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.

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.

A retrospective cohort study investigating the comparative effectiveness of pneumococcal vaccines against hospitalisation with otitis media and pneumonia in New Zealand.

BACKGROUND: Since 2008 New Zealand has used three different formulations of pneumococcal vaccines on the national infant schedule, PCV7, PCV10 and PCV13, switching between PCV10 and PCV13 twice in 10 years. We have used New Zealand's linkable, administrative health data to examine the comparative risk of otitis media (OM) and pneumonia hospitalisations among children receiving three different pneumococcal conjugate vaccines (PCV). METHODS: This was a retrospective cohort study using linked administrative data. Outcomes were otitis media, all cause pneumonia and bacterial pneumonia related hospitalisation for children in three cohorts representing periods where PCVs transitioned between PCV7, PCV10, PCV13 and back to PCV10 between 2011 and 2017. Cox's proportional hazard regression was used to provide hazard ratio estimates to compare outcomes for children vaccinated with different vaccine formulations and to adjust for different sub population characteristics. RESULTS: Each observation period, where different vaccine formulations coincided, and therefore comparable with respect to age and the environment, included over fifty-thousand infants and children. PCV10 was associated with a reduced risk for OM compared with PCV7 (Adjusted HR 0.89, 95 %CI 0.82-0.97). There were no significant differences between PCV10 and PCV13 in risk of hospitalisation with either otitis media or all-cause pneumonia amongst the transition 2 cohort. In the 18 -month follow-up, after transition 3, PCV13 was associated with a marginally higher risk of all-cause pneumonia and otitis media compared to PCV10. CONCLUSION: These results should offer reassurance about the equivalence of these pneumococcal vaccines against the broader pneumococcal disease outcomes OM and pneumonia.

Multisystem Inflammatory Syndrome in New Zealand Children.

New Zealand (NZ) initially adopted an elimination approach to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pre-Omicron variant, the NZ pediatric population was immunologically naïve to SARS-CoV-2. This study, utilizing national data sources, describes the NZ incidence of multisystem inflammatory syndrome in children (MIS-C) following infection with the Omicron variant. MIS-C incidence was 1.03 of 100,000 age-specific population and 0.04 of 1000 recorded SARS-CoV-2 infections.

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 epidemiology of aseptic meningitis in New Zealand children from 1991 to 2020.

AIM: Aseptic meningitis, including culture negative and viral meningitis, contributes a significant health-care burden, including unnecessary antibiotic use and hospitalisation to treat possible bacterial meningitis. This study analysed aseptic meningitis hospitalisations in New Zealand (NZ) children over 29 years. METHODS: In this population-based study, aseptic meningitis hospitalisations in NZ children <15 years old were analysed from 1991 to 2020. Incident rate ratios were calculated using Poisson regression models. Variations in hospitalisations by age, year, sex, ethnicity, geographical region and socio-economic deprivation were analysed. RESULTS: There were 5142 paediatric aseptic meningitis hospitalisations from 1991 to 2020. Most were unspecified viral meningitis (64%), followed by enterovirus (29%). Hospitalisation rates varied annually with a median of 18.4/100 000 children including a peak in 2001 of 56.4/100 000 (51.7-61.6). From 2002 to 2019, rates increased by 8.4%/year (7.2-9.5%) in infants <90 days old but decreased in all other age groups. In 2020, a reduction in hospitalisations to 9.6/100 000 (7.9-11.8) occurred, and in infants <90 days old were 0.37 times expected. Hospitalisations were 1.50 times (1.49-1.68) higher in males than females; higher in children of Maori (P < 0.001) and Pacific (P < 0.001) versus European ethnicity; and higher for children living in the most (2.44 times, (2.16-2.75)) versus least deprived households; and in northern versus southern NZ. CONCLUSIONS: Aseptic meningitis hospitalisations increased in young infants during 29 years of surveillance, apart from 2020 when admissions reduced during the COVID-19 pandemic. In contrast, hospitalisations decreased in children aged >1 year. Further investigation into reasons for higher admissions by ethnic group, geographical location and increased deprivation are required.

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.

Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-ß). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses.

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.

Treatment of Impetigo with Antiseptics-Replacing Antibiotics (TIARA) trial: a single blind randomised controlled trial in school health clinics within socioeconomically disadvantaged communities in New Zealand.

BACKGROUND: Impetigo is a common and contagious bacterial skin infection, affecting children worldwide, but it is particularly prevalent in socioeconomically disadvantaged communities. In New Zealand, widespread prescribing of the topical antibiotic fusidic acid had led to an increase in antimicrobial resistance of Staphylococcus aureus. Alternative treatments are urgently being sought, and as impetigo is a superficial infection, it has been suggested that topical antiseptics such as hydrogen peroxide or simple wound care alone may treat impetigo while avoiding the risk of increased antimicrobial resistance. METHODS: This protocol for a non-inferiority, single-blind randomised controlled trial compares topical fusidic acid with topical hydrogen peroxide and with simple wound care in the treatment of childhood impetigo. Participants are randomised to one of the three treatments for 5 days. The primary outcome is clinical improvement assessed through paired photographs analysed by graders blinded to treatment arm. The trial is based in school health clinics in an urban centre in New Zealand. Comparison of antimicrobial resistance patterns pre- and post-treatment is also performed. DISCUSSION: Special note is made of the need to involve the communities most affected by impetigo in the design and implementation of the clinical trial to recruit the children most in need of safe and effective treatments. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) 12616000356460 . Registered on March 10, 2016  Protocol amendment number: 05 EB and AL contributed equally as senior authors.

COVID-19 vaccination in children and adolescents aged 5 years and older undergoing treatment for cancer and non-malignant haematological conditions: Australian and New Zealand Children's Haematology/Oncology Group consensus statement.

INTRODUCTION: The Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19. There remains a paucity of data regarding the immune response to COVID-19 vaccines in immunosuppressed paediatric populations, with data suggestive of reduced immunogenicity of the vaccine in immunocompromised adults. RECOMMENDATIONS: Considering the safety profile of mRNA COVID-19 vaccines and the increased risk of severe COVID-19 in immunocompromised children and adolescents, COVID-19 vaccination is strongly recommended for this at-risk population. We provide a number of recommendations regarding COVID-19 vaccination in this population where immunosuppressive, chemotherapeutic and/or targeted biological agents are used. These include the timing of vaccination in patients undergoing active treatment, management of specific situations where vaccination is contraindicated or recommended under special precautions, and additional vaccination recommendations for severely immunocompromised patients. Finally, we stress the importance of upcoming clinical trials to identify the safest and most efficacious vaccination regimen for this population. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement provides recommendations for COVID-19 vaccination in children and adolescents aged ≥ 5 years with cancer and immunocompromising non-malignant haematological conditions, based on evidence, national and international guidelines and expert opinion. ENDORSED BY: The Australian and New Zealand Children's Haematology/Oncology Group.

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.

High Incidence of Congenital Syphilis in New Zealand: A New Zealand Pediatric Surveillance Unit Study.

BACKGROUND: Syphilis, a disease once in decline, has made a resurgence worldwide. New Zealand has had increasing syphilis rates since enhanced syphilis surveillance was initiated in 2013. This study reports epidemiologic, descriptive and treatment data on management of infants prenatally exposed or vertically infected with syphilis across New Zealand as reported by pediatricians. METHODS: Over a 26-month period from April 2018 to May 2020 (inclusive), pediatricians throughout New Zealand notified potential, probable and confirmed cases of congenital syphilis to the New Zealand Pediatric Surveillance Unit. National reporting numbers were concurrently ascertained to demonstrate reporting accuracy. RESULTS: Thirty-two cases were notified, comprised of 25 infants born to women with positive antenatal syphilis serology (5 whom developed congenital syphilis), and 7 infants diagnosed with congenital syphilis after birth where syphilis was not diagnosed in pregnancy. There were 12 cases of congenital syphilis; an incidence rate of 9.4 cases per 100,000 live births. Nine of the 12 infants had clinical features of congenital syphilis. One-third of maternal infections were early syphilis, and the women who gave birth to infected infants were less likely to have received antenatal care, adequate treatment and follow-up monitoring of treatment for syphilis during pregnancy. CONCLUSIONS: This study quantifies an important burden of disease from congenital syphilis in our population. Case finding and treatment of syphilis in pregnancy are critical to prevent this. Our findings support the urgent need for measures such as repeat maternal syphilis screening in early third trimester; whether by affected region or instituted for all, in the context of rising cases.

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

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.

Surveillance of pediatric parapneumonic effusion/empyema in New Zealand.

AIM: The incidence of childhood empyema has been increasing in some developed countries despite the introduction of pneumococcal vaccination. This study aimed to document the incidence, bacterial pathogens, and morbidity/mortality of parapneumonic effusion/empyema in New Zealand. METHODS: A prospective study of 102 children <15 years of age requiring hospitalization with parapneumonic effusion/empyema between May 1, 2014 and May 31, 2016 notified via the New Zealand Paediatric Surveillance Unit. Parapneumonic effusion/empyema was defined as pneumonia and pleural effusion persisting ≥7 days, and/or any pneumonia, and pleural effusion necessitating drainage. Notifying pediatricians completed standardized questionnaires. RESULTS: Annual pediatric parapneumonic effusion/empyema incidence was 5.6/100,000 (95% confidence interval [CI]: 4.7-6.9). Most children (80%) required surgical intervention and 31% required intensive care. A causative organism was identified in 71/102 (70%) cases. Although Staphylococcus aureus (25%) and Streptococcus pneumoniae (25%) infection rates were equal, prolonged hospitalization and intensive care admission were more common in children with S. aureus PPE/E. Maori and Pasifika children were over-represented at 2.2 and 3.5 times, their representation in the New Zealand pediatric population. Pneumococcal vaccination was incomplete, with only 61% fully immunized and 30% unimmunized. Haemophilus influenzae type b vaccine uptake was near complete at 89/94 (95%), with influenza immunization only 3/78 (4%). CONCLUSIONS: New Zealand has a high incidence of pediatric complicated parapneumonic effusion/empyema with significant morbidity. S. aureus was a significant cause of severe empyema in New Zealand, particularly for Maori and Pasifika children. Improvements in vaccine coverage are needed along with strategies to reduce S. aureus disease morbidity.