X Ma, KH Yao, SJ Yu, L Xue, YH Yang

Dear Editor,

Although some data have shown that Streptococcus pneumoniae were high resistance to erythromycin in some Asia countries and areas,¹ data from cases of invasive pneumococcal diseases (IPD) were rare and the characterisation of these isolates had not been well detected in the hinterland of China.

Recently, we detected the susceptibility to antimicrobial for 171 Streptococcus pneumoniae isolates which were collected from 11 medical centers in China from children under 14 years with invasive pneumococcal diseases² and analysed the characterisation of erythromycin-resistant isolates. To our knowledge, this is the largest collection of IPD isolates recovered and characterised in Chinese children.

Among the 171 isolates, 164 (95.9%) were resistant to erythromycin. Resistance to erythromycin was generally with high minimal inhibitory concentration (MIC) level (MIC₅₀ and MIC₉₀ ≥256 µg/ml for 162 isolates among all the 164 strains. The level of MIC didn't show significant differences in distinct geographic regions, age groups and penicillin-resistant isolates or penicillin-susceptible isolates. Meanwhile, there were 104 (63.4%) isolates carried the ermB gene only and 59 (36.0%) were found to harbor both ermB and mefA/E genes, which suggested that the mechanism of ribosomal methylation encoded by the ermB gene was the major resistance mechanism in the IPD isolates from China. It maybe responsible to the high MIC levels of erythromycin because ermB gene is usually associated with high-level resistance and the mefA/E gene is related to low level resistance. The distribution of resistant genes didn't show significant differences in distinct geographic regions. Furthermore, all the serotypes showed similar resistance levels to erythromycin. However, in Europe, erythromycin resistance was often associated with pneumococcal serotype 14.³ This maybe the result of wide and inappropriate using of macrolide antibiotics, such as azithromycin and clarithromycin in the hinterland of China.

An interesting finding concerning the distribution of resistance determinants was the high rate of dual presence of the ermB and mefA/E genes in serygroup 19. Most of them (54/59, 91.5%) belonged to the serotype 19F and 19A and had an identical PFGE pattern (C pattern). Furthermore, 54 of these strains had an MLST profile similar to the reference strain of Taiwan^19F-14 clone (ST236:15-16-19-15-6-20-26). Based on the data from PFGE and MLST in this study, the serotype 19F and 19A isolates with the ermB and mefA/E genes could be the variants of the Taiwan^19F-14 clone. Since the Taiwan^19F-14 clone was originally known to have only a mefA/E gene, horizontal transfer of the ermB gene into this clone, and subsequent dissemination of this variant, could be responsible for the high rate of dual presence of the ermB and mefA/E genes in Chinese children.

This study was limited by the number of isolates in each region was relatively small and all the isolates were collected from tertiary hospitals in Chinese big cities. In that regards, there maybe some bias in isolate collection (i.e. the cultures more likely to be obtained from children who failed treatment or who have the more severe form of infections).

In summary, surveillance has showed that the erythromycin resistance rate is very high among S.pneumoniae causing IPD in chinese children. The major mechanism was the ribosomal methylation encoded by the ermB gene among most of the major serotype, furthermore, the mechanism of efflux encoded by the mefA/E gene mainly were detected in serogroup19. In addition, molecular studies suggested the spread of resistant strains (Taiwan^19F-14 clone) in the mainland of China.

We thank all the participants from the 11 hospitals and the Lanzhou Vaccine Institute. We thank for Lesley McGee from Centers for Diseases Control and Prevention, Atlanta, USA, for performing the PFGE analysis.

This study was supported by Beijing guidance teacher technology item of excellent doctorship thesis (grant YB20091002502) and Special fund for high-level personnel development in Beijing health system (2011-3-052).

Reference

1. Song JH, Chang HH, Suh JY, et al. Macrolide resistance and genotypic characterisation of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens(ANSORP). J Antimicrob Chemother 2004;53:457-63.

2. Xue L, Yao K, Xie G, et al. Serotype Distribution and Antimicrobial Resistant of Strepotococcus pneumoniae Isolates That Cause Invasive Disease among Chinese Children.Clin Infect Dis 2010;50:741-4.

3. Isaacman DJ, McIntosh ED, Reinert RR. Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines. Int J Infect Dis 2010;14:e197-209.