OBJECTIVES: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration. METHODS: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort. RESULTS: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]). CONCLUSION: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.

Streptococcus pyogenes (S. pyogenes) is a Gram-positive bacteria which causes a spectrum of diseases ranging from asymptomatic infection to life-threatening sepsis. Studies report up to 2000 times greater risk of invasive S. pyogenes disease in close contacts of index cases within 30-days of symptom onset. Despite this, there is variability in the management of asymptomatic carriage of S. pyogenes and those at risk of secondary cases of invasive S. pyogenes infection. OBJECTIVE: Our systematic review assessed the efficacy of different antibiotic regimens used for eradication of S. pyogenes from the pharynx in asymptomatic individuals. METHODS: We searched Pubmed, EMBASE (1974-), OVID Medline (1948-) and the Cochrane CENTRAL registry. We included randomised controlled trials (RCTs) with asymptomatic participants with >50% with pharyngeal cultures positive with S. pyogenes at baseline. Only studies with microbiological methods including culture (+/- polymerase chain reaction, PCR) were included. We included studies published in English. Each included study was assessed by two independent reviewers for data extraction and risk of bias. RESULTS: Of 1166 unique records identified, three RCTs were included in the review. Two of the three included RCTs found oral clindamycin for 10-days was the most efficacious regimen, compared to intramuscular benzathine penicillin G followed by 4 days of oral rifampicin, or monotherapy using benzathine penicillin, phenoxymethylpenicillin or erythromycin. Two RCTs were assessed as being at high risk of bias, with the third study demonstrating low/some risk of bias. CONCLUSIONS: Current available evidence for the optimal antibiotic in eradicating pharyngeal S. pyogenes carriage is limited. Future RCTs should include penicillin, first-generation cephalosporins, rifampicin, macrolides (such as azithromycin) and clindamycin.

Fungi from the order Entomophthorales are rare but well recognized cause of tropical fungal infection, typically causing subcutaneous truncal or limb lesions in immunocompetent hosts. They may also mimic malignancy by causing intrabdominal mass, sometimes resulting in obstructive gastrointestinal or renal presentations. A 4-year-old female presented with a progressively growing abdominal wall lesion over several months, developing into acute inflammation of the abdominal wall with systemic symptoms. She underwent surgical debridement and fungal culture of subcutaneous tissue was positive for Basidiobolus spp with characteristic histopathological findings. Treatment with voriconazole followed by itraconazole over a total duration of 6 weeks led to complete resolution. Basidiobolus spp is an unusual cause of infection with characteristic mycological and histopathological findings. Infection can present in a number of ways ranging from a slow-growing mass in the subcutaneous soft tissue to an invasive mass in the gastrointestinal tract. Identification of its unique beak-like zygospore and Splendore-Hoeppli phenomenon on histopathological specimens can be pathognomonic and could provide the key to early diagnosis. Review of the literature found that timely diagnosis and commencement of antifungal therapy can be curative with or without surgical treatment. Considering the rarity of this tropical infection, this case provides the opportunity for revision of the typical presentations and diagnostic findings of Basidiobolus spp. With early recognition and suitable treatment, outcomes are generally favorable.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

AIMS: Despite the declining incidence of acute post-streptococcal glomerulonephritis (APSGN) in Australia, there is still a significant burden of disease amongst Aboriginal and Torres Strait Islander people in the Northern Territory. Childhood APSGN has been highlighted as a predictor of chronic kidney disease in this population. We aimed to describe clinical characteristics and outcomes of hospitalised children with APSGN in the Northern Territory. METHODS: Single-centre, retrospective cohort study of children (<18 years) with APSGN admitted to a tertiary hospital in the Top End of the Northern Territory between January 2012 and December 2017. Cases were confirmed using the Centre for Disease Control case definition guidelines. Data were extracted from the case notes and electronic medical records. RESULTS: There were 96 cases of APSGN with median age of 7.1 years (interquartile range (IQR) 6.7-11.4). Majority were Aboriginal and Torres Strait Islander (90.6%) and from rural and remote areas (82.3%). Preceding skin infections were identified in 65.5% and sore throat in 27.1%. Severe complications included hypertensive emergencies (37.4%), acute kidney injury (43.8%) and nephrotic-range proteinuria (57.7%). All children improved from their acute illness with supportive medical therapy; however, only 55 out of 96 (57.3%) children were followed up within 12 months of their acute illness. CONCLUSIONS: APSGN disproportionately affects Aboriginal and Torres Strait Islander children and highlights the need for continued and improved public health response. There is room for significant improvement in the medium- and long-term follow-up of affected children.

Soil-transmitted helminths (STHs), are recognised neglected tropical diseases and have been endemic in patients in tropical Northern Australia. We reviewed the temporal trends in detections of STHs and Hymenolepis nana in faecal samples from Northern Territory (NT) Government Health facilities, representing patients with acute illnesses and comorbidities between 2008 and 2018. Ascaris lumbricoides is not detected in patients in the NT. The number of faecal samples examined yearly was relatively constant with a median of 4458 (range 4246-4933). Faecal samples from patients under the age of 5 years declined by 45% over the 11 years of the study. Detections of Trichuris trichiura, Strongyloides spp., and hookworm ova fell significantly by 89% (p<0.001), 71% (p<0.001), and 43% (p<0.01), respectively, over the 11 years. Detections of H. nana declined by 33% absolutely, but not significantly, when assessed relative to the reduction in faecal samples from patients under the age of 5 years. The marked reduction in STH numbers coincided with a 10-fold increase in NT dispensing of ivermectin, predominantly used for scabies control, in widely geographically spaced locations throughout the NT, over the 11 years of the study. Our data support previous findings of the beneficial collateral effects of ivermectin therapy. Ivermectin is not recognised as having anti-cestode activity, hence the continued presence of H. nana endemically in the NT, suggests declines in STHs are not related to other changes in health hardware or existing mass drug administration programs. The reduction in T. trichiura detections may not be explained by this association, as unlike Strongyloides spp., the anti-helminthic effect of ivermectin has been less marked.

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.

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.