Age at first exposure to antibiotics and neurodevelopmental outcomes in childhood.

RATIONALE: Viral illnesses in children are common and are frequently treated with antibiotic medication. Antibiotics reduce the diversity and composition of the gut microbiota, leading to poor developmental outcomes. OBJECTIVES: To investigate the relationship between age at first exposure to antibiotics and cognitive and behavioural development at 4.5 years while controlling for multiple confounders, including otitis media. METHODS: Study participants were 5589 children enrolled in the broadly generalisable Growing Up in New Zealand cohort study, with antibiotic exposure data, maternal antenatal information, and age 4.5-year behaviour and cognitive outcome data. Children were categorised as first exposed to antibiotics according to the following mutually exclusive ages: 0-2 months; 3-5 months; 6-8 months; 9-11 months; 12-54 months or not exposed by 54 months. Developmental outcome measures included the Strengths and Difficulties Questionnaire, Luria hand clap task, and the Peabody Picture Vocabulary Test-III. RESULTS: In univariate analysis, there was an evident dose-response relationship where earlier exposure to antibiotics in the first year of life was associated with behavioural difficulties, lower executive function scores, and lower receptive language ability. After adjusting for confounders, pairwise comparisons showed that first antibiotic exposure between birth and 3 months or between 6 and 9 months was associated with lower receptive vocabulary. Antibiotic exposure at any age prior to 12 months was associated with increases in behavioural difficulties scores at 4.5 years. CONCLUSIONS: Following adjustment for socioeconomic factors and otitis media, there is evidence that antibiotic exposure during potentially sensitive windows of development is associated with receptive language and behaviour later in childhood.

Prenatal antibiotic exposure in pregnancy and early childhood socioemotional development.

Background: Antibiotic exposure in pregnancy is associated with reduced microbiome diversity in the infant gut. Given that recent research has shown that early microbiome health can impact child socioemotional development, we examined the relationship between prenatal antibiotic exposure in pregnancy and childhood socioemotional developmental outcomes using a large, nationally representative longitudinal dataset. Methods: A sample of 4800 diverse families were assessed from the population cohort of the Growing Up in New Zealand Study (GUiNZ), which prospectively follows children starting in the last trimester of pregnancy into early childhood. Socioemotional development was measured using a composite score derived from seven commonly used socioemotional tasks administered between 9 months and 4.5 years of child age, addressing emotional expression understanding, regulation of emotions and behavior, and social problem solving and relationship skills. A national comprehensive pharmaceutical database was used to determine children's prenatal antibiotic exposure. Multivariate linear regressions models were used to examine the effects of the timing (trimester) and dosage (number of courses) of prenatal antibiotic exposure on socioemotional development, with and without statistically adjusting for confounding factors addressing maternal health, socioeconomic status, maternal age, and child sex. Results: In unadjusted analyses, antibiotic exposure was inversely associated with child socioemotional development. However, after statistically adjusting for important confounds, socioemotional development was not associated with prenatal antibiotic exposure at any dosage or trimester of pregnancy (all ß ≤ -0.02). Conclusion: Prenatal antibiotic exposure does not appear to impact early childhood socioemotional development. Maternal health and sociodemographic factors are confounded with antibiotic exposure and socioemotional development, a fact that should be considered in future research examining the effects of prenatal antibiotic exposure on child health. These findings may be reassuring to families who are concerned about the long-term effects of antibiotics in pregnancy on child health outcomes.

An observational study of high- and low-abundance anti-retroviral resistance mutations among treatment-naïve people living with HIV in New Zealand between 2012 and 2017.

HIV resistance genotyping detects drug resistance mutations (DRMs) in ≥20% of circulating virus within an infected individual (high-abundance DRMs). Deep sequencing also detects DRMs in smaller viral subpopulations (low-abundance DRMs), although these are of uncertain importance. In this retrospective analysis of 292 treatment-naïve patients, high-abundance DRMs were present in 30/292 (10%) patients, but only one (0.3%) had resistance to first-line anti-retrovirals. Low-abundance DRMs were present in 36/247 (15%) patients, but none who received anti-retrovirals for which these were present had virologic failure. These findings demonstrate that starting first-line therapy in treatment-naïve patients need not be delayed while awaiting resistance testing.

Association of the Dundee severity classification with mortality, length of stay and readmission in adult inpatients with cellulitis.

Background: The Dundee classification is a simple severity assessment tool that could optimize treatment decisions and clinical outcomes in adult patients with cellulitis; however, it has not been validated in a large cohort. Objectives: To determine whether the Dundee classification reliably identified those patients with cellulitis who had a higher mortality, a longer length of hospital stay or an increased risk of readmission. Methods: We performed a retrospective study of all adults with a primary discharge diagnosis of cellulitis admitted to Auckland City Hospital from August 2013 to June 2015. We classified patients by severity using the Dundee scoring system. Results: The 30 day all-cause mortality in adult patients with a discharge diagnosis of cellulitis was 2% (29/1462) overall, and was 1% (10/806), 2% (6/271), 3% (10/353) and 9% (3/32) in Classes 1, 2, 3 and 4 of the Dundee classification, respectively (P = 0.01). Mortality was strongly associated with age >65 years (OR 9.37, 95% CI 3.00-41.23) and with heart failure (OR 6.16, 95% CI 2.73-14.23). There were significant associations between the Dundee classification and the incidence of bacteraemia, the length of hospital stay and the rate of readmission to hospital. Conclusions: The Dundee classification is a simple, reliable tool that can be easily applied in clinical settings to predict risk of mortality in order to determine which patients can be managed in the community with oral or intravenous therapy, and which require inpatient care.

How differing methods of ascribing ethnicity and socio-economic status affect risk estimates for hospitalisation with infectious disease.

Significant ethnic and socio-economic disparities exist in infectious diseases (IDs) rates in New Zealand, so accurate measures of these characteristics are required. This study compared methods of ascribing ethnicity and socio-economic status. Children in the Growing Up in New Zealand longitudinal cohort were ascribed to self-prioritised, total response and single-combined ethnic groups. Socio-economic status was measured using household income, and both census-derived and survey-derived deprivation indices. Rates of ID hospitalisation were compared using linked administrative data. Self-prioritised ethnicity was simplest to use. Total response accounted for mixed ethnicity and allowed overlap between groups. Single-combined ethnicity required aggregation of small groups to maintain power but offered greater detail. Regardless of the method used, Maori and Pacific children, and children in the most socio-economically deprived households had a greater risk of ID hospitalisation. Risk differences between self-prioritised and total response methods were not significant for Maori and Pacific children but single-combined ethnicity revealed a diversity of risk within these groups. Household income was affected by non-random missing data. The census-derived deprivation index offered a high level of completeness with some risk of multicollinearity and concerns regarding the ecological fallacy. The survey-derived index required extra questions but was acceptable to participants and provided individualised data. Based on these results, the use of single-combined ethnicity and an individualised survey-derived index of deprivation are recommended where sample size and data structure allow it.

Staphylococcus aureus colonisation and its relationship with skin and soft tissue infection in New Zealand children.

New Zealand children suffer from high rates of skin and soft tissue infection (SSTI). Staphylococcus aureus colonisation is known to increase the risk of nosocomial infection. We aimed to determine whether S. aureus colonisation also increased the risk of community-onset SSTI. This study, performed within the Growing Up in New Zealand cohort, used interview and administrative data, and bacterial culture results from the nose, throat, and skin swabs collected at 4½ years of age. Multivariable log-binomial regression was used to derive adjusted risk ratios. S. aureus was isolated from 2225/5126 (43.4%) children. SSTI affected 1509/5126 (29.4%) children before age five. S. aureus colonisation at any site was associated with SSTI (aRR = 1.09, 95%CI 1.01-1.19), particularly in the year prior to swab collection (aRR = 1.18, 95%CI 1.02-1.37). The strongest association was between skin colonisation and SSTI within the year prior to swab collection (aRR = 1.47, 95%CI 1.14-1.84). Socioeconomic and ethnic variables remained independent determinants of SSTI. S. aureus colonisation was associated with an increased risk of community-onset SSTI. Socioeconomic and ethnic factors and eczema had independent effects on SSTI risk. Interventions which reduce the prevalence of S. aureus colonisation may be expected to reduce the incidence of community-onset SSTI.

Antibiotic consumption by New Zealand children: exposure is near universal by the age of 5 years.

Background: Increasing concerns about antibiotic resistance and microbiome disruption have stimulated interest in describing antibiotic consumption in young children. Young children are an age group for whom antibiotics are frequently prescribed. Objectives: To describe community antibiotic dispensing during the first 5 years of life in a large, socioeconomically and ethnically diverse cohort of children, and to determine how antibiotic dispensing varied between population subgroups. Methods: This study was performed within the Growing Up in New Zealand longitudinal cohort study ( www.growingup.co.nz ) with linkage to national administrative antibiotic dispensing data. Descriptive statistics and univariate and multivariable associations were determined. Results: The 5581 cohort children received 53 052 antibiotic courses, of which 54% were amoxicillin. By age 5 years, 97% of children had received one or more antibiotic courses, and each child had received a median of eight antibiotic courses (IQR 4-13). The mean incidence of antibiotic dispensing was 1.9 courses/child/year. Multivariable negative binomial regression showed that Maori and Pacific children received more antibiotic courses than European children, as did children in the most-deprived compared with the least-deprived areas. A distinct seasonal pattern was noted. Conclusions: This study provided a detailed description of antibiotic dispensing within a large and diverse child cohort. Antibiotic exposure was near universal by age 5 years. The predominance of amoxicillin use and the seasonal pattern suggest much antibiotic use may have been for self-limiting respiratory infections. There is a need for safe and effective interventions to improve antibiotic prescribing practices for New Zealand children.

Ethnic disparities in infectious disease hospitalisations in the first year of life in New Zealand.

AIM: Infectious disease (ID) hospitalisation rates are increasing in New Zealand (NZ), especially in pre-school children, and Maori and Pacific people. We aimed to identify risk factors for ID hospitalisation in infancy within a birth cohort of NZ children, and to identify differences in risk factors between ethnic groups. METHODS: We investigated an established cohort of 6846 NZ children, born in 2009-2010, with linkage to a national data set of hospitalisations. We used multivariable logistic regression to obtain odds ratios (OR) for factors associated with ID hospitalisation in the first year of life, firstly for all children, and then separately for Maori or Pacific children. RESULTS: In the whole cohort, factors associated with ID hospitalisation were Maori (OR: 1.49, 95% CI: 1.17-1.89) or Pacific (2.51; 2.00-3.15) versus European maternal ethnicity, male gender (1.32; 1.13-1.55), low birthweight (1.94, 1.39-2.66), exclusive breastfeeding for <4 months (1.22, 1.04-1.43), maternal experience of health-care racism (1.60, 1.19-2.12), household deprivation (most vs. least deprived quintile of households (1.50, 1.12-2.02)), day-care attendance (1.43, 1.12-1.81) and maternal smoking (1.55, 1.26-1.91). Factors associated with ID hospitalisation for Maori infants were high household deprivation (2.16, 1.06-5.02) and maternal smoking (1.48, 1.02-2.14); and for Pacific infants were delayed immunisation (1.72, 1.23-2.38), maternal experience of health-care racism (2.20, 1.29-3.70) and maternal smoking (1.59, 1.10-2.29). CONCLUSIONS: Maori and Pacific children in NZ experience a high burden of ID hospitalisation. Some risk factors, for example maternal smoking, are shared, while others are ethnic-specific. Interventions aimed at preventing ID hospitalisations should address both shared and ethnic-specific factors.

Epidemiology and diagnostic testing for meningitis in adults as the meningococcal epidemic declined at Middlemore Hospital.

AIMS: To describe changes in epidemiology and diagnostic techniques for adult meningitis at Middlemore Hospital following the decline of the meningococcal epidemic. METHODS: Retrospective audit of cases of meningitis from 2000 to 2009. RESULTS: Microbiologically-confirmed diagnosis (MCD) was established in 296 of 743 episodes (40%), most commonly enterovirus (123/296, 42%), Neisseria meningitidis (43/296, 15%) and Streptococcus pneumoniae (34/296, 11%). N. meningitidis meningitis declined and herpes viruses increased over time, without significant change in overall meningitis case numbers. By 2009, S. pneumoniae constituted a greater proportion of cases than N. meningitidis. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and pneumococcal immunochromatographic testing (PICT) increased over time as did the proportion of cases with MCD. CSF Gram stain was positive in 45% (53/118) and CSF culture made MCD in 37% (44/118) of confirmed bacterial episodes (CBE). PCR provided MCD in 59% (26/54) of CBE and 99% (168/170) of viral episodes. CSF PICT was tested in 76% (26/34) of S. pneumoniae meningitis (positive in 92% (24/26). CONCLUSIONS: As the epidemic waned, local incidence of meningococcal meningitis decreased without significant decreasing meningitis overall. Empiric treatment for meningitis in New Zealand adults should routinely include pneumococcal cover. Increased PCR testing increases MCD in meningitis.

Colovesical fistula presenting as Listeria monocytogenes bacteraemia.

We present a case of colovesical fistula presenting with a clinical syndrome of urosepsis subsequently demonstrated to be due to Listeria monocytogenes bacteraemia. The patient had a history of previous rectal cancer with a low anterior resection and a covering ileostomy that had been reversed 6 months prior to this presentation. L. monocytogenes was also isolated among mixed enteric organisms on urine culture. There were no symptoms or signs of acute gastrointestinal listeriosis or meningoencephalitis. This unusual scenario prompted concern regarding the possibility of communication between bowel and bladder, which was subsequently confirmed with CT and a contrast enema. The patient recovered well with intravenous amoxicillin and to date has declined surgical management of his colovesical fistula. This case illustrates the importance of considering bowel pathology when enteric organisms such as Listeria are isolated from unusual sites.

An observational study of antiretroviral drug resistance in treatment-naïve patients with HIV infection in New Zealand, from 2007 to 2011.

UNLABELLED: Background Genotypic testing for antiretroviral drug resistance is recommended for all patients newly diagnosed with HIV infection. This study sought to quantify the prevalence of antiretroviral drug resistance in treatment-naïve patients with HIV infection in New Zealand. METHODS: All genotypic antiretroviral drug resistance testing in New Zealand is performed at LabPLUS, Auckland City Hospital. The clinicians who requested antiretroviral drug resistance testing during the period 2007-2011 were contacted and were asked to identify which patients with HIV infection were treatment-naïve at the time of testing. Results of the antiretroviral drug resistance tests for treatment-naïve patients with HIV infection were reviewed and the prevalence of resistance determined. RESULTS: Two hundred and 10 treatment-naïve patients with HIV infection who had antiretroviral drug resistance testing performed were included; 20 (10%) were found to have a significant resistance mutation. Nine patients had virus resistant to one or more nucleoside reverse transcriptase inhibitors, 13 to non-nucleoside reverse transcriptase inhibitors and one to protease inhibitors. CONCLUSIONS: The prevalence of antiretroviral drug resistance in treatment-naïve patients with HIV infection identified in this study is comparable to rates identified in studies from North America, the UK and Europe. This prevalence demonstrates the need for antiretroviral drug resistance testing for all treatment-naïve patients with HIV infection in New Zealand.

Electronic health records for biological sample collection: feasibility study of statin-induced myopathy using the Clinical Practice Research Datalink.

AIMS: Electronic healthcare records (EHRs) are increasingly used to store clinical information. A secondary benefit of EHRs is their use, in an anonymized form, for observational research. The Clinical Practice Research Datalink (CPRD) contains EHRs from primary care in the UK and, despite 1083 peer-reviewed research publications, has never been used to obtain pharmacogenetic samples. Using a statin-induced myopathy paradigm, we evaluated using the CPRD to obtain patient samples for a pharmacogenetic study targeting 250 cases and 500 controls from UK general practitioner (GP) practices. METHODS: The CPRD identified potential patients fitting specific case-definition criteria (active rhabdomyolysis or creatine phosphokinase > four times the upper limit of normal), and corresponding GP practices were asked to invite patient participation. Consenting patients were requested to provide either saliva or blood samples and to complete an ethnicity questionnaire. Control subjects were recruited from the same GP practice (saliva) or a small number of practices (blood). Samples were forwarded for DNA extraction. RESULTS: Thirty-six months of recruitment yielded DNA samples from 149 statin-induced myopathy cases and 587 tolerant controls. Data show that contacting patients through their GP is a reliable method for obtaining samples without compromising anonymity. Saliva collection directly from patients was considerably less effective than blood sampling. After 10 months of recruitment, saliva sampling was suspended in favour of blood sampling. CONCLUSIONS: We demonstrate the potential of EHRs for identifying accurately phenotyped cases and controls for pharmacogenetic studies. Recruitment was successful only because of the willingness of GP practices to participate and the existence of strong doctor-patient relationships. The present study provides a model that can be implemented in future genetic analyses using EHRs.

An uncommon complication of infective bacterial endocarditis.

Coronary artery septic embolisation resulting in cardioembolic myocardial infarction (MI) is a rare complication of bacterial infective endocarditis (IE), representing <1% of complications related to IE. Diagnosis requires a combination of high clinical suspicion, coronary angiography, echocardiography and cultures of peripheral blood and/or embolic material. The associated mortality rate remains high despite early diagnosis. Optimal interventional therapy is unknown with published international experience over the past two decades limited to very small case series and individual case reports. We present a case of ST elevation MI resulting from coronary artery septic embolisation with an accompanying comprehensive review of the literature.

The health status of asylum seekers screened by Auckland Public Health in 1999 and 2000.

AIM: Approximately 1500 to 1800 applications for refugee status are made to the New Zealand Immigration Service each year. Approximately one third of these asylum seekers receive health screening from Auckland Public Health. We report here key findings from this screening programme for the period 1999 to 2000. METHODS: The files of patients attending the Auckland Public Health Protection Asylum Seekers Screening Clinic at Green Lane Hospital were reviewed. Data on demographics, medical examination, diagnostic testing and referrals were analysed. RESULTS: Nine hundred people, mainly from Middle Eastern countries, received screening. Important findings were: symptoms of psychological illness (38.4%); Mantoux skin test positivity ( 36.4%); active tuberculosis (0.6%); TB infection requiring chemoprophylaxis (18%) or chest X-ray monitoring (15%); gut parasite infection; carrier state for alpha and beta thalassaemia and the heterozygous states for HbS and HbE; incomplete immunisation; and the need for referral to a secondary care service (32.6%). CONCLUSIONS: Immigrant communities in New Zealand have special healthcare needs, as well as experiencing language barriers, cultural differences and economic difficulties. Healthcare providers should be alert to these needs. Appropriate resources are required to address these issues in a timely fashion.