Characterization of gram-negative bloodstream infections in hospitalised Australian children and their clinical outcomes.

BACKGROUND: Gram-negative bloodstream infections (GNBSI) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSI in children that relate the clinical presentation, pathogen characteristics and outcomes. METHODS: A 3-year prospective study of GNBSI in children aged <18 years was conducted in five Australian children's hospitals between 2019-2021. The clinical characteristics, disease severity and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. RESULTS: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (IQR 0.6-8.5). 576/931 episodes (62%) were community onset though 661/931 (71%) occurred in children with comorbidities and a central venous catheter (CVC) was present in 558/931 (60%). CVC (145/931) and urinary tract (149/931) were the most common sources (16% each). 100/931 (11%) children required Intensive Care Unit (ICU) admission and a further 11% (105/931) developed GNBSI in ICU. 659/927 (71%) isolates were Enterobacterales of which 22% (138/630) were third generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes (ESBL) were confirmed in 65/138 (47%) 3GCR-Enterobacterales. Most common ESBL genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted OR 3.2, 95%CI 1.6-6.4). CONCLUSION: GNBSI in children are frequently healthcare-associated and affect children under 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritise future antimicrobial clinical trials.

Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines.

There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery.

Non-typhoidal Salmonella infections in children: Review of literature and recommendations for management.

Non-typhoidal Salmonellae are a major cause of infectious diarrhoea worldwide and can cause invasive diseases, including bacteraemia, meningitis and osteomyelitis. Young or immunocompromised children and those with underlying conditions such as sickle cell disease are particularly vulnerable to invasive disease. There has been an increase in the rate of resistant non-typhoidal Salmonella, which is associated with invasive disease and hospitalisation. The intracellular nature of non-typhoidal Salmonella protects against extracellular antibiotics and can facilitate disease relapse, particularly meningitis. Effective antimicrobial agents with good intracellular penetration include azithromycin, fluoroquinolones and third-generation cephalosporins. Antibiotic treatment of non-typhoidal Salmonella gastroenteritis is only indicated if there are risk factors for invasive disease as it can prolong excretion and does not shorten the duration of gastrointestinal symptoms. Optimal choice and length of therapy for gastroenteritis and invasive disease in children is not clear. Here, we provide a review of the literature and treatment recommendations.

Tetanus in New Zealand children: Intensive care management of a vaccine preventable disease.

AIM: To review management of children admitted with tetanus to Starship Children's Hospital from 2000 to 2013. METHODS: Retrospective chart review of children aged 0-15 years admitted to Starship Children's Hospital with tetanus from 2000 to 2013. Follow-up of immunisation status was via the National Immunisation Register and/or phone contact with patient's primary health care provider. RESULTS: Four cases of tetanus occurred, all in unimmunised children. All four required paediatric intensive care unit admission (length of stay (LOS) 2.5-7 weeks) for ventilatory support; three required tracheostomy. Specific tetanus treatment included metronidazole, tetanus immunoglobulin and antispasmodic medications such as magnesium sulphate and benzodiazepines. Three remain partially or unimmunised following discharge. CONCLUSION: Tetanus in children is a rare but preventable life-threatening disease, requiring costly intensive care management. Immunisation is cheap and effective in preventing tetanus and should be offered to all children, including tetanus cases for their future protection.