This study describes the changing trends in antimicrobial resistance and serotype distribution of pneumococcal isolates collected from Asian countries during 2008 to 2009. With regard to the changing trends in antimicrobial resistance in the Asian region, the first remarkable finding was a distinctive and persistent increase in macrolide resistance, which was consistent with other reports (10
). Previous ANSORP studies with clinical isolates and nasopharyngeal isolates have already revealed that many Asian countries showed a much higher prevalence of macrolide resistance in pneumococci than did Western countries (14
). More seriously, the level of macrolide resistance has remarkably increased with very high MIC90
s (64 to ≥128 μg/ml) in China, Hong Kong, Japan, South Korea, Malaysia, Sri Lanka, Taiwan, Thailand, and Vietnam. With regard to the mechanism of macrolide resistance, erm
(B)-mediated high-level resistance is the major mechanism in most Asian countries and Europe and is also increasing in the United States recently (10
), while the mef
(A) gene is still predominant in Canada (16
). Compared with our previous study (24
), the frequency of macrolide-resistant isolates with erm
(B) has increased in Asian countries. An interesting finding was the persistently high prevalence of pneumococci carrying both erm
(B) and mef
(A) in South Korea (43.3%) and Vietnam (41.0%) and the increased prevalence of those isolates in Hong Kong (8.9% in 1998 to 2001 to 26.4%), Taiwan (0% in 1998 to 2001 to 21.4%), and Thailand (0% in 1998 to 2001 to 11.7%) (24
). Major reasons for the high prevalence of macrolide resistance in Asian countries would be widespread use of macrolides in clinical practice and clonal spread of macrolide-resistant strains. Given the current epidemiology of macrolide resistance, an empirical use of macrolides alone for the treatment of community-acquired pneumonia or presumed pneumococcal pneumonia may not be an appropriate choice in many Asian countries, where it may cause the clinical failure of antimicrobial therapy.
The second important finding of pneumococcal resistance in the Asian region was the increasing prevalence of MDR. We found a high prevalence of MDR pneumococci in Asian countries, particularly in China, Vietnam, South Korea, Hong Kong, and Taiwan. The prevalence of MDR pneumococci in Asian countries (59.3%) shown in this study was significantly higher than those reported from other parts of the world such as 9 to 24% in North America and 0 to 43% in Europe (17
Third, we found a dramatic decrease in the prevalence of penicillin resistance in nonmeningeal isolates according to the revised CLSI breakpoints for resistance to parenteral penicillin, although penicillin MICs have increased in some countries such as China and India compared with our previous studies. Most of the nonmeningeal isolates from Asian countries were susceptible to parenteral penicillin, a finding consistent with other studies worldwide (0 to 7%) (17
). However, we found 15 nonmeningeal isolates with a very high level of resistance to penicillin (MIC, ≥8 μg/ml), suggesting that a continued monitoring of PNSP in the region is important.
The overall rates of resistance to fluoroquinolones in pneumococci remained low in most Asian countries, while levofloxacin and gatifloxacin resistance was more frequent in South Korea and Taiwan. We found 10 isolates from South Korea and Taiwan which showed high-level fluoroquinolone resistance with MICs of ≥16 μg/ml for levofloxacin, gatifloxacin, and ciprofloxacin, simultaneously. Therefore, given the popular use of respiratory fluoroquinolones in clinical practice, the emergence of these strains highly resistant to fluoroquinolones could be a concern in the future in the treatment of pneumococcal pneumonia.
With regard to the serotype distribution, this study revealed significant changes in the distribution of serotypes in Asian countries after the introduction of PCV7 vaccination. In the Asian region, the frequency of serotypes covered by PCV7 (52.5%) in this study was lower than 74% and 61% in 1996 to 1997 and 2000 to 2001, respectively (22
). PCV7 was recently licensed and introduced into the Asian countries of South Korea (2003); Malaysia, Philippines, and Taiwan (2005); China (2008); and Japan (2009) (19
). However, it was included in the National Immunization Program in only a very few Asian countries and areas, including Hong Kong (from 2009), Macau (from 2009), and Singapore (from 2009) (15
). Although the PCV7 vaccination rate in most Asian countries has not been investigated, it seems to be very low in most Asian countries due to lack of awareness among both the general public and physicians and due to vaccination cost, while the vaccination rate in children under 5 years of age is relatively high in South Korea (over 60% in urban areas) (12
). Vietnam, where PCV7 was not available at the time of the study, showed the highest coverage rate of PCV7 serotypes in this study, while the coverage rates have decreased in most other Asian countries compared with our previous studies. The PCV7 coverage rate in Asian countries was much lower, particularly in Philippines (16.1%), than that in Western countries (80 to 90% in North America and 70 to 75% in Europe) (6
). However, the PCV13 coverage rate was 74.5% in overall isolates and 83.8% in isolates from children <5 years of age from Asian countries, which was due to the coverage of non-PCV7 serotypes 19A, 3, and 6A by PCV13.
Emergence of nonvaccine serotypes was associated with increasing prevalence of antimicrobial resistance (8
). In the Asian region, serotype 19A was the most prevalent nonvaccine serotype. Compared with our previous ANSORP study in 2000 to 2001 (23
), serotype 19A has significantly increased in Asian countries, particularly in China, India, and South Korea. Serotype 19A showed a high rate of penicillin nonsusceptibility, erythromycin resistance, and MDR. The prominent increase in serotype 19A and other non-PCV7 serotypes would be one of the major reasons for a high prevalence of macrolide resistance and MDR in Asian countries. This increase in serotype 19A in Asian countries might be due to the selection of nonvaccine serotypes after PCV7 vaccination, clonal spread of serotype 19A strains (2
), or injudicious use of antibiotics in clinical practice.
Since a limited number of isolates were collected from a few hospitals which are mostly located in urban areas, data from this study may not reflect the national status of antimicrobial resistance and serotype distribution. Therefore, nationwide surveillance of pneumococcal resistance and serotypes is strongly warranted.
The current study has provided updated information and changing trends in antimicrobial resistance and serotype distribution of S. pneumoniae in Asian countries. Data showed an extremely high prevalence of macrolide resistance and an increasing prevalence of MDR in many Asian countries. After the introduction of PCV7 vaccination into Asian countries, a distinctive emergence of serotype 19A was observed which was also associated with the increasing prevalence of antimicrobial resistance in S. pneumoniae in the region. Given the high prevalence of resistance and its clinical impact, continuous surveillance of pneumococcal epidemiology and active application of pneumococcal vaccination that can cover non-PCV7 serotypes are strongly warranted in Asian countries.