Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome.

BACKGROUND: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood. METHODS: ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017-2018). RESULTS: Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8; 95% confidence interval [CI], 1.6-296.9), multifocal infection (aOR, 22.6; CI, 1.4-498.5), necrotizing pneumonia (aOR, 38.9; CI, 1.7-1754.6), multiorgan dysfunction (aOR, 26.5; CI, 4.1-268.8), and empiric vancomycin (aOR, 15.7; CI, 1.6-434.4); while infectious diseases (ID) consultation (aOR, 0.07; CI .004-.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival; however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1; 95% CI 1.3-8.1). CONCLUSIONS: High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity; therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes.

Antifungal use in children with acute leukaemia: state of current evidence and directions for future research.

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.

Cost-effectiveness of home-based care of febrile neutropenia in children with cancer.

INTRODUCTION: Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. METHODS: A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). FINDINGS: The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. CONCLUSION: Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.

Characteristics and outcomes of SARS-CoV-2 infection in Victorian children at a tertiary paediatric hospital.

AIM: Victoria experienced two 'waves' of COVID-19 between March and September 2020 and more cases than any other jurisdiction in Australia. Although world-wide reports of COVID-19 reflect that children are less likely to experience severe disease compared with adults, hospitalisations and deaths have been reported. We report testing and outcomes of children with SARS-CoV-2 infection presenting to a tertiary paediatric hospital in Melbourne. METHODS: We conducted a prospective cohort study at The Royal Children's Hospital (RCH), including all children and adolescents (aged 0-18 years) who presented and were tested for SARS-CoV-2 over a 6-month period, between 21 March 2020, up to the 21 September 2020. Detailed epidemiological and clinical data were recorded. RESULTS: A total of 19 708 tests for SARS-CoV-2 were performed in 14 419 patients. One hundred and eighty patients tested positive for SARS-CoV-2 (1.2%). 110 (61%) were symptomatic, 60 (33%) were asymptomatic and 10 (6%) were pre-symptomatic. Close contacts of a positive case were associated with a higher risk of a testing positive for SARS-CoV-2 (120/2027 (6%) vs. 60/14589 (0.4%), RD 5.5 (95% CI 4.5 to 6.5), P < 0.001). Eighteen (10%) SARS-CoV-2-positive patients were admitted to hospital with one patient requiring intensive care. All patients recovered fully with no deaths. CONCLUSION: In Victorian children presenting to a tertiary hospital, SARS-CoV-2 infection caused predominantly mild or asymptomatic infection, with most children not requiring hospitalisation.

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

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.

Consensus guidelines for the diagnosis and management of invasive fungal disease due to moulds other than Aspergillus in the haematology/oncology setting, 2021.

Invasive fungal disease (IFD) due to moulds other than Aspergillus is a significant cause of mortality in patients with malignancies or post haemopoietic stem cell transplantation. The current guidelines focus on the diagnosis and management of the common non-Aspergillus moulds (NAM), such as Mucorales, Scedosporium species (spp.), Lomentospora prolificans and Fusarium spp. Rare but emerging NAM including Paecilomyces variotii, Purpureocillium lilacinum and Scopulariopsis spp. are also reviewed. Culture and histological examination of tissue biopsy specimens remain the mainstay of diagnosis, but molecular methods are increasingly being used. As NAM frequently disseminate, blood cultures and skin examination with biopsy of any suspicious lesions are critically important. Treatment requires a multidisciplinary approach with surgical debridement as a central component. Other management strategies include control of the underlying disease/predisposing factors, augmentation of the host response and the reduction of immunosuppression. Carefully selected antifungal therapy, guided by susceptibility testing, is critical to cure. We also outline novel antifungal agents still in clinical trial which offer substantial potential for improved outcomes in the future. Paediatric recommendations follow those of adults. Ongoing epidemiological research, improvement in diagnostics and the development of new antifungal agents will continue to improve the poor outcomes that have been traditionally associated with IFD due to NAM.

Impact of an antimicrobial stewardship intervention in neonatal intensive care: Recommendations and implementation.

AIM: To (i) determine the appropriateness of antimicrobial prescribing in the neonatal intensive care unit (NICU) and (ii) assess the impact of a collaborative antimicrobial stewardship (AMS) intervention on prescribing practices. METHODS: The intervention was a weekly AMS audit-feedback joint ward round (6-month period) of Neonatology and Infectious Diseases clinicians in a tertiary neonatal intensive care unit in Melbourne, Australia. Antibiotic prescriptions were audited and recommendations delivered in real time. The proportion of recommendations implemented was used to assess acceptability of the intervention. RESULTS: During the study period, there were 23 AMS rounds, during which 249 patients were reviewed at 627 separate episodes. Of these, 233 (37%) episodes were for patients receiving antimicrobials. Of these, 147 (63%) received empirical antimicrobial treatment, 43 (18%) targeted antimicrobial treatment and 43 (18%) antimicrobial prophylaxis. There were 58 (25%) of 233 episodes of inappropriate antibiotic use, and 62 recommendations for improvement. Most common recommendations were to narrow (33/62, 53%) or stop (12/62, 19%) antimicrobials. The majority (45, 73%) of recommendations were accepted, resulting in significant improvement in the proportion of the 233 episodes that had completely appropriate antibiotic prescribing: 175 (75%) to 217 (93%) (relative risk 1.2, 95% confidence intervals 1.1-1.3, P < 0.001). CONCLUSIONS: A collaborative audit-feedback AMS intervention was effective in identifying inappropriate antimicrobial prescriptions and impacted positively on treatment plans. Ancillary benefits were improved communication between departments and the revision of antimicrobial prescribing guidelines.

Planning and clinical role of acute medical home care services for COVID-19: consensus position statement by the Hospital-in-the-Home Society Australasia.

During a pandemic when hospitals are stretched and patients need isolation, the role of hospital-in-the-home (HITH) providing acute medical care at home has never been more relevant. We aimed to define and address the challenges to acute home care services posed by the COVID-19 pandemic. Planning for service operation involves staffing, equipment availability and cleaning, upskilling in telehealth and communication. Planning for clinical care involves maximising cohorts of patients without COVID-19 and new clinical pathways for patients with COVID-19. The risk of SARS-CoV-2 transmission, specific COVID-19 clinical pathways and the well-being of patients and staff should be addressed in advance.

Antimicrobial stewardship in children: Where to from here?

Antimicrobial resistance (AMR) is an ever-developing global threat and children are becoming increasingly affected. In addition to established antimicrobial stewardship (AMS) measures, it is important to recognise the need for a paediatric focus to manage the physiological and pathological differences unique to children. Most studies on paediatric AMS are drawn from resource-rich, hospital settings. They support interventions including AMS programmes, bundled groups of interventions, guidelines and education initiatives. These must be tailored to specific institutions, populations and resources as translating interventions between these may not be effective. There are knowledge gaps in paediatric AMS, which pose challenges to designing both interventions and research in this area. These include quantifying antimicrobial consumption, defining AMS outcomes and understanding the development of AMR. Finding answers to fill these gaps needs urgent attention. There is also a need to think outside the box to improve AMS in children. Potential opportunities include intravenous antibiotics at home via hospital-in-the-home programmes, earlier switching to oral antibiotics, repurposing old antibiotics and re-evaluating children labelled as having antibiotic allergy. Using all of the possibilities available gives us the best chance of staying ahead of the relentless march of AMR in children.

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

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.

Does discharging asthma patients after one hour of treatment if clinically well affect emergency department length of stay.

AIM: Asthma is a major contributor to direct and indirect health-care costs and resource use. In May 2015, the Royal Children's Hospital (RCH) amended its clinical practice guideline for acute asthma management from discharging patients if the anticipated salbutamol requirement was every 3-4 h to discharging patients who were clinically well at 1 h after initial treatment. Our objective was to examine the impact of the new discharge recommendation on emergency department (ED) length of stay (LOS), rates of admission and representation. METHODS: We retrospectively audited the case notes of children presenting with mild or moderate asthma to the RCH ED over the equivalent 2-week periods in winter 2014 (pre-implementation of the new guideline) and 2015 (post-implementation). RESULTS: A total of 105 patients in 2014 and 92 patients in 2015 were included. In both years, all patients who initially presented with mild or moderate asthma either improved or stayed within the same severity classification at the 1-h assessment. For patients who were clinically well by the 1-h assessment, there was a significant reduction in admissions between 2014 and 2015 (40 vs. 10%, P = 0.001). There was also a reduction for these patients in median LOS from 3 h 13 min in 2014 to 2 h 31 min in 2015 (P = 0.03). In both years, all patients who were moderate at 1 h were admitted. There was no difference in the rate of representation or subsequent deterioration in those patients who were discharged at 1 h between the 2 years. CONCLUSION: Early discharge of patients who are clinically well 1 h after initial therapy may be associated with a reduction in LOS and admission rate without an apparent compromise in patient safety. Further evaluation of this intervention is required to determine whether this is a true causal relationship.

Pulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline.

The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug-related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection.

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

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.

Evaluating an admission avoidance pathway for children in the emergency department: outpatient intravenous antibiotics for moderate/severe cellulitis.

OBJECTIVE: Children with moderate/severe cellulitis requiring intravenous antibiotics are usually admitted to hospital. Admission avoidance is attractive but there are few data in children. We implemented a new pathway for children to be treated with intravenous antibiotics at home and aimed to describe the characteristics of patients treated on this pathway and in hospital and to evaluate the outcomes. METHODS: This is a prospective, observational cohort study of children aged 6 months-18 years attending the ED with uncomplicated moderate/severe cellulitis in March 2014-January 2015. Patients received either intravenous ceftriaxone at home or intravenous flucloxacillin in hospital based on physician discretion. Primary outcome was treatment failure defined as antibiotic change within 48 hours due to inadequate clinical improvement or serious adverse events. Secondary outcomes include duration of intravenous antibiotics and complications. RESULTS: 115 children were included: 47 (41%) in the home group and 68 (59%) in the hospital group (59 hospital-only, 9 transferred home during treatment). The groups had similar clinical features. 2/47 (4%) of the children in the home group compared with 8/59 (14%) in the hospital group had treatment failure (P=0.10). Duration of intravenous antibiotics (median 1.9 vs 1.8 days, P=0.31) and complications (6% vs 10%, P=0.49) were no different between groups. Home treatment costs less, averaging $A1166 (£705) per episode compared with $A2594 (£1570) in hospital. CONCLUSIONS: Children with uncomplicated cellulitis may be able to avoid hospital admission via a home intravenous pathway. This approach has the potential to provide cost and other benefits of home treatment.

Quick-Wee: a novel non-invasive urine collection method.

BACKGROUND: Clean catch urine (CCU) collection in precontinent children is often time-consuming, with associated collection failure. We hypothesise that stimulating cutaneous reflexes hastens voiding for CCU. METHODS: 40 children aged 1-24 months in the ED. Standard CCU was augmented with gentle suprapubic cutaneous stimulation using saline-soaked gauze (Quick-Wee method). RESULTS: 12/40 (30%) children voided within 5 min for successful CCU. Parental and clinician satisfaction was high. CONCLUSIONS: Quick-Wee appears to be a simple method to speed CCU in young children.

Alternatives to ward admission from the emergency department.

There is ever-increasing pressure on hospital resources in general and emergency departments (ED) in particular. At the same time, there is increasing recognition that traditional inpatient ward-based care is not necessary for the majority of children presenting to the ED with acute illness, and that there are patient, family and hospital benefits to pursuing other options. Here, we describe alternative pathways for children presenting to the ED, including short stay and observational medicine, hospital-in-the-home and non-admission enhanced care, in other words, additional management practices or pathways for children who are discharged from the ED. We discuss the principles, models and practical considerations involved in each of these.

Antimicrobial stewardship resources and activities for children in tertiary hospitals in Australasia: a comprehensive survey.

OBJECTIVE: To identify current antimicrobial stewardship (AMS) resources and activities for children in hospitals throughout Australasia, to identify gaps in services. DESIGN, SETTING AND PARTICIPANTS: Tertiary paediatric hospitals (children's hospitals and combined adult and paediatric hospitals that offer tertiary paediatric care) in every state and territory of Australia and the North and South Islands of New Zealand were surveyed in June 2013 regarding AMS resources and activities. MAIN OUTCOME MEASURE: A description of AMS resources and activities for children in tertiary hospitals. RESULTS: We surveyed 14 hospitals, with paediatric bed numbers ranging from 40 to 300. Seven had a dedicated paediatric AMS team or AMS team with a paediatric representative and 11 had an AMS pharmacist position, although only four had committed ongoing funding for a permanent paediatric AMS pharmacist and only two had committed funding for a paediatric infectious diseases physician for AMS. All hospitals had empirical antimicrobial prescribing guidelines, and all 10 hospitals with haematology and oncology services had febrile neutropenia guidelines. However, most did not have guidelines for antifungal prophylaxis, surgical prophylaxis, neonatology or paediatric intensive care. All hospitals had restricted drugs but only four had electronic approval systems. Auditing methods differed widely but were mostly ad hoc, with results fed back in an untargeted way. There was a paucity of AMS education: no hospitals provided education for senior medical staff, and four had no education for any staff. The commonest perceived barriers to successful AMS were lack of education (11 hospitals) and lack of dedicated pharmacy (eight) and medical (seven) staff. CONCLUSIONS: Australasian paediatric hospitals have implemented some AMS activities, but most lack resources. There was consensus among the staff who completed our survey that barriers to successful AMS include lack of education and lack of personnel.

Susceptibility to acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis.

It is unknown why only some individuals are susceptible to acute rheumatic fever (ARF). We investigated whether there are differences in the immune response, detectable by gene expression, between individuals who are susceptible to ARF and those who are not. Peripheral blood mononuclear cells (PBMCs) from 15 ARF-susceptible and 10 nonsusceptible (control) adults were stimulated with rheumatogenic (Rh+) group A streptococci (GAS) or nonrheumatogenic (Rh-) GAS. RNA from stimulated PBMCs from each subject was cohybridized with RNA from unstimulated PBMCs on oligonucleotide arrays to compare gene expression. Thirty-four genes were significantly differentially expressed between ARF-susceptible and control groups after stimulation with Rh+ GAS. A total of 982 genes were differentially expressed between Rh+ GAS- and Rh- GAS-stimulated samples from ARF-susceptible individuals. Thirteen genes were differentially expressed in the same direction (predominantly decreased) between the two study groups and between the two stimulation conditions, giving a strong indication of their involvement. Seven of these were immune response genes involved in cytotoxicity, chemotaxis, and apoptosis. There was variability in the degree of expression change between individuals. The high proportion of differentially expressed apoptotic and immune response genes supports the current model of autoimmune and cytokine dysregulation in ARF. This study also raises the possibility that a "failed" immune response, involving decreased expression of cytotoxic and apoptotic genes, contributes to the immunopathogenesis of ARF.