Publications by authors named "Gabrielle M Haeusler"

48 Publications

An Infant Presenting With Fever, Abdominal Distension, Diarrhea and Vomiting.

Pediatr Infect Dis J 2020 Dec;39(12):1134-1137

From the Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1097/INF.0000000000002890DOI Listing
December 2020

Optimising Antimicrobial Selection and Duration in the Treatment of Febrile Neutropenia in Children.

Infect Drug Resist 2021 30;14:1283-1293. Epub 2021 Mar 30.

Royal Marsden Hospital and Institute of Cancer Research, Sutton, SM2 5PT, UK.

Febrile neutropenia (FN) is a frequent complication of cancer treatment in children. Owing to the potential for overwhelming bacterial sepsis, the recognition and management of FN requires rapid implementation of evidenced-based management protocols. Treatment paradigms have progressed from hospitalisation with broad spectrum antibiotics for all patients, through to risk adapted approaches to management. Such risk adapted approaches aim to provide safe care through incorporating antimicrobial stewardship (AMS) principles such as implementation of comprehensive clinical pathways incorporating de-escalation strategies with the imperative to reduce hospital stay and antibiotic exposure where possible in order to improve patient experience, reduce costs and diminish the risk of nosocomial infection. This review summarises the principles of risk stratification in FN, the current key considerations for optimising empiric antimicrobial selection including knowledge of antimicrobial resistance patterns and emerging technologies for rapid diagnosis of specific infections and summarises existing evidence on time to treatment, investigations required and duration of treatment. To aid treating physicians we suggest the key features based on current evidence that should be part of any FN management guideline and highlight areas for future research. The focus is on treatment of bacterial infections although fungal and viral infections are also important in this patient group.
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http://dx.doi.org/10.2147/IDR.S238567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019605PMC
March 2021

Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality.

Antibiotics (Basel) 2021 Mar 5;10(3). Epub 2021 Mar 5.

Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada.

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of and vancomycin resistance in 40% of . Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.
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http://dx.doi.org/10.3390/antibiotics10030266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000765PMC
March 2021

Candidemia in Children: A 16-year Longitudinal Epidemiologic Study.

Pediatr Infect Dis J 2021 Jun;40(6):537-543

From the Department of Pediatrics, The University of Melbourne, Parkville, Victoria, Australia.

Background: Candida species are the most common cause of systemic fungal infections in children. Risk factors for candidemia vary in different patient populations, posing challenges for clinical prediction of infection. We describe the epidemiology and clinical disease of candidemia in children admitted to a tertiary pediatric hospital.

Methods: Retrospective audit of children ≤18 years of age with candidemia at a tertiary pediatric hospital over a 16-year period.

Results: There were 139 episodes of candidemia in 124 children. A central venous catheter was present in 94% of episodes, prior antibiotic exposure in 86% and parenteral nutrition in 43%. During the study period, the proportion of candidemia due to non-albicans Candida spp. increased primarily due to a rise in C. krusei. Colonization with Candida spp. in the 30 days before developing candidemia was identified in 40% of episodes and the species was concordant in 60%. Infection at other sites was rare, including pulmonary dissemination (9/38, 24%), renal fungal disease (9/114, 8%), fungal endophthalmitis (8/102, 8%) and hepatosplenic nodules (5/92, 5%). Overall, 8/127 (6%) isolates were fluconazole-resistant (7 C. krusei and 1 C. glabrata) and 7/127 (6%) had intermediate susceptibility to fluconazole. The overall 30-day mortality was 12% and significant risk factors for mortality on multivariate analysis were male sex, liver disease and mucositis.

Conclusions: Our study outlines low rates of disseminated candidiasis and low mortality associated with candidemia at our institution. Additionally, it suggests that prior colonization may be an important risk factor, however, this should be validated in large prospective controlled studies.
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http://dx.doi.org/10.1097/INF.0000000000003082DOI Listing
June 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 Feb 3. 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
February 2021

Guidance regarding COVID-19 for survivors of childhood, adolescent, and young adult cancer: A statement from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Pediatr Blood Cancer 2020 12 23;67(12):e28702. Epub 2020 Sep 23.

Department of Malignant Haematology, Great Ormond Street Hospital for Children NHS Trust, London, UK.

Childhood, adolescent, and young adult (CAYA) cancer survivors may be at risk for a severe course of COVID-19. Little is known about the clinical course of COVID-19 in CAYA cancer survivors, or if additional preventive measures are warranted. We established a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) to summarize existing evidence and worldwide recommendations regarding evidence about factors/conditions associated with risk for a severe course of COVID-19 in CAYA cancer survivors, and to develop a consensus statement to provide guidance for healthcare practitioners and CAYA cancer survivors regarding COVID-19.
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http://dx.doi.org/10.1002/pbc.28702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537044PMC
December 2020

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

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

Clinical Practice Guideline for Systemic Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients.

J Clin Oncol 2020 09 27;38(27):3205-3216. Epub 2020 May 27.

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Purpose: To develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients.

Methods: Recommendations were developed by an international multidisciplinary panel that included a patient advocate. We conducted a systematic review of systemic antifungal prophylaxis in children and adults with cancer and HSCT recipients. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to make strong or weak recommendations and to classify level of evidence as high, moderate, low, or very low. The panel considered directness of the data to pediatric patients.

Results: There were 68 randomized trials included in the systematic review, of which 6 (9%) were conducted in a solely pediatric population. Strong recommendations were made to administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia, to those undergoing allogeneic HSCT pre-engraftment, and to those receiving systemic immunosuppression for graft-versus-host disease treatment. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. For children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested. Posaconazole may also be used in those age 13 years or older. A strong recommendation against routine administration of amphotericin as systemic antifungal prophylaxis was made.

Conclusion: We developed a clinical practice guideline for systemic antifungal prophylaxis administration in pediatric patients with cancer and HSCT recipients. Implementation and assessment of guideline-concordant rates and impacts are important future steps.
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http://dx.doi.org/10.1200/JCO.20.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499615PMC
September 2020

Managing haematology and oncology patients during the COVID-19 pandemic: interim consensus guidance.

Med J Aust 2020 06 13;212(10):481-489. Epub 2020 May 13.

Peter MacCallum Cancer Centre, Melbourne, VIC.

Introduction: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic.

Main Recommendations: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning.

Changes In Management As A Result Of This Statement: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence.

Endorsed By: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.
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http://dx.doi.org/10.5694/mja2.50607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273031PMC
June 2020

Diagnostic Yield of Initial and Consecutive Blood Cultures in Children With Cancer and Febrile Neutropenia.

J Pediatric Infect Dis Soc 2021 Mar;10(2):125-130

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

Background: The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics.

Methods: Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected divided by the number of FN episodes that had a BC taken.

Results: A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P < .001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures.

Conclusions: In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals.
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http://dx.doi.org/10.1093/jpids/piaa029DOI Listing
March 2021

Risk stratification in children with cancer and febrile neutropenia: A national, prospective, multicentre validation of nine clinical decision rules.

EClinicalMedicine 2020 Jan 7;18:100220. Epub 2020 Jan 7.

Centre for Reviews and Dissemination, University of York, York, United Kingdom.

Background: Reduced intensity treatment of low-risk febrile neutropenia (FN) in children with cancer is safe and improves quality of life. Identifying children with low-risk FN using a validated risk stratification strategy is recommended. This study prospectively validated nine FN clinical decision rules (CDRs) designed to predict infection or adverse outcome.

Methods: Data were collected on consecutive FN episodes in this multicentre, prospective validation study. The reproducibility and discriminatory ability of each CDR in the validation cohort was compared to the derivation dataset and details of missed outcomes were reported.

Findings: There were 858 FN episodes in 462 patients from eight hospitals included. Bacteraemia occurred in 111 (12·9%) and a non-bacteraemia microbiological documented infection in 185 (21·6%). Eight CDRs exhibited reproducibility and sensitivity ranged from 64% to 96%. Rules that had >85% sensitivity in predicting outcomes classified few patients (<20%) as low risk. For three CDRs predicting a composite outcome of any bacterial or viral infection, the sensitivity and discriminatory ability improved for prediction of bacterial infection alone. Across all CDRs designed to be implemented at FN presentation, the sensitivity improved at day 2 assessment.

Interpretation: While reproducibility was observed in eight out of the nine CDRs, no rule perfectly differentiated between children with FN at high or low risk of infection. This is in keeping with other validation studies and highlights the need for additional safeguards against missed infections or adverse outcomes before implementation can be considered.
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http://dx.doi.org/10.1016/j.eclinm.2019.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978200PMC
January 2020

Individual participant data validation of the PICNICC prediction model for febrile neutropenia.

Arch Dis Child 2020 05 5;105(5):439-445. Epub 2019 Nov 5.

Research Institute for Primary Care and Health Sciences, Keele University, Keele, UK.

Background: Risk-stratified approaches to managing cancer therapies and their consequent complications rely on accurate predictions to work effectively. The risk-stratified management of fever with neutropenia is one such very common area of management in paediatric practice. Such rules are frequently produced and promoted without adequate confirmation of their accuracy.

Methods: An individual participant data meta-analytic validation of the 'Predicting Infectious ComplicatioNs In Children with Cancer' (PICNICC) prediction model for microbiologically documented infection in paediatric fever with neutropenia was undertaken. Pooled estimates were produced using random-effects meta-analysis of the area under the curve-receiver operating characteristic curve (AUC-ROC), calibration slope and ratios of expected versus observed cases (E/O).

Results: The PICNICC model was poorly predictive of microbiologically documented infection (MDI) in these validation cohorts. The pooled AUC-ROC was 0.59, 95% CI 0.41 to 0.78, tau=0, compared with derivation value of 0.72, 95% CI 0.71 to 0.76. There was poor discrimination (pooled slope estimate 0.03, 95% CI -0.19 to 0.26) and calibration in the large (pooled E/O ratio 1.48, 95% CI 0.87 to 2.1). Three different simple recalibration approaches failed to improve performance meaningfully.

Conclusion: This meta-analysis shows the PICNICC model should not be used at admission to predict MDI. Further work should focus on validating alternative prediction models. Validation across multiple cohorts from diverse locations is essential before widespread clinical adoption of such rules to avoid overtreating or undertreating children with fever with neutropenia.
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http://dx.doi.org/10.1136/archdischild-2019-317308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212933PMC
May 2020

Guideline for Antibacterial Prophylaxis Administration in Pediatric Cancer and Hematopoietic Stem Cell Transplantation.

Clin Infect Dis 2020 06;71(1):226-236

Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT.

Methods: An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature.

Results: The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia.

Conclusions: We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.
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http://dx.doi.org/10.1093/cid/ciz1082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312235PMC
June 2020

Invasive fungal infections in children with acute lymphoblastic leukaemia: Results from four Australian centres, 2003-2013.

Pediatr Blood Cancer 2019 10 16;66(10):e27915. Epub 2019 Jul 16.

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

Background: Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL.

Methods: IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a 'modified-possible' category included.

Results: A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified-possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8-11.4%) overall and 23.5% (95% CI 14.5-32.5%) for relapsed/refractory ALL. For non-relapsed ALL, the IFI prevalence was significantly higher for children with high-risk compared to standard-risk ALL (14.5% vs 7.3%, P = .009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non-mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI.

Conclusions: IFI is more common in children with high-risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.
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http://dx.doi.org/10.1002/pbc.27915DOI Listing
October 2019

Impact of a hospital-wide sepsis pathway on improved quality of care and clinical outcomes in surgical patients at a comprehensive cancer centre.

Eur J Cancer Care (Engl) 2019 May 13;28(3):e13018. Epub 2019 Feb 13.

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

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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http://dx.doi.org/10.1111/ecc.13018DOI Listing
May 2019

Nonneutropenic fever in children with cancer: A scoping review of management and outcome.

Pediatr Blood Cancer 2019 06 5;66(6):e27634. Epub 2019 Feb 5.

The Paediatric Integrated Cancer Service, Parkville, Victoria, Australia.

To date, very few studies have addressed nonneutropenic fever (NNF) in children with cancer, and there are no consensus guidelines. This scoping review aims to describe the rate of bacteremia, risk factors for infection and management, and outcomes of NNF in this population. Across 15 studies (n = 4106 episodes), the pooled-average bacteremia rate was 8.2%, and risk factors included tunneled external central venous catheter, clinical instability, and higher temperature. In two studies, antibiotics were successfully withheld in a subset of low-risk patients. Overall outcomes of NNF appear favorable; however, further research is required to determine its true clinical and economic impact.
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http://dx.doi.org/10.1002/pbc.27634DOI Listing
June 2019

Epidemiology of invasive fungal infections in immunocompromised children; an Australian national 10-year review.

Pediatr Blood Cancer 2019 04 4;66(4):e27564. Epub 2018 Dec 4.

Lady Cilento Children's Hospital, Children's Health Queensland, South Brisbane, Australia.

Background: A thorough understanding of local and contemporary invasive fungal infection (IFI) epidemiology in immunocompromised children is required to provide a rationale for targeted prevention and treatment strategies.

Methods: Retrospective data over 10 years from four tertiary pediatric oncology and hematopoietic stem cell transplant (HSCT) units across Australia were analyzed to report demographic, clinical, and mycological characteristics of IFI episodes, and crude IFI prevalence in select oncology/HSCT groups. Kaplan-Meier survival analyses were used to calculate 180-day overall survival.

Results: A total of 337 IFI episodes occurred in 320 children, of which 149 (44.2%), 51 (15.1%), and 110 (32.6%) met a modified European Organization for Research and Treatment of Cancer (mEORTC) criteria for proven, probable, and possible IFI, respectively. There were a further 27 (8.0%) that met a "modified possible IFI" criteria. Median age at IFI diagnosis was 8.4 years. Crude mEORTC IFI prevalence in acute lymphoblastic leukemia, acute myeloid leukemia, solid tumor, and allogeneic HSCT cohorts was 10.6%, 28.2%, 4.4%, and 11.7%, respectively. Non-Aspergillus species represented 48/102 (47.1%) molds identified, and non-albicans Candida represented 66/93 (71.0%) yeasts identified. There were 56 deaths among 297 children who met mEORTC criteria, with 180-day overall survival for proven, probable, and possible IFIs of 79.7%, 76.2%, and 84.4%, respectively.

Conclusion: Non-Aspergillus molds and non-albicans Candida contributed substantially to pediatric IFI in our study, with high IFI prevalence in leukemia and allogeneic HSCT cohorts. Inclusion of IFIs outside of European Organization for Research and Treatment of Cancer criteria revealed an IFI burden that would go otherwise unrecognized in published reports.
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http://dx.doi.org/10.1002/pbc.27564DOI Listing
April 2019

Guideline for the Management of Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.

J Clin Oncol 2018 Nov 14;36(31):3162-3171. Epub 2018 Sep 14.

Caroline Diorio, Paula D. Robinson, and Sandra Cabral, Pediatric Oncology Group of Ontario; Caroline Diorio, L. Lee Dupuis, and Lillian Sung, The Hospital for Sick Children; L. Lee Dupuis, University of Toronto, Toronto; Caroline Diorio, McMaster Children's Hospital, Hamilton; Susan Kuczynski, Ontario Parents Advocating for Children with Cancer, Barrie, Ontario, Canada; Roland A. Ammann, Bern University Hospital, University of Bern, Bern, Switzerland; Elio Castagnola, Istituto Giannina Gaslini, Genova, Italy; Kelley Erickson and Brian T. Fisher, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA; Adam Esbenshade, Vanderbilt-Ingram Cancer Centre, Nashville, TN; Gabrielle M. Haeusler, Peter MacCallum Cancer Centre, Melbourne; Gabrielle M. Haeusler, Royal Children's Hospital, Parkville; Gabrielle M. Haeusler, Paediatric Integrated Cancer Service, Victoria, Australia; Thomas Lehrnbecher, Hospital for Children and Adolescents, Johann Wolfgang Goethe University, Frankfurt, Germany; Robert Phillips, Leeds Teaching Hospital, National Health Service Trust, Leeds; and Robert Phillips, University of York, York, United Kingdom.

Purpose: The aim of this work was to develop a clinical practice guideline for the prevention and treatment of infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients.

Methods: An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations.

Results: The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research.

Conclusion: We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.
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http://dx.doi.org/10.1200/JCO.18.00407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209092PMC
November 2018

Implementation of a whole of hospital sepsis clinical pathway in a cancer hospital: impact on sepsis management, outcomes and costs.

BMJ Open Qual 2018 6;7(3):e000355. Epub 2018 Jul 6.

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

Infection and sepsis are common problems in cancer management affecting up to 45% of patients and are associated with significant morbidity, mortality and healthcare utilisation.

Objective: To develop and implement a whole of hospital clinical pathway for the management of sepsis (SP) in a specialised cancer hospital and to measure the impact on patient outcomes and healthcare utilisation.

Methods: A multidisciplinary sepsis working party was established. Process mapping of practices for recognition and management of sepsis was undertaken across all clinical areas. A clinical pathway document that supported nurse-initiated sepsis care, prompt antibiotic and fluid resuscitation was implemented. Process and outcome measures for patients with sepsis were collected preimplementation (April-December 2012), postimplementation cohorts (April-December 2013), and from January to December 2014.

Results: 323 patients were evaluated (111 preimplementation, 212 postimplementation). More patients with sepsis had lactate measured (75.0% vs 17.2%) and appropriate first dose antibiotic (90.1% vs 76.1%) (all p<0.05). Time to antibiotics was halved (55 vs 110 min, p<0.05). Patients with sepsis had lower rates of intensive care unit admission (17.1% vs 35.5%), postsepsis length of stay (7.5 vs 9.9 days), and sepsis-related mortality (5.0% vs 16.2%) (all p<0.05). Mean total hospital admission costs were lower in the SP cohort, with a significant difference in admission costs between historical and SP non-surgical groups of $A8363 (95% CI 81.02 to 16645.32, p=0.048) per patient on the pathway. A second cohort of 449 patients with sepsis from January to December 2014 demonstrated sustained improvement.

Conclusions: The SP was associated with significant improvement in patient outcomes and reduced costs. The SP has been sustained since 2013, and has been successfully implemented in another hospital with further implementations underway in Victoria.
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http://dx.doi.org/10.1136/bmjoq-2018-000355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045757PMC
July 2018

Management of fever and neutropenia in children with cancer: A survey of Australian and New Zealand practice.

J Paediatr Child Health 2018 07 14;54(7):761-769. Epub 2018 Apr 14.

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

Aim: Variation in the management of fever and neutropenia (FN) in children is well described. The aim of this study was to explore the current management of FN across Australia and New Zealand and highlight areas for improvement.

Methods: A practice survey was administered to paediatric health-care providers via four clinical and research networks. Using three clinical case vignettes, we explored risk stratification, empiric antibiotics, initial investigations, intravenous-oral switch, ambulatory management and antibiotic duration in children with cancer and FN.

Results: A response was received from 104 participants from 16 different hospitals. FN guideline compliance was rated as moderate or poor by 24% of respondents, and seven different fever definitions were described. There was little variation in the selected empiric monotherapy and dual-therapy regimens, and almost all respondents recommended first-dose antibiotics within 1 h. However, 27 different empiric antibiotic combinations were selected for beta-lactam allergy. An incorrect risk status was assigned to the low-risk case by 27% of respondents and to the high-risk case by 41%. Compared to current practice, significantly more respondents would manage the low-risk case in the ambulatory setting provided adequate resources were in place (43 vs. 85%, P < 0.0001). There was variation in the use of empiric glycopeptides as well as use of aminoglycosides beyond 48 h.

Conclusion: Although the antibiotics selected for empiric management of FN are appropriate and consistent, variation and inaccuracies exist in risk stratification, the selection of monotherapy over dual therapy, empiric antibiotics chosen for beta-lactam allergy, use of glycopeptides and duration of aminoglycosides.
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http://dx.doi.org/10.1111/jpc.13899DOI Listing
July 2018

Antibiotic-resistant Gram-negative Blood Stream Infections in Children With Cancer: A Review of Epidemiology, Risk Factors, and Outcome.

Pediatr Infect Dis J 2018 05;37(5):495-498

The Paediatric Integrated Cancer Service, Parkville, Victoria, Australia.

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http://dx.doi.org/10.1097/INF.0000000000001938DOI Listing
May 2018

The clinical utility of fluorodeoxyglucose-positron emission tomography for investigation of fever in immunocompromised children.

J Paediatr Child Health 2018 May 13;54(5):487-492. Epub 2017 Dec 13.

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

Aim: Fever in immunocompromised children presents significant challenges. We aimed to determine the clinical impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in combination with computed tomography (CT) in children with malignancy or following haematopoietic stem cell transplantation with prolonged or recurrent fever.

Methods: Immunocompromised children who underwent FDG-PET/CT for investigation of prolonged or recurrent fever were identified from hospital databases. The clinical impact of the FDG-PET/CT was considered 'high' if it contributed to any of the following: diagnosis of a new site infection/inflammation, change to antimicrobials or chemotherapy, or additional investigations or specialist consult contributing to final diagnosis.

Results: Fourteen patients underwent an FDG-PET/CT for prolonged or recurrent fever. Median age was 11 years and 46% had diagnosis of acute lymphoblastic leukaemia. The median absolute neutrophil count on the day of FDG-PET/CT was 0.47 cells/μL. The clinical impact of FDG-PET/CT was 'high' in 11 (79%) patients, contributing to rationalisation of antimicrobials in three, and cessation of antimicrobials in five. Compared to conventional imaging, FDG PET/CT identified seven additional sites of clinically significant infection/inflammation in seven patients. Of the 10 patients who had a cause of fever identified, FDG-PET/CT contributed to the final diagnosis in six (60%).

Conclusion: This study has identified potential utility for FDG-PET/CT in immunocompromised children with prolonged or recurrent fever. Further prospective studies are needed to compare FDG-PET/CT versus conventional imaging, to identify the optimal timing of FDG-PET/CT and to study the role of subsequent scans to monitor response to therapy.
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http://dx.doi.org/10.1111/jpc.13809DOI Listing
May 2018

External Validation of Six Pediatric Fever and Neutropenia Clinical Decision Rules.

Pediatr Infect Dis J 2018 04;37(4):329-335

Background: Fever and neutropenia (FN) clinical decision rules (CDRs) are recommended to help distinguish children with cancer at high and low risk of severe infection. The aim of this study was to validate existing pediatric FN CDRs designed to stratify children with cancer at high or low risk of serious infection or medical complication.

Methods: Pediatric CDRs suitable for validation were identified from a literature search. Relevant data were extracted from an existing data set of 650 retrospective FN episodes in children with cancer. The sensitivity and specificity of each of the CDR were compared with the derivation studies to assess reproducibility.

Results: Six CDRs were identified for validation: 2 were designed to predict bacteremia and 4 to predict adverse events. Five CDRs exhibited reproducibility in our cohort. A rule predicting bacteremia had the highest sensitivity (100%; 95% confidence interval (CI): 93%-100%) although poor specificity (17%), with only 15% identified as low risk. For adverse events, the highest sensitivity achieved was 84% (95% CI: 75%-90%), with specificity of 29% and 27% identified as low risk. A rule intended for application after a 24-hour period of inpatient observation yielded a sensitivity of 80% (95% CI: 73-86) and specificity of 46%, with 44% identified as low risk.

Conclusions: Five CDRs were reproducible, although not all can be recommended for implementation because of either inadequate sensitivity or failure to identify a clinically meaningful number of low-risk patients. The 24-hour rule arguably exhibits the best balance between sensitivity and specificity in our population.
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http://dx.doi.org/10.1097/INF.0000000000001777DOI Listing
April 2018

Predicting Infectious ComplicatioNs in Children with Cancer: an external validation study.

Br J Cancer 2017 Jul 13;117(2):171-178. Epub 2017 Jun 13.

Centre for Reviews and Dissemination, University of York, Heslington, York YO10 5DD, UK.

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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http://dx.doi.org/10.1038/bjc.2017.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520507PMC
July 2017

Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update.

J Clin Oncol 2017 Jun 1;35(18):2082-2094. Epub 2017 May 1.

Thomas Lehrnbecher, Hospital for Children and Adolescents, Johann Wolfgang Goethe University, Frankfurt; Andreas H. Groll, University Children's Hospital, Muenster, Germany; Paula Robinson, Pediatric Oncology Group of Ontario; Sarah Alexander, L. Lee Dupuis, and Lillian Sung, The Hospital for Sick Children, Toronto, Ontario, Canada; Brian Fisher and Theo Zaoutis, Children's Hospital of Philadelphia, Philadelphia, PA; Roland A. Ammann, Bern University Hospital, University of Bern, Switzerland; Melissa Beauchemin, Columbia University/Herbert Irving Cancer Center, New York, NY; Fabianne Carlesse, Pediatric Oncology Institute, GRAACC/Federal University of Sao Paulo, Sao Paulo, Brazil; Gabrielle M. Haeusler, Peter MacCallum Cancer Centre, Melbourne; Monash Children's Hospital, Clayton, Victoria, Australia; Maria Santolaya, Hospital Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile; William J. Steinbach, Duke University Medical Center, Durham, NC; Elio Castagnola, Istituto Giannina Gaslini, Genova, Italy; Bonnie L. Davis, High Tor Limited, Nassau, Bahamas; Aditya H. Gaur, St Jude Children's Research Hospital, Memphis, TN; Wim J.E. Tissing, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Robert Phillips, Leeds Teaching Hospital, NHS Trust, Leeds; University of York, York, United Kingdom.

Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.
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http://dx.doi.org/10.1200/JCO.2016.71.7017DOI Listing
June 2017

Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology.

Support Care Cancer 2017 11 28;25(11):3289-3290. Epub 2017 Mar 28.

Infection Management Prevention Service, Lady Cilento Children's Hospital, Brisbane, QLD, Australia.

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http://dx.doi.org/10.1007/s00520-017-3681-0DOI Listing
November 2017