Publications by authors named "Brendan McMullan"

73 Publications

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

Pediatr Blood Cancer 2021 Nov 6;68(11):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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.29275DOI Listing
November 2021

A not so innocuous playground fall: lymphocutaneous nocardiosis in an immunocompetent boy.

Arch Dis Child 2021 Aug 2. Epub 2021 Aug 2.

School of Women and Children's Health, The University of NSW, Sydney, New South Wales, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2021-322392DOI Listing
August 2021

ESCAPE-Allergy: Evaluating screening for children and adolescents with penicillin allergy.

J Paediatr Child Health 2021 Jul 29. Epub 2021 Jul 29.

School of Women's and Children's Heath, University of New South Wales, Sydney, New South Wales, Australia.

Aim: Penicillin allergy labels are frequently encountered in children and are associated with significant harms. Most children are falsely labelled and can safely tolerate a penicillin but delabelling strategies are underutilised and paediatric-specific resources are lacking. The aim of this study was to evaluate an allergy assessment tool for children in hospital.

Methods: We evaluated a paediatric-adapted penicillin allergy assessment tool, using an online survey of clinicians in a tertiary paediatric hospital, with 10 hypothetical potential penicillin allergy or adverse reaction cases (including non-allergy reactions). For each case, respondents were asked to use the tool to assign a reaction phenotype and recommend management. We determined the tool's sensitivity, specificity and acceptability to end users.

Results: We evaluated 30 complete survey responses from senior and junior medical staff, nurses and pharmacists. The tool's overall sensitivity was 80.7% (95% confidence interval (CI) 74.2-87.1%) for assigning the correct reaction phenotype and 85.3% (95% CI 79.4-91.3%) for appropriate management. The tool had high sensitivity for identifying immediate hypersensitivity reactions at 95.6% (95% CI 90.2-100%). Most respondents agreed or strongly agreed that they would use the tool in their practice (22/30, 73.3%).

Conclusion: This survey evaluated a paediatric-adapted penicillin allergy assessment tool in a tertiary paediatric hospital among multidisciplinary clinician groups. The tool performed well overall and had high safety in identifying immediate hypersensitivity reactions. Further research to support implementation of allergy assessment and delabelling programmes among children is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.15657DOI Listing
July 2021

The role of Kingella kingae in pre-school aged children with bone and joint infections.

J Infect 2021 09 12;83(3):321-331. Epub 2021 Jul 12.

Department of Paediatrics, University of Otago, Christchurch School of Medicine, New Zealand. Electronic address:

Objectives: The Pre-school Osteoarticular Infection (POI) study aimed to describe the burden of disease, epidemiology, microbiology and treatment of acute osteoarticular infections (OAI) and the role of Kingella kingae in these infections.

Methods: Information about children 3-60 months of age who were hospitalized with an OAI to 11 different hospitals across Australia and New Zealand between January 2012 and December 2016 was collected retrospectively.

Results: A total of 907 cases (73%) were included. Blood cultures grew a likely pathogen in only 18% (140/781). The peak age of presentation was 12 to 24 months (466/907, 51%) and Kingella kingae was the most frequently detected microorganism in this age group (60/466, 13%). In the majority of cases, no microorganism was detected (517/907, 57%). Addition of PCR to culture increased detection rates of K. kingae. However, PCR was performed infrequently (63/907, 7%).

Conclusions: This large multi-national study highlights the need for more widespread use of molecular diagnostic techniques for accurate microbiological diagnosis of OAI in pre-school aged children. The data from this study supports the hypothesis that a substantial proportion of pre-school aged children with OAI and no organism identified may in fact have undiagnosed K. kingae infection. Improved detection of Kingella cases is likely to reduce the average length of antimicrobial treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2021.06.028DOI Listing
September 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/mmy/myab037DOI Listing
June 2021

Echinocandins in Pediatric Invasive Candidiasis and the Challenges of Antifungal Use in Children.

J Pediatric Infect Dis Soc 2021 Aug;10(7):755-756

Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piab039DOI Listing
August 2021

Pediatric Staphylococcus aureus bacteremia: clinical spectrum and predictors of poor outcome.

Clin Infect Dis 2021 Jun 5. Epub 2021 Jun 5.

Department of Infectious Diseases, Perth Children's Hospital, Nedlands.

Background: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology, and predictors of poor outcome remain inadequately defined in childhood.

Methods: ISAIAH 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/yr [95% confidence interval (CI) 2.2-8.8]), with methicillin-susceptible (84%), community onset (78%) infection predominating. Indigenous children (8.1/100,000/yr [CI 4.8-14.4]), those from lower-socioeconomic areas (5.5/100,000/yr [CI 2.8-10.2]) and neonates (6.6/100,000/yr (CI 3.4-11.7) were over-represented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), ICU admission (20%), relapse (4%), or death (3%).Predictors of mortality included prematurity (aOR 16.8 [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]); whilst Infectious Diseases (ID) consultation (aOR 0.07 [CI 0.004-0.9]) was protective. Neither MRSA nor vancomycin trough-targets impacted survival; however, empiric-vancomycin was associated with significant nephrotoxicity (OR 3.1 [CI 1.3-8.1]).

Conclusions: High SAB incidence was demonstrated, with at-risk populations identified for future prioritized care. For the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, whilst ID consultation was protective. The need to re-evaluate pediatric vancomycin trough-targets and limit unnecessary empiric-vancomycin exposure, to reduce poor outcomes and nephrotoxicity is highlighted. One in three children experienced considerable SAB morbidity, therefore pediatric inclusion in future SAB comparator trials is paramount to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab510DOI Listing
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.15330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013774PMC
June 2021

Kingella kingae sternal osteomyelitis presenting as chest lump in a child.

J Paediatr Child Health 2021 Jan 19. Epub 2021 Jan 19.

Department of Immunology and Infectious Diseases, Sydney Children's Hospital Network, Sydney, New South Wales, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.15335DOI Listing
January 2021

Impact of Infectious Diseases Consultation on Management and Outcome of Staphylococcus aureus Bacteremia in Children.

J Pediatric Infect Dis Soc 2021 May;10(5):569-575

Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Sydney, New South Wales, Australia.

Background: To examine the impact of infectious diseases consultation (IDC) on the management and outcome of Staphylococcus aureus bacteremia (SAB) in children.

Methods: A retrospective cohort study of children with SAB at a teritary pediatric hospital (January 2009-June 2015) identified by medical record review as to whether they received an IDC for SAB at the discretion of the admitting physician or surgeon was conducted. Differences in management and outcomes for those with and without IDC were evaluated, and multivariate regression analysis was used to determine factors associated with cure.

Results: There were 100 patients included in the analysis. Fifty-five patients received IDC and 45 had no IDC (NIDC). Appropriate directed therapy within 24 hours (54/55 = 98.2% vs 34/45 = 75.6%, P < .01), choice (54/55 = 98.2% vs 37/45 = 82.2%, P < .01), dose (54/55 = 98.2% vs 36/45 = 80%, P < .01), and duration (52/55 = 94.5% vs 24/45 = 53.3%, P < .01) of directed antibiotic therapy were appropriate in more IDC group patients. Achievement of source control in indicated cases was also more common in the IDC group (28/32 = 87.5% vs 5/26 = 19.1%, P < .01). Appropriate investigation with repeat blood cultures and echocardiograms was not significantly different. All 55 patients in the IDC group had a complete response (cure) compared with 40 of the 45 (88.9%) patients in the NIDC group: 2 patients died and 3 patients had a relapse of infection with subsequent cure. In multivariate regression analysis, methicillin-susceptible SAB and IDC were factors independently associated with cure.

Conclusions: Children who received IDC for SAB in a tertiary pediatric setting were more likely to have appropriate investigations and management and had improved outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piaa155DOI Listing
May 2021

New Names for Fungi of Medical Importance: Can We Have Our Cake and Eat It Too?

J Clin Microbiol 2021 02 18;59(3). Epub 2021 Feb 18.

Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP), Microbiology Section, St. Leonards, Sydney, New South Wales, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.02730-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106714PMC
February 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238787PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494114PMC
November 2020

SARS-CoV-2 in children: spectrum of disease, transmission and immunopathological underpinnings.

Pathology 2020 Dec 19;52(7):801-808. Epub 2020 Aug 19.

Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, NSW, Australia. Electronic address:

As the SARS-CoV-2 pandemic unfolds across the globe, consistent themes are emerging with regard to aspects of SARS-CoV-2 infection and its associated disease entities in children. Overall, children appear to be less frequently infected by, and affected by, SARS-CoV-2 virus and the clinical disease COVID-19. Large epidemiological studies have revealed children represent less than 2% of the total confirmed COVID-19 cases, of whom the majority experience minimal or mild disease that do not require hospitalisation. Children do not appear to be major drivers of SARS-CoV-2 transmission, with minimal secondary virus transmission demonstrated within families, schools and community settings. There are several postulated theories regarding the relatively low SARS-CoV-2 morbidity and mortality seen in children, which largely relate to differences in immune responses compared to adults, as well as differences in angiotensin converting enzyme 2 distribution that potentially limits viral entry and subsequent inflammation, hypoxia and tissue injury. The recent emergence of a multisystem inflammatory syndrome bearing temporal and serological plausibility for an immune-mediated SARS-CoV-2-related disease entity is currently under investigation. This article summarises the current available data regarding SARS-CoV-2 and the paediatric population, including the spectrum of disease in children, the role of children in virus transmission, and host-virus factors that underpin the unique aspects of SARS-CoV-2 pathogenicity in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pathol.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437539PMC
December 2020

Clinical Management of Bacteremia in Neonates, Children, and Adolescents.

Pediatrics 2020 09 5;146(3). Epub 2020 Aug 5.

Department of Infectious Diseases, Perth Children's Hospital, Nedlands, Western Australia, Australia.

is a common cause of community and health care-associated bacteremia, with authors of recent studies estimating the incidence of bacteremia (SAB) in high-income countries between 8 and 26 per 100 000 children per year. Despite this, <300 children worldwide have ever been randomly assigned into clinical trials to assess the efficacy of treatment of SAB. A panel of infectious diseases physicians with clinical and research interests in pediatric SAB identified 7 key clinical questions. The available literature is systematically appraised, summarizing SAB management in children in relation to these priority clinical questions. The management of neonates, children, and adolescents with SAB is predominantly based on clinical experience and trial data extrapolated from adult studies, with limited high-quality evidence available to guide management. The optimal, comprehensive management strategies for SAB in children will remain unknown until the questions outlined are answered through prospective observational cohorts and inclusion of children with SAB in clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2020-0134DOI Listing
September 2020

Successful treatment of invasive carbapenemase-producing Enterobacteriaceae infections in children using carbapenem-aminoglycoside combination therapy: A case series.

Infect Dis Health 2020 11 19;25(4):314-318. Epub 2020 Jul 19.

Department of Immunology and Infectious Diseases, The Sydney Children's Hospital Network, Randwick Australia; School of Women and Children's Health, The University of NSW, Sydney Australia.

Multidrug-resistant infections present a treatment challenge for pediatric clinicians and these infections have been associated with increased morbidity and mortality. There are very limited published data to support safe and effective treatment regimens for carbapenemase-producing Enterobacteriaceae (CPE) infections, particularly in children. We report the successful treatment of three children with invasive CPE infections using a combination of extended-infusion meropenem and amikacin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.idh.2020.06.002DOI Listing
November 2020

Penicillin - getting prescribing right for children.

Aust Prescr 2020 06 2;43(3):81-84. Epub 2020 Jun 2.

Sydney Children's Hospital.

Penicillins are commonly prescribed to children. Recommendations in the product information may not be the most appropriate doses for children and may list clinical indications that are preferably treated with other antibiotics Reputable guidelines, for example Therapeutic Guidelines: Antibiotic, offer up-to-date advice on optimal choice, route, dosage and duration of oral penicillins in children In most instances, the child’s weight should be used to calculate the dose in mg per kg without exceeding the maximum adult dose When prescribing higher weight-based doses of amoxicillin or flucloxacillin, check the volume of oral liquid required to complete a treatment course to ensure adequate supply
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18773/austprescr.2020.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358052PMC
June 2020

Utility of bronchoscopy in immunocompromised paediatric patients: Systematic review.

Paediatr Respir Rev 2020 Apr 29;34:24-34. Epub 2020 Feb 29.

University Women's and Children's Division, Southern Adelaide Local Health Network, Australia.

Purpose: The objective of this study was to describe the diagnostic yield and safety of bronchoalveolar lavage (BAL) in the evaluation of pulmonary lesions in immunocompromised children.

Methods: We conducted a systematic review of literature published during the past 20 years, searching Medline, Medline EPub, EMBASE, and Scopus. Studies included involved paediatric patients (<18 years) on treatment for an oncological diagnosis or other immune compromise who underwent BAL for evaluation of pulmonary lesions. Only English language publications were included.

Results: In all, 272 studies were screened and 19 included. All were observational studies with moderate (11/19) or serious (8/19) risk of bias. BAL yielded a potential pathogen in 43% of cases (496/1156). Two papers reported improved diagnostic yield with early BAL (less than 3 days of presentation). A change in patient management after BAL was reported in 53% of cases (275/519). Adverse events were reported in 19% of cases following BAL (193/993) but were generally mild with no procedure-related mortality reported.

Conclusion: BAL appears to be useful for evaluation of pulmonary lesions in immunocompromised children with generally acceptable safety, though included studies had at least moderate risk of bias. Future prospective studies may provide more definitive estimates of benefit, timing and risk of BAL in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.02.003DOI Listing
April 2020

Antibiotic prescribing in neonatal sepsis: an Australian nationwide survey.

BMJ Paediatr Open 2020 17;4(1):e000643. Epub 2020 Mar 17.

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

Objective: To evaluate quality and variation in antibiotic prescribing for neonatal sepsis.

Design: We analysed prescribing in hospitalised neonates using the National Antimicrobial Prescribing Survey in Australian neonates from 1 January 2014 to 31 December 2018.

Setting: Data from antibiotic point prevalence surveys performed in hospitals, ranging from rural hospitals to tertiary paediatric and maternity hospitals within Australia.

Patients: Admitted neonates <28 days of age from participating hospitals.

Main Outcome Measures: Variation and appropriateness in prescribing for neonatal sepsis and variation in dosing for gentamicin and benzylpenicillin across hospitals.

Results: A total of 415 prescriptions among 214 neonates from 39 different hospitals were included. The majority of prescriptions (342, 82.4%) were for neonates <7 days of age. The most commonly prescribed antibiotics were gentamicin and benzylpenicillin, with 323 (77.8%) prescriptions. Dosing variability was substantial, with doses ranging from 2 to 8 mg/kg for gentamicin (median 5 mg/kg, IQR 4-5) and from 45 to 72 mg/kg for benzylpenicillin (median 60 mg/kg, IQR 50-60), although only 13 (3.2%) and 19 (4.6%) prescriptions were locally assessed as inappropriate or non-compliant with guidelines, respectively. At time of audit, 22% of antibiotics had been given for more than 48 hours and 9% more than 72 hours, although microbiologically confirmed infection was documented in only nine (4.2%) neonates.

Conclusions: Prescribing for neonatal sepsis was dominated by use of benzylpenicillin and gentamicin with substantial variation in dosing. A small minority had culture-confirmed infection. Efforts to standardise antibiotic dosing and duration for suspected neonatal sepsis are recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjpo-2020-000643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101048PMC
March 2020

Epidemic and Inter-epidemic Burden of Pediatric Human Parechovirus Infection in New South Wales, Australia, 2017-2018.

Pediatr Infect Dis J 2020 06;39(6):507-511

From the Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Westmead, NSW, Australia.

Background: Human parechovirus (HPeV) typically infects young children, and although infection is often asymptomatic, some types (eg, HPeV3) are associated with severe clinical manifestations, including central nervous system infection or sepsis-like syndrome, particularly affecting young infants. The third documented national epidemic of HPeV occurred in Australia in 2017-2018.

Methods: Four public laboratories that perform almost all of the HPeV PCR testing in New South Wales provided data regarding HPeV tests performed from July 1, 2017 to June 30, 2018. Limited demographic and clinical data were obtained from electronic medical records for laboratory test-positive cases that presented to each of the 3 pediatric hospitals in New South Wales.

Results: Five hundred eighty-one HPeV-positive samples obtained from 395 cases were included in the analysis. The peak of the outbreak occurred in late November 2017 (approximately 35 new cases each week), with the main HPeV epidemic occurring between the spring and summer months of September 2017 to January 2018; although this seasonality was observed primarily in infants less than 12 months of age. Among the 388 pediatric cases, almost half were younger than 2 months (188; 47%) and only 10 were children older than 2 years. The annualized estimated incidence of laboratory confirmed HPeV infection in children was approximately 142.4 cases per 100,000 children younger than 5 years in New South Wales during the epidemic season.

Conclusions: The large burden of HPeV infection and disease identified in young infants in this and previous Australian studies highlight the need for more comprehensive national surveillance of HPeV infections and improved prevention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002615DOI Listing
June 2020

Early Life Parechovirus Infection Neurodevelopmental Outcomes at 3 Years: A Cohort Study.

J Pediatr 2020 04 28;219:111-117.e1. Epub 2020 Jan 28.

Discipline of Child and Adolescent Health and Marie Bashir Institute Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Sydney Children's Hospitals Network, Sydney, Australia; Department of Pediatrics, University of Melbourne, Melbourne, Australia.

Objective: To investigate the long-term developmental and behavioral outcomes in an established cohort of children hospitalized as infants with human parechovirus (HPeV) infection and sepsis-like illness.

Study Design: The HPeV cohort was composed of children 3 years of age after HPeV infection and hospitalization in early infancy that occurred during a well-documented HPeV genotype 3 outbreak in Australia. We assessed neurodevelopmental and behavioral outcomes using the Bayley Scales of Infant and Toddler Development-III and the Child Behavior Checklist. We compared their outcomes with a subsample of healthy control infants drawn from the independently sampled Triple B Pregnancy Cohort Study.

Results: Fifty children, with a mean age of 41 months, were followed for 3 years after hospital admission with HPeV infection. There were 47 children whose original illness was fever without source or sepsis-like illness and 3 who had encephalitis. All children in the HPeV cohort showed age-specific development within the population normal range on the Bayley Scales of Infant and Toddler Development-III. There was no difference in developmental attainment compared with 107 healthy control infants after adjusting for measured confounders. The HPeV cohort showed higher average scores on the Child Behavior Checklist and a higher frequency of clinical range scores compared with healthy controls.

Conclusions: Although HPeV sepsis-like illness did not result in neurodevelopmental delay at 3 years of age, it was associated with increased behavioral problems compared with healthy controls. The behavioral problems reached a clinical threshold in a minority of children. Results inform clinical management and planning for children after severe HPeV infection in infancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2019.12.026DOI Listing
April 2020

Cryptococcal infections in children: retrospective study and review from Australia.

Future Microbiol 2019 12 29;14:1531-1544. Epub 2020 Jan 29.

Department of Immunology & Infectious Disease, Sydney Children's Hospital, Randwick, New South Wales, 2031, Australia.

Cryptococcosis causes significant morbidity and mortality worldwide, but pediatric data are limited. A retrospective literature review of Australian pediatric cryptococcosis and additional 10-year audit of cases from a large pediatric network. 22 cases of cryptococcosis in children were identified via literature review: median age was 13.5 years (IQR 7.8-16 years), 18/22 (82%) had meningitis or central nervous system infection. Where outcome was reported, 11/18 (61%) died. Of six audit cases identified from 2008 to 2017, 5 (83%) had disease and survived. One child with acute lymphoblastic leukemia and infection died. For survivors, persisting respiratory or neurological sequelae were reported in 4/6 cases (67%). Cryptococcosis is uncommon in Australian children, but is associated with substantial morbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/fmb-2019-0215DOI Listing
December 2019

Antibiotic appropriateness and guideline adherence in hospitalized children: results of a nationwide study.

J Antimicrob Chemother 2020 03;75(3):738-746

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

Background: Information on the nature and appropriateness of antibiotic prescribing for children in hospitals is important, but scarce.

Objectives: To analyse antimicrobial prescribing and appropriateness, and guideline adherence, in hospitalized children across Australia.

Patients And Methods: We analysed data from the National Antimicrobial Prescribing Survey (NAPS) from 2014 to 2017. Surveys were performed in hospital facilities of all types (public and private; major city, regional and remote). Participants were admitted children <18 years old. Risk factors associated with inappropriate prescribing were explored using logistic regression models.

Results: Among 6219 prescriptions for 3715 children in 253 facilities, 19.6% of prescriptions were deemed inappropriate. Risk factors for inappropriate prescribing included non-tertiary paediatric hospital admission [OR 1.37 (95% CI 1.20-1.55)] and non-major city hospital location [OR 1.52 (95% CI 1.30-1.77)]. Prescriptions for neonates, immunocompromised children and those admitted to an ICU were less frequently inappropriate. If a restricted antimicrobial was prescribed and not approved, the prescription was more likely to be inappropriate [OR 12.9 (95% CI 8.4-19.8)]. Surgical prophylaxis was inappropriate in 59% of prescriptions.

Conclusions: Inappropriate antimicrobial prescribing in children was linked to specific risk factors identified here, presenting opportunities for targeted interventions to improve prescribing. This information, using a NAPS dataset, allows for analysis of antimicrobial prescribing among different groups of hospitalized children. Further exploration of barriers to appropriate prescribing and facilitators of best practice in this population is recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz474DOI Listing
March 2020

Importance of vaccine history in suspected measles.

J Paediatr Child Health 2020 05 15;56(5):804-805. Epub 2019 Oct 15.

Department of Paediatric Immunology and Infectious Diseases, Sydney Children's Hospital, Sydney, New South Wales, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.14647DOI Listing
May 2020

Multidrug-resistant organisms in urinary tract infections in children.

Pediatr Nephrol 2020 09 15;35(9):1563-1573. Epub 2019 Aug 15.

School of Women's & Children's Health, UNSW Medicine, University of New South Wales, Sydney, Australia.

The global spread of multidrug-resistant organisms has led to an increase in urinary tract infections (UTIs) in children that are difficult to treat. This review explores the current literature regarding multidrug-resistant UTIs in childhood and proposes an approach to management. Multidrug-resistant organisms include a wide range of potential urinary tract pathogens and, while most literature on drug resistance in UTIs during childhood has focused on extended-spectrum beta-lactamase producing organisms, in this review, we have included a discussion of multidrug resistance including and beyond beta-lactamase production. We provide definitions for multidrug-resistant organisms in line with current consensus guidelines and summarise clinically relevant mechanisms of resistance. Additionally, in this review, we outline the global epidemiology of multidrug-resistant UTIs in children, summarising published prevalence rates, which range from 5 to 90% in different settings. Finally, we also critically review the evidence on risk factors for colonisation and infection of the urinary tract with multidrug-resistant organisms, including prior antibiotic use, hospitalisation and underlying urological malformations. We also highlight multidrug-resistant UTI occurring in children without any identifiable risk factors, reflecting an increasing prevalence of colonisation with these organisms in the general community. Taken as a whole, this emphasises a need for careful and evidence-based use of antibiotics when treating UTIs in children and, to aide clinicians, we have outlined here potential management strategies for when infection with a multidrug-resistant organism is suspected or confirmed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-019-04316-5DOI Listing
September 2020

Overview of paediatric tuberculosis cases treated in the Sydney Children's Hospitals Network, Australia.

Public Health Res Pract 2019 Jul 31;29(2). Epub 2019 Jul 31.

Infectious Diseases and Microbiology Department, The Children's Hospital at Westmead, Sydney, NSW, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, NSW, Australia.

Background: Sydney has a large and highly mobile immigrant community. The pattern of paediatric tuberculosis (TB) disease in this highly cosmopolitan city is not well documented.

Methods: We reviewed data on all children notified with TB in New South Wales (NSW), Australia, from January 2014 to December 2015, complemented by an expanded dataset for children managed within the Sydney Children's Hospitals Network (SCHN).

Results: Over the 2-year study period, 921 TB cases were identified in NSW, including 26 (2.8%) children younger than 15 years of age. Of 23 children and adolescents treated for TB in the SCHN, 21 (91.3%) had a history of recent immigration from, or travel to, a country with high TB incidence, and 7 (30.4%) reported contact with an infectious TB case in Australia. Fourteen (60.9%) children had microbiologically confirmed TB; of these, 5 (21.7%) had acid-fast bacilli on microscopy, 8 (34.8%) were positive by polymerase chain reaction and 11 (47.8%) were positive by culture. All Mycobacterium tuberculosis isolates were susceptible to first-line drugs. Ten (43.5%) cases were not vaccinated with bacille Calmette-Guérin (BCG), including all cases with severe disease: 2 with disseminated (miliary) TB and 3 with tuberculous meningitis.

Conclusion: Our findings emphasise the need for improved TB prevention and surveillance in children at high risk of exposure, particularly young children travelling to areas of high TB incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17061/phrp28231807DOI Listing
July 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27915DOI Listing
October 2019

CASSETTE-clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: study protocol for a randomised controlled trial.

Trials 2019 Jun 13;20(1):353. Epub 2019 Jun 13.

Menzies School of Health Research, Darwin, Australia.

Background: Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking.

Methods: An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to β-lactams or lincosamides will be excluded. The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed.

Discussion: This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT.

Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12617001416381p . Registered on 6 October 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-019-3452-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567404PMC
June 2019

Management and prevention of cytomegalovirus infection in paediatric hematopoietic stem cell transplant (HSCT) recipients: A binational survey.

Pediatr Transplant 2019 08 12;23(5):e13458. Epub 2019 May 12.

Immunology and Infectious Diseases Department, Sydney Children's Hospital, Sydney, New South Wales, Australia.

CMV infection is an important cause of morbidity and mortality among HSCT recipients. Optimal strategies for prevention and management of CMV disease following haematopoietic stem cell transplantation remain uncertain. We conducted an online survey of Australasian paediatric allogeneic HSCT centres on management and prevention of CMV disease in this patient group. We asked for one response from a representative of the HSCT team and one from a representative of the ID team at each centre. All Australasian paediatric HSCT centres responded to our survey. Management of CMV in pre-transplant setting was consistent between centres. All centres used a pre-emptive strategy to prevent CMV disease, guided by quantitative CMV PCR. In the post-transplant post engraftment setting, all centres recommended using ganciclovir (5mg/kg/dose twice daily) as a first-line therapy for CMV reactivation or disease, with treatment duration of 14 days, provided declining CMV quantitative PCR. There was substantial variability of practice between centres in post-transplant management of CMV reactivation, especially during the pre-engraftment phase. Similarly, there was lack of uniformity in indication, dosing and duration of maintenance therapy. Divergence was noted between responses from HSCT and ID physicians within centres. This study identifies areas of uniformity and others of great variability in prevention and management strategies for CMV in paediatric HSCT. Data on CMV infection and management in HSCT patients should be routinely collected as part of prospective trials to inform guidelines and improve prevention and treatment of this important complication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13458DOI Listing
August 2019
-->