95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05-72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis.

Conclusion: ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238889PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480858PMC
October 2020

Identifying targets for improvement using a nationally standardized survey: Surgical antimicrobial prophylaxis in orthopedic surgery.

Infect Control Hosp Epidemiol 2020 12 25;41(12):1419-1428. Epub 2020 Aug 25.

National Health and Medical Research Council Centre of Research Excellence: National Centre for Antimicrobial Stewardship (NCAS), Peter Doherty Research Institute for Infection and Immunity Melbourne, Melbourne, Victoria, Australia.

Background: Surgical antimicrobial prophylaxis (SAP) is commonly administered in orthopedic procedures. Research regarding SAP appropriateness for specific orthopedic procedures is limited and is required to facilitate targeted orthopedic prescriber behavior change.

Objectives: To describe SAP prescribing and appropriateness for orthopedic procedures in Australian hospitals.

Design, Setting, And Participants: Multicenter, national, quality improvement study with retrospective analysis of data collected from Australian hospitals via Surgical National Antimicrobial Prescribing Survey (Surgical NAPS) audits from January 1, 2016, to April 15, 2019, were analyzed.

Methods: Logistic regression identified hospital, patient and surgical factors associated with appropriateness. Adjusted appropriateness was calculated from the multivariable model. Additional subanalyses were conducted on smaller subsets to calculate the adjusted appropriateness for specific orthopedic procedures.

Results: In total, 140 facilities contributed to orthopedic audits in the Surgical NAPS, including 4,032 orthopedic surgical episodes and 6,709 prescribed doses. Overall appropriateness was low, 58.0% (n = 3,894). This differed for prescribed procedural (n = 3,978, 64.7%) and postprocedural doses (n = 2,731, 48.3%). The most common reasons for inappropriateness, when prophylaxis was required, was timing for procedural doses (50.9%) and duration for postprocedural prescriptions (49.8%). The adjusted appropriateness of each orthopedic procedure group was low for procedural SAP (knee surgery, 54.1% to total knee joint replacement, 74.1%). The adjusted appropriateness for postprocedural prescription was also low (from hand surgery, 40.7%, to closed reduction fractures, 68.7%).

Conclusions: Orthopedic surgical specialties demonstrated differences across procedural and postprocedural appropriateness. The metric of appropriateness identifies targets for quality improvement and is meaningful for clinicians. Targeted quality improvement projects for orthopedic specialties need to be developed to support optimization of antimicrobial use.
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http://dx.doi.org/10.1017/ice.2020.320DOI Listing
December 2020

The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study.

Clin Infect Dis 2021 08;73(3):487-496

Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Australia.

Background: Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for low-risk penicillin allergies in hospitalized inpatients.

Methods: Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days).

Results: Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51 [95% confidence interval {CI}, 5.39-20.48]), improved appropriate antibiotic prescribing (adjusted OR, 2.13 [95% CI, 1.45-3.13]), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 [95% CI, .27-.54]). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 [95% CI, 5.09-23.31]) and β-lactam/β-lactamase inhibitors (OR, 6.68 [95% CI, 3.94-11.35]) and a reduction in restricted antibiotic use (OR, 0.52 [95% CI, .36-.74]) and inappropriate prescriptions (relative risk ratio, 0.43 [95% CI, .26-.72]) in the delabeled group compared with the group who retained their allergy label.

Conclusions: This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.
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http://dx.doi.org/10.1093/cid/ciaa653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326579PMC
August 2021

Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital.

Support Care Cancer 2021 Mar 1;29(3):1609-1617. Epub 2020 Aug 1.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Background: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact.

Method: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety.

Results: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned.

Conclusion: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program.
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http://dx.doi.org/10.1007/s00520-020-05654-zDOI Listing
March 2021

Re-evaluating and recalibrating predictors of bacterial infection in children with cancer and febrile neutropenia.

EClinicalMedicine 2020 Jun 15;23:100394. Epub 2020 Jun 15.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia.

Background: Numerous paediatric febrile neutropenia (FN) clinical decision rules (CDRs) have been derived. Validation studies show reduced performance in external settings. We evaluated the association between variables common across published FN CDRs and bacterial infection and recalibrated existing CDRs using these data.

Methods: Prospective data from the Australian-PICNICC study which enrolled 858 FN episodes in children with cancer were used. Variables shown to be significant predictors of infection or adverse outcome in >1 CDR were analysed using multivariable logistic regression. Recalibration included re-evaluation of beta-coefficients (logistic model) or recursive-partition analysis (tree-based models).

Findings: Twenty-five unique variables were identified across 17 FN CDRs. Fourteen were included in >1 CDR and 10 were analysed in our dataset. On univariate analysis, location, temperature, hypotension, rigors, severely unwell and decreasing platelets, white cell count, neutrophil count and monocyte count were significantly associated with bacterial infection. On multivariable analysis, decreasing platelets, increasing temperature and the appearance of being clinically unwell remained significantly associated. Five rules were recalibrated. Across all rules, recalibration increased the AUC-ROC and low-risk yield as compared to non-recalibrated data. For the SPOG-adverse event CDR, recalibration also increased sensitivity and specificity and external validation showed reproducibility.

Interpretation: Degree of marrow suppression (low platelets), features of inflammation (temperature) and clinical judgement (severely unwell) have been consistently shown to predict infection in children with FN. Recalibration of existing CDRs is a novel way to improve diagnostic performance of CDRs and maintain relevance over time.

Funding: National Health and Medical Research Council Grant (APP1104527).
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http://dx.doi.org/10.1016/j.eclinm.2020.100394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329706PMC
June 2020

A Nationwide Survey of Australian General Practitioners on Antimicrobial Stewardship: Awareness, Uptake, Collaboration with Pharmacists and Improvement Strategies.

Antibiotics (Basel) 2020 Jun 8;9(6). Epub 2020 Jun 8.

Department of General Practice, Monash University, Building 1, 270 Ferntree Gully Road, Notting Hill, Victoria 3168, Australia.

Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners' (GPs') awareness of AMS, uptake of AMS strategies, attitudes towards GP-pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists' recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP-pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP-pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP-pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care.
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http://dx.doi.org/10.3390/antibiotics9060310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345044PMC
June 2020

Developing a Clinical Decision Support Tool for Appropriate Antibiotic Prescribing in Australian General Practice: A Simulation Study.

Med Decis Making 2020 05 8;40(4):428-437. Epub 2020 Jun 8.

The National Centre for Antimicrobial Stewardship, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

Inappropriate antibiotic prescribing can lead to antimicrobial resistance and drug side effects. Tools that assist general practitioners (GPs) in prescribing decisions may help to optimize prescribing. The aim of this study was to explore the use, acceptability, and feasibility of a clinical decision support (CDS) tool that incorporates evidence-based guidelines and consumer information that integrates with the electronic medical record (EMR). Eight GPs completed an interview and brief survey after participating in 2 simulated consultations. The survey consisted of demographic questions, perception of realism and representativeness of consultations, Post-Study System Usability Questionnaire, and System Usability Scale. Qualitative data were analyzed using framework analysis. Video data were reviewed, with length of consultation and time spent using the CDS tool documented. Survey responses indicated that all GPs thought the consultations were "real" and representative of real-life consultations; 7 of 8 GPs were satisfied with usability of the tool. Key qualitative findings included that the tool assisted with clinical decision making and informed appropriate antibiotic prescribing. Accessibility and ease of use, including content (guideline and patient education resources), layout, and format, were key factors that determined whether GPs said that they would access the tool in everyday practice. Integration of the tool at multiple sites within the EMR facilitated access to guidelines and assisted in ensuring that the tool fit the clinical workflow. Our CDS tool was acceptable to GPs. Key features required for the tool were easy navigation, clear and useful guideline content, ability to fit into the clinical workflow, and incorporation into the EMR. Piloting of the tool in general practices to assess the impact and feasibility of use in real-world consultations will now be undertaken.
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http://dx.doi.org/10.1177/0272989X20926136DOI Listing
May 2020
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