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Staphylococcus aureus is a common disease-causing bacterium that has developed resistances to a wide variety of antibiotics. This increasing antibiotic resistance has made management of these infections difficult. A better understanding of the general differences among clinical S. aureus strains beyond the well characterized resistance mechanisms may help in identifying new anti-microbial targets. This study aimed to identify and compare the general differences in protein profiles among clinical strains of S. aureus sensitive and resistant to methicillin. The proteomic profiles of five methicillin sensitive (MSSA) and five methicillin resistant (MRSA) S. aureus strains were analyzed by ultra-performance liquid chromatography-mass spectrometry. Protein identification was done using Progenesis QI for Proteomics and the UniProt S. aureus database. Proteins that play roles in virulence, metabolism, and protein synthesis were found to be present at different abundances between MSSA and MRSA (Data available via ProteomeXchange with identifier PXD021629). This study shows differences in protein profiles between antibiotic sensitive and antibiotic resistant clinical strains of S. aureus that may affect the resistance mechanism. Further research on these differences may identify new drug targets against methicillin resistant S. aureus strains.

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BACKGROUND: We aimed to describe the burden, severity, and underlying factors of associated impairments among children with cerebral palsy (CP) in rural Bangladesh. METHODS: This study reports findings from the Bangladesh Cerebral Palsy Register-the first population-based surveillance of children with CP in any LMIC, where children with confirmed CP aged < 18 years are registered by a multidisciplinary team following a standard protocol. Associated impairments were documented based on clinical assessment, available medical records, and a detailed clinical history provided by the primary caregivers. Descriptive analysis, as well as unadjusted and adjusted logistic regression, were completed using R. RESULTS: Between January 2015 and February 2022, 3820 children with CP were registered (mean (SD) age at assessment: 7.6 (5.0) y; 39% female). Overall, 81% of children had ≥1 associated impairment; hearing: 18%, speech: 74%, intellectual: 40%, visual: 14%, epilepsy: 33%. The presence of a history of CP acquired post-neonatally and having a gross motor function classification system levels III-V significantly increased the odds of different types of associated impairments in these children. Most of the children had never received any rehabilitation services and were not enrolled in any mainstream or special education system. CONCLUSIONS: The burden of associated impairments was high among children with CP, with comparatively low receipt of rehabilitation and educational services in rural Bangladesh. Comprehensive intervention could improve their functional outcome, participation, and quality of life.

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Antimicrobial resistance is a growing public health crisis, propelled by inappropriate antibiotic prescription, in particular the over-prescription of antibiotics, prolonged duration of antibiotic therapy and the overuse of broad-spectrum antibiotics. The paediatric population, in particular, those presenting to emergency settings with respiratory symptoms, have been associated with a high rate of antibiotic prescription rates. Further research has now shown that many of these antibiotic prescriptions may have been avoided, with more targeted diagnostic methods to identify underlying aetiologies. The purpose of this systematic review was to assess the impact of rapid diagnostic testing, for paediatric respiratory presentations in the emergency setting, on antibiotic prescription rates. To review the relevant history, a comprehensive search of Medline, EMBASE and Cochrane Database of Systematic Reviews was performed. Eighteen studies were included in the review, and these studies assessed a variety of rapid diagnostic testing tools and outcome measures. Overall, rapid diagnostic testing was found to be an effective method of diagnostic antibiotic stewardship with great promise in improving antibiotic prescribing behaviours. Further studies are required to evaluate the use of rapid diagnostic testing with other methods of antibiotics stewardship, including clinical decisions aids and to increase the specificity of interventions following diagnosis to further reduce rates of antibiotic prescription.

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BACKGROUND: Staphylococcus aureus is a common cause of infectious diseases in humans. It has become resistant to many antibacterial agents making management of infections difficult. A better understanding of differences among S. aureus strains that are sensitive and resistant to antibiotics may offer insights into the resistant phenotype and identify new antimicrobial targets. This study aimed at comparing general differences in lipid profiles among clinical strains of S. aureus sensitive and resistant to antibiotics. The cell wall thickness and cell surface charge were also compared. METHODS: Five methicillin sensitive (MSSA) and five methicillin resistant (MRSA) S. aureus strains were compared both individually and as MSSA and MRSA groups in the absence of antibiotics. Lipids were compared by ultra-performance liquid chromatography-mass spectrometry, cell wall thickness was compared by scanning transmission electron microscopy and whole-cell surface charge was compared using a cytochrome c binding assay. RESULTS: Twenty-two lipid species were identified in all ten strains of S. aureus. The abundance of three lipid species (two lysyl-phosphatidylglycerol and one diglycosyldiacylglycerol) were found to be different between MSSA and MRSA. Differences in cell wall thickness were identified between strains but not between MSSA and MRSA. No difference in whole-cell surface charge was observed between MSSA and MRSA. CONCLUSION: This study shows differences in membrane lipids between antibiotic sensitive and antibiotic resistant clinical strains of S aureus that may affect resistance mechanisms related to cell membrane structure and fluidity. Further research on these differences may identify new drug targets against resistant strains.

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Antimicrobial resistance occurs due to the propensity of microbial pathogens to develop resistance to antibiotics over time. Antimicrobial stewardship programs (ASPs) have been developed in response to this growing crisis, to limit unnecessary antibiotic prescription through initiatives such as education-based seminars, prescribing guidelines, and rapid respiratory pathogen (RRP) testing. Paediatric patients who present to the emergency setting with respiratory symptoms are a particularly high-risk population susceptible to inappropriate antibiotic prescribing behaviours and are therefore an ideal cohort for focused ASPs. The purpose of this systematic review was to assess the efficacy and safety of ASPs in this clinical context. A systematic search of PubMed, Medline, EMBASE and the Cochrane Database of Systematic Reviews was conducted to review the current evidence. Thirteen studies were included in the review and these studies assessed a range of stewardship interventions and outcome measures. Overall, ASPs reduced the rates of antibiotic prescription, increased the prescription of narrow-spectrum antibiotics, and shortened the duration of antibiotic therapy. Multimodal interventions that were education-based and those that used RRP testing were found to be the most effective. Whilst we found strong evidence that ASPs are effective in reducing antibiotic prescribing, further studies are required to assess whether they translate to equivalent clinical outcomes.

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Antibiotic-resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus are a threat to human health, and effective treatment options against them are needed. This study aimed to determine whether the insecticide permethrin was capable of inhibiting the growth of S. aureus or if some other component of a permethrin cream was responsible for a decrease in scabies associated bacterial infection previously observed. Ten S. aureus strains were grown in the presence of permethrin and formaldehyde both alone and in combination with percent inhibition determined by viable counts. Also, a time-kill assay was conducted on S. aureus exposed to the same conditions. Finally, the morphology of S. aureus grown in the presence of permethrin was examined by scanning electron microscopy. Bacterial inhibition by permethrin ranged from 0% to 41% whereas inhibition by formaldehyde was 100%. The time-kill curves of permethrin exposed cells were very similar to the positive growth control while the formaldehyde and combination exposure showed complete inhibition even at the 0-hr time point. The scanning electron micrographs of permethrin grown S. aureus showed healthy cocci cells with no sign of cell damage. Our results show that permethrin is not capable of inhibiting the growth of bacteria enough for it to be termed bactericidal. Formaldehyde is a known antiseptic and therefore was responsible for the antibacterial effect observed after the use of permethrin cream.

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Introduction: Antibiotic-resistant strains of bacteria are an increasing problem in hospitals and in the community. This has resulted in bacterial infections such as impetigo becoming difficult to treat. Alternative treatment options are needed. Areas covered: In this paper, a past study that assessed the health burden of scabies in North Queensland is described and from it, the potential for formaldehyde as an alternative antimicrobial treatment is discussed. In doing so, antibiotic resistance, impetigo, permethrin, and formaldehyde are introduced and the current understanding and limitations of the effects of formaldehyde on humans are outlined. The limited cases of formaldehyde resistance in bacteria are also discussed. Expert opinion: Formaldehyde is currently used as a preservative in cosmetics and medicinal creams due to its antibacterial activity. It, therefore, has the potential to be used as an alternative antibacterial treatment for infections with antibiotic-resistant bacteria. The harmful side effects of airborne formaldehyde and exposure in allergic individuals have been extensively studied. Significantly less research has been conducted on formaldehyde skin contact in healthy individuals. If formaldehyde is safe for topical use in humans, it has the potential to assist with combating antibiotic resistance.

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BACKGROUND: Bloodstream infections (BSIs) cause significant morbidity and mortality of children worldwide. The aim of this study was to investigate BSI in children and determine the identity of causative organism and their susceptibility patterns in a metropolitan public hospital in Australia. METHODS: We retrospectively reviewed children aged 0-16 years admitted to a public hospital from January 1, 2010 to August 31, 2014 inclusive, and whose blood cultures revealed bacteraemia. Data were collected regarding patient demographics, species of bacteria isolated, antimicrobial susceptibility of these isolates, and clinical outcomes. RESULTS: Out of 96 patients with BSI, 55 (57.3%) were males. The median age was 3.35 years (IQR 0.44-7.46), and there were 2 mortalities. Common sites of infection were the respiratory tract (16.6%, n = 16), bone and joints (15.6%, n = 15) and the urinary tract (11.5%, n = 11). The most frequent isolates were Staphylococcus aureus (27.0%), Escherichia coli (14.0%) and Streptococcus pneumoniae (12.0%). Whilst most bacterial isolates displayed susceptibility (> 90%) to common antimicrobial agents, only 57.1% (8/14) of Escherichia coli isolates were susceptible to ampicillin and 58.3% (7/12) were susceptible to co-trimoxazole. CONCLUSIONS: Gram-positive bacteria accounted for the majority of pediatric BSIs, of which invasive pneumococcal disease remains a noteworthy cause. The majority of isolates, except Escherichia coli, were susceptible to commonly used antimicrobials. This study confirms the knowledge of high rates of resistance of Escherichia coli to ampicillin. Therefore, empirical treatment should still include gentamicin. Monitoring of resistance patterns is warranted to ensure that antibiotic therapy remains appropriate.

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OBJECTIVE: Although the number of national measles cases has greatly decreased since 1980s, there has been resurgence in disease incidence in recent years. While parental knowledge and attitudes toward both disease and vaccinations are known to influence vaccine uptake, the contribution of these factors toward vaccination rates in NSW populations has not been studied. The aim of this study was to investigate the knowledge and opinions on measles and MMR vaccine in NSW Central and North Coast regions. METHODS: Parents (n=201) of children <12 years were surveyed with a purpose design survey at public beaches at the Central Coast and community markets at the North Coast. RESULTS: Eight per cent of respondents reported not immunising their child with MMR vaccine. Most respondents recognised that measles is a highly contagious disease. Non-immunisers were found to be older, had a lower perceived severity of measles, were less likely to agree with the efficacy and safety of the vaccine, and were more likely to have encountered someone who had suffered side-effects of the vaccine. CONCLUSIONS: There is considerable concern over safety of MMR vaccine among non-immunisers. Implications for public health: Improving confidence in MMR vaccine should be a target of future public health interventions.

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BACKGROUND: Infant feeding practices are known to influence the child's long-term health. Studies have associated obesity and other diseases with reduced breastfeeding and early introduction of high calorie beverages (HCBs). The rising prevalence of obesity is already a problem in most developed countries, especially Australia, but cultural differences are influential. Our aim is to examine and compare infant feeding practices and educational levels of respondents through questionnaires in three culturally different sites: Campbelltown (South Western Sydney), Australia, Singapore and Ho Chi Minh City, Vietnam (HCMC). METHODS: Consenting parents and carers (aged ≥18 years old) of at least one child (≤6 years old) were recruited from paediatric clinics in Campbelltown, Singapore and HCMC. Participants completed an infant feeding practices questionnaire regarding breastfeeding, beverage and solid initiation in addition to the parent's ethnicity, age, and educational level. Data was analysed quantitatively using SPSS. RESULTS: Two hundred eighty-three participants were recruited across the three sites, HCMC (n = 84), Campbelltown (n = 108), and Singapore (n = 91). 237 (82.6%) children were breastfed but in all only 100 (60.2%) were exclusively breastfed for five months or more. There was a statistical difference in rates of breast feeding between each region. HCMC (n = 18, 21.4%) had the lowest, followed by Campbelltown (n = 35, 32.4%), and then Singapore (n = 47, 51.7%). There was also a difference in rates of introduction of HCBs by 3 years of age, with those in HCMC (n = 71, 84.5%) were higher than Campbelltown (n = 71, 65.8%) and Singapore (n = 48, 52.8%). The educational level of respondents was lower in Vietnam where only 46.4% (n = 39) had completed post-secondary education, compared to 75.0% (n = 81) in Campbelltown and 75.8% (n = 69) in Singapore. CONCLUSIONS: Rates of breast feeding were inversely correlated with rates of introduction of HCB and positively related to educational achievement. Vietnam had lowest rates of breast feeding, higher rates of introduction of HCBs, and lower rates of education. Given rising rates of obesity, there is a need for more effective programmes to promote breast feeding and restrict false advertising of HCBs.

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BACKGROUND: Aggregatibacter actinomycetemcomitans most commonly causes periodontitis but has been reported to infect heart valves, soft tissue, brain and lungs, and distal bones. Osteomyelitis distal to the jaw is rarely described. CASE PRESENTATION: We report an unusual and rare case of chronic osteomyelitis caused by A. actinomycetemcomitans in the toe of a paediatric patient, and review the available literature. The infection was managed with intravenous antibiotics followed by oral antibiotics. CONCLUSION: This is an unusual presentation of A. actinomycetemcomitans causing chronic osteomyelitis presumed due to nidation in a minimally damaged bone, associated with bacteraemia of an oral commensal. It occurred in the toe, without obvious dental predisposition; associated with minimal clinical disturbance and with muted immune response.

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There are no published reports of patients harboring microdeletions involving the 7p22.1 region. Although 7p22.1 microdeletions are rare, some reports have shown microduplications encompassing this region. In this study, we report five patients with overlapping deletions of the 7p22.1 region. The patients exhibited clinical similarities including non-specific developmental delay, short stature, microcephaly, and other distinctive features. The shortest region of overlap within the 7p22.1 region includes five genes, FBXL18, ACTB, FSCN1, RNF216, and ZNF815P. Of these genes, only ACTB is known to be associated with an autosomal dominant trait. Dominant negative mutations in ACTB are responsible for Baraitser-Winter syndrome 1. We analyzed ACTB expression in immortalized lymphocytes derived from one of the patients and found that it was reduced to approximately half that observed in controls. This indicates that ACTB expression is linearly correlated with the gene copy number. We suggest that haploinsufficiency of ACTB may be responsible for the clinical features of patients with 7p22.1 microdeletions.

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AIMS: Over 200 000 Australian children suffer significant disability. How should medical students be prepared for this challenge? Community engagement has become fundamental to education, but there is little experience with engagement of undergraduates with children with disabilities. This paper reviews such experience in Western Sydney. METHODS: Since 2011, UWS paediatric students have been rotated through local special schools for 2 weeks each term. In 2013, feedback was solicited in a questionnaire from the 129 students involved that year with 109 being returned. It had been solicited from school staff and parents in formal and informal communication from the beginning. RESULTS: Fourteen per cent of students reported no prior exposure to disabled children: 55% only chance, 24% regular and 7% extensive. Thirty-seven per cent reported greatly increased understanding: 39% moderately, 15% somewhat, 7% a little and 2% not. Forty-three per cent declared understanding of impact on family greatly increased: 40% moderately, 11% somewhat, 5% a little and 1% not. Twenty-seven per cent declared greatly increased knowledge of services, 43% moderately, 25% somewhat, 4% a little and 1% none. Fifteen per cent declared greatly increased preparation for caring, 44% moderately, 30% somewhat, 6% a little and 5% none. Thirty-six per cent declared greatly increased understanding of role of schools, 30% moderately, 20% somewhat, 10% a little, and 2% none and 2% cannot recall. School staff and parents reported very favourably. Problems involved professionalism in students and some fatigue in parents. CONCLUSION: The engagement has been successful. Professionalism has been emphasised, and rotations have been designed to prevent fatigue.

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BACKGROUND: Molybdenum cofactor deficiency (MOCD) is a severe autosomal recessive neonatal metabolic disease that causes seizures and death or severe brain damage. Symptoms, signs and cerebral images can resemble those attributed to intrapartum hypoxia. In humans, molybdenum cofactor (MOCO) has been found to participate in four metabolic reactions: aldehyde dehydrogenase (or oxidase), xanthine oxidoreductase (or oxidase) and sulfite oxidase, and some of the components of molybdenum cofactor synthesis participate in amidoxime reductase. A newborn girl developed refractory seizures, opisthotonus, exaggerated startle reflexes and vomiting on the second day of life. Treatment included intravenous fluid, glucose supplementation, empiric antibiotic therapy and anticonvulsant medication. Her encephalopathy progressed, and she was given palliative care and died aged 1 week. There were no dysmorphic features, including ectopia lentis but ultrasonography revealed a thin corpus callosum. OBJECTIVES: The aim of this study is to provide etiology, prognosis and genetic counseling. METHODS: Biochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression. RESULTS: Uric acid level was low in blood, and S-sulfo-L-cysteine and xanthine were elevated in urine. Compound Z was detected in urine. Two MOCS2 gene mutations were identified: c.501 + 2delT, which disrupts a conserved splice site sequence, and c.419C > T (pS140F). Protein expression studies confirmed that the p.S140F substitution was pathogenic. The parents were shown to be heterozygous carriers. CONCLUSIONS: Mutation analysis confirmed that the MOCD in this family could not be treated with cPMP infusion, and enabled prenatal diagnosis and termination of a subsequent affected pregnancy.

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OBJECTIVE: To compare the rates of acute lower respiratory tract infection (ALRI) among children in north-west Queensland, according to age, sex and Indigenous status. DESIGN, SETTING AND PATIENTS: Retrospective chart review of hospitalisations at Mt Isa Base Hospital, Queensland, from 1 January 2007 to 31 December 2011 among children < 15 years of age. MAIN OUTCOME MEASURES: Rates of admission for bronchiolitis, pneumonia and bronchiectasis, calculated using population data from the Australian Bureau of Statistics. RESULTS: There were 356 admissions for ALRI, involving 276 children. Of the 162 children aged < 12 months old, 125 (77.2%) were Indigenous. Hospitalisations increased over the study period, and rates were significantly higher among Indigenous children compared with non-indigenous children (24.1 v 4.5 per 1000 population per year). There were 195 admissions of 164 children with pneumonia, 126 (76.8%) of whom were Indigenous. Annual rates for Indigenous children were higher than for non-Indigenous children (13.7 v 2.3 per 1000 population). Multiple admissions were common. One-third presented with gastrointestinal symptoms and signs. Pneumococcal disease persisted despite vaccination. There were 160 hospitalisations for bronchiolitis; 114 occasions (71.3%) involved Indigenous children. Seven children had bronchiectasis; all were Indigenous. CONCLUSION: Rates of ALRI in Mt Isa are comparable to those in the Northern Territory, which is reported to have rates of pneumonia among the highest in the world for children < 12 months of age. Multiple admissions are common, suggesting an even higher rate of bronchiectasis. Pneumonia may present as gastrointestinal disease, and invasive pneumococcal infection must be suspected despite vaccination.

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Introduction: A five-year-old year old girl developed fever of 40.3° C, vomiting, mild general abdominal pain, followed by bloody diarrhea. Description: Ultrasonography revealed a length of symmetrically thickened terminal ileum, more than 20 cm long, with walls greater than 0.5 cm containing a long narrow lumen < 1 mm wide. Conclusion: Given the difficulty of diagnosing the cause of enteritis in young children, ultrasonography represents a simple, non invasive technique which may demonstrate suggestive mural thickening.