Emerging macrolide resistance in Bordetella pertussis in mainland China: Findings and warning from the global pertussis initiative

Abstract

Whooping cough, or pertussis, is a highly communicable infectious disease caused by the bacterium Bordetella pertussis. Vaccination once reduced the incidence of the disease, but a global resurgence of the infection happened during the past two decades, likely due to the waning immunity of vaccination. Macrolides such as erythromycin and azithromycin are the drugs of primary choice for treatment. In this personal view, we call for attention to macrolide-resistant B. pertussis (MRBP), which has emerged and prevailed in mainland China for years and are exclusively mediated by mutations in the 23S rRNA gene. Whether the prevalence of MRBP in China results from overuse of azithromycin in clinical medicine remains unknown. The incidence of MRBP is low in other countries, but this could be a technical illusion since China employs culture as the mainstream diagnostic method whereas nucleic-acid amplification test being widely used in other countries fail to test antimicrobial susceptibility. Given the increasingly frequent global travel that facilitates microbial transmission worldwide, there is a pressing need to perform international surveillance on MRBP to prevent the potential circulation of the organism. Finding alternative agents that possess good activity against B. pertussis is also urgently required.

Association Between Real-time Polymerase Chain Reaction Cycle Threshold Value and Clinical Severity in Neonates and Infants Infected With Bordetella pertussis

“…Macrolides, especially erythromycin and azithromycin, are the drugs of choice; however, detection of macrolide-resistant B. pertussis (MRBP) in 23S rRNA has been a concern in mainland China. 5 Vietnam shares a border with China, and the mutation was detected in Chinese pertussis patients during 2016–2017. 24 MRBP might allow more efficient disease transmission, as the effect of the drugs is limited to decreasing the burden of B. pertussis in patients with pertussis.…”

JMM Profile: Bordetella pertussis and whooping cough (pertussis): still a significant cause of infant morbidity and mortality, but vaccine-preventable

“…Macrolide resistance in B. pertussis is mediated by A2047G transition in the 23S rRNA gene which prevents the binding of erythromycin and was first reported in the USA in 1994 [17]. Although rare in most countries, a high prevalence of macrolide resistance has been reported in mainland China and it has been hypothesised that this may be linked to the overuse of macrolides in clinical medicine [18][19][20][21][22]. There have also been calls from the pertussis community for wider phenotypic and genotypic testing to improve antimicrobial resistance surveillance data [22].…”

“…Although rare in most countries, a high prevalence of macrolide resistance has been reported in mainland China and it has been hypothesised that this may be linked to the overuse of macrolides in clinical medicine [18–22]. There have also been calls from the pertussis community for wider phenotypic and genotypic testing to improve antimicrobial resistance surveillance data [22].…”

Genomic library of Bordetella

“…Besides the large-scale evolution of Bordetellae , the population dynamics within Bp are an important topic of epidemiological surveillance, in light of vaccine-escape evolution and the possible emergence and global dissemination of antimicrobial resistance [23–25]. Major evolutionary events in vaccine antigen-related genomic features have been described, including within the promoter region of the pertussis toxin gene cluster ( ptxP) and in the fimbriae gene fim3 [23].…”

“…Besides the large-scale evolution of Bordetellae, the population dynamics within Bp are an important topic of epidemiological surveillance, in light of vaccine-escape evolution and the possible emergence and global dissemination of antimicrobial resistance [23][24][25].…”