Changes in serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from adult patients in Asia: Emergence of drug-resistant non-vaccine serotypes

This study was performed to investigate the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in Asian countries. A prospective surveillance study on S. pneumoniae collected from adult patients (≥50 years old) with invasive pneumococcal disease or community-acquired pneumonia was performed at 66 hospitals in Asian countries (Korea, China, Malaysia, Singapore, the Philippines, and Thailand) in 2012-2017. Serotyping and antimicrobial susceptibility tests of 850 pneumococcal isolates were performed. The proportions of isolates with serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) were 37.0% in Korea, 53.4% in China, 77.2% in Malaysia, 35.9% in the Philippines, 68.7% in Singapore, and 60.2% in Thailand. Major serotypes were 19F (10.4%), 19A (10.1%), and 3 (8.5%) in 2012-2017, with different serotype distributions in each country. Macrolide resistance in pneumococci was high (66.8%) and prevalence of multidrug resistance (MDR) also remained high (50.8%). MDR non-PCV13 serotypes such as 11A, 15A, 35B, and 23A have emerged in Asian countries. This study showed the persistent prevalence of 19F and 19A with a noteworthy increase of certain non-PCV13 serotypes in Asian countries. High prevalence of macrolide resistance and MDR was also found in pneumococcal isolates. These data emphasize the need for continued surveillance of pneumococcal epidemiology in Asia in the post-pneumococcal vaccine era.     

Serotypes,antimicrobial susceptibility,and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012–2014

Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6–71.4%, p = 0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p = 0.029 and p = 0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden^15A-25 clone).     

Distribution, dynamics and antibiotic resistance patterns of Streptococcus pneumoniae serotypes causing acute otitis media in children in southern Israel during the 10 year-period before the introduction of the 7-valent pneumococcal conjugate vaccine

Objectives

To determine the dynamics of serotype prevalence, potential coverage by pneumococcal conjugate vaccines (PCV) and antibiotic resistance patterns of Streptococcus pneumoniae causing acute otitis media (AOM) in children in southern Israel before PCV7 introduction in the routine immunization program in Israel.

Methods

All S. pneumoniae isolates from middle ear fluid from children with AOM during 1999-2008 were included. Prospectively collected demographic data on S. pneumoniae serotypes and antibiotic resistance patterns were analyzed.

Results

A total of 14,911 tympanocenteses yielded 5281(35%) S. pneumoniae. Proportion of S. pneumoniae-AOM did not vary significantly (overall 35%; 33% in 2007; 38% in 2002 and 2003). The most frequent serotypes were 19F, 14, 23F and 19A; in both Jewish and Bedouin children; serotypes 6A and 19A contributed 6% and 10%, respectively, of all S. pneumoniae isolates. Serotypes included in PCV7, PCV10 and PCV13 represented 60%, 64%, 85% in Jewish children vs. 49%, 55% and 74%, respectively, in Bedouin children (P < 0.001). Nonsusceptibility to TMP/SMX decreased significantly, in parallel with a significant increase in the nonsusceptibility to erythromycin, clindamycin and in multidrug resistant (MDR) isolates. No changes were recorded in the proportion of S. pneumoniae isolates with penicillin MIC ≥ 1.0 μg/ml. The proportion of penicillin- and erythromycin-nonsusceptible and of MDR serotype 6A and 19A isolates increased significantly in Bedouin children.

Conclusions

1) No significant changes were recorded in the yearly proportions of serotypes 23F, 19F, 19A, 14 and 6A in both ethnic populations; 2) Potential coverage of the 3 PCVs was higher in Jewish children than in Bedouin children; 3) The relatively high coverage of macrolides- and multidrug-resistant S. pneumoniae by PCV13 and lack of increase in penicillin, erythromycin and multidrug nonsusceptibility among non-PCV13 isolates is encouraging.     

Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia

Background

In Bogotá, the Heptavalent Conjugate Vaccine (PCV7) was introduced into childhood immunization schedule since 2009. The aim of this study was to assess the changes in serotype distribution and penicillin susceptibility of Streptococcus pneumoniae isolates recovered from nasopharyngeal samples and invasive disease among children living in Bogotá, before and after PCV7 introduction.

Methods

Nasopharyngeal swabs were collected from healthy children aged between 12 and 18 months of age before (years 2005–2006) and after (2011) PCV7 introduction. Identification of S. pneumoniae was performed by multiplex PCR. Serotype was determined by PCR and Quellung reaction. Susceptibility to penicillin, ceftriaxone, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline and erythromycin was evaluated. In addition, distribution of serotypes and antimicrobial susceptibility before and after vaccine introduction among invasive isolates recovered from children ≤2 years old living in Bogotá was analyzed.

Results

Prevalence of pneumococcal nasopharyngeal carriage declined from 55.7% (137/246) in unvaccinated to 44.2% (87/197) (p = 0.01) in vaccinated children. The proportion of children carrying PCV7 serotypes decreased from 23.6% (58/246) to 7.6% (15/197) (p < 0.001). The decrease was counterbalanced by an increase in the proportion of non-PCV7 serotypes. The most prevalent among emerging serotypes were 15A, 15B, 15 C, 11A and 35B. Among IPD isolates, PCV7 serotypes decreased from 69.1% (235/340) in 2005/2009 to 38.0% (32/84) in 2010/2011 (p < 0.001). The increase of non-PCV7 serotypes was significant. Resistance to penicillin among invasive isolates recovered from meningitis decreased from 41.1% (30/73) in the pre-vaccine period to 14.2% (2/14) in post-vaccine period (p = 0.02).

Conclusions

A decrease in the prevalence of pneumococcal nasopharyngeal carriage following the introduction of PCV7 vaccine, have been overshadowed by an important surge in the prevalence of non-PCV7 serotypes. Systematic surveillance combining nasopharyngeal carriage surveys and IPD detection could help in evaluating the impact of conjugate vaccines.     

Serotype distribution and antibiotic resistance of 140 pneumococcal isolates from pediatric patients with upper respiratory infections in Beijing, 2010

In the present study, the serotype distribution and antibiotic resistance of S. pneumoniae from pediatric patients with upper respiratory infections in Beijing, 2010 were described. 140 pneumococcal isolates were obtained, and the prevailing five serotypes were 19F (18.6%), 23F (9.3%), 14 (9.3%), 15 (9.3%), and 6A (7.1%). The vaccine coverage of PCV7, PCV10, and PCV13 were 43.6%, 43.6%, and 60.0%, respectively. According to the CLSI 2010 criteria, 99.3% of the S. pneumoniae isolates were susceptible to penicillin. The resistance rates to erythromycin and azithromycin were 96.4% and 97.1%, respectively. Meanwhile, 64.3% (90/140) of all pneumococcal isolates were multidrug-resistant S. pneumoniae (MDRSP). PCV13 covered 68.9% (62/90) of MDRSP strains, whereas it was 47.8% (43/90) for PCV7. ErmB was the dominant macrolide-resistance gene, whereas 30.4% pneumococcal isolates expressed both ermB and mefA. No isolate expressed ermTR. The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 6A and 19A, and the conjugate vaccines could prevent the spread of MDRSP. S. pneumoniae is still sensitive to penicillin. The resistance rate of S. pneumoniae to macrolides is high and ermB is the dominant macrolide-resistance gene in China, so continued surveillance of the antimicrobial susceptibility of S. pneumoniae may be necessary.     

Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece

In order to study whether the use of the heptavalent pneumococcal conjugate vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 2649 nasopharyngeal samples were obtained between 2005 and 2009, from children attending day-care centers in Central Greece. The percentage of attendees vaccinated with ≥1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non-PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the only PCV7 serotype that continued to circulate. A significant increase in the frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates coincided with a marked reduction in isolates with high resistance to penicillin. Several non-PCV7 serotypes colonized the children, but their frequency varied substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e. 6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted for ≥2% of pneumococcal isolates in at least 2 annual surveillances. An increase in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred. Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C, 15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive disease remains to be seen in the years ahead.     

One cross-sectional investigation revealed that non-vaccine serotypes of Streptococcus pneumoniae could be identified more frequently in elderly Chinese people

ObjectiveTo analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from hospitalized patients of all ages in Zhongjiang county, Sichuan province, where the young children have just begun to vaccinate the PCV13 in private sector.MethodsSerotypes were determined for 387 isolates of S. pneumoniae by Quellung reaction. Antibiotic susceptibility was tested with the E-test or disc diffusion method.ResultsThe most common serotypes were type 19F and confirmed for 88 isolates (22.7%), followed by 19A (15.0%), 6B (7.8%), 16F (7.8%), 23F (7.0%) and 15A (4.4%). The coverage rates of PCV13 and PPSV23 were 63.3% and 65.1%. With the increase of age, the proportion of PCV13 types decreased significantly, from 71.3% (<2 years old) to 41.9% (≥60 years old). The intermediate rate and resistance rate of the isolates to oral penicillin were 48.6% and 45.2%, respectively. The resistance rate of erythromycin was high (94.4%). The PCV13 isolates was more resistant to penicillin than the non-PCV13 ones.ConclusionThe PCV13 coverage rate in pediatric isolates was higher than those in adult isolates. The adults, especially the elderly, may be the reservoir of non-PCV13 types. It is necessary to investigate the serotype distribution of S. pneumoniae based on all age population to assess potential epidemics of non-vaccine serotype associated with PCVs administration.     

Invasive Streptococcus pneumoniae isolates from pediatric population in Argentina for the period 2006–2019. Temporal progression of serotypes distribution and antibiotic resistance

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. A total of 2908 pneumococcal isolates were analyzed between 2006 and 2019. Gold standard pneumococcal serotyping (the Neufeld-Quellung reaction) was performed to identify the serotypes associated with infection in children < 5 years in Argentina and agar dilution method was carried out to determine their profiles to 14 antimicrobial agents.In 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) was included in the National Immunization Program. In this work we have analyzed the local epidemiology of invasive pneumococcal diseases before and after the introduction of this vaccine in order to understand the epidemiological relevance and impact of PCV13.During the periods compared in the present study there was a significant increase in the proportion of non-PCV13 serotypes, serogroup 24 (246.7%) and 12F (85.7%), and a significant decrease in PCV13 serotypes, including serotypes 14 (91.2%), 5 (95.6%) and 1 (84.6%) among others. Another observation was that serotypes 3 (7.4%) and 19A (4.9%) still remain among the most frequent serotypes despite being part of the PCV13 formulation. Regarding antimicrobial resistance, in the present study we observed an increase in erythromycin resistance during the period of study mainly associated to serotype 14 in the pre-PCV13 period and to serogroup 24 in the post-PCV13 period, which also was the major NVT serotype associated with antimicrobial resistance and MDR. Serotypes 14, 24A/B/F and 19A were in the first three places among isolates resistant to all the antibiotics tested.Our data highlight the importance of continuous surveillance to assess the impact of pneumococcal vaccines and the use of antibiotics in the dynamic of pneumococcal serotypes.     

Dynamics of pneumococcal carriage among day-care center attendees during the transition from the 7-valent to the higher-valent pneumococcal conjugate vaccines in Greece

Background

In Greece recently, higher-valent pneumococcal conjugate vaccines (PCVs) replaced the 7-valent (PCV7); the 10-valent (PCV10) became available in May 2009 and the 13-valent (PCV13) in June 2010.

Methods

We investigated the nasopharyngeal colonization with Streptococcus pneumoniae in day-care center attendees in Athens and the prefecture of Viotia. Between December 2010 and June 2011, nasopharyngeal cultures were obtained 4 times, at enrollment and then every 6 to 8 weeks.

Results

Among the 233 children, 225 (96.6%) had been vaccinated with ≥1 dose of PCV7. One tenth of the PCV7 vaccinated attendees had also received ≥1 dose of PCV13 or PCV10. During the 4 samplings, 358 isolates were recovered from a total of 874 samples. Of the 233 children, 183 (78.5%) were found to carry S. pneumoniae at least once. The overall serotype distribution among carriers was similar regardless of the time lapsed since the last PCV7 dose. A high frequency of 19A (17.1%) coincided with a low frequency of 19F (1.4%). Non-PCV13 serotypes accounted for 73.1% of the isolates; 23B, 15B/C, 16F, 21, 11A, 15A, 6C, 10A, 22F and 23A were the most common. Among attendees aged 24–59 months (median age 42 months), prolonged carriage of a non-PCV13 serotype was relatively common, mainly for 21 and 16F. One out of 4 cases of colonization with the prevalent non-PCV13 serotypes was followed by persistent carriage for 5 to 14 weeks.

Conclusions

During this period of transition to the higher-valent PCVs in the day-care center setting, non-PCV13 serotypes dominated and exhibited prolonged colonization. The frequency and the duration of prolonged carriage tends to be increased, if sampling frequency increases and the carriage time before and after positive cultures is taken into consideration. Further studies regarding the fitness of the colonizing non-PCV13 serotypes will likely to be seen in the future.     

Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE)

BackgroundThe pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described.MethodsThe first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype.ResultsA total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p < 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49–4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02–2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes.ConclusionsThe occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.     

Pneumococcal serotype distribution and antimicrobial resistance in Chinese children hospitalized for pneumonia

A prospective study was performed to determine serotype distribution and antimicrobial resistance in Streptococcus pneumoniae (S. pneumoniae) from Chinese children <5 years old meeting pneumonia criteria. A total of 3865 children were enrolled and 338 S. pneumoniae isolates were obtained. The most frequent serotypes were 19F (55.6%), 19A (13.9%), 23F (10.1%), 6B (4.7%), and 14 (3.6%). The 7-, 10- and 13-valent conjugate vaccines, respectively, covered 76.3%, 76.9%, and 92.3% of isolates. Out of the isolates, six (1.8%) were penicillin resistant. All except 1 of the isolates were resistant to erythromycin. Serotype 19A showed the highest drug resistance. The use of PCV7 has the potential to prevent a substantial number of pneumococcal infections. However, PCV13 is likely to prevent more episodes of pneumococcal disease in China because of the high rates of 19A.     

Pneumococcal disease caused by serotype 19A: Review of the literature and implications for future vaccine development

Streptococcus pneumoniae serotype 19A is associated with all forms of pneumococcal disease and was the first reported pneumococcal serotype with high-level penicillin and multidrug resistance. While the seven-valent pneumococcal conjugate vaccine (PCV7), which contains serotype 19F, has reduced rates of disease among children and adults, the incidence of disease due to nonvaccine and increasingly drug-resistant serotypes – predominantly serotype 19A – has increased. This review summarizes the published literature to analyze the factors contributing to the emergence of serotype 19A, the diseases associated with this serotype, and the importance of including this serotype in novel pneumococcal conjugate vaccines. A recently approved 13-valent vaccine includes this serotype, and is likely to significantly reduce the burden of disease due to serotype 19A.     

Serotype coverage of pneumococcal conjugate vaccine and drug susceptibility of Streptococcus pneumoniae isolated from invasive or non-invasive diseases in central Thailand, 2006–2009

The serotype of 172 S. pneumoniae isolates obtained from normally sterile sites from January 2006 to February 2009 in Thai patients was evaluated. The most common serotypes were 6B, 23F, 14, 19F, and 19A in patients <5 year-old, and 6B, 19A, 23F, 4, 9V in patients >65-year old. Seven-valent pneumococcal conjugated vaccine (PCV-7) covered 70.3%, 43.6%, and 43.5% of patients <5, 5–64 and ≥65 years of age, respectively, while PCV-13 covered 81.2%, 59.7%, and 60.9%, respectively. PCV-9, PCV-10, PCV-11 had very similar coverage as PCV-7. The antibiotic susceptibility rates of the isolates from sterile sites were 88.7–95.7% for penicillin, 90.6–98.4% for cefotaxime, 92.2–100% for ofloxacin and 100% for ciprofloxacin. PCV-7 covered 83% and 100%, respectively, of penicillin and cefotaxime non-susceptible isolates in patients <5-year old.     

Increase in Streptococcus pneumoniae serotype 3 associated parapneumonic pleural effusion/empyema after the introduction of PCV13 in Germany

IntroductionPediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs).MethodsIn a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped.ResultsS. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1–4.3 years] vs. median 5.6 years [IQR 3.8–8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1.ConclusionFollowing the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3.     

Effect of the introduction of pneumococcal conjugate vaccines on serotype prevalence in Kuwait and Saudi Arabia

BackgroundStreptococcus pneumoniae infection is a major cause of morbidity and mortality. Although pneumococcal disease burden in Kuwait and Saudi Arabia is considered high, comprehensive surveillance data on pneumococcal conjugate vaccine (PCV) effects are lacking.MethodsSterile isolates from patients in Kuwait (2003–2016) and Saudi Arabia (aged ≤5 years, 2000–2010; all patients, 2011–2015) were included. Serotyped isolates were classified by inclusion in the 7-valent (PCV7) or 13-valent PCV (PCV13); isolates of other serotypes were classified as “non-PCV13”. Isolate frequency (number of isolates/year) and classification of isolates according to vaccine type were assessed by period (before PCV, after PCV7, and after PCV13 introduction).ResultsIn Kuwait, the frequency of collected isolates was highest after PCV7 introduction. Decreased frequency of PCV7 serotypes was seen after PCV13 introduction compared with before PCV and after PCV7 introduction. Increased frequency of the 6 additional serotypes in PCV13 and non-PCV13 serotypes was observed after PCV7 introduction with a subsequent decrease in the 6 additional serotypes in PCV13 and non-PCV13 serotypes after PCV13 introduction. The percentage of isolates of vaccine serotypes in Kuwait decreased over time. In Saudi Arabia, the frequency of collected isolates was highest after PCV7 introduction. An increased frequency of PCV7 serotypes was observed after PCV7 introduction, with a further decrease after PCV13 introduction. For the 6 additional serotypes in PCV13, an increased frequency was seen after PCV7 and PCV13 introduction compared to before PCV introduction. For non-PCV13 serotypes, an increased frequency was observed after PCV13 introduction compared to after PCV7 introduction. The percentage of isolates covered by PCV13 serotypes was similar across periods, while a substantial decrease in isolates covered by PCV7 was seen after PCV13 introduction.ConclusionPCVs in Kuwait and Saudi Arabia resulted in decreased frequency of some vaccine serotypes and an emergence of some non-PCV13 serotypes. Further investigation is warranted.     

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea

BackgroundThis study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs).MethodsFrom April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility.ResultsA total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P < 0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P = 0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one.ConclusionHigh rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea.     

Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study

Background

In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected.

Methods

Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003–2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007–2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively.

Findings

The proportion of PCV7 serotypes among all IPD cases (n = 7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P < 0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P = 0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P = 0.008), 19A (P = 0.03) and 19F (P = 0.005), compared to serotype 1 and 7F.

Conclusion

There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.     

Predominance of nontypeable Haemophilus influenzae in children with otitis media following introduction of a 3+0 pneumococcal conjugate vaccine schedule

In Australia the 7-valent pneumococcal conjugate vaccine (PCV7) is administered at 2, 4 and 6 months of age, with no booster dose. Information on bacterial carriage and the aetiology of recurrent acute otitis media (rAOM) after introduction of PCV7 using the 3 + 0 schedule is required to evaluate the potential impact of second generation pneumococcal vaccines. We found that 2-4 years after introduction of PCV7 in the National Immunisation Program, nontypeable Haemophilus influenzae (NTHi) was the predominant pathogen isolated from the nasopharynx and middle ear of children with a history of rAOM. Compared with healthy controls (n = 81), NTHi and Streptococcus pneumoniae carriage rates were significantly higher in children with a history of rAOM (n = 186) (19% vs. 56% p < 0.0001 and 26% vs. 41%, p = 0.02, respectively). Carriage of PCV7 pneumococcal serotypes was rare, whereas PCV7-related and non-PCV7 serotypes were isolated of 38% of cases and 24% of controls. Serotype 19A was the most common serotype isolated from the nasopharynx and middle ear and accounted for 36% (14/39) of total pneumococcal isolates with reduced susceptibility to cotrimoxazole. Of the 119 children carrying NTHi, 17% of isolates were β-lactamase positive.The scarcity of PCV7 serotypes in children with and without a history of rAOM indicates that the 3 + 0 PCV7 schedule is preventing carriage and rAOM from PCV7 serotypes. Introduction of new vaccines in Australia with increased pneumococcal serotype and pathogen coverage, including 19A and NTHi, should decrease the circulation of antibiotic-resistant bacteria and reduce the burden of rAOM.     

Dynamic of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 introduction in France

To determine whether the use of seven valent pneumococcal conjugate vaccine (PCV7) caused a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 3291 nasopharyngeal swabs were obtained between 2001 and 2006, from children aged 6–24 months with acute otitis media. Following the implementation of PCV7, we observed a slight reduction in the overall pneumococcal carriage, a marked decrease of vaccine serotypes, an increase in non-vaccine serotypes carriage and a reduction in the carriage of penicillin non-susceptible strains. Most of the serotype 19A replacement was related to the clonal expansion of ST276 which was found to be the predominant ST among penicillin non-susceptible isolates.     

The changing phenotypes and genotypes of invasive pneumococcal isolates from children in Shenzhen during 2013–2017

BackgroundThe phenotypes and genotypes of Streptococcus pneumoniae isolated from invasive pneumococcal diseases (IPDs) were changing all the time. To monitor these changes of phenotypes and genotypes of S. pneumoniae isolates from children, we examined antibiotic susceptibility, serotype distribution and sequence types (STs) of S. pneumoniae, which were isolated before the 13-valent pneumococcal conjugate vaccine (PCV13) introduced into China.MethodsStrains were isolated from children less than 14 years old between January 2013 and May 2017 from Shenzhen Children’s Hospital. Serotypes, antibiotic resistance, and genotypes of these isolates were determined using capsular swelling, E-test, and multi-locus sequence typing, respectively.ResultsA total of 94 S. pneumoniae strains were isolated, which belonged to 15 serotypes. The five most prevalent serotypes were 19F (25.5%), 19A (19%), 14 (17%), 23F (7.5%), and 6B (9.6%). We found 42 STs for these isolates. The most abundant STs were ST271 (24.4%), ST876 (17%), and ST320 (10.6%), mainly related to 19F, 14, and 19A, respectively. The potential coverage of PCV13 was 87.2%. Among non-meningitis isolates, the resistance rates to penicillin and ceftriaxone were 0% and 2%. However, the meningitis isolates showed high resistance to penicillin (80%) and ceftriaxone (20%). Most of these isolates (95.7%) were resistant to erythromycin, and 66 (70.2%) strains carried the ermB gene and 24 (25.5%) strains carried both the ermB and mefA/E genes. Serotype 19A showed the highest mean minimum inhibitory concentration (MIC) for penicillin (MIC = 1.486) than the other serotypes, but no significant difference in penicillin MIC among the three main STs (ST271, ST320, and ST876).ConclusionsThe phenotypes and genotypes of invasive pneumococcal isolates from Shenzhen Children’s Hospital have changed with the passage of time. Compared with PCV7, PCV13 can more effectively protect Chinese children from IPDs. To some extent, these changes are possibly related to the usage of antibiotics and vaccines.