Colonization, Density, and Antibiotic Resistance of Streptococcus pneumoniae, Haemophilus Influenzae, and Moraxella catarrhalis among PCV13-Vaccinated Infants in the First Six Months of Life in Rochester, New York: A Cohort Study.

BACKGROUND: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hflu), and Moraxella catarrhalis (Mcat) nasopharyngeal colonization precedes disease pathogenesis and varies among settings and countries. We sought to assess colonization prevalence, density, Spn serotypes, and antibiotic resistance in children in the first 6 months of life in pediatric primary care settings. METHODS: Prospective cohort study in Rochester, NY during 2018-2020. Nasopharyngeal swabs were collected from 101 children at age 1, 2, and 3 weeks, then 1, 2, 4, 6, 9, 12, 15, 18, and 24 months. Spn serotypes were determined by Quellung. Oxacillin resistance for Spn and ß-lactamase production by Hflu and Mcat was tested. All children received PCV13 vaccine according to U.S. recommended schedule. RESULTS: Spn, Hflu, and Mcat colonization was detected in only 5% of infants before age 2 months old. Cumulative prevalence was 34% for Spn, 10% for Hflu, and 53% for Mcat in children ≤6 months of age. Nasopharyngeal bacterial density of Spn, Hflu, and Mcat (x = 2.71 log) in children ≤6 months of age was lower than at 7-24 months of age (x = 3.15 log, p < 0.0001). Predominant serotypes detected ≤6 months of age were 23B (16.7%), 22F (12.9%), 15B/C (11%), and 16F (9.2%). In total, 14.8% of Spn isolates were oxacillin resistant and 66.7% of Hflu isolates were ß-lactamase producing. CONCLUSION: Spn, Hflu, and Mcat nasopharyngeal colonization was uncommon and of low density among children ≤6 months old, especially among children <2 months of age. Non-PCV13 serotypes predominated and a different serotype distribution was observed in ≤6-month olds compared to 7- to 24-month olds.

Novel N-Substituted 3-Aryl-4-(diethoxyphosphoryl)azetidin-2-ones as Antibiotic Enhancers and Antiviral Agents in Search for a Successful Treatment of Complex Infections.

A novel series of N-substituted cis- and trans-3-aryl-4-(diethoxyphosphoryl)azetidin-2-ones were synthesized by the Kinugasa reaction of N-methyl- or N-benzyl-(diethyoxyphosphoryl)nitrone and selected aryl alkynes. Stereochemistry of diastereoisomeric adducts was established based on vicinal H3-H4 coupling constants in azetidin-2-one ring. All the obtained azetidin-2-ones were evaluated for the antiviral activity against a broad range of DNA and RNA viruses. Azetidin-2-one trans-11f showed moderate inhibitory activity against human coronavirus (229E) with EC50 = 45 µM. The other isomer cis-11f was active against influenza A virus H1N1 subtype (EC50 = 12 µM by visual CPE score; EC50 = 8.3 µM by TMS score; MCC > 100 µM, CC50 = 39.9 µM). Several azetidin-2-ones 10 and 11 were tested for their cytostatic activity toward nine cancerous cell lines and several of them appeared slightly active for Capan-1, Hap1 and HCT-116 cells values of IC50 in the range 14.5-97.9 µM. Compound trans-11f was identified as adjuvant of oxacillin with significant ability to enhance the efficacy of this antibiotic toward the highly resistant S. aureus strain HEMSA 5. Docking and molecular dynamics simulations showed that enantiomer (3R,4S)-11f can be responsible for the promising activity due to the potency in displacing oxacillin at ß-lactamase, thus protecting the antibiotic from undesirable biotransformation.