Reduction in Acute Post-Streptococcal Glomerulonephritis Incidence in Counties Manukau, New Zealand, after the COVID-19 Pandemic.

The COVID-19 pandemic has altered the epidemiology of many common childhood infections, including Group A streptococcal (GAS) disease. Acute post-streptococcal glomerulonephritis (APSGN) is a nonsuppurative complication of GAS pharyngitis and pyoderma. It remains the most common cause of pediatric acute glomerulonephritis globally. In Counties Manukau, New Zealand, APSGN rates have previously been shown to be the highest in the country, with marked ethnic and socioeconomic disparities. We performed a retrospective review of children aged 0-14 years who were discharged from Kidz First Hospital, Counties Manukau, between 2015 and 2023 and met the Strep A Vaccine Global Consortium consensus definition of APSGN. We describe a marked, sustained reduction in APSGN hospitalizations, temporally associated with the COVID-19 pandemic. This ongoing reduction in APSGN incidence is notable in light of contrasting reports of increasing incidence of rheumatic fever in New Zealand and invasive GAS disease internationally.

Fifteen-minute consultation: Group A streptococcal pharyngitis, diagnosis and treatment in children.

Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis in children. GAS causes significant suppurative and non-suppurative complications including invasive GAS disease and acute rheumatic fever. This article describes the current epidemiology and clinical presentation of GAS pharyngitis and explores how diagnostic and treatment decisions differ globally. Several key decision support tools are discussed including international guidelines, clinical decision scores and laboratory tests along with the evidence for treatment choice and duration. With recent international reports describing an increase in GAS infections, clinicians should be familiar with their local GAS pharyngitis guidelines and the rationale for diagnosis and treatment of this common childhood illness.

Trends in penicillin dispensing during an acute rheumatic fever prevention programme.

AIM: Acute rheumatic fever (ARF), a serious inflammatory condition, often leads to rheumatic heart disease (RHD). Between 2011 and 2016, Aotearoa New Zealand implemented a rheumatic fever prevention programme (RFPP) to reduce high rates of ARF through improved community access to timely diagnosis and early treatment of group A streptococcal (GAS) pharyngitis, which has been shown to prevent subsequent ARF. This study aimed to quantify the change in penicillin antibiotic dispensing rates among children aged 18 years or younger during the RFPP. METHOD: This retrospective analysis utilised administrative data from the National Pharmaceutical Collection. Using a controlled, interrupted time series analysis, the effect of the RFPP on antibiotic dispensing rates was explored. Poisson regression models were used to assess the change in dispensing rates during the RFPP among control regions (those not in the RFPP) and regions participating in the RFPP. The primary measure was rate ratio (RR) for the difference between the observed versus counterfactual rates of penicillin dispensing. RESULT: A total of 12,154,872 dispensing records between 2005 and 2018 were included. Amoxicillin was the most frequently dispensed penicillin (57.7%), followed by amoxicillin-clavulanate (23.4%). Amoxicillin dispensing increased by 4.3% in regions operating the RFPP compared to the increase in control regions (p<0.001). The overall rate of penicillin dispensing decreased, driven by a rapid decline in amoxicillin-clavulanate dispensing. CONCLUSION: During the RFPP an increase in amoxicillin dispensing was seen in regions participating in the programme and regions outside of the programme, indicating the programmatic approach led to improved adherence to recommended first-line antibiotics.

Group A Streptococcus Primary Peritonitis in Children, New Zealand.

Group A Streptococcus (GAS) primary peritonitis is a rare cause of pediatric acute abdomen (sudden onset of severe abdominal pain); only 26 pediatric cases have been reported in the English language literature since 1980. We discuss 20 additional cases of pediatric primary peritonitis caused by GAS among patients at Starship Children's Hospital, Auckland, New Zealand, during 2010-2022. We compare identified cases of GAS primary peritonitis to cases described in the existing pediatric literature. As rates of rates of invasive GAS increase globally, clinicians should be aware of this cause of unexplained pediatric acute abdomen.

Increasing the time-to-freezing for clinical apheresis plasma meets quality specifications.

BACKGROUND AND OBJECTIVES: In Australia, the vast distances between blood collection centres and processing facilities make it challenging to align supply with demand. Increasing the time to freezing for clinical plasma beyond 6 h would alleviate supply issues. This study aimed to determine the quality of clinical apheresis plasma frozen within 12 h of collection. MATERIALS AND METHODS: Apheresis plasma (n = 20) collected at donor centres was immediately transported to a blood processing facility, stored at 26°C and sampled aseptically at 6, 8 and 12 h post collection. Frozen samples were thawed, and coagulation factors (F) II, V, VII, VIII and XIII, von Willebrand factor (vWF) and fibrinogen were measured using a coagulation analyser. RESULTS: FVIII concentrations declined in plasma frozen at 6, 8 and 12 h post collection (1.22 ± 0.27, 1.21 ± 0.25 and 1.16 ± 0.24 IU/mL, respectively) but not significantly (p = 0.3338). Importantly, all components met the FVIII specification (>0.7 IU/mL) for clinical plasma. Fibrinogen concentrations were stable from 6 to 12 h (p = 0.3100), as were vWF concentrations (p = 0.1281). Coagulation factors II, V, VII and XIII were not significantly different (p > 0.05 for all factors). CONCLUSION: Clinical apheresis plasma can be frozen within 12 h of collection, allowing collections from donor centres further from processing centres and increasing supply.

Improved paediatric antimicrobial prescribing with a smartphone application: a before and after interventional study.

INTRODUCTION: Children have a high consumption of antimicrobials that require complicated decision-making by prescribers. Despite this, antimicrobial stewardship (AMS) interventions are often not translated into paediatric medicine. Script is a smartphone application (app) launched in Auckland, New Zealand to support decision-making for antimicrobial prescribers. The aim was to improve adherence to existing local clinical guidelines for both adult and paediatric infections. METHODS: Inpatient and emergency department antimicrobial prescriptions were prospectively collected and evaluated for guideline adherence. Baseline prescribing data were collected and compared with prescribing at 4 months and 1 year after the app was launched. Prescriptions were graded as 'appropriate' or 'inappropriate' by investigators. Grading was done blinded to timing of the prescription relative to the intervention. RESULTS: Following the launch of the Script app, guideline adherence significantly increased from 241 of 348 (69%) antimicrobial prescriptions graded as appropriate during the baseline period to 301 of 359 (83%) after 4 months (p<0.0001). This improvement from baseline was sustained at 1 year with 263 of 323 (81%) adherence (p<0.001). At 1 year, this improvement could be demonstrated separately for medical, surgical and emergency department prescriptions. CONCLUSION: There was a significant and sustained improvement in adherence to paediatric antimicrobial guidelines following the introduction of a prescribing support app. The need to seek guidance for antimicrobial doses due to the age-based and weight-based calculations in paediatrics may mean that AMS interventions such as decision support and prescribing tools are particularly well suited to paediatric prescribing.

High burden of rheumatic heart disease confirmed by echocardiography among Pacific adults living in New Zealand.

BACKGROUND: Despite numerous echocardiographic screening studies of children in high incidence acute rheumatic fever (ARF)/rheumatic heart disease (RHD) communities, little is known about the prevalence of RHD in adults in these populations.We sought to determine the prevalence of RHD in an urban area of South Auckland, New Zealand, where previous studies had shown the prevalence of RHD in children to be around 2%. METHODS: A cross-sectional screening study was conducted between 2014 and 2016. Echocardiography clinics were conducted at an urban Pacific-led primary healthcare clinic in New Zealand. Eligible persons aged 16-40 years were recruited according to a stratified randomised approach. Echocardiograms were performed with a standardised image acquisition protocol and reported by cardiologists. RESULTS: There were 465 individuals who underwent echocardiograms. The overall prevalence of RHD (define and borderline) was 56 per 1000 (95% CI 36 to 78 per 1000). Definite RHD was found in 10 individuals (4 of whom were already under cardiology review at a hospital clinic) with a prevalence of 22 per 1000 (95% CI 9 to 36 per 1000). Non-rheumatic cardiac abnormalities were found in 29 individuals. CONCLUSIONS: There is a high burden of both rheumatic and non-rheumatic cardiac abnormalities in this population. Rates described in New Zealand are as high as lower-middle-income countries in Africa. Addressing knowledge gaps regarding the natural history of RHD detected by echocardiography in adults is a priority issue for the international RHD community.

Internal consistency reliability of mental health questionnaires in college student athletes.

OBJECTIVES: To examine the internal consistency reliability and measurement invariance of a questionnaire battery designed to identify college student athletes at risk for mental health symptoms and disorders. METHODS: College student athletes (N=993) completed questionnaires assessing 13 mental health domains: strain, anxiety, depression, suicide and self-harm ideation, sleep, alcohol use, drug use, eating disorders, attention deficit hyperactivity disorder (ADHD), bipolar disorder, post-traumatic stress disorder (PTSD), gambling and psychosis. Internal consistency reliability of each measure was assessed and compared between sexes as well as to previous results in elite athletes. Discriminative ability analyses were used to examine how well the cut-off score on the strain measure (Athlete Psychological Strain Questionnaire) predicted cut-offs on other screening questionnaires. RESULTS: Strain, anxiety, depression, suicide and self-harm ideation, ADHD, PTSD and bipolar questionnaires all had acceptable or better internal consistency reliability. Sleep, gambling and psychosis questionnaires had questionable internal consistency reliability, although approaching acceptable for certain sex by measure values. The athlete disordered eating measure (Brief Eating Disorder in Athletes Questionnaire) had poor internal consistency reliability in males and questionable internal consistency reliability in females. CONCLUSIONS: The recommended mental health questionnaires were generally reliable for use with college student athletes. To truly determine the validity of the cut-off scores on these self-report questionnaires, future studies need to compare the questionnaires to a structured clinical interview to determine the discriminative abilities.

Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004-2020.

New Zealand (Aotearoa) experienced a Neisseria meningitidis serogroup B epidemic during 1991-2006, and incidence remains twice that of other high-income countries. We reviewed clinical, laboratory, and immunization data for children <15 years of age with laboratory-confirmed invasive meningococcal disease in Auckland, New Zealand, during January 1, 2004-December 31, 2020. Of 319 cases in 318 children, 4.1% died, and 23.6% with follow-up data experienced sequelae. Children of Maori and Pacific ethnicity and those living in the most deprived areas were overrepresented. Eighty-one percent were positive for N. meningitidis serogroup B, 8.6% for serogroup W, 6.3% for serogroup C, and 3.7% for serogroup Y. Seventy-nine percent had bacteremia, and 63.9% had meningitis. In New Zealand, Maori and Pacific children are disproportionately affected by this preventable disease. N. meningitidis serogroup B vaccine should be included in the New Zealand National Immunization Schedule to address this persistent health inequity.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

PURPOSE: The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. METHODS: Retrospective study of all culture positive IMD in adult patients (age ≥ 15 years) in the Auckland region from 2004 to 2017. RESULTS: One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. CONCLUSIONS: This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

The association between warfarin usage and international normalized ratio increase: systematic analysis of FDA Adverse Event Reporting System (FAERS).

Introduction: Elevated international normalized ratio (INR) has been commonly reported as an adverse drug event (ADE) for patients taking warfarin for anticoagulant therapy. Aim: The purpose of this study was to determine the association between increased INR and the usage of warfarin by using the pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS). Methods: The ADEs in patients who took warfarin (N = 77,010) were analyzed using FAERS data. Association rule mining was applied to identify warfarin-related ADEs that were most associated with elevated INR (n = 15,091) as well as possible drug-drug interactions (DDIs) associated with increased INR. Lift values were used to identify ADEs that were most commonly reported alongside elevated INR based on the correlation between both item sets. In addition, this study sought to determine if the increased INR risk was influenced by sex, age, temporal distribution, and geographic distribution and were reported as reporting odds ratios (RORs). Results: The top 5 ADEs most associated with increased INR in patients taking warfarin were decreased hemoglobin (lift = 2.31), drug interactions (lift = 1.88), hematuria (lift = 1.58), asthenia (lift = 1.44), and fall (lift = 1.32). INR risk increased as age increased, with individuals older than 80 having a 63% greater likelihood of elevated INR compared to those younger than 50. Males were 9% more likely to report increased INR as an ADE compared to females. Individuals taking warfarin concomitantly with at least one other drug were 43% more likely to report increased INR. The top 5 most frequently identified DDIs in patients taking warfarin and presenting with elevated INR were acetaminophen (lift = 1.81), ramipril (lift = 1.71), furosemide (lift = 1.64), bisoprolol (lift = 1.58), and simvastatin (lift = 1.58). Conclusion: The risk of elevated INR increased as patient age increased, particularly among those older than 80. Elevated INR frequently co-presented with decreased hemoglobin, drug interactions, hematuria, asthenia, and fall in patients taking warfarin. This effect may be less pronounced in women due to the procoagulatory effects of estrogen signaling. Multiple possible DDIs were identified, including acetaminophen, ramipril, and furosemide.

Cohort profile: methodology and cohort characteristics of the Aotearoa New Zealand Rheumatic Heart Disease Registry.

PURPOSE: To create a cohort with high specificity for moderate and severe rheumatic heart disease (RHD) in New Zealand, not reliant on International Classification of Diseases discharge coding. To describe the demography and cardiac profile of this historical and contemporary cohort. DESIGN AND PARTICIPANTS: Retrospective identification of moderate or severe RHD with disease onset by 2019. Case identification from the following data sources: cardiac surgical databases, RHD case series, percutaneous balloon valvuloplasty databases, echocardiography databases, regional rheumatic fever registers and RHD clinic lists. The setting for this study was a high-income country with continued incidence of acute rheumatic fever (ARF). FINDINGS TO DATE: A Registry cohort of 4959 patients was established. The initial presentation was RHD without recognised prior ARF in 41%, and ARF in 59%. Ethnicity breakdown: Maori 38%, Pacific 33.5%, European 21.9%, other 6.7%. Ethnic disparities have changed significantly over time. Prior to 1960, RHD cases were 64.3% European, 25.3% Maori and 6.7% Pacific. However, in contrast, from 2010 to 2019, RHD cases were 10.7% European, 37.4% Maori and 47.2% Pacific.Follow-up showed 32% had changed region of residence within New Zealand from their initial presentation. At least one cardiac intervention (cardiac surgery, transcatheter balloon valvuloplasty) was undertaken in 64% of the cohort at a mean age of 40 years. 19.8% of the cohort had multiple cardiac interventions. At latest follow-up, 26.9% of the cohort died. Of those alive, the mean follow-up is 20.5+19.4 years. Maori and Pacific led governance groups have been established to provide data governance and oversight for the registry. FUTURE PLANS: Detailed mortality and morbidity of the registry cases will be defined by linkage to New Zealand national health data collections. The contemporary cohort of the registry will be available for future studies to improve clinical management and outcomes for the 3450 individuals living with chronic RHD.

Cytokine imbalance in acute rheumatic fever and rheumatic heart disease: Mechanisms and therapeutic implications.

Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) are autoimmune sequelae of Group A Streptococcus infection with significant global disease burden. The pathogenesis of these diseases is poorly understood, and no immune modulating therapies are available to stop progression from ARF to RHD. Cytokines and chemokines are immune signaling molecules critical to the development of autoimmune diseases. An increasing number of studies point to a central role for pro-inflammatory cytokines and chemokines in ARF and RHD pathogenesis, in particular IL-6, IL-8/CXCL8, and TNFα, which are elevated in circulation in both ARF and RHD patients. Histological studies of RHD valve tissue implicates Th1 and Th17 associated pro-inflammatory cytokines, chemokine CXCL9, and the fibrosis-associated cytokine TGF-ß in progressive cycles of inflammatory damage and fibrotic repair. Taken together, this suggests immune molecules contribute to both the acute inflammatory disease stage of ARF, as well as cardiac remodeling and valve dysfunction in RHD. Monoclonal antibody blockade of pro-inflammatory cytokines IL-6 and TNFα are approved therapies for many autoimmune diseases and the most successful immunomodulating therapies for rheumatoid arthritis. Current evidence suggests possible benefit for ARF patients from IL-6 and TNFα blockade, in particular to interrupt progression to RHD, and warrants immediate investigation.

Red cells manufactured from lipaemic whole blood donations: Do they have higher haemolysis?

BACKGROUND AND OBJECTIVES: Lipaemia in blood donations is thought to influence haemolysis in stored red blood cell (RBC) components. Higher lipid concentrations are believed to increase red cell fragility, exacerbating haemolysis during collection and subsequent red cell storage. This study aimed to investigate associations between lipoproteins in plasma and haemolysis of red cells stored in saline-adenine-glucose-mannitol (SAGM). MATERIALS AND METHODS: Fifty-four plasma and matched RBCs were obtained from lipaemic whole blood donations. Plasma was tested for coagulation factors, triglycerides and cholesterol. Haemolysis, glucose, lactate, extracellular potassium, lactate dehydrogenase and adenosine triphosphate (ATP) were measured in RBC on Days 7, 21 and 42 of storage. Additionally, 20 plasma and matched RBCs from non-lipaemic donations were tested as controls. RESULTS: Lipaemic plasma had significantly higher triglyceride concentrations compared with non-lipaemic plasma. However, there was no significant difference in plasma cholesterol between the two groups. There were no significant differences in glucose, extracellular potassium or ATP concentrations in RBC from either group. There was no significant difference in haemolysis at expiry in lipaemic-derived and control RBC, with a weak correlation between haemolysis and either triglycerides or cholesterol. CONCLUSION: There was no significant difference in haemolysis in RBC manufactured from lipaemic and non-lipaemic whole blood donations when stored in SAGM; however, the proportion of RBC from lipaemic donations with higher haemolysis was greater than in the controls. There was a weak correlation between red cell haemolysis and plasma triglycerides. Therefore, RBCs derived from lipaemic donations are suitable for blood bank inventories.

Medical Treatment for Rheumatic Heart Disease: A Narrative Review.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are rare in high-income countries; however, in Aotearoa New Zealand ARF and RHD disproportionately affect Indigenous Maori and Pacific Peoples. This narrative review explores the evidence regarding non-surgical management of patients with clinically significant valve disease or heart failure due to RHD. METHODS: Medline, EMBASE and Scopus databases were searched, and additional publications were identified through cross-referencing. Included were 28 publications from 1980 onwards. RESULTS: Of the available interventions, improved anticoagulation management and a national RHD register could improve RHD outcomes in New Zealand. Where community pharmacy anticoagulant management services (CPAMS) are available good anticoagulation control can be achieved with a time in the therapeutic range (TTR) of more than 70%, which is above the internationally recommended level of 60%. The use of pharmacists in anticoagulation control is cost-effective, acceptable to patients, pharmacists, and primary care practitioners. There is a lack of local data available to fully assess other interventions; including optimal therapy for heart failure, equitable access to specialist RHD care, prevention, and management of endocarditis. CONCLUSION: As RHD continues to disproportionately affect Indigenous and minority groups, pro-equity tertiary prevention interventions should be fully evaluated to ensure they are reducing disease burden and improving outcomes in patients with RHD.

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.

Microbiology of septic arthritis in young Auckland children.

BACKGROUND: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known. METHODS: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management. RESULTS: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin. CONCLUSIONS: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae.

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.