Victorian Specialist Immunisation Services (VicSIS) - bolstering adult clinics for COVID-19 vaccines.

The Victorian Specialist Immunization Services (VicSIS) was established in Victoria, Australia, in February 2021, aiming to enhance vaccine safety services for Coronavirus disease (COVID-19) vaccines. VicSIS supports practitioners and patients with complex vaccine safety questions, including those who experience adverse events following immunization (AEFI) after COVID-19 vaccines. VicSIS provides individual vaccination recommendations, allergy testing, vaccine challenges, and vaccination under supervision. VicSIS initially comprised of eight adult COVID-19 specialist vaccination clinics, subsequently, expanding to better support pediatric patients as the Australian vaccine roll-out extended to adolescents and children. Since their establishment to September 2021, the inaugural VicSIS clinics received a total of 26,401 referrals and reviewed 6,079 patients. Consults were initially predominantly for pre-vaccination reviews, later predominantly becoming post-vaccination AEFI reviews as the program progressed. Regardless of the type of consult, the most common consult outcome was a recommendation for routine vaccination (73% and 55% of consult outcomes respectively). VicSIS is an integral component of the COVID-19 vaccination program and supports confidence in COVID-19 vaccine safety by providing consistent advice across the state. VicSIS aims to strengthen the health system through the pandemic, bolstering specialist immunization services beyond COVID-19 vaccines, including training the next generation of vaccinology experts.

Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on respiratory microbiota composition.

BACKGROUND: G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised. METHODS: Twenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing. RESULTS: No significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P=0.95, square root ECV=-4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time (P<0.0001, Mann Whitney U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P=0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered (P=0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor (P=0.004, two-tailed paired Student's t-test). CONCLUSIONS: The short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.

Managing Pseudomonas aeruginosa respiratory infections in cystic fibrosis.

PURPOSE OF REVIEW: The current guidelines and recent clinical research in the management of Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF) are reviewed. Areas where further research is required will also be highlighted. RECENT FINDINGS: P. aeruginosa is a key respiratory pathogen in CF. Inhaled tobramycin or colistin is recommended for early eradication to prevent establishment of chronic infection. Other antibiotic options are currently being investigated. The long-term success of eradication strategies is also now being assessed. The use of inhaled antibiotics in the management of chronic P. aeruginosa infection is an area of active investigation. Acute pulmonary exacerbations are still a major cause of morbidity and mortality. Guidelines continue to recommend combination intravenous therapy but further research is required to clarify the advantage of this approach. Multidrug resistance is common and potentially more effective antipseudomonal antibiotics may soon become available. SUMMARY: The management of P. aeruginosa respiratory infection in CF remains a challenging area, especially in the setting of multidrug resistance. The role of inhaled antibiotics continues to be expanded. Further research is required in the key areas of eradication and management of chronic infection and acute pulmonary exacerbations to identify those treatments that optimize long-term, clinical benefits.

Pharmacokinetics of short versus extended infusion meropenem dosing in critically ill patients: a pilot study.

OBJECTIVE: To test whether a prolonged 3-hour infusion of meropenem 500mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (%TMIC) to that of meropenem 1000mg given over 30 minutes. DESIGN, SETTING AND PARTICIPANTS: A randomised crossover study in 10 critically ill patients. METHOD: We administered meropenem as a 1000mg, 30-minute infusion or as a 500mg, 3-hour infusion. We determined serial plasma concentrations for each dosing episode and performed comparisons of %TMIC at different MICs. OUTCOME MEASURES: The percentage of time that meropenem was above its MIC. RESULTS: For low MICs (≤2 mg/L), both regimens attained a %TMIC >40% in all patients. For an MIC of 4mg/L, this target was attained in all but one patient, but with an MIC of 8mg/L, three patients in each group had a %TMIC <40%. There was no difference in target attainment between the two regimens for MICs up to 8mg/L. There was marked variability in the pharmacokinetic and hence the pharmacokinetic-pharmacodynamic parameters between individuals. Several patients had elevated creatinine clearances and, with both regimens, their target attainment was poor. CONCLUSIONS: Meropenem at 1000mg over 30 minutes achieved a similar %TMIC to meropenem at 500mg given over 3 hours. Meropenem pharmacokinetics were highly variable from individual to individual.

Post-exposure prophylaxis in resource-poor settings: review and recommendations for pre-departure risk assessment and planning for expatriate healthcare workers.

It is estimated that more than 3 million healthcare workers worldwide suffer needlestick and splash injuries whilst at work resulting in the potential transmission of blood-borne pathogens via exposure to bodily fluids. Under-reporting and the subsequent management of occupational injuries is a problem both in the United Kingdom and abroad. Many expatriate health care workers will work in low resource settings where the risk of transmission is greatest but in contrast to wealthier countries such as the United Kingdom, there is often a lack of effective systems for its safe management. This article provides important information about this risk and how to minimise it. The reasons for an increased risk in transmission, its subsequent management and pre-departure planning are discussed, together with the evidence for initiation of post-exposure prophylaxis; current National and International guidelines as well as the urgent need for International standardisation of these is also discussed.