Increasing Incidence of Penicillin- and Cefotaxime-resistant Streptococcus pneumoniae Causing Meningitis in India: Time for Revision of Treatment Guidelines?

Purpose: Pneumococcal meningitis is a life-threatening infection, requiring prompt diagnosis and effective treatment. Penicillin resistance in pneumococcal infections is a concern. Here, we present the antibiotic susceptibility profile of pneumococcal meningeal isolates from January 2008 to August 2016 to elucidate treatment guidelines for pneumococcal meningitis. Materials and Methods: Invasive pneumococcal isolates from all age groups, were included in this study. Minimum inhibitory concentrations for the isolates were identified by agar dilution technique and VITEK System 2. Serotyping of isolates was done by co-agglutination technique. Results: Out of 830 invasive pneumococcal isolates, 167 (20.1%) isolates were from meningeal infections. Cumulative penicillin resistance in pneumococcal meningitis was 43.7% and cefotaxime non-susceptibility was 14.9%. Penicillin resistance amongst meningeal isolates in those younger than 5 years, 5–16 years of age and those aged 16 years and older was 59.7%, 50% and 27.3%, respectively, with non-susceptibility to cefotaxime in the same age groups being 18%, 22.2% and 10.4%. Penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016. Serotypes 14, 19F, 6B, 6A, 23F, 9V and 5 were the most common serotypes causing meningitis, with the first five accounting for over 75% of resistant isolates. Conclusions: The present study reports increasing penicillin resistance and cefotaxime non-susceptibility to pneumococcal meningitis in our setting. This highlights the need for empiric therapy with third-generation cephalosporins and vancomycin for all patients with meningitis while awaiting results of culture and susceptibility testing.     

The antimicrobial susceptibility in adult invasive pneumococcal disease in the era of pneumococcus vaccination: A hospital-based observational study in Taiwan

BackgroundA regional antibiotic susceptibility data of common pathogens is crucial to first-line physician for clinical judgment and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiology data of drug resistance of pneumococcus causing invasive pneumococcal disease (IPD) in adults.MethodsFrom the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients in three hospitals in Taiwan from July 2011 to June 2015. Antibiotic resistance and serotypes of the isolates and clinical manifestations were further analyzed.ResultsA total of 150 non-duplicated isolates were collected. According to CLSI meningitis breakpoint, the proportion of ceftriaxone non-susceptible pneumococcus (CNSP) showed an increasing trend from 4.5% in 2011 to > 40% in 2013–2015 (p = 0.007). Serotypes 19A and 23F were significantly associated with CNSP. Imipenem and meropenem had a relative low susceptible rate of 36.7% and 50.7%, respectively. Serotypes 6A, 14, 19A and 19F were significantly associated with the non-susceptibility to these carbepanems.ConclusionThe increase in the prevalence of CNSP using meningitis breakpoint was observed. For treating pneumococcal meningitis, empirical monotherapy with ceftriaxone might not be adequate. Imipenem and meropenem might not be a good choice for empirical treatment of adult IPDs. Antibiotic resistance of pneumococcus to ceftriaxone, cefepime, imipenem and meropenem were associated with 13-velent pneumococcal conjugate vaccine serotypes.     

Emerging non-13-valent pneumococcal conjugate vaccine (PCV13) serotypes causing adult invasive pneumococcal disease in the late-PCV13 period in Spain

ObjectiveAn early reduction of adult invasive pneumococcal disease (IPD) was observed after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction for children in Spain. We analysed the epidemiology of adult IPD in the late-PCV13 period.MethodsThis was a prospective multicentre study of adult IPD involving six hospitals. Strains were serotyped, genotyped and studied for antimicrobial susceptibility. The late-PCV13 period was compared with the pre- and early-PCV13 periods.ResultsA total of 2197 episodes were collected—949 in 2008–2009, 609 in 2012–2013 and 639 in 2015–2016. The initial decrease of IPD observed (from 12.3/100 000 to 8.1/100 000; 2008–2009 versus 2012–2013) plateaued in 2015–2016 (8.3/100 000). IPD due to PCV13 serotypes decreased (from 7.7 to 3.5 to 2.3/100 000; p < 0.05), whereas IPD caused by non-PCV13 serotypes increased (from 4.5 to 4.6 to 6.0/100 000; p < 0.05). The most frequent serotypes in the late-PCV13 period were: 8 (15.1%), 3 (10.5%), 12F (7.9%) and 9N (5.4%). These serotypes were related to major genotypes: CC53 (59.8%) and CC404 (30.4%) for serotype 8, CC180 (64.1%) and CC260 (28.1%) for serotype 3, CC989 (91.7%) for serotype 12F and CC67 (84.8%) for serotype 9N. Penicillin-non-susceptibility (21.2%) was associated with serotypes 11A (CC156), 14 (CC156) and 19A (CC320), and macrolide-resistance was related to serotypes 24F and 19A. Rates of pneumococcal meningitis remained stable throughout the periods (ranges 0.9, 0.8 and 1.0/100 000).ConclusionsThe initial decrease of adult IPD observed after PCV13 introduction for children has been balanced by the rise of non-PCV13 serotypes. The spread of antibiotic-resistant lineages related to non-PCV13 serotypes (11A and 24F) could be a threat for the treatment of serious pneumococcal diseases.     

The clinical implication of serotype distribution and drug resistance of invasive pneumococcal disease in children: A single center study in southern Taiwan during 2010–2016

BackgroundThe regional study of pediatric invasive pneumococcal disease (IPD) is still limited in Taiwan. The aim of this study is to update the epidemiologic data of pediatric IPD in Taiwan, focusing on the trend of non-13-valent pneumococcal conjugate vaccines (PCV13)-specific serotypes and antimicrobial susceptibility.MethodsThis was a single-center retrospective study by chart reviewing and recruited patients aged <18 years who were reported having IPD between January 2010 and December 2016. Clinical manifestations, serotypes of pneumococcus and antimicrobial susceptibility were compared and analyzed.ResultsA total of 46 patients were enrolled in this study. Serotype 19 A was the most common serotype (32.6%) in pediatric IPD and significantly correlated with empyema. Non-PCV13-specific serotypes such as serotype 15, 15B, 15C and 22 were reported during this period. There was no mortality or significant morbidity associated with these emerging strains. Using the meningitis breakpoint of minimum inhibitory concentration (MIC), although it showed no significant linear trend of the prevalence of ceftriaxone non-susceptible pneumococcus (CNSP) (p = 0.392), the prevalence of CNSP increased from 50% (11 over 22) before 2013 to 83% (20 over 24) after 2013 with statistical significance (p = 0.027).ConclusionThe increase in the prevalence of CNSP using meningitis breakpoint was observed since 2013. For treating pneumococcal meningitis, empirical therapy with vancomycin and ceftriaxone is warranted. Although the non-PCV13-specific serotypes reported in our study caused no morbidity and mortality, further monitoring and surveillance are still recommended.     

Antimicrobial susceptibility and serotype replacement of Streptococcus pneumoniae in children before and after PCV13 introduction in Taiwan

BackgroundSince 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections.MethodsChildren with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration.ResultsIn total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p < 0.001). The prevalence of serotype 19 A had increased gradually since 2010 but declined rapidly after 2013. Serotypes 15 A and 23 A were the most common serotypes after 2015. The non-susceptibility of the S. pneumoniae isolates to penicillin, cefotaxime, and ceftriaxone decreased. Based on meningitis breakpoints, the non-susceptibility to cefotaxime and ceftriaxone gradually decreased, but increased in 2020.ConclusionPCV13 was considerably effective in reducing the incidence of IPD in children; however, the prevalence of serotypes 15 A and 23 A increased. The increase in antimicrobial non-susceptibility caused by non-vaccine serotypes must be continuously monitored.     

Changes in serotypes causing invasive pneumococcal disease (2005–2007 vs. 1997–1999) in children under 2 years of age in a population with intermediate coverage of the 7-valent pneumococcal conjugated vaccine

Serotypes causing invasive pneumococcal disease (IPD) in children aged <2 years in Catalonia (Spain) before and after licensing of the 7-valent pneumococcal conjugated vaccine (7vPCV) were assessed, using samples taken during 1997–1999 and 2005–2007 respectively. The distribution of serotypes causing IPD within these groups was obtained by serotyping strains sent by 22 Catalan hospitals to the Carlos III Health Institute, Madrid. Between 1997–99 and 2005–2007, the proportion of vaccine serotypes causing IPD in Catalonia fell from 70.54% to 31.67% (p <0.0001). The proportion of vaccine-related serotypes, mainly serotype 19A, increased from 9.82% to 32.50% (p <0.0001). The proportion of non-vaccine, non-related serotypes (serotypes not related to vaccine serotypes) rose from 19.64% to 35.83% (p <0.05). Within this group, the proportions of serotype 24F increased significantly. There has been a change in the distribution of serotypes isolated from cases of IPD in children <2 years old in Catalonia, comprising a reduction in the proportion of 7-valent vaccine serotypes, a rise in vaccine-related serotypes, especially 19A, and a smaller rise in non-vaccine, non-related serotypes, especially serotype 24F. A new 13-valent vaccine will cover 77.91% of the serotypes causing IPD in children <2 years old in Catalonia from 2005 to 2007.     

The role of ZmpC in the clinical manifestation of invasive pneumococcal disease

IntroductionThe clinical severity and course of invasive pneumococcal disease (IPD) differs substantially between patients. Streptococcus pneumoniae harbors large genetic variability. Zinc metalloproteinase C (ZmpC), a secreted pneumococcal protein involved in neutrophil extravasation, inflammation and tissue remodeling, is present in a minority of IPD isolates. We investigated whether the presence of zmpC was associated with the clinical manifestation of IPD.Material and methodsIPD patients admitted to two Dutch hospitals between 2000 and 2013 were included in the study. Detailed clinical data were collected and the serotype and presence of zmpC were determined in the corresponding blood culture isolates.ResultsZmpC was present in 21% of the 542 included IPD cases and was mainly associated with serotypes 8, 4, 33A/F and 11A/D. Infection with S. pneumoniae positive for zmpC was more frequently observed in females (p = 0.048) and patients with a history of smoking (p = 0.033). Although no relation to clinical syndrome was observed, zmpC positive cases more often presented with cough, dyspnea and sepsis (p-values 0.026, 0.001 and 0.018), and more frequently required ICU admission (p = 0.011) compared to zmpC negative cases.ConclusionThe presence of zmpC was associated with a more severe clinical manifestation of IPD. This study demonstrates that information on pneumococcal genetic background may be useful to identify vulnerable individuals, to monitor clinical presentation and to predict the course of IPD.     

A twenty years’ results of the antimicrobial resistance profile and multidrug resistance trend of invasive Streptococcus pneumoniae isolates recovered from adult patients in Turkey: A literature review

PurposeThe aim of this study is to analyze antimicrobial resistance and multidrug (MDR)/extensively (XDR) resistance trend among Streptococcus pneumoniae isolates causing invasive disease in adult patients.MethodsWe analyzed antimicrobial resistance and multidrug resistance trend among invasive S.pneumoniae isolates recovered from adult patients (≥18-years) in a tertiary University Hospital, Turkey between 1996 and 2018. The antibiotic susceptibility pattern was determined by using gradient-test for penicillin and cefotaxime and disk-diffusion method for other antibiotics.ResultsA total of 272 isolates (74.3% from the bloodstream) of S. pneumoniae were collected during the study period. The highest non-susceptibility rate was obtained for tetracycline (63.5%), followed by trimethoprim/sulfamethoxazole (48%), penicillin-oral (30.4%), erythromycin (21.7%), clindamycin (15.8%), ciprofloxacin/levofloxacin (5.9%), penicillin-parenteral (5.5%), cefotaxime (2.2%), and rifampisin (1.8%), respectively. No resistance was observed against vancomycin during the years studied. Over the study period, a significant increase in the rate of antimicrobial resistance among invasive pneumococcal isolates was detected with a peak at period 2014–2018. Although there was an increase in the rates of non-susceptibility to penicillin oral, parenteral penicillin, cefotaxime, erythromycin and clindamycin in adult patients, the results were not statistically significant except erythromycin. Prevalence of MDR and XDR S. pneumoniae were 29% and 9.2% respectively. When the serotypes of MDR isolates were examined, it was noted that serotype 19F (35%) and 14 (12.5%) were the most common.ConclusionsOur study showed an overall increase in non-susceptibility rates of penicillin and erythromycin in invasive S.pneumoniae isolates recovered from Turkish adult patients. Although the prevalence of MDR showed fluctuation between years, the incidence of MDR remained stable. These data indicate the necessity for continuous monitoring and assessment of serotypes and antimicrobial resistance trends in S.pneumoniae in different age groups at both the national and the regional levels as it can be affected by the serotypes dominant in that region, rational use of antibiotics and the vaccination programs.     

The Association between Asthma and Invasive Pneumococcal Disease: A Nationwide Study in Korea

The purpose of this study was to investigate the association between asthma and invasive pneumococcal disease (IPD) in Korea. A retrospective population-based cohort study was conducted using the Korean Health Insurance Review and Assessment database 2010-2011. The subjects included 935,106 (2010) and 952,295 (2011), of whom 398 (2010) and 428 (2011) patients with IPD were identified. There was significant difference in the prevalence of IPD in patients with and without asthma (0.07% vs. 0.02% in 2010 and 0.08% vs. 0.01% in 2011; P<0.001). After adjusting for age and gender, patients with asthma showed over a three-fold increased risk of IPD compared with patients without asthma (adjusted odds ratio [aOR] 3.90, 95% confidence interval [CI] 3.02-5.03 in 2010 / aOR, 5.44; 95% CI, 4.10-7.22 in 2011; P<0.001). These findings were also significant in children (aOR, 2.08; 95% CI, 1.25-3.45 in 2010; P=0.005 / aOR, 3.26; 95% CI, 1.74-6.11 in 2011; P<0.001). Although diabetes mellitus was also significantly associated with IPD, relatively low ORs compared with those of asthma were noted (aOR, 1.85; 95% CI, 1.35-2.54 in 2010 / aOR, 2.40; 95% CI, 1.78-3.24 in 2011; P<0.001). Both children and adults with asthma are at increased risk of developing IPD.

Graphical Abstract

相似文献   

Invasive pneumococcal disease caused by ceftriaxone-resistant Streptococcus pneumoniae in Taiwan

Background

Invasive pneumococcal disease (IPD) was associated with mortality, but the risk factors associated with mortality remains controversial.

Pneumococcal Conjugate Vaccine Rollout in India: Expectations and Challenges

India is one among the four Asian countries with the greatest number of deaths due to pneumococcal infection among children under 5 years. pneumococcal conjugate vaccine (PCV) has been introduced in a phased manner in five major Indian states. Ambiguity remains in choosing the appropriate type of PCV and optimum schedule with maximum effectiveness specific for each country. Here, we discuss the evidences with respect to serotype coverage, immunogenicity, reactogenicity and dosage schedule for introduction of PCV13 in India. In addition, the expected PCV impact and the challenges are detailed. PCV13 is expected to provide >75% serotype coverage for invasive pneumococcal disease (IPD) serotypes in Indian children combined with the replacement by nonvaccine serotypes which is unpredictable due to lack of complete data. Nasopharyngeal (NP) surveillance is easy, feasible and can replace IPD surveillance in resource-poor settings. Continuous IPD as well as NP surveillance in all the regions are necessary to assess the impact of PCV in India.     

Phenotypic and genotypic characteristics of non-invasive S. pneumoniae isolates recovered from PCV10-vaccinated children in Bulgaria

PurposeThe non-invasive pneumococcal disease (NIPD) is a common infection during childhood. We aimed to define the clonal spread of pediatric non-invasive isolates recovered during the PCV10-period in Bulgaria concerning the serotype and antimicrobial susceptibility.Materials and methodsSerogrouping/serotyping were performed using latex agglutination and capsular swelling reaction. Serogroup 6 strains were subjected to serotype-specific PCR's. The antibiotic susceptibilities were assessed by broth microdilution. MLST was performed to define the clonal composition.ResultsWe analyzed 154 pediatrics non-invasive S. pneumoniae isolates. The PCV10-vaccinated children were 94.1%. We disclosed 88% non-vaccine serotypes (NVTs) and 12% PCV10 - serotypes. All common serotypes among PCV10-vaccinated children (n ?= ?145) were non-vaccine types (NVTs): 19A (13.8%), 6C (11.7%), 3 (9.6%), 15A (8.3%) and 23A (5.5%). Antimicrobial non-susceptibility showed highest levels in erythromycin (50.0%), oral penicillin (49.4%), clindamycin (45.4%), trimethoprim-sulfamethoxazole (43.5%), tetracycline (42.2%), and ceftriaxone (14.3%). The multidrug-resistant strains (MDR) were 51.3%. MDR-serotypes were 6C (20.2%), 19A (17.7%), 15A (11.4%), 19F (10.1%), and 23A (8.9%). MLST presented 17 clonal complexes (CCs) with prevalence of CC320, CC386, CC505, CC8029 and CC2613 clustered 83% MDR isolates.ConclusionsAll emergent pediatric non-invasive serotypes in our geographic area during the studied PCV10-period were NVTs (19A, 6C, 3, 15A, and 23A). The fifth widespread CCs: CC320, CC386, CC505, CC8029 and CC2613 clustered 83% MDR isolates. Future surveillance of vaccine-induced changes in the clonality and the antimicrobial resistance of the pneumococcal population is needed.     

Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates among Croatian adults during a fifteen-year period (2005-2019)

AimTo assess serotype distribution, antibiotic resistance, and vaccine coverage against Streptococcus pneumoniae causing invasive infections in Croatian adults from 2005 to 2019.MethodsIn this retrospective study, invasive pneumococcal strains were collected through a microbiological laboratory network with country coverage >95%. Capsular typing was performed with the Quellung reaction. In vitro susceptibility testing was carried out according to the European Committee on Antimicrobial Susceptibility Testing guidelines. In macrolide-resistant isolates, the presence of ermB and mefA genes was evaluated.ResultsDuring the fifteen-year study period, 1123 invasive pneumococcal isolates were obtained. The most prevalent serotypes were 3, 14, 19A, 9V, 7F, and 23F, comprising 60% of all invasive pneumococcal isolates. Serotype 3 was the dominant serotype, with the highest prevalence in patients ≥65 years of age. Penicillin susceptibility, increased exposure was 18.6%, mostly associated with serotypes 14 and 19A. Resistance to penicillin was low (<1%). Macrolide resistance was 23%, mostly associated with serotypes 14, 19A, and 19F. The coverage with 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) was 80.2% and 93.6%, respectively.ConclusionsThe incidence of invasive pneumococcal disease in adults is highest in patients ≥65 years of age. Penicillin susceptibility, increased exposure and macrolide resistance were mostly associated with serotypes 14 and 19A. PCV13 and PPV23 provide very high serotype coverage. Future studies should evaluate the effects of the 10-valent vaccine, introduced in the Croatian National Immunization Program in June 2019, on serotype distribution and antibiotic resistance rates.

Streptococcus pneumoniae is among the most concerning human pathogens, with high morbidity and mortality rates worldwide. Pneumococcal infections range from non-invasive mucosal diseases (including acute otitis media, acute sinusitis, and pneumonia) to invasive, life-threatening infections (such as meningitis, sepsis, and bacteremic pneumonia) (1). Invasive pneumococcal disease (IPD) mostly affects children younger than 5 years and patients ≥65 years old (2). Every year, 500 000 children under 5 years of age die of IPD (3). Both morbidity and mortality rates are higher in developing countries (3). Community-acquired pneumonia is the most common pneumococcal disease worldwide, being responsible for more than 1.5 million of deaths annually. A significant fraction of these deaths are caused by Streptococcus pneumoniae (4,5).Antimicrobial resistance of Streptococcus pneumoniae is a growing global health problem, mostly affecting penicillin and macrolides. The patterns of antimicrobial susceptibility differ among serotypes and geographic regions (6). Penicillin resistance has emerged within a few decades after penicillin introduction and has spread worldwide (7). The prevalence of antibiotic-resistant Streptococcus pneumoniae has been increasing (8,9). In Europe, the resistance rate in France, Spain, and Eastern European countries is concerning (10). Worldwide, some regions, such as South Africa, have antibiotic non-susceptibility rates of up to 79% (11). However, in the past several years some countries have reported decreased resistance rates (12-15).Macrolide resistance is commonly present among invasive and non-invasive Streptococcus pneumoniae isolates. The main mechanisms are drug efflux system encoded by mef genes (M phenotype) and target modification mainly due to ermB genes, (MLS_B phenotype) (16,17).The new fluoroquinolones or respiratory quinolones (levofloxacin, gatifloxacin, and moxifloxacin) have enhanced in vitro activity against Streptococcus pneumoniae and are used to treat respiratory tract infections in adults. Increasing resistance to fluoroquinolones has been reported in Asia and Africa (18,19). In addition, ineffectiveness of fluoroquinolones in the treatment of pneumococcal infections is associated with acquired resistance of Streptococcus pneumoniae to this group of antibiotics (20,21).Increased resistance of Streptococcus pneumoniae to routinely used antibiotics warrants pneumococcal vaccine introduction as a tool for IPD prevention. In Europe, two pneumococcal vaccines are registered for use in adults: a 13-valent pneumococcal conjugate vaccine (PCV13, including serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, and 19A) and a 23-valent pneumococcal polysaccharide vaccine (PPV23, including PCV13 serotypes plus 1, 2, 5, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) (22,23). In June 2019, a 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Croatian National Immunization Program (NIP) for children only (scheme: 8 weeks – 16 weeks – 12 months) (24). In January 2021, the Croatian Public Health Institute revised its recommendations for pneumococcal vaccination of adults. Immunocompetent adults are now advised to be vaccinated with PPV23 only, while immunocompromised and asplenic patients are recommended to receive both vaccines, starting with PCV13 as the first dose (25). The aim of this study was to analyze the serotype distribution and antibiotic resistance of invasive Streptococcus pneumoniae isolates before the introduction of PCV10 in the childhood vaccination schedule, together with the coverage of currently available vaccines (PCV13 and PPV23). This study is the first and the most comprehensive so far in Croatia, analyzing invasive pneumococcal isolates collected during 15 consecutive years. These data will help us assess the impact of different vaccines in the IPD prevention among adults, especially those ≥65 years old.     

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.     

Invasive pneumococcal disease among children in a health district of Barcelona: early impact of pneumococcal conjugate vaccine

This study evaluated the impact of heptavalent pneumococcal conjugate vaccine (HPCV) on invasive pneumococcal disease (IPD) in children aged < or = 5 years in Barcelona, Spain. The incidence of IPD, vaccine uptake and prevalence of nasopharyngeal colonisation were analysed in two different periods: 1999-2001 (pre-licence period), and 2002-2004 (post-licence period). In total, 121 cases of IPD were identified. The overall incidence of IPD decreased from 96.9 cases/100,000 to 90.6 cases/100,000 (OR 0.93, 95% CI 0.69-1.26, p 0.71) between the two periods. The proportion of cases caused by non-vaccine-related serotypes (NVS) increased from 21% to 43.7% (OR 2.9, 95% CI 1.2-7, p 0.01). IPD was diagnosed in seven vaccinated children, six of whom were infected by NVS. There was a trend of diminishing prevalence of resistance to penicillin and macrolides in 2002-2004. The incidence of empyema increased from 1.7 to 8.5/100,000 (OR 4.5, 95% CI 0.91-18, p 0.06). The rate of vaccination ranged from 4.8% to 34%. It was concluded that the rates of IPD in this area did not decrease following the introduction of HPCV. The low uptake of vaccine and the greater proportion of colonisation/infection by NVS probably explain these findings. A trend of increasing empyema was also apparent. A decrease in the prevalence of penicillin and macrolide resistance paralleled the progressive uptake of vaccine.     

Clonal Similarities and Sequence-Type Diversity of Invasive and Carriage Streptococcus pneumoniae in India among Children under 5 Years

Background: Pneumococcal pneumonia is one of the major causes of mortality in children less than 5 years in Asia, especially in India. Available PCVs have less serotype coverage in India compared to western countries. Moreover, the baseline pneumococcal serotype and sequence type data is limited and available data doesn’t represent the entire India. With this background we aimed to characterize invasive and carriage isolates of S. pneumoniae from a tertiary care hospital in South India. Materials and Methods: A total of 221 S. pneumoniae isolates, invasive (n=138) and carriage (n=83) between the time period of 2012-2018 were included. Isolates was identified and confirmed using standard laboratory protocols. Serotyping was performed by Customized sequential multiplex PCR and MLST as described in www.pubmlst.org. Results: The major serotypes were 19F, 6B, 14, 6A and 19A and the sequence types (ST) were ST63, 236 and 230. Predominant STs in invasive was ST 63 whereas in carriage were ST4894 and 1701. High level ST diversity in carriage was observed. Majority of the STs were SLVs or DLVs of previously reported STs or PMEN clones. Phylogenetic analyses of the STs revealed gradual expansion of three PMEN CCs CC320, 63 and 230. Conclusion: The vaccine serotypes were the predominant ones found to be associated with IPD, PMEN clones, new STs and antimicrobial resistance. Accordingly, PCV13 is expected to provide invasive serotype coverage of 75% in Indian children less than 5 years. This study provides baseline serotype and sequence type data prior to the introduction of PCV in South India.     

Epidemiological characterisation of Streptococcus pneumoniae from India using multilocus sequence typing

Objective: The aim of this study was to utilize the multilocus sequence typing (MLST) technique to characterise Streptococcus pneumoniae among clinical isolates in India. MLST was used to determine clonality, to establish genetic relatedness, to check for correlation between serotypes and sequence types (STs) and its relevance associated with antibiotic resistance. Methods: Forty consecutive invasive S. pneumoniae isolates in children <5 years were characterised. Preliminary identification of serotype and antibiotic susceptible profile was followed with MLST technique to identify the STs of the isolates. STs were then analysed for clonality using an eBURST algorithm and genetic relatedness using Sequence Type Analysis and Recombinational Tests version 2 software. Results: The most common ST was ST63. Among the forty isolates, we identified nine novel STs, six of which had known alleles but in new combinations, three of which had new alleles in their sequence profile. The new STs assigned were 8501–8509. One clonal complex was found among the 40 strains characterised. The most common serotypes in this study were serotype 19F, 14 and 5. Non-susceptibility to penicillin and erythromycin was observed in 2.5% and 30% of the isolates, respectively. Conclusion: This study shows a significant number of novel STs among the 40 isolates characterised (9/40, 22.5%), however, internationally recognised strains were also circulating in India, indicating, there could be greater geographical variation in pneumococcal STs in India. Molecular epidemiology data is essential to understand the population dynamics of S. pneumoniae in India before the introduction of pneumococcal vaccines in NIP in India.     

Global prevailing and emerging pediatric pneumococcal serotypes

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths among children younger than 5 years of age worldwide. The 7-valent pneumococcal conjugate vaccine (PCV7) is currently licensed in more than 90 countries and has contributed to significant declines in the incidence of invasive pneumococcal disease (IPD). Recent studies report an increased incidence of IPD caused by non-PCV7 vaccine serotypes (NVTs). Seroepidemiology of IPD caused by NVTs following the introduction of PCV7 is of interest, and this article provides a comprehensive global summary of the prevailing and emerging serotypes causing IPD in children. Currently, globally emerging or persistent NVTs include serotypes 1, 3, 5, 6A, 7F and 19A. Serotypes included in the recently licensed 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) account for pneumococcal disease burdens in most developed countries of 65-85% and 80-90%, respectively. The seroprevalence of NVTs after widespread use of PCV10 and PCV13 requires ongoing monitoring.     

Invasive <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> infections in children and older adults in the north of Spain before and after the introduction of the heptavalent pneumococcal conjugate vaccine

In the last two decades, an increasing trend in the incidence of pneumococcal disease in Europe has been reported. We investigated the effect of the use of the heptavalent pneumococcal conjugate vaccine (PCV7) in an area of northern Spain, where all recorded cases of invasive pneumococcal diseases (IPD) were included (n = 450; 91 between 1996–2007 in children aged <5 years and 359 between 1998–2007 in adults aged >64 years). All isolates were serotyped. In children, the overall IPD incidence did not significantly decrease after the introduction, in late 2001, of PCV7. However, the incidence of PCV7 serotypes significantly decreased by 137.2% from 31.59 cases/100,000 population in 1996–2001 to 13.42 in 2002–2007 (95% confidence interval [CI] −27.2 to −342.4%), as did the overall rates of penicillin resistance (from 45.6 to 18.6%) and multiresistance (from 30.3 to 11%). In older adults, the overall IPD incidence showed a non-significant increase due to non-PCV7 serotypes, which seemed to continue a previous trend in our region.     

High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease

Susceptibility to invasive pneumococcal disease (IPD) correlates with age, younger children being the group with the highest burden of disease. The relevance of the innate immune response and particularly the role of mannose-binding lectin (MBL) in combating IPD is not well known. This is a 2-year prospective study (February 2011 to March 2013) including patients with IPD who attended two hospitals from Catalonia, Spain. Variables including attack rate of pneumococcal serotype (high or low invasive potential serotypes) and genotypes associated with low serum MBL levels were recorded. One hundred and forty-seven patients were included in the study. One hundred and two (69.4%) patients were children or adolescents <18 years and 45 (30.6%) were adults. Overall, low-MBL genotypes (O/O; XA/O) were detected in 23 (15.6%) patients. Children <2 years showed a higher frequency of low-MBL genotypes compared with other patients (31.0% vs. 11.9%; p = 0.031). Further sub-analysis revealed a higher proportion of low-MBL genotypes in children <2 years with IPD caused by opportunistic or low-attack-rate serotypes when compared with older patients (46.2% vs. 13.2%; p = 0.02). However, no statistically significant differences between the two groups were observed when including patients infected with invasive or high-attack-rate serotypes (18.8% vs. 10.0%; p = 0.59). Our data suggest that young children with a genetically determined low-MBL production are at a higher risk of developing IPD, particularly that caused by opportunistic or low-attack-rate pneumococcal serotypes.