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Winkie Fong

Publications and source records attributed to Winkie Fong.

2 recordsLinked to original sources

Genome-sequencing-based benchmarking of antimicrobial resistance, treatment outcomes and healthcare transmission events for Clostridioides difficile infection in Australian hospitals.

BACKGROUND: Clostridioides difficile infection (CDI) remains a priority for infection prevention and control in health care, particularly with the emergence of hypervirulent strains and antimicrobial resistance (AMR). AIM: To characterize the genomic epidemiology and AMR profiles of culture-confirmed CDI cases within tertiary hospitals in Australia. METHODS: A total of 155 C. difficile isolates from 142 patients with CDI diagnosed in four hospitals between 2023 and 2025 were studied. Data collected included patient demographics, severity of infection, antibiotic treatment and clinical outcomes at 8 weeks. Phenotypic susceptibility to vancomycin, fidaxomicin, metronidazole, moxifloxacin, meropenem, tetracycline and rifaximin were determined by agar dilution. Isolates underwent whole-genome sequencing (WGS) for genotyping and resistome assessment. FINDINGS: WGS differentiated 39 distinct sequence types among CDI isolates across different healthcare services. In total, 100 isolates were singletons and 55 (35% clustering rate) isolates were considered to be genomically related (difference of two or fewer single-nucleotide polymorphisms). Of these, 12 patients (8.5%) with close hospital contact formed six epidemiologically linked clusters. Phenotypic susceptibility results were obtained for 134 (86.4%) CDI isolates. There was no phenotypic resistance to vancomycin [minimum inhibitory concentration required to inhibit the growth of 90% of isolates (MIC90) 1 mg/L], metronidazole (MIC90 0.5 mg/L) or fidaxomicin (MIC90 0.5 mg/L). There was no association in the study cohort between the presence of resistance genes or reduced phenotypic susceptibility and CDI recurrence. CONCLUSION: Genomic analysis of C. difficile isolates did not identify any outbreaks or an association between the sequence type or presence of a resistance gene and clinical outcomes. High-resolution characterization and identification of antibiotic resistance, CDI clinical relapse and recent transmission offered by genome sequencing can provide important benchmarks for hospital infection control.

Antibiotic resistance

Characterisation of Bordetella pertussis virulence and macrolide resistance in Australia by targeted culture-independent sequencing: a genomic epidemiology study.

BACKGROUND: Bordetella pertussis continues to circulate globally despite widespread vaccination, with a notable epidemic in 2024. Its resurgence is confounded by the emergence of pertactin-deficient, macrolide-resistant B pertussis strains in Asia and Europe, which are under-recognised by conventional diagnostics. We aimed to apply targeted culture-independent next-generation sequencing (tNGS) of respiratory specimens to improve global B pertussis diagnostic capability and genomic surveillance. METHODS: We did a nationwide genomic epidemiology study of B pertussis RT-PCR-positive respiratory specimens that were retrospectively and prospectively collected by diagnostic and public health laboratories in six of seven states and territories of Australia. Specimens underwent tNGS and macrolide-resistant B pertussis-specific PCR, and an opportunistic subset from New South Wales and Queensland were cultured for confirmatory susceptibility testing and whole-genome sequencing. Sequencing data were analysed for genome recovery, virulence profiles, and macrolide resistance mutations, and were compared with international macrolide-resistant B pertussis genomes and ancestral Australian genomes. The performance of the tNGS approach was assessed with logistic regression relative to RT-PCR cycle threshold values, and sensitivity and specificity values were calculated. FINDINGS: 255 respiratory specimens positive for B pertussis were included in the study. 64 (25%) were retrospectively collected between Jan 12, 2012, and Dec 31, 2023, and 191 (75%) were prospectively collected between Jan 1 and Oct 28, 2024. Of these 255 specimens, 148 (58%) yielded near-complete B pertussis genomes through tNGS. Seven co-circulating lineages of B pertussis were documented, including two associated with macrolide-resistance. Eight epidemiologically unrelated and geographically dispersed cases of macrolide-resistant B pertussis with a 23S rRNA 2037A→G mutation were identified by tNGS and confirmed by whole-genome sequencing. Three of these were further validated by phenotypic testing. The estimated prevalence of macrolide resistance among Australian cases positive for B pertussis was 4% (eight of 188). INTERPRETATION: tNGS can recover near-complete B pertussis genomes directly from clinical specimens, enabling identification of macrolide resistance mutations and high-resolution phylogenetic analysis. These findings show that tNGS complements PCR-based surveillance by providing genome-wide assessment of resistance, virulence, and genomic diversity in a single workflow. FUNDING: NSW Health Prevention Research Support Program.

Macrolides