Clonal spread of macrolide-resistant Mycoplasma pneumoniae sequence type-3 and type-17 with recombination on non-P1 adhesin among children in Taiwan

Abstract

Objectives: Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolideresistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan. Methods: We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae. Results: A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n ¼ 93) and its singlelocus variant ST17 (n ¼ 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4e8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3. Conclusions: In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in

Increased Macrolide Resistance Rate of M3562 Mycoplasma pneumoniae Correlated With Macrolide Usage and Genotype Shifting

“…Taken together, we deduced that the present high rates of MRMP with type M4572 predominantly resulted from a rapid clonal dissemination of MRMP strains of this type. Likewise, clonal expansion of macrolide-resistant strains of a specific type has also been reported in Hong Kong , Taiwan (Hung et al, 2020), Japan (Suzuki et al, 2017), and South Korea (Lee et al, 2018). Given that type M3562 is currently increasing in several countries, measures should be taken to prevent the global expansion of this clone.…”

Epidemiology and clinical manifestations of children with macrolide-resistant Mycoplasma pneumoniae pneumonia in Southern Taiwan

“…1,9,11,12 A recent study, which mainly enrolled children in northern Taiwan, showed a high MR rate of up to 77% between 2017 and 2019. 10 We found that the MR rates varied greatly during our study period. M. pneumoniae infection is known to occur in cyclical epidemic periods, and macrolide resistance has been variable within individual regions over the decade these studies span.…”

“…The research groups from the Linkou Chang Gung Children's Hospital showed that the prevalence of MR-MPP in children was 12.3% in 2011 and 77% during 2017e2019. 9,10 The prevalence of MR-MPP was 18e30% from 2010 to 2017, as reported by research groups from the National Taiwan University Hospital in Taipei city. 1,11,12 The distance between northern and southern Taiwan is approximately 300 km.…”

“…Lastly, only a point 2063 mutation was detected in our study due to budget constraints; however, 2063 was reported as the resistant loci in the majority of the cases in Taiwan. 10 The bacteria can mutate from one generation to the other, and new resistant loci can develop, and the detection may have been limited. Our data may have underestimated the prevalence of MR-MPP in children.…”

Macrolide Resistance, Clinical Features, and Cytokine Profiles in Taiwanese Children With Mycoplasma pneumoniae Infection

“…Second, potential viral or bacterial coinfection was not investigated in our study. The coinfection rate with M pneumoniae is approximately 20% in some studies, the most common of which is human rhinovirus [ 31 , 32 ]. Third, pathogen detection and comparison of clinical features of the other 151 patients with positive serum M pneumoniae IgM report but negative M pneumoniae PCR or culture report were not further analyzed.…”