Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolated from invasive infections after optional use of the 7-valent conjugate vaccine in Korea, 2006–2010

This study examined the serotype distribution and antimicrobial resistance of pneumococcal isolates from invasive infections in children between 2006 and 2010, when the 7-valent pneumococcal conjugate vaccine (PCV7) was offered as an optional vaccine in Korea. Among 140 isolates collected from 8 centers, the common serotypes were 19A (22.9%), 19 F (12.1%), and 6B (8.6%). Between 2006 and 2010, PCV7 serotypes decreased from 62.5% to 21.4% (P = 0.002), whereas three 13-valent pneumococcal conjugate vaccine (PCV13)–specific serotypes (3, 6A, and 19A) increased from 18.8% to 42.9% (P = 0.016). Among 102 multidrug-resistant isolates, the proportion of PCV7 serotypes decreased from 65.2% to 21.7% (P = 0.001), and 3 PCV13-specific serotypes increased from 17.4% to 47.8% (P = 0.008). Optional PCV7 vaccination has influenced the proportion of PCV7 serotypes in Korea, resulting in a decrease, whereas the proportions of 3 PCV13-specific serotypes, particularly 19A, have increased.     

Comparison of genotypes of Streptococcus pneumoniae serotypes 6A and 6B before and after the introduction of PCV7 vaccination in Korea

We investigated changes of serotypes in Streptococcus pneumoniae and the characteristics of serotypes 6A and 6B in Korean hospitals after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). PCV7 serotypes decreased significantly from 66.8% in 1996-2001 to 41.3% in 2008-2009 (P<0.001). However, serotype 6B did not decrease during these 2 periods (5.7% to 6.4%). Non-PCV7 serotypes that increased significantly were 3 (3.6% to 9.1%), 6A (3.1% to 8.5%), 13/28 (0 to 3.7%), 15 (2.2% to 6.7%), 16.36.37 (0 to 1.2%), 19A (1.2% to 9.7%), and 23A (0 to 1.5%). Multilocus sequence typing indicated that 9 STs were identified among 36 isolates of serotype 6A and 19 among 35 isolates of serotype 6B. No STs were found both in the 2 serotypes. The increase in serotype 6A was associated mainly with ST81, a Spain-23F clone genotype. The association of serotype 6A and ST81 is unique to Korea. Clones of serotype 6B isolates changed between the 2 periods. ST282, the main clone of serotype 6B in the PCV7 period, was found only in Korea. Our study demonstrates changing characteristics of pneumococcal serotypes 6A and 6B isolates in Korea and suggests selective evolution of certain clones in the era of PCV7 vaccination.     

Noninvasive Streptococcus pneumoniae Serotypes Recovered from Hospitalized Adult Patients in the United States in 2009 to 2012

This study was conducted to determine the serotype distribution and trends over time of Streptococcus pneumoniae strains associated with noninvasive infections among adult patients ≥18 years of age in the United States (2009 to 2012). A total of 2,927 S. pneumoniae isolates recovered from patients presenting with respiratory infections and obtained mainly (87.0%) from lower respiratory tract specimens (sputum) were included. The levels of the 7-valent pneumococcal conjugate vaccine (PCV7) serotypes remained stable over the 4-year study period (4.6% to 5.5%; P = 0.953). Overall, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were identified in 32.7% of samples, declining from 33.7% to 35.5% in 2009 to 2011 to 28.2% in 2012 (P = 0.007), with a significant decrease in the levels of serotypes 7F (P = 0.013) and 6A (P = 0.010). The levels of 19A remained constant (15.8% to 17.1%) during 2009 to 2011, dropping to 12.2% in 2012 (P = 0.089). The prevalence of serotypes associated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), but not PCV13, remained generally stable; however, the prevalence of serotypes 15B and 15C (15B/15C) increased from 2.7% to 6.3% (P = 0.010). The proportion of nonvaccine serotypes increased gradually during the study period (P = 0.044), particularly for serotype 35B (from 3.6% in 2009 to 8.2% in 2012; P = 0.001). Nonsusceptibility rates for penicillin (susceptible breakpoint, ≤2 μg/ml) and clindamycin against PCV7 serotypes decreased over the period. These results suggest the emergence of indirect effects following introduction of PCV13 for infants and young children; continued surveillance is needed to assess the burden of PCV13 serotypes in the adult population after the implementation of age-based recommendations in the United States.     

Impact of the pneumococcal conjugate vaccine on serotype distribution and susceptibility trends of pediatric non-invasive Streptococcus pneumoniae isolates in Tokai,Japan over a 5-year period

Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in February 2010 markedly reduced the burden of invasive pneumococcal disease (IPD) and changed serotype distribution in Japan. We investigated the serotype distribution and susceptibility trends of non-invasive Streptococcus pneumoniae isolates collected from pediatric patients. A total of 564 pneumococcal isolates were collected over a 5-year period between 2008 and 2012. The coverage of PCV7 significantly decreased throughout the study period, from 49.3% in period 1 (between June 2008 and April 2009) to 23.4% in period 4 (between October 2011 and March 2012). This change was mainly due to a large decrease in the frequency of 19F (from 20.6% to 9.9%) and 6B (from 10.3% to 2.7%) and an increase in serotype 3 (from 5.1% to 13.5%) and serogroup 15 (from 4.4% to 9.0%). According to serotype replacement, the susceptible ratios of S. pneumoniae to β-lactams increased slightly while macrolide resistance remained high. The high frequency of macrolide-resistant pneumococcal isolates may continue because of the high frequency of erm(B) in replace serotypes such as serotype 3 and serogroup 15. The continuous surveillance study is essential following the introduction of a second generation 13-valent pneumococcal conjugate vaccine (PCV13).     

Distribution of capsular serotypes and macrolide resistance mechanisms among macrolide-resistant Streptococcus pneumoniae isolates in Korea

The mechanism of macrolide resistance was investigated in 251 Streptococcus pneumoniae isolates with reduced susceptibility to erythromycin (erythromycin-resistant S. pneumoniae [ERSP]) collected during the period from 2000 to 2004 in Korea. Among these strains, erm(B) was the most prevalent pneumococcal macrolide resistance genotype. In particular, dual mechanisms of both the erm(B) and mef(A) genes were detected in 77 (30.7%) of 251 ERSP isolates. All of the 77 ERSP isolates, with dual erm(B) and mef(A), showed resistance to 2 or more antimicrobial agents, including penicillin, cefotaxime, clindamycin, tetracycline, and levofloxacin. Serotypes 19F, 23F, 19A, 14, 11A, 6B, 6A, and 9V accounted for 73.3% of ERSP isolates. Most of the strains with serotypes 19F (77.2%) or 19A (87.5%) had the dual erm(B) and mef(A) genes. The prevalence and spread of serotype 19F or 19A isolates may have contributed to the high rate of macrolide-resistant pneumococci in Korea. In addition, we identified the emergence of a macrolide-nonsusceptible nonvaccine serotype 35B, which carries mef(A)-mediated resistance to macrolides. These findings emphasize the need for a continuous monitoring of macrolide-resistant S. pneumoniae in Korea.     

Pneumococcal carriage in children attending a hospital outpatient clinic in the era of pneumococcal conjugate vaccines in Barcelona

Between April 2004 and March 2006 an oropharyngeal swab was obtained from 502 asymptomatic children, aged 6 months to 6 years, at a tertiary children's hospital outpatient department to assess the pneumococcal colonisation rate, risk factors, serotype distribution and antimicrobial susceptibility. Only 126 (25.3%) children had received ≥ 1 dose of PCV7. The pneumococcal carriage rate was 23.5%. Carrier rates were significantly higher in children aged ≥ 24 months and children attending daycare center. Thirty six (31.0%) of the isolates were contained in PCV7, 39 (33.6%) in PCV10 and 62 (53.4%) in PCV13. Forty-four strains (37.9%) were resistant to penicillin. Vaccine serotype (VT) strains were more likely to be penicillin-nonsusceptible S. pneumoniae than non-PCV7 serotype (NVT) strains (66.7% vs. 21.6%; P < 0.001). In our pediatric population, NVT were predominant among pneumococcal carriers whereas antibiotic resistance was significantly associated with VT. PCV13 can substantially increase the serotype coverage of S.pneumoniae in healthy carriers.     

Increased nasopharyngeal carriage of serotypes 6A, 6C,and 6D Streptococcus pneumoniae after introduction of childhood pneumococcal vaccination in Hong Kong

Active surveillance on nasopharygeal carriage of Streptococcus pneumoniae in children was conducted in 5581 children under 16 years old admitted with respiratory illness to the pediatric wards in a Hong Kong teaching hospital during 2008–2010. The isolation rate of S. pneumoniae was 14.5%. The most common serotypes/groups from 911 isolates were 19F, 6B, 23F, 14, 6C, 6A, and 3. Considering only children under 2 years old, the percentage serotype belonging to that of the 7-, 10- and 13-valent conjugate pneumococcal vaccines in S. pneumoniae were 56.0% (115/205), 57% (117/205), and 80.5% (165/205), respectively. The prevalence of penicillin-nonsusceptibility (MIC ≥4.0 μg/mL) was 9.1% and for cefotaxime (MIC ≥2.0 μg/mL) was 14.7%. A high prevalence of non-6B serotype, including 6A, 6C, and 6D was noted after the introduction of PCV7 conjugate pneumococcal vaccines in Hong Kong.     

Distribution and annual changes in the proportion of Streptococcus pneumoniae serotypes in Japanese adults with pneumococcal pneumonia from 2011 to 2017

In 2014, vaccinations with 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) were implemented in Japan for all adults aged ≥65 years. We previously clarified reductions in the proportions of PCV7-, PCV13-, and PPSV23-covered serotypes in patients with pneumococcal pneumonia after the initiation of PCV7 and PCV13 vaccinations for Japanese children; however, information about the annual changes in the proportion of Streptococcus pneumoniae serotypes in patients with pneumococcal pneumonia after the initiation of routine PPSV23 vaccinations remains unclear. We retrospectively studied 229 adults with pneumococcal pneumonia which S. pneumoniae was cultured from their lower respiratory tract samples between 2011 and 2017 and investigated the annual changes in the proportion of S. pneumoniae serotypes. The proportion of PPSV23-covered serotypes decreased from 71.4% in 2011 to 52.2% in 2014, but it remained essentially unchanged from 2015 to 2017. The proportions of PCV7-covered serotypes decreased from 46.4% in 2011 to 4.3% in 2014; however, this rate increased beginning in 2015 and reached 20.6% in 2017. Among the PCV7-covered serotypes, the proportion of the 19F serotype increased from 2015 to 2017. In conclusion, there were no obvious changes in the proportion of PPSV23-covered and PCV13-covered serotypes in patients with pneumococcal pneumonia after the initiation of routine PPSV23 vaccinations.     

Epidemiological and molecular characterization of invasive Streptococcus pneumoniae isolated following introduction of 7-valent conjugate vaccine in Kinki region,Japan, 2008–2013

Streptococcus pneumoniae is one of the most common bacteria causing community-acquired pneumonia and meningitis. The use of 7-valent pneumococcal conjugate vaccine (PCV7) has reduced the incidence of pneumococcal disease while changing pneumococcal population through herd immunity and non-vaccine pneumococci replacement. This study investigated molecular epidemiologic characteristics of pneumococcal strains in the Kinki region of Japan from 2008 to 2013. A total of 159 invasive pneumococcal isolates were characterized by serotyping, antibiotic susceptibility testing, PCR analysis of penicillin-binding protein genes, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). In adult populations, pediatric PCV7 introduction decreased isolates expressing PCV7 serotypes via herd immunity and increased isolates expressing non-PCV7 serotypes. The rate of penicillin resistance and isolates with alterations in all three pbp genes was higher in PCV7 type isolates than in non-PCV7 type isolates. In MLST analysis, all of serotype 19F isolates were of the same sequence type, ST236, which is the antimicrobial-resistant clone Taiwan^19F-14, and the majority of serotypes 23F and 19A isolates were of ST1437 and ST3111 respectively, which are the predominant clones of antimicrobial-resistant pneumococci in Japan. In PFGE profiles, serotype 6B-ST2224, serotype 19F-ST236, serotype 19A-ST3111, and serotype 23F-ST1437 formed six separate clusters composed of genetically identical strains, and genetically identical serotype 22F-ST433 formed two different clusters between the pre- and post-PCV7 period. The results of molecular analysis suggest the spread and persistence of these identical antimicrobial resistant clones in the Kinki region and genetic changes of epidemic clone serotype 22F-ST433 before and after pediatric PCV7 introduction.     

Prevalence and molecular characterisation of Streptococcus pneumoniae serotype 6C in Queensland,Australia

Streptococcus pneumoniae serotype 6C was first identified in 2007, although retrospective studies have since identified serotype 6C among stored isolates dating back to 1962. We investigated the incidence and genetic diversity of serotype 6C strains isolated from Queensland patients between 2001 and 2011. Isolates were identified by Quellung reaction and antimicrobial susceptibility testing was performed. The incidence of serotype 6C among serogroup 6 Queensland invasive pneumococcal disease increased from 6.8% (2001–2004) to 39% (2005–2010) of serogroup 6 isolates (P = 0). Genetic diversity of Queensland 6C isolates was high, with molecular analysis identifying 19 sequence types by multi-locus sequence typing, and 35 types by multi-locus variable-number tandem repeat analysis.     

Changes in Pneumococcal Serotypes and Antimicrobial Resistance after Introduction of the 13-Valent Conjugate Vaccine in the United States

Ongoing surveillance for Streptococcus pneumoniae is needed to assess the impact of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S. centers submitted S. pneumoniae isolates between 1 October 2012 and 31 March 2013. Susceptibility testing was performed by use of a broth dilution method as recommended by the Clinical and Laboratory Standards Institute. Serotyping was performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR) was defined as nonsusceptibility to penicillin (PNSP; MIC ≥ 0.12 μg/ml) combined with resistance to ≥2 non-β-lactam antimicrobials. Penicillin-resistant S. pneumoniae (PRSP) was defined as a penicillin MIC of ≥2 μg/ml. For the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and 21.0%, respectively. These percentages were lower than rates obtained in a surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%, respectively). The most common serotypes identified in 2012-13 were 3, 35B, and 19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%). Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional increases were observed in serotypes 35B, 15B, and 23A.     

Changes in nasopharyngeal carriage and serotype distribution of antibiotic-resistant Streptococcus pneumoniae before and after the introduction of 7-valent pneumococcal conjugate vaccine in Hong Kong

This study assessed the changes in serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates in children before and after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Hong Kong. Nasopharyngeal specimens were collected from 1978 and 2211 children (ages, 2 to 6 years) attending day care centers or kindergartens in period 1 (1999-2000) and period 2 (2009-2010), respectively. Carriage of PCV7 serotypes decreased from 12.8% to 8.6% (P < 0.01). The relative contribution of PCV7 serotypes 14 and 18C had decreased, whereas that for non-PCV7 serotypes 19A, 6A, 6C, 23A, and 15B had increased. In period 2, PCV7 penetration rate (at least 1 dose) for children aged 2, 3, 4, and 5 years was 43%, 35.7%, 26.7%, and 20.4%, respectively. In multivariate analysis, PCV7 use was the only independent variable associated with fewer PCV7 serotype carriages (odds ratio 0.5; P = 0.001). In period 2, high rates of dual penicillin/erythromycin nonsusceptibility were found in serotypes 6B (77.3%), 14 (100%), 19F (100%), 23F (78%), 19A (75%), 6A (87.8%), 6C (59.3%), and 23A (78.9%).     

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

In Spain, rates of ciprofloxacin resistance in pneumococci were low during the last decade (2.6% in 2002 and 2.3% in 2006). In 2012, the rate remained at 2.3%, equivalent to 83 of 3,621 isolates. Of the 83 resistant isolates, 15 showed a low level (MIC of 4 to 8 μg/ml) and 68 a high level (MIC of 16 to 128 μg/ml) of ciprofloxacin resistance. Thirteen low-level-resistant isolates had single changes in ParC, one had a single ParE change, and one did not present any mutations. High-level-resistant isolates had GyrA changes plus additional ParC and/or ParE changes: 51, 15, and 2 isolates had 2, 3, or 4 mutations, respectively. Although 24 different serotypes were observed, 6 serotypes accounted for 51.8% of ciprofloxacin-resistant isolates: 8 (14.5%), 19A (10.8%), 11A (7.2%), 23A (7.2%), 15A (6.0%), and 6B (6.0%). A decrease in pneumococcal 7-valent conjugate vaccine (PCV7) serotypes was observed from 2006 (35.7%) to 2012 (16.9%), especially of serotype 14 (from 16.3% to 2.4%; P < 0.001). In comparison with findings in 2006, multidrug resistance was greater in 2012 (P = 0.296), mainly due to the increased presence and/or emergence of clonal complexes associated with non-PCV7 serotypes: CC63 expressing serotypes 8, 15A, and 19A; CC320 (with serotype 19A); and CC42 (with serotype 23A). Although rates of ciprofloxacin resistance remained low and stable throughout the last decade, changes in serotype and genotype distributions were observed in 2012, notably the expansion of a preexisting multidrug-resistant clone, CC63, and the emergence of the CC156 clone expressing serotype 11A.     

Genetic structure of Streptococcus pneumoniae isolated from children in a tertiary care university hospital, in Korea, 1995 to 2005

We investigated the genetic structure of Streptococcus pneumoniae isolated from Korean children prior to the use of heptavalent pneumococcal conjugate vaccine (PCV7). A total of 278 pneumococcal isolates were obtained from invasive (n = 77) and noninvasive (n = 201) specimens from children < 5 years of age that visited the Seoul National University Children's Hospital between 1995 and 2005; these samples were serotyped. Two hundred seventy-eight isolates were characterized by multilocus sequence typing, antibiotic susceptibility pattern testing with the E-test. The common serotypes were 19F (22.7%), 23F (19.1%), 19A (14.4%), 6B (11.2%), 6A (8.3%), 14 (5.4%), and 9V (4.3%); these 7 serotypes accounted for 85.3% of the 278 isolates. The isolates belonged to 23 serotypes and 81 sequence types (STs) (including 48 newly discovered STs). The eBURST analysis showed 7 clonal complexes (CCs). CC271 was the main CC of serogroup 19; CC81 and CC3115, serotype 6A; CC81 and CC880, serotype 23F; CC90, serotype 6B; CC166, serotype 9V; and CC554, serotype 14. Nonsusceptibility rates to penicillin and erythromycin among the invasive isolates were 9.1% and 94.8%, respectively. The resultant database may be useful for postvaccine surveillance.     

Multicenter study of serotype distribution of Streptococcus pneumoniae nasopharyngeal isolates from healthy children in the Russian Federation after introduction of PCV13 into the National Vaccination Calendar

Russia introduced PCV13 in 2014. We studied the serotype composition of S. pneumoniae isolated from the nasopharynx of healthy children younger than 6 years in St. Petersburg, Smolensk, Perm, Krasnoyarsk, Khanty-Mansiysk and Khabarovsk, between 2016 and 2018. 2.4% of children had completed a 3-dose course of PCV13, while 25.6% had received 1 or 2 doses.Pneumococcal DNA detection by PCR demonstrated S. pneumoniae in 37.2% of samples with regional variation between sites (27.3 to 56.9%). There was little difference between vaccinated, partially vaccinated and un-vaccinated children. Children who had received at least 1 dose of PCV13 had lower carriage rates of vaccine serotypes than their unvaccinated peers (49.9 vs. 61.4%; p < 0.001). Children who had received at least 1 dose of PCV13 showed increased carriage rates of non-vaccine serotypes (50 vs 38.6%; P < 0.001). Especially serogroup 15AF was more prevalent among fully immunized children than among their peers (12.5 vs 2.7%; P < 0.05).     

Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan

IntroductionStreptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era).MethodsA total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined.ResultsThe prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166).ConclusionsOur findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents.     

Noninvasive Pneumococcal Clones Associated with Antimicrobial Nonsusceptibility Isolated from Children in the Era of Conjugate Vaccines

Carriage and noninvasive pneumococcal isolates frequently have a higher prevalence of antimicrobial nonsusceptibility than invasive isolates. From 2009 to 2014, we determined the associated clones in 169 pediatric noninvasive nonsusceptible pneumococci from a total of 506 isolates collected after 7- and 13-valent conjugate vaccine introduction (PCV7/13) to the Irish childhood immunization schedule in 2008 and 2010, respectively. We compared our results to those from 25 noninvasive pediatric pneumococcal isolates collected in 2007, the year before introduction of conjugate vaccines. In 2007, England¹⁴-9 and Spain^9V-3 accounted for 12% and 32% of nonsusceptible clones, respectively, but in 2009 to 2014, their prevalence fell to 0% and 2.4%. Furthermore, there was a significant decline in Spain^6B-2 and its variants from 2009 to 2014 (P = 0.0024). Fluctuations occurred in clonal complex 320 associated with serotype 19A. The prevalence of Sweden^15A-25 and its variants and ST558 (a single-locus variant of Utah^35B-24) associated with nonvaccine serotypes (NVT) 15A and 35B increased from 0% and 8% in 2007 to 19% and 16% in 2013 to 2014, respectively. Pilus locus 1 (PI-1) is associated with the spread of some nonsusceptible pneumococcal clones. PI-1 was more frequently associated with PCV7/13 serotypes than NVT (P = 0.0020). Our data highlight the value of surveillance of noninvasive pneumococci following conjugate vaccine introduction. Importantly, emerging clones associated with NVT may limit the effectiveness of PCV7/13 in reducing the high rate of nonsusceptibility among pediatric noninvasive pneumococci, with implications for empirical treatment strategies.     

High prevalence of multiresistance in levofloxacin-nonsusceptible Streptococcus pneumoniae isolates in Korea

Korea exhibits the highest rates of multidrug resistance among Streptococcus pneumoniae. The increasing use of levofloxacin has raised concern about the dissemination of levofloxacin resistance in dominant multidrug-resistant (MDR) clones of our pneumococcal population. A total of 50 levofloxacin-nonsusceptible S. pneumoniae (MIC, ≥4 μg/mL) collected from a multihospital network from 1996 to 2006 were analyzed for serotype, antibiotic resistance profile, quinolone resistance–determining region mutation, and multilocus sequence type. Most levofloxacin-nonsusceptible S. pneumoniae (94.0%) exhibited an MDR phenotype. This phenotype was closely associated with a limited number of epidemic MDR clones that are well-known key agents of the global spread of antimicrobial resistance in S. pneumoniae. However, the clonal dissemination of levofloxacin-nonsusceptible S. pneumoniae was rare. Levofloxacin-nonsusceptible clones with nonvaccine serotypes increased during the post-vaccine era in this study. This result suggests that Korean clinicians must be aware of the levofloxacin resistance trend and need to be more prudent for the first choice of fluoroquinolone for empiric treatment of respiratory tract infections in clinical setting. Moreover, the emergence of new clones and their variations may be more frequently associated with resistance under this selective pressure, such as the introduction of a 7-valent pneumococcal conjugate vaccine into our community.     

Changes in nasopharyngeal carriage of Streptococcus pneumoniae,Haemophilus influenzae and Moraxella catarrhalis among healthy children attending a day-care centre before and after official financial support for the 7-valent pneumococcal conjugate vaccine and H. influenzae type b vaccine in Japan

The 7-valent pneumococcal conjugate vaccine (PCV7) and Haemophilus influenzae type b (Hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria, which may in turn influence the presence of other nasopharyngeal bacterial pathogens. To investigate this possibility, nasopharyngeal carriage of potential pathogens was examined before and after official financial support was provided to offer the PCV7 and Hib vaccines in healthy children attending a day care centre in Japan during 2011–2012. Despite a virtual disappearance of PCV7 serotypes over time, the overall pneumococcal carriage rate remained unchanged. Although others have reported an increase in PCV13 serotypes following PCV7 vaccination, only non-PCV13 serotypes were observed to have increased in this study. The majority of H. influenzae isolates were non-typeable and Hib was not found. Our data identified an unexpected pattern of pneumococcal serotype replacement following PCV7. Continuous monitoring of pneumococcal carriage is important for decisions regarding the future of national vaccination policy in Japan.     

Evolving microbiology of complicated acute otitis media before and after introduction of the pneumococcal conjugate vaccine in France

We compare the microbiology of otopathogens causing recurrent acute otitis media (AOM) or AOM treatment failure in 600 children during 2000 to 2008 before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV-7). Streptococcus pneumoniae predominated before PCV-7 introduction and during 2007 to 2008, whereas Haemophilus influenzae predominated during 2005 to 2006. S. pneumoniae 19A became the most frequent serotype after PCV-7 introduction.