Joshua R. Francis

Australian Bat Lyssavirus in a Child: The First Reported Case

Human infection with Australian Bat Lyssavirus is extremely rare and has not previously been reported in a child. We describe a fatal case of Australian Bat Lyssavirus in an 8-year-old child, and review the literature pertaining to the diagnosis and management of lyssavirus infection with consideration of its applicability to this emerging strain.

Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines

Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research.

Bacillus cereus bacteremia and multiple brain abscesses during acute lymphoblastic leukemia induction therapy.

Bacillus cereus can cause serious infections in immunosuppressed patients. This population may be susceptible to B. cereus pneumonia, bacteremia, cellulitis, and rarely cerebral abscess. Here we report an 8-year-old boy undergoing induction therapy for acute lymphoblastic leukemia who developed multifocal B. cereus cerebral abscesses, highlighting the propensity for B. cereus to develop cerebral abscesses. A review of the literature over the past 25 years identified another 11 cases (3 children and 8 adults) of B. cereus cerebral abscess in patients undergoing cancer therapy. B. cereus cerebral abscesses were associated with a high mortality rate (42%) and significant morbidity. Notably, B. cereus bacteremia with concomitant cerebral abscess was associated with induction chemotherapy for acute leukemia in both children and adults (10 of 12 case reports). Our case report and review of the literature highlights the propensity for B. cereus to develop cerebral abscess(es). Therefore, early consideration for neuroimaging should be given for any neutropenic cancer patient identified with B. cereus bacteremia, in particular those with acute leukemia during induction therapy.

Australia-wide Point Prevalence Survey of Antimicrobial Prescribing in Neonatal Units: How Much and How Good?

Background: There is increasing recognition of the threat to neonatal patients from antibiotic resistance. There are limited data on antimicrobial prescribing practices for hospitalized neonates. We aimed to describe antimicrobial use in hospitalized Australian neonatal patients, and to determine its appropriateness. Methods: Multicentre single-day hospital-wide point prevalence survey in 2012, in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. The appropriateness of antimicrobial prescriptions was also assessed. All patients admitted at 8 am on the survey day, in 6 neonatal units in tertiary children’s hospitals across 5 states, were included in an analysis of the quantity and quality of all antimicrobial prescriptions. Results: The point prevalence survey included 6 neonatal units and 236 patients. Of 109 patients (46%) receiving at least 1 antimicrobial, 66 (61%) were being treated for infection, with sepsis the most common indication. There were 216 antimicrobial prescriptions, 134 (62%) for treatment of infection and 82 (38%) for prophylaxis, mostly oral nystatin. Only 15 prescriptions were for targeted as opposed to empirical treatment. Penicillin and gentamicin were the most commonly prescribed antibiotics, with vancomycin third most common. Half of all treated patients were receiving combination antimicrobial therapy. There was marked variation in vancomycin and gentamicin dosing. Overall, few prescriptions (4%) were deemed inappropriate. Conclusion: This is the first Australia-wide point prevalence survey of neonatal antimicrobial prescribing in tertiary children’s hospitals. The findings highlight positive practices and potential targets for quality improvement.

Perspective: ‘The forgotten children: National inquiry into children in immigration detention (2014)’

Perspective: ‘The forgotten children: National inquiry into children in immigration detention (2014)’ Georgia Paxton, Shidan Tosif, Hamish Graham, Andrea Smith, Colette Reveley, Jane Standish, Kate McCloskey, Grant Ferguson, David Isaacs, Hasantha Gunasekera, Ben Marais, Philip Britton, Ameneh Khatami, Karen Zwi, Shanti Raman, Elizabeth Elliott, David Levitt, Joshua Francis, Paul Bauert, Peter Morris, Annie Whybourne, Sarah Cherian, Raewyn Mutch, David Forbes, David Rutherford and Suzanne Packer

Exome sequencing reveals primary immunodeficiencies in children with community-acquired pseudomonas aeruginosa sepsis

One out of three pediatric sepsis deaths in high income countries occur in previously healthy children. Primary immunodeficiencies (PIDs) have been postulated to underlie fulminant sepsis, but this concept remains to be confirmed in clinical practice. Pseudomonas aeruginosa (P. aeruginosa) is a common bacterium mostly associated with health care-related infections in immunocompromised individuals. However, in rare cases, it can cause sepsis in previously healthy children. We used exome sequencing and bioinformatic analysis to systematically search for genetic factors underpinning severe P. aeruginosa infection in the pediatric population. We collected blood samples from 11 previously healthy children, with no family history of immunodeficiency, who presented with severe sepsis due to community-acquired P. aeruginosa bacteremia. Genomic DNA was extracted from blood or tissue samples obtained intravitam or postmortem. We obtained high-coverage exome sequencing data and searched for rare loss-of-function variants. After rigorous filtrations, 12 potentially causal variants were identified. Two out of eight (25%) fatal cases were found to carry novel pathogenic variants in PID genes, including BTK and DNMT3B. This study demonstrates that exome sequencing allows to identify rare, deleterious human genetic variants responsible for fulminant sepsis in apparently healthy children. Diagnosing PIDs in such patients is of high relevance to survivors and affected families. We propose that unusually severe and fatal sepsis cases in previously healthy children should be considered for exome/genome sequencing to search for underlying PIDs.[This corrects the article on p. 357 in vol. 7, PMID: 27703454.].

Challenges to delivery of isoniazid preventive therapy in a cohort of children exposed to tuberculosis in Timor-Leste.

To evaluate the number and geographic location of children aged <5 years exposed to sputum smear‐positive tuberculosis (TB) in Timor‐Leste, to determine the proportion evaluated for isoniazid preventive therapy (IPT) and to review the programmatic challenges present in delivering IPT to this cohort.

Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital.

Objectives: To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use.

Multidrug-resistant tuberculosis in Western Australia, 1998-2012

Objective: To describe the epidemiology, clinical features, health care resource use, treatment and outcomes of multidrug‐resistant tuberculosis (MDR‐TB) cases diagnosed in Western Australia, compared with matched controls with drug‐susceptible TB.

Australian bat lyssavirus: implications for public health.

Australian bat lyssavirus (ABLV) infection in humans is rare but fatal, with no proven effective therapy. ABLV infection can be prevented by administration of a post‐exposure prophylaxis regimen of human rabies immunoglobulin and rabies vaccine. All Australian bats (flying foxes and microbats) should be considered to be carrying ABLV unless proven otherwise. Any bat‐related injury (bite, scratch or mucosal exposure to bat saliva or neural tissue) should be notified immediately to the relevant public health unit — no matter how small the injury or how long ago it occurred. Human‐to‐human transmission of ABLV has not been reported but is theoretically possible. Standard infection control precautions should be employed when managing patients with suspected or confirmed ABLV infection.