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.

Respiratory virus detection and co-infection in children and adults in a large Australian hospital in 2009-2015.

AIM: This hospital network-based retrospective observational study aimed to describe the prevalence and seasonality of paediatric and adult viral respiratory pathogens and their rates of co-infections, following the introduction of a rapid multiplex molecular diagnostic assay. METHODS: All nasopharyngeal samples tested in patients presenting to Monash Health, Melbourne, Australia, from August 2009 to July 2015 by means of multiplex tandem polymerase chain reaction using the Respiratory Pathogen 12Plex kit (AusDiagnostics) were included in the analysis. RESULTS: There were 28 729 patient samples analysed after duplicate samples were excluded. Positive results were twice as likely in paediatrics, 7573/11 491 (65.9%), compared to adults, 5410/17 238 (31.4%). Co-infection was more frequent in paediatrics, 1642/7573 (21.7% of positives), compared to adults 299/5410 (5.5%). Adenovirus had a high prevalence as a co-infection, 639/990 (64.5%), in paediatrics. Testing frequency increased by 179% in the paediatric group and by 949% for adults over the 6 years of observation. CONCLUSIONS: This study demonstrated a significant difference in the positive detection rate of pathogens and co-infections between the population groups. Adenovirus had a surprisingly high prevalence as a co-infection, especially in paediatric patients. Over the study period, rapid uptake of the test was observed, especially in adults. This raises concerns about how we can ensure that testing remains rational and is able to be provided in a cost-effective manner in the future.

Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia.

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.

Breastfeeding and Risk of Late-Onset Group B Streptococcal Disease.

BACKGROUND: Group B Streptococcus (GBS) is a major contributor to neonatal sepsis worldwide. Late-onset group B Streptococcus disease (LOGBS) and its risk factors remain poorly understood. The isolation of GBS from breast milk has been described in cases of LOGBS. This potential association has raised concerns for mothers and clinicians regarding the safety of ongoing breastfeeding. In this study, we aimed to investigate whether exposure to breast milk is associated with increased risk of LOGBS. METHODS: A case-control study of LOGBS was conducted across 4 hospital networks in Victoria, Australia, including the 2 major tertiary pediatric centers in the state, to evaluate 11 years of data (2007-2017). Cases were captured initially from microbiology databases and recaptured with International Classification of Diseases discharge coding. Each case patient was matched with 4 controls to assess feeding status. Patients were matched for chronological age, gestation, discharge status, recruitment site, and calendar year. RESULTS: We identified 92 cases of LOGBS: 73 cases on initial capture and 76 cases on the recapture analysis. Case patients were matched with 368 controls: 4 controls to each patient. Seventy-two patients were exposed to breast milk at the time of LOGBS (78.3%), compared with 274 controls (74.5%; odds ratio 1.2 [95% confidence interval 0.7-2.3]). CONCLUSIONS: Breastfeeding was not associated with increased risk of LOGBS. Breast milk should not be tested for GBS during a first episode of LOGBS.

Prospective Surveillance of Pediatric Invasive Group A Streptococcus Infection.

BACKGROUND: Invasive group A Streptococcus (GAS) disease has an incidence in high-income countries of 3 to 5 per 100000 per annum and a case-fatality ratio of 10% to 15%. Although these rates are comparable to those of invasive meningococcal disease in Australia before vaccine introduction, invasive GAS disease currently requires reporting in only 2 jurisdictions. METHODS: Data were collected prospectively through active surveillance at the Royal Children's Hospital, Melbourne (October 2014 to September 2016). Isolation of GAS from a sterile site was required for inclusion. Comprehensive demographic and clinical data were collected, and emm typing was performed on all isolates. Disease was considered severe if the patient required inotropic support or mechanical ventilation. RESULTS: We recruited 28 patients. The median age of the patients was 3.5 years (range, 4 days to 11 years). Ten (36%) patients had severe disease. Fifteen (54%) children had presented to a medical practitioner for review in the 48 hours before their eventual admission, including 7 of the 10 patients with severe GAS infection. Complications 6 months after discharge persisted in 21% of the patients. emm1 was the most common emm type (29%). CONCLUSION: We found considerable short- and longer-term morbidity associated with pediatric invasive GAS disease in our study. Disease manifestations were frequently severe, and more than one-third of the patients required cardiorespiratory support. More than one-half of the patients attended a medical practitioner for assessment but were discharged in the 48-hour period before admission, which suggests that there might have been a window for earlier diagnosis. Our methodology was easy to implement as a surveillance system.