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.     

Serotype distribution and antimicrobial resistance patterns of nasopharyngeal and invasive Streptococcus pneumoniae isolates in Hong Kong children

A study was conducted to determine the vaccine coverage of prevalent carriage and invasive pneumococci from children aged less than 6 years in Hong Kong. A total of 383 nasopharyngeal carriage isolates and 88 invasive isolates from diverse sources were serotyped and their antimicrobial susceptibilities determined. The most common carriage serotypes were the same as the invasive isolates (6B, 14, 19F and 23F), although the rank order of specific serotypes was different. Serotypes in the 7-valent conjugate pneumococcal vaccine (4, 6B, 9V, 14, 18C, 19F and 23F) accounted for 89.7 and 66.1% of the invasive and carriage isolates, respectively. The same seven serotypes comprised 87.5% invasive isolates and 82.8% carriage isolates with resistance to penicillin, erythromycin and/or cefotaxime.     

Long-term antibody levels and booster responses in South African children immunized with nonavalent pneumococcal conjugate vaccine

Children who had initially received three doses of either a nonavalent pneumococcal conjugate vaccine containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, and 23F or placebo at 6, 10, and 14 weeks of age were bled at 9 and 18 months for determination of antibody concentrations. The children were then randomized to receive a booster dose of either the 9-valent pneumococcal conjugate vaccine or a 23-valent polysaccharide vaccine and antibody levels determined 1 month later. At 9 months, the geometric mean concentrations (GMCs) were significantly higher for all vaccine serotypes in vaccinated children compared with controls (means varied from 0.49 microg/ml for serotype 4 to 2.37 microg/ml for serotype 14). At 18 months, antibody concentrations remained significantly higher in vaccinated children (means varied from 0.19 microg/ml for serotype 4 to 1.1 microg/ml for serotype 14). In children who had received conjugate vaccine in infancy, the conjugate vaccine at 18 months produced a significant booster response for serotypes 1, 6B, 14, 19F, and 23F (means varied from 2.74 microg/ml for serotype 19F to 15.52 microg/ml for serotype 6B) and produced a comparable response to a first dose of conjugate at this age for serotypes 4, 5, 9V, and 18C. Boosting at 18 months with polysaccharide vaccine produced higher antibody concentrations to all serotypes in children who had previously received conjugate vaccine compared to children who had not received the conjugate vaccine in infancy. In conclusion, the 9-valent pneumococcal conjugate vaccine given in infancy elicits significant and long-lasting antibody responses which can be boosted with either the conjugate or polysaccharide vaccines.     

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.     

Active surveillance of Streptococcus pneumoniae bacteremia in Italian children

There are few data published regarding the incidence of Streptococcus pneumoniae bacteremia in Italian children. A 14-month surveillance study was conducted in 10 paediatric hospitals to investigate the rate of Sp bacteremia in children aged less than 5 years. The serotype prevalence and antimicrobial susceptibility of isolates were determined. A total of 55 Sp isolates were obtained from 4576 blood cultures (incidence rate, 1.2%). In order of frequency, the most common serotypes were 14, 23F, 19F, 9V, 1. Serotypes in the 7-valent conjugate pneumococcal vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 70% of isolates under 2 years of age, and 58% in the interval between 2 and 5 years of age.     

Serotype prevalence and antibiotic resistance in Streptococcus pneumoniae clinical isolates among global populations

Streptococcus pneumoniae remains a leading cause of disease in children and adults. Serotypes differ in invasiveness, virulence, and antibiotic resistance; therefore, serotype surveillance is necessary to monitor the burden of pneumococcal disease, especially in the setting of pneumococcal vaccination programs. The Tigecycline Evaluation Surveillance Trial, (TEST), is an on-going global antibiotic susceptibility surveillance program. Serotypes and antibiotic susceptibilities of 2173 invasive S. pneumoniae in this existing database during 2004–2008 were evaluated. Worldwide, serotypes 19A (28%), 19F (10%) and 14 (9%) were the most common in children under 5 years. In adults over 16 years, 19A (13%), 3, 6A and 7F (all 7%) were most common. Serotypes 19A, 6A, 19F, 6B, 15A, 9V, and 14 exhibited significantly higher levels of erythromycin resistance (P < 0.05), while 19A, 19F, 35B, 6A, 6B, 23A, 9V, 15A, and 14 demonstrated higher rates of penicillin resistance (P < 0.05). This analysis of an existing pathogen database provides a snapshot of global serotype data and describes the consequential issue of antibiotic resistance in specific serotypes, many of which are increasingly common causes of invasive pneumococcal disease.     

Serum and salivary anti-capsular antibodies in infants and children vaccinated with octavalent pneumococcal conjugate vaccines, PncD and PncT

We studied the immunogenicity of two octavalent pneumococcal (Pnc) conjugate vaccines; Pnc polysaccharides (PS) of serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and 23F were conjugated to diphtheria or tetanus toxoid (PncD and PncT, respectively). Fifty healthy Finnish infants were vaccinated at the ages of 2, 4, 6, and 15 months with either PncD or PncT. Serum IgG antibodies to the vaccine serotypes were analysed by enzyme-linked immunosorbent assay (EIA). All eight PSs induced a significant antibody response both after the primary series and after the booster. Response to PncD was higher for PSs 3, 9V, 14 and 18C and to PncT for serotype 4. Salivary IgA and IgG anti-Pnc antibodies were measured for serotypes 4, 6B, 9V, 14, 18C, and 19F. Mucosal antibodies were found rarely after the primary series but in a greater proportion after the booster. In conclusion, both vaccines were immunogenic.     

Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: Potential implications for pneumococcal conjugate vaccines

Acute otitis media (AOM) is the most common infection following pneumococcal colonization of the upper respiratory tract. Streptococcus pneumoniae causes 30–60% of AOM cases worldwide. However, not all pneumococcal serotypes cause disease and an association exists with nasopharyngeal colonization by certain serotypes and their propensity to cause AOM. This review examines the global serotype distribution relationship between pneumococcal serotypes and AOM in children aged <18 years and demonstrates that the most common pneumococcal serotypes causing AOM globally are 3, 6A, 6B, 9V, 14, 19A, 19F, and 23F.     

Opsonophagocytic activity against Streptococcus pneumoniae in Indigenous and non-Indigenous patients with severe chronic kidney disease immunized with 13-valent pneumococcal conjugate vaccine

Adults with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive pneumococcal immunization. Some studies suggest that previous immunization with 23-valent pneumococcal polysaccharide vaccine (PPV23) may decrease the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13). Via quantitation of serum IgG, IgM, and IgA specific to 7 pneumococcal serotypes (3, 6B, 9V, 14, 19A, 19F, 23F), we recently found that the response to PCV13 in previously PPV23 immunized patients with severe CKD was inferior compared to PPV23 naïve patients. As a follow-up of the previous study, we assessed the titers of opsonizing antibodies specific to 13 vaccine serotypes in sera collected as per the original clinical trial protocol.Opsonophagocytic activity (OPA) titers were determined in 57 previously PPV23-immunized (Group 1) and 72 PPV23-naïve (Group 2) patients pre- and post-PCV13 immunization (days 28 and 365).Pre-immunization, the geometrical mean titers (GMT) for 3/13 serotype-specific antibodies were significantly higher in Group 1 than in Group 2. PCV13 induced a significant GMT rise in both groups; an increase in 5/13 serotype-specific GMTs in Group 1 and 12/13 GMTs in Group 2 was present at one year post-immunization. Fold increase in GMTs by day 28 ranged between 2.4 (serotype 1) and 24.6 (serotype 6A) in Group 1, and between 4.3 (serotype 3) and 67.0 (serotype 6A) in Group 2. The fold increase was significantly larger in Group 2 than in Group 1 for serotypes 1, 4, 7F, and 18C. Patients of Indigenous ethnic background had significantly higher GMT for serotypes 6B and 23F at baseline, and for serotypes 5, 6B, 14, 18C, 19A, 19F, and 23F at Day 28 post-immunization, compared to the non-Indigenous counterpart.Conclusions: Patients with severe CKD developed functionally active pneumococcal antibodies post-PCV13 immunization. Previously administered PPV23 had a negative impact on several serotype-specific OPA responses to PCV13 that lasted for at least one year post-immunization.ClinicalTrials.gov ID: NCT02370069.     

Serotypes and antimicrobial susceptibilities of invasive Streptococcus pneumoniae before and after introduction of 7-valent pneumococcal conjugate vaccine, Hong Kong, 1995-2009

This study analyzed 828 isolates causing invasive pneumococcal disease (IPD) before (1995-2001, n = 265) and after (2007-2009, n = 563) the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Hong Kong. In children <5 years, serotype 14 had declined (36-15.7%, P < 0.01) while 19A had increased (0-12.9%, P < 0.01) in the before and after periods, respectively. In children aged <5 years, the proportion of PCV7 serotypes declined from 89.5% to 65.7% (72.8% if included cross protection against 6A) with time but that of PCV13 serotypes remained stable (91.4-93.2%). In elderly ≥65 years, 9V and 23F decreased from 3.8% to 0.3% (P = 0.01) and from 18.9% to 7.4% (P <0.01), respectively while 7F increased significantly from 0% to 4.1% (P = 0.04) over the same periods. Among isolates from aged <5 years, dual penicillin/erythromycin resistance increased from 44.1% to 64.2% (P = 0.01). The types that often had dual penicillin/erythromycin resistance were 6B, 14, 19F, 23F, 6A and 19A. The emergence of serotype 19A was associated with expansion of sequence type 320.     

241株肺炎链球菌血清分型及耐药性研究

目的了解肺炎链球菌（Streptococcus pneumoniae,S．p）对常用抗菌药物的敏感性及血清型构成。方法采用纸片扩散法检测241株S．P对6种常用抗菌药物的敏感性;采用荚膜肿胀试验对菌株进行血清学分型。结果241株s．p对利福平、米诺环素、氧氟沙星、复方新诺明、阿奇霉素、氯霉素的耐药率分别为0．41％、77．18％、0％、78．00％、95．44％、22．00％。229株S．P可分为24个血清型／群,主要的流行血清型／群为19F、6B、19A、23F、15、14、6A、3、6C;12株s．p未能分型。多重耐药菌株分布在6B、19A、19F、23F血清型。结论S．P的耐药情况严重,大多数菌株呈多重耐药特征。     

Immunogenicity of PCV24, an expanded pneumococcal conjugate vaccine,in adult monkeys and protection in mice

Invasive pneumococcal disease (IPD) is responsible for serious illnesses such as bacteremia, sepsis, meningitis, and pneumonia in young children, older adults, and persons with immunocompromising conditions and often leads to death. Although the most recent pneumococcal conjugate vaccines (PCVs) have been designed to target serotypes identified as the primary causative agents of IPD, the epidemiological landscape continues to change stressing the need to develop new PCVs. We have developed an investigational 24-valent PCV (PCV24) including serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F all conjugated to CRM197 and evaluated this vaccine in adult monkeys. PCV24 was shown to be immunogenic and induced functional antibody for all vaccine serotypes. Of the serotypes common to PCV13 and V114 (PCV15), PCV24 had a similar immunogenic response with the exceptions of 23F which had higher IgG GMCs for PCV13 and V114, and 7F which had higher GMCs for PCV13. Functional antibody responses were similar for the serotypes in common between PCV24, PCV13 and V114 vaccines, with the exception of serotype 7F which was greater for PCV13. Overall, this study shows that PCV24 provided similar immunogenicity as the lower valent vaccines in adult monkeys with no apparent serotype interference. In addition, PCV24 also provided protection against pneumococcal infection in a mouse challenge model.     

Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children, 2 to 24 months of age, in New-Caledonia

OBJECTIVES: The aims of this study were to determine the prevalence of pneumococcal nasopharyngeal carriage in New-Caledonian children less than two years of age, to define risk factors for carriage, and to document the serotypes present in New Caledonia prior to the implementation of the conjugate pneumococcal vaccine. METHOD AND RESULTS: From August 2002 to April 2003, nasopharyngeal samples were collected on 1040 children less than two years of age during scheduled visits to dispensaries for routine immunization. Of the 1040 samples, 544 (52%) were positive for Streptococcus pneumoniae. The percentage of pneumococcal strains with reduced susceptibility to penicillin (PRSP) was 21%. Several risk factors for pneumococcal carriage were identified. These included the Province that the child lived in, the ethnic group, age, and having a sibling less than 6 years of age. Risk factors for carriage of PRSP carriage were similar but also included additional risk factors such as attendance at day care and a history of antibiotic treatment. The eight most frequent serotypes were 6B, 19F, 14, 23F, 6A, 19A, 11A, and 16F. These serotypes accounted for 60% of all strains detected. The most frequent serotypes of PRSP were 14, 9 V, 19F, 23F, and 6B. They were more often identified in european children and 80% were vaccine serotypes. However, overall 250/544 (46%) of all pneumococcal isolates were those included in the 7 serotype vaccine.     

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype 19F and 23F strains in Japan

A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40 (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%) were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.     

Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model

The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar^® (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar^® at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar^® were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.     

Association of serotype with respiratory presentations of pneumococcal infection,Ontario, Canada, 2003–2011

BackgroundPneumococcal disease burden is difficult to quantify due to limited data regarding non-bacteremic disease. We assessed serotype-specific differences in pneumococcal disease presentations in adults in Toronto, Canada.MethodsFrom 2003 to 2011, population-based surveillance for invasive pneumococcal disease was conducted and respiratory pneumococcal isolates collected in Metropolitan Toronto/Peel Region, Canada. Episodes of care were classified into disease categories.ResultsOf 3105 eligible cases of IPD, 2060 cases were bacteremic pneumonia, and 1045 bacteremia without pneumonia. Of 2751 eligible respiratory cases, 1542 (56.0%) were non-bacteremic pneumonia (NBPP), 467 (17.0%) were other acute respiratory infection (oARI), and 742 (27.0%) were isolates representing colonization. Serotypes 3 (11.3%), 19A (8.4%) and 22F (6.2%) were the most common; serotypes 1,5, and 8 were rare. Serotypes 4, 14, 7F, 9V, 12F, 14, 19A and 6C were over-represented in bacteremic disease, and serotypes 3, 6A, 11A, 19F, 23A, 23F, 35B, 35F were more common in NBPP. The proportion of cases due to PCV7 serotypes declined from 48.7% to 8.7% in bacteremic pneumonia, from 35.3% to 10.9% in NBPP, from 34.2% to 7.5% in oARI, and from 38.7% to 12.2% in colonizing isolates. In 2010–2011, PCV13 serotypes accounted for 62.6% of isolates associated with bacteremic pneumonia, 42.0% of bacteremia without pneumonia, 41.1% of NBPP, 25.7% of oARI, and 32.9% of colonizing isolates.ConclusionsSerotype distributions differ significantly in different presentations of pneumococcal disease. Herd protection due to PCV7 has changed serotype distribution, but PCV13 serotypes remain important in all categories of disease.     

Incidence of invasive pneumococcal disease and distribution of capsular types of pneumococci in Denmark, 1989-94.

During the period 1989-94, 4620 strains of Streptococcus pneumoniae (4063 from blood and 557 from cerebrospinal fluid), from cases of invasive disease in Denmark, were received for capsular typing and penicillin susceptibility testing. During the study period the incidence of bacteraemic pneumococcal disease increased from 10 to 18 cases per 100000 inhabitants per year. The highest rates were seen in the very young, age less than 5 years (23/100000/year, in 1994), and in the elderly, age greater than 60 years (55/100000/year, in 1994). The annual number of cases of meningitis did not vary. Overall, 92% (93% blood, 87% CSF) of isolates and 94% of all childhood isolates belonged to the 23 vaccine types. The capsular types occurring most commonly among the 4123 pneumococcal strains from adults were types 1, 4, 14, 6A + 6B, 7F, 9V, 3, 12F, and 8 (in order of frequency). The ten most frequently occurring types from children (6A + 6B, 18C, 14, 1, 7F, 19F, 9V, 4, and 23F) covered 84% of the cases of bacteraemia and meningitis. Reduced susceptibility to penicillin was rare (< 1%).     

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.     

The immunogenicity of pneumococcal polysaccharides in infants and children: a meta-regression

The immunogenicity of plain (not conjugated) pneumococcal polysaccharides in children and infants was reviewed using a systematic literature search. Immunogenicity was defined as the fold-increase in serotype specific antibody concentration after a single dose of plain polysaccharide vaccine in unprimed subjects. Meta-regression was used to calculate the influence of study treatments including subject age, sampling time, dosage, immunization route, vaccine composition and study location. Immunogenicity increased with age for all serotypes, and the increase was more rapid in the first 11 months of life. Study location was the next most significant study variable, with higher responses in countries with lower GDP. A flat dose-response curve was observed over a range from 5 to 50 μg polysaccharide. Serotypes 6A, 6B, 14, 19F and 23F were significantly less immunogenic than serotypes 2, 3, 4, 7F, 8, 9N, 9V and 18C in 11 month old children, but continued to increase in immunogenicity with age until reaching similar levels at 6 years. Some proposed T-independent immune mechanisms could explain the differences in serotype immunogenicity.     

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).