Keith Grimwood

Description:Limited information exists for when potentially pathogenic bacteria first colonize the airways. Weekly nasal swabs from an Australian birth cohort (N = 158) revealed the median (interquartile range) ages when Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were first detected as 3.0 (0.8-7.1), 5.5 (2.8-8.7) and 11.2 (6.4-18.0) months, respectively. RNA viruses were associated with first H. influenzae detections.

Description:Background: Acute lower respiratory infections (ALRIs) remain the leading causes of repeated hospitalisations among young disadvantaged Australian and New Zealand First Nations and Timorese children. Severe (hospitalised) and recurrent ALRIs in the first years of life are associated with future chronic lung diseases (eg, bronchiectasis) and impaired lung function. Despite the high burden and long-term consequences of severe ALRIs, clinical, evidence-based and feasible interventions (other than vaccine programmes) that reduce ALRI hospitalisations in children are limited. This randomised controlled trial (RCT) will address this unmet need by trialling a commonly prescribed macrolide antibiotic (azithromycin) for 6-12 months. Long-term azithromycin was chosen as it reduces ALRI rates by 50% in Australian and New Zealand First Nations children with chronic suppurative lung disease or bronchiectasis. The aim of this multicentre, international, double-blind, placebo-containing RCT is to determine whether 6-12 months of weekly azithromycin administered to Australian and New Zealand First Nations and Timorese children after their hospitalisation with an ALRI reduces subsequent ALRIs compared with placebo. Our primary hypothesis is that children receiving long-term azithromycin will have fewer medically attended ALRIs over the intervention period than those receiving placebo. Methods: We will recruit 160 Australian and New Zealand First Nations and Timorese children aged <2 years to a parallel, superiority RCT across four hospitals from three countries (Australia, New Zealand and Timor-Leste). The primary outcome is the rate of medically attended ALRIs during the intervention period. The secondary outcomes are the rates and proportions of children with ALRI-related hospitalisation, chronic symptoms/signs suggestive of underlying chronic suppurative lung disease or bronchiectasis, serious adverse events, and antimicrobial resistance in the upper airways, and cost-effectiveness analyses. Background: The Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Health Research (Australia), Health and Disability Ethics Committee (New Zealand) and the Institute National of Health-Research Technical Committee (Timor-Leste) approved this study. The study outcomes will be disseminated to academic and medical communities via international peer-reviewed journals and conference presentations, and findings reported to health departments and consumer-based health organisations. Background: Australia New Zealand Clinical Trial Registry ACTRN12619000456156.

Description:Despite significant global reductions in cases of pneumonia during the last 3 decades, pneumonia remains the leading cause of post-neonatal mortality in children aged <5 years. Beyond the immediate disease burden it imposes, pneumonia contributes to long-term morbidity, including lung function deficits and bronchiectasis. Viruses are the most common cause of childhood pneumonia, but bacteria also play a crucial role. However, the optimal duration of antibiotic therapy for bacterial pneumonia remains uncertain in both low- and middle-income countries and in high-income countries. Knowing the optimal duration of antibiotic therapy for pneumonia is crucial for effective antimicrobial stewardship. This is especially important as concerns mount over rising antibiotic resistance in respiratory bacterial pathogens, which increases the risk of treatment failure. Numerous studies have focused on the duration of oral antibiotics and short-term outcomes, such as clinical cure and mortality. In contrast, only one study has examined both intravenous and oral antibiotics and their impact on long-term respiratory outcomes following pneumonia hospitalisation. However, study findings may be influenced by their inclusion criteria when children unlikely to have bacterial pneumonia are included. Efforts to differentiate between bacterial and non-bacterial pneumonia continue, but a validated, accurate, and simple point-of-care diagnostic test remains elusive. Without certainty that a child has bacterial pneumonia, determining the optimal duration of antibiotic treatment is challenging. This review examines the evidence for the recommended duration of antibiotics for treating uncomplicated pneumonia in otherwise healthy children and concludes that the question of duration is unresolved.

Description:Streptococcus pyogenes (Group A Streptococcus, GAS) is a human-restricted pathogen that causes a wide range of diseases from pharyngitis and scarlet fever to more severe, invasive infections such as necrotising fasciitis and streptococcal toxic shock syndrome. There has been a global increase in both scarlet fever and invasive infections during the COVID-19 post-pandemic period. The aim of this study was the molecular characterisation of 17 invasive and non-invasive clinical non-emm1 GAS isolates from an Australian tertiary hospital collected between 2021 and 2022. Whole genome sequencing revealed a total of nine different GAS emm types with the most prevalent being emm22, emm12 and emm3 (each 3/17, 18%). Most isolates (14/17, 82%) carried at least one superantigen gene associated with contemporary scarlet fever outbreaks, and the carriage of these toxin genes was non-emm type specific. Several mutations within key regulatory genes were identified across the different GAS isolates, which may be linked to an increased expression of several virulence factors. This study from a single Australian centre provides a snapshot of non-emm1 GAS clinical isolates that are multiclonal and linked with distinct epidemiological markers commonly observed in high-income settings. These findings highlight the need for continual surveillance to monitor genetic markers that may drive future outbreaks.

Description:Objective: As children hospitalised with community-acquired pneumonia (CAP) are at risk of persistent chest radiograph (CXR) abnormalities and respiratory sequelae, we investigated factors associated with incomplete CXR resolution at 4 weeks and 12 months post-discharge in children from populations at high-risk of chronic lung disease. Methods: Secondary analysis-multicentre, placebo-controlled, randomised controlled trial. Methods: 324 children aged 3 months to ≤5 years hospitalised with radiographic-confirmed CAP were enrolled from seven hospitals in Australia, New Zealand and Malaysia. After 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, they were randomised to extended (13-14 days) or standard (5-6 days) courses of antibiotics. Methods: CXRs were performed at admission, 4 weeks, and 12 months post-discharge and reviewed in a blinded manner. Methods: Radiographic changes of pneumonia at 4 weeks and 12 months post-discharge compared with admission CXRs. Results: Among children with interpretable CXRs, incomplete resolution was seen in 42/253 (17%) at 4 weeks, and 29/212 (14%) at 12 months. Characteristics at admission associated with incomplete CXR resolution at 4 weeks were previous pneumonia hospitalisation (adjusted odds ratio [ORadj])=6.46, 95% confidence interval [CI] 2.21 to 18.85) and increasing age (ORadj=0.60 per-year, 95% CI 0.38 to 0.94). Continuing respiratory symptoms/signs at 4 weeks post-discharge was also associated with incomplete resolution (OR=5.63, 95% CI 2.38 to 13.32). At 12 months, previous pneumonia hospitalisation was associated with persistent incomplete CXR resolution (OR=4.03, 95 % CI 1.25 to 13.02). Conclusions: In high-risk settings, younger age, those with previous pneumonia hospitalisation, or ongoing respiratory symptoms/signs 4 weeks post-discharge from hospitalised CAP may be associated with incomplete CXR resolution. Consequently, follow-up imaging and monitoring may be warranted in these children.