Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare disorder described after vaccination with adenoviral vector-based COVID-19 vaccines. Co-occurring thrombosis with thrombocytopenia reported after vaccination can be a proxy for identification of TTS. METHODS: Descriptive database review of all cases of co-occurring (within 42 days) thrombosis with thrombocytopenia in participants in Ad26.COV2.S clinical trials or recipients of Ad26.COV2.S in real-world clinical practice. Cases were retrieved from Janssens' clinical trial and Global Medical Safety databases. RESULTS: There were 34 cases of co-occurring thrombosis with thrombocytopenia in Ad26.COV2.S recipients (46 per 100,000 person-years) and 15 after placebo (75 per 100,000 person-years) in clinical trials. Among Ad26.COV2.S recipients, mean age at the time of the event was 63 years (range 25-85), 82 % were male, mean time-to-onset 112 days (range 8-339) post-last Ad26.COV2.S dose, 26 events occurred post-dose-1, and 7 within a 28-day risk window post-vaccination. Diagnostic certainty was evaluated using Brighton Collaboration, US Centers for Disease Control and Prevention, and European Medicines Agency Pharmacovigilance Risk Assessment Committee case definitions. One case met the highest level of diagnostic certainty for all 3 definitions. There were 355 spontaneous reports of co-occurring thrombosis with thrombocytopenia in the Global Medical Safety database, 47 % males, 85 % within 28-days after vaccination. Twenty-seven cases met the highest level of diagnostic certainty for all definitions, 21 female, 19 with cerebral venous sinus thrombosis, age-range 18-68 years. Time-to-onset was 7-14 days post-vaccination in 20 cases. There were 8 fatalities. CONCLUSION: TTS induced by Ad26.COV2.S is very rare. Most co-occurring thrombosis with thrombocytopenia does not constitute TTS.

Characteristics of the antibiotic regimen that affect antimicrobial resistance in urinary pathogens.

Background: Treatment duration, treatment interval, formulation and type of antimicrobial (antibiotic) are modifiable factors that will influence antimicrobial selection pressure. Currently, the impact of the route of administration on the occurrence of resistance in humans is unclear. Methods: In this retrospective multi-center cohort study, we assessed the impact of different variables on antimicrobial resistance (AMR) in pathogens isolated from the urinary tract in older adults. A generalized estimating equations (GEE) model was constructed using 7397 Escherichia coli (E. coli) isolates. Results: Resistance in E. coli was higher when more antibiotics had been prescribed before isolation of the sample, especially in women (significant interaction p = 0.0016) and up to nine preceding prescriptions it was lower for higher proportions of preceding parenteral prescriptions (significant interactions p = 0.0067). The laboratory identity, dying, and the time between prescription and sampling were important confounders (p < 0.001). Conclusions: Our model describing shows a dose-response relation between antibiotic use and AMR in E. coli isolated from urine samples of older adults, and, for the first time, that higher proportions of preceding parenteral prescriptions are significantly associated with lower probabilities of AMR, provided that the number of preceding prescriptions is not extremely high (≥10 during the 1.5 year observation period; 93% of 5650 included patients). Trial registration: Retrospectively registered.