Genomic surveillance reveals global spread of macrolide-resistant Bordetella pertussis linked to vaccine changes

The resurgence of whooping cough in regions utilizing acellular pertussis vaccines underscores emerging public health challenges. Here, we characterized 178 Bordetella pertussis isolates collected from patients across all age groups in Shanghai (2018–2024) to assess genomic evolution and antibiotic susceptibility. Macrolide resistance to erythromycin, azithromycin, and clarithromycin escalated from ≤50% (pre-2020) to nearly 100% (post-2020), mechanistically linked to the 23S rRNA A2047G mutation. Genome-based analysis identified a genotype MT28- ptxP3 -MRBP rapidly dominated post-2020, exhibiting significantly higher prevalence in adults than in other age groups. Phylogenetic analysis of 178 Shanghai and 1,596 global genomes revealed two major lineages corresponding to ptxP1 and ptxP3 alleles. MT28- ptxP3 -MRBP cluster was identified in France, Japan, and the United States in 2024, indicating potential cross-border transmission. These findings advocate for integrated surveillance spanning all ages and international borders to contain the global spread of macrolide-resistant B. pertussis . IMPORTANCE In recent years, despite high coverage of acellular pertussis vaccines in China, pertussis cases have increased substantially. Drawing on 178 Bordetella pertussis isolates obtained through age-inclusive active surveillance in Shanghai (2018–2024), we found that macrolide resistance rose from ≤50% before 2020 to nearly 100% thereafter, with all resistant isolates harboring the 23S rRNA A2047G mutation. A resistant MT28- ptxP3 lineage became dominant after 2020 (61.7%) and was disproportionately represented among older age groups; the primary affected population shifted from children ≤36 months toward those aged 37 months to 18 years. Incorporating NCBI public genome data, we further observed that this resistant lineage is not confined locally, suggesting a risk of cross-border spread. These findings provide an early warning of the expansion of macrolide-resistant pertussis and underscore the need for age-inclusive, cross-regional genomic surveillance and re-evaluation of diagnostic workflows, antimicrobial stewardship, and immunization strategies.