Serotype 19F Research Articles

Association of pili with widespread multidrug-resistant genetic lineages of non-invasive pediatric Streptococcus pneumoniae isolates.

The study aimed to evaluate the presence of pili in non-invasive pediatric pneumococcal isolates and to elucidate possible links with genetic lineages, serotypes, and antimicrobial resistance. We examined 147 Streptococcus pneumoniae isolates from children with respiratory tract infections and acute otitis media. Serotyping was performed by latex agglutination and capsule swelling reaction. Serogroup 6 was subjected to PCR-serotyping. Minimum inhibitory concentrations were determined according to EUCAST breakpoints. PCRs for rlrA and pitB genes were performed to detect a presence oftype 1 and type 2 pili. MLST was conducted to define the clonal structure of the piliated strains. Almost all children (96.5%) were vaccinated with the pneumococcal conjugate vaccine PCV10. We detected 76.8% non-PCV10 - serotypes (NVTs) and 14.3% PCV10 serotypes. The predominant serotypes were NVTs: 19A (14.3%), 6C (12.2%), 3 (9.5%), 15A (7.5%) and 6A (6.8%). PI-1 was detected among 10.9% non-PCV10 serotypes 6A, 6C, and 19A and 6.1% PCV10 serotypes 19F and 23F. Type 2 pili were not found in the studied population. High levels of antimicrobial nonsusceptibility to erythromycin (58.5%), oral penicillin (55.8%), clindamycin (46.9%), trimethoprim-sulfamethoxazole (45.6%), tetracycline (39.5%) and ceftriaxone (16.3%) were revealed. The multidrug-resistant strains (MDR) were 55.1%. MLST represented 18 STs and three CCs among the piliated pneumococci: CC386, CC320, and CC81. More than half of the piliated strains (56.0%) belonged to successfully circulating international clones. PI-1 was associated mainly with MDR 6A, 6C, 19A, 19F, and 23F isolates from the widespread CC386, CC320, and CC81.

Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study

Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months). We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure. A 3 + 0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control. Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research.

Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018-2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20-0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018-2020 was 28% (P = 0.0001 for comparison with 2006-2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018-2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.

Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study

SummaryBackgroundSerotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.MethodsWhole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590).FindingsSerotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3–5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain.InterpretationOur work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases.FundingBill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.

Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004–20: a national surveillance study

BackgroundEpidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied.MethodsIn this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004–20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance.FindingsSerotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to β-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the β-lactam with the lowest minimum inhibitory concentration (MIC)50 or MIC90 values, and had the highest proportion of susceptible strains throughout 2004–20.InterpretationThe increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.FundingThe Spanish Ministry of Science and Innovation and Meiji-Pharma Spain.TranslationFor the Spanish translation of the abstract see Supplementary Materials section.

Investigation of Concurrent Pneumococcal Meningitis in Two Children Attending the Same Day-Care Center

Only a few clusters of invasive pneumococcal disease have been described globally in children, and most of these cases occurred before pneumococcal vaccination implementation. Two unusual cases of pneumococcal meningitis, occurring in the same daycare center over a 3-day period, were reported. Both cerebrospinal fluid (CSF) were sent to the National reference center for pneumococci. In addition, we decided to perform a pneumococcal carriage study on all children and staff of the daycare center to analyze the pneumococcal serotypes circulating in this DCC and to discuss an antibiotic chemoprophylaxis. CSF culture was positive for pneumococcus, and serotype 25A was identified by latex agglutination. The second case had negative CSF culture, but CSF antigen test and gene amplification results were positive for Streptococcus pneumoniae. Serotype 12F was identified by using molecular biology. The absence of correlation between these strains was confirmed by multi-locus sequence typing. In the carriage study, we included 29 children (median age 1.9 years, interquartile range 1.4–2.5) and 10 adults. Among the children, 24 carried Streptococcus pneumoniae (83%). The main serotypes isolated were 23A for 6 children and 25A for 5 children; serotypes were non-typeable for 3 children. Only 1 of 10 adults tested carried Streptococcus pneumoniae (serotype 12F). Despite this temporo-spatial pattern, the cases were unrelated and not due to carriage of a particular serotype. No specific action has been taken for the other children attending this DCC, and no other case of bacterial meningitis occurred.

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.

P1576: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, COMPARATOR-CONTROLLED STUDY TO EVALUATE SAFETY, TOLERABILITY AND IMMUNOGENICITY OF V114 PNEUMOCOCCAL VACCINE IN HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS (PNEU-STEM)

Background: Allogeneic hematopoietic cell transplant (allo-HCT) represents a definitive therapy for a variety of hematological diseases. Immunosuppressive therapy following allo-HCT and graft-vs-host disease (GVHD) render the patient susceptible to infectious complications, including invasive pneumococcal disease. Post-allo-HCT pneumococcal vaccination is recommended 3-6 months after transplant in a multi-dose series to help prevent pneumococcal disease. Aims: V114 is a 15-valent pneumococcal conjugate vaccine (PCV) approved in adults, containing all 13 serotypes in Prevnar 13™ (PCV13; contains serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) as well as epidemiologically important serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 when given to allo-HCT recipients. Methods: Individuals ≥3 years of age were randomized 1:1 to receive 3 doses of V114 or PCV13 in one-month intervals starting 3-6 months after allo-HCT. At 12 months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV if they experienced chronic GVHD. All participants or their legal representatives provided informed consent at enrollment. Primary safety objective was to evaluate the proportion of participants with adverse events (AEs) within each vaccination group for 3 to <18 years old and ≥18 years old age groups. Primary immunogenicity objective was to evaluate serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) for all 15 V114 serotypes at 30 days following the third PCV dose (Day 90) in each vaccination group. A key secondary objective was to evaluate opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes at Day 90. Results: A total of 274 subjects (14 children [3 to <18 years of age] and 260 adults ≥18 years old) were enrolled and vaccinated in the study. The proportion of participants with systemic AEs and serious AEs after any dose of study vaccine were generally comparable between intervention groups in the pediatric and adult cohorts. V114 recipients reported a higher proportion of injection-site AEs and vaccine-related systemic AEs compared to PCV13 in the adult cohort. Of all vaccinated participants, 32.4% experienced serious AEs during the study (28.8% in V114 group, 36.3% in PCV13 group). Seventeen participants (5.8% in V114 group, 6.7% in PCV13 group) died during the study. None of the deaths were determined by the investigator to be related to study vaccines. For both IgG GMCs (Table 1) and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. Image:Summary/Conclusion: V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13 for both pediatric and adult participants. Despite the immunocompromised status of the participants, the study vaccines induced serotype-specific immunogenicity and V114 induced generally comparable responses to PCV13 by IgG GMCs and OPA for the 13 shared serotypes at Day 90. In addition, V114 induced higher antibody responses than PCV13 for serotypes unique to V114 (22F and 33F). Study results support the use of V114 in allo-HCT recipients.

Population genomics of pneumococcal carriage in South Africa following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) immunization.

Streptococcus pneumoniae is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, respectively, a decrease in both invasive pneumococcal infections and asymptomatic carriage of vaccine-type pneumococci were reported. In this study, we described the changing epidemiology of the pneumococcal carriage population in South Africa, by sequencing the genomes of 1825 isolates collected between 2009 and 2013. Using these genomic data, we reported the changes in serotypes, Global Pneumococcal Sequence Clusters (GPSCs), and antibiotic resistance before and after the introduction of PCV13. The pneumococcal carriage population in South Africa has a high level of diversity, comprising of 126 GPSCs and 49 serotypes. Of the ten most prevalent GPSCs detected, six were predominantly found in Africa (GPSC22, GPSC21, GPSC17, GPSC33, GPSC34 and GPSC52). We found a significant decrease in PCV7 serotypes (19F, 6B, 23F and 14) and an increase in non-vaccine serotypes (NVT) (16F, 34, 35B and 11A) among children <2 years of age. The increase in NVTs was driven by pneumococcal lineages GPSC33, GPSC34, GPSC5 and GPSC22. Overall, a decrease in antibiotic resistance for 11 antimicrobials was detected in the PCV13 era. Further, we reported a higher resistance prevalence among vaccine types (VTs), as compared to NVTs; however, an increase in penicillin resistance among NVT was observed between the PCV7 and PCV13 eras. The carriage isolates from South Africa predominantly belonged to pneumococcal lineages, which are endemic to Africa. While the introduction of PCV resulted in an overall reduction of resistance in pneumococcal carriage isolates, an increase in penicillin resistance among NVTs was detected in children aged between 3 and 5 years, driven by the expansion of penicillin-resistant clones associated with NVTs in the PCV13 era.

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.

930 SAFETY, TOLERABILITY AND IMMUNOGENICITY OF 15-VALENT PNEUMOCOCCAL CONJUGATE VACCINE + PPV23 12 MONTHS LATER IN HEALTHY ADULTS ≥ 50

Abstract Background Older adults are at increased risk of pneumococcal disease (PD). V114, an investigational 15-valent Pneumococcal Conjugate Vaccine (PCV), contains all serotypes in 13-valent PCV (PCV13) plus serotypes 22F and 33F. This phase 3 trial evaluated the safety, tolerability and immunogenicity of V114 or PCV13 followed 12 months later by PPSV23 in healthy adults aged ≥50 years. Materials/Method 652 eligible adults were randomised 1:1 to receive V114 or PCV13 followed by PPSV23 12 months later. Solicited and non-solicited adverse events (AEs) were collected after each vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were measured at Day 1, Day 30, Month 12 and Month 13. Results The most common solicited AEs following PCV were injection-site pain, fatigue and myalgia; higher proportions of participants with solicited AEs were observed in the V114 group; however, the differences were not clinically significant, as most AEs were mild and of short duration. The most common solicited AEs following PPSV23 were injection-site pain, injection-site swelling, fatigue and myalgia; these events were comparable across both intervention groups. The proportion of participants with serious AEs were low in both groups and none reported to be vaccine related. No deaths occurred during the study. Serotype-specific OPA geometric mean titres (GMTs) and IgG geometric mean concentrations (GMCs) were comparable between the groups for all 15 serotypes 30 days post-vaccination with PPSV23. OPA GMTs and IgG GMCs were comparable between PCV groups for the 13 shared serotypes and higher in V114 than PCV13 for serotypes 22F and 33F 30 days and 12 months post-vaccination with PCV. V114 elicited an immune response that persisted for at least 12 months. Conclusion Sequential administration of V114 and PPSV23 is well tolerated, immunogenic and generally comparable to PCV13 followed by PPSV23 in healthy adults ≥50 years of age.

Nasopharyngeal carriage rate, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae isolated from children under five years old in Kotabaru, South Kalimantan, Indonesia.

Streptococcus pneumoniae is a bacterial pathogen that colonizes the human nasopharynx. Colonization is frequently reported to be high in young children. In this study, we investigated the nasopharyngeal (NP) carriage rate, serotype distribution, and antibiotic susceptibility of S. pneumoniae in children under five years of age in Kotabaru, South Kalimantan, Indonesia. NP swab specimens were collected from 399 young children (mean age: 30 months) who participated in the Rampa Village Community Health Center, with 74% of the participants being Bajau children. S. pneumoniae was identified using optochin susceptibility and bile solubility tests. Serotyping was performed by sequential multiplex PCR, and antimicrobial susceptibility profiling was performed by disk diffusion and microdilution methods. The NP carriage rate of S. pneumoniae was 45% (180/399). The most commonly serotypes were 6A/6B (18%), followed by 15B/15C (17%), 19F (16%), 34 (8%), and 23F (5%); 46% of them were identified as strains of the PCV13 vaccine type. Additionally, almost half of the pneumococcal isolates were non-susceptible to penicillin (40%), whereas non-susceptibility to tetracycline (36.8%), trimethoprim/sulfamethoxazole (29.7%), erythromycin (16.8%), chloramphenicol (9.7%), and clindamycin (8.6%) was also found. We identified 18% (n=34) of S. pneumoniae isolates as multidrug-resistant (MDR) strains, and serotype 19F was the most common (74%) among them. MDR S. pneumoniae vaccine type strains were dominated by serotype 19F. The implementation of a pneumococcal conjugate vaccine program in Indonesia might reduce MDR strains circulating in the community in the future.

Molecular Characterization of Predominant Serotypes, Drug Resistance, and Virulence Genes of Streptococcus pneumoniae Isolates From East China

Streptococcus pneumoniae is a common diplococcus pathogen found worldwide. The characterization of predominant serotypes, drug resistance, and virulence genes of S. pneumoniae isolates prevailing in different areas and countries is clinically important for choice of antibiotics and improvement of vaccines. In this study, pneumonia (78.7%) and meningitis (37.0%) were the predominant diseases observed in the 282 (children) and 27 (adults) S. pneumoniae-infected patients (p < 0.05) from seven hospitals in different areas of East China. Of the 309 pneumococcal isolates, 90.3% were classified by PCR into 15 serotypes, with serotypes 19F (27.2%) and the 6A/B (19.1%) being most predominant (p < 0.05). Importantly, serotypes 15A and 15B/C combined for a total of 10.4% of the isolates, but these serotypes are not included in the 13-valent pneumococcal capsule conjugate vaccine used in China. Antimicrobial susceptibility analysis by the E-test showed that >95% of the 309 pneumococcal isolates were susceptible to moxifloxacin and levofloxacin, as well as 18.4, 85.8, and 81.6% of the isolates displayed susceptibility to penicillin, cefotaxime, and imipenem, respectively. A significant correlation between the prevalence of predominant serotypes and their penicillin resistance was observed (p < 0.05). In particular, >95% of all the pneumococcal isolates showed resistance to erythromycin and azithromycin. Of the nine detected virulence genes, the lytA, ply, hysA, and nanA were the most common with 95–100% positive rates in the 309 pneumococcal isolates, while the pavA and psaA genes displayed a significant correlation with pneumococcal bacteremia and meningitis (p < 0.05). Overall, our data suggested that the predominant serotypes, drug resistance, and virulence genes of the S. pneumoniae isolates prevailing in East China are distinct from those observed in other areas of China and adjacent countries.

Streptococcus pneumoniae vaccination strategies and its expected impact on penicillin non-susceptibility in children under the age of five: Let's recap!

The impact of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease (IPD) burden has been extensively studied in children aged<5 years; however, a pooled estimation of the effect of PCVs on penicillin non-susceptible pneumococci (PNSP) has not yet been performed. We aimed to identify whether the introduction of PCV-10 and PCV-13 had led to the decrease of the overall PNSP rate in children < 5 years. We conducted a systematic review of published surveillance studies reporting the rate of PNSP rates in children < 5 in countries where PCV10/13 were introduced. The overall observed trend onwards the introduction of PCV-10 and PCV-13 is a decrease in PNSP among children < 5 years in surveillance sites located in PCV-13 countries. We identified an increase of PNSP rates (serotype 19A) in PCV-10 settings. Resistant NVT strains are emerging in IPD in children < 5 years mainly serotypes 24F, 15A, 11A and 33F along with serotype 19A in PCV-10 settings. Continuous surveillance is necessary in IPD in children under five to monitor the long-term effect of PCV-10 and PCV-13 on penicillin resistance trends.

Pathogen- and Type-Specific Changes in Invasive Bacterial Disease Epidemiology during the First Year of the COVID-19 Pandemic in The Netherlands.

COVID-19 control measures have resulted in a decline in invasive bacterial disease caused by Neisseria meningitidis (IMD), Streptococcus pneumoniae (IPD), and Haemophilus influenzae (Hi-D). These species comprise different serogroups and serotypes that impact transmissibility and virulence. We evaluated type- and pathogen-specific changes in invasive bacterial disease epidemiology in the Netherlands during the first year of the SARS-CoV-2 pandemic. Cases were based on nationwide surveillance for five bacterial species with either respiratory (IMD, IPD, Hi-D) or non-respiratory (controls) transmission routes and were compared from the pre-COVID period (April 2015–March 2020) to the first COVID-19 year (April 2020–March 2021). IMD, IPD, and Hi-D cases decreased by 78%, 67%, and 35%, respectively, in the first COVID-19 year compared to the pre-COVID period, although effects differed per age group. Serogroup B-IMD declined by 61%, while serogroup W and Y-IMD decreased >90%. IPD caused by serotypes 7F, 15A, 12F, 33F, and 8 showed the most pronounced decline (≥76%). In contrast to an overall decrease in Hi-D cases, vaccine-preventable serotype b (Hib) increased by 51%. COVID-19 control measures had pathogen- and type-specific effects related to invasive infections. Continued surveillance is critical to monitor potential rebound effects once restriction measures are lifted and transmission is resumed.

Antibiotics and Immunizations: A Complex Interaction.

Antibiotics and Immunizations: A Complex Interaction.

Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in Korea and Hong Kong

ABSTRACT Use of pneumococcal conjugate vaccines (PCVs) has greatly reduced the incidence of invasive pneumococcal disease (IPD). V114 (VAXNEUVANCE™, Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA) is a 15-valent PCV currently approved in adults in the United States, containing the 13 serotypes in licensed PCV13 and 2 additional serotypes (22F and 33F) which are important contributors to residual pneumococcal disease. This study quantified the health and economic burden of IPD attributable to V114 serotypes in hypothetical birth cohorts from Korea and Hong Kong. A Markov model was used to estimate the case numbers and costs of IPD in unvaccinated birth cohorts over 20 years. The model was applied to 3 scenarios in Korea (pre-PCV7, pre-PCV13, and post-PCV13) and to 2 scenarios in Hong Kong (pre-PCV7 and post-PCV13). For Korea, the model predicted 62, 26, and 8 IPD cases attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 scenarios, respectively. Costs of V114-type IPD fell from $1.691 million pre-PCV7 to $.212 million post-PCV13. For Hong Kong, the model estimated 62 V114-associated IPD cases in the pre-PCV7 scenario and 46 in the post-PCV13 scenario. Costs attributed to all V114 serotypes were $2.322 million and $1.726 million in the pre-PCV7 and post-PCV13 periods, respectively. Vaccine-type serotypes are predicted to cause continuing morbidity and cost in Korea (19A) and Hong Kong (3 and 19A). New pediatric pneumococcal vaccines must continue to protect against serotypes in licensed vaccines to maintain disease reduction, while extending coverage to non-vaccine serotypes.

Incidence rates, emerging serotypes and genotypes, and antimicrobial susceptibility of pneumococcal disease in Taiwan: A multi-center clinical microbiological study after PCV13 implementation

Objectives The multi-center clinical microbiological study in Taiwan aimed to evaluate the impact of childhood PCV13 immunization on pneumococcal disease, and the magnitude of serotype replacement in invasive and non-invasive pneumococcal disease among all age groups. Methods The study of culture-confirmed pneumococcal disease (CCPD) was conducted at four hospitals across Taiwan in 2015-2018. Pneumococcal pneumonia was defined as clinical diagnosis with positive sputum or bronchoalveolar lavage culture. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing for penicillin and ceftriaxone were performed. Results A total of 1413 CCPD cases were identified. Invasive pneumococcal disease (IPD) accounted for 13.4% (190/1413) of CCPD. PCV7-type CCPD incidence declined among all age groups between 2015 and 2018. In adults aged 50-64 years, PCV7-type pneumococcal pneumonia incidence in 2018 was 72% lower than that in 2015, and all pneumococcal pneumonia incidence was 35% lower than that in 2015. In children, CCPD incidence was higher in 2018 than in 2015 (IRR 1.75 for age <5 years, IRR 1.56 for age 5-17 years). Incidence of CCPD caused by non-PCV13-types, mainly 15A and 23A, increased significantly in those younger than 50 years. Serotypes 19A and 19F constituted the largest clonal complex, CC236/320 (n=280, 19.8%). The rates of penicillin and ceftriaxone non-susceptibility were higher in PCV13-type isolates. Conclusions Childhood PCV13 immunization exerted an indirect protection to vaccine serotype clinically defined non-bacteremic pneumococcal pneumonia among adults, especially those between 50 and 64 years of age. Emerging non-PCV13 serotypes mainly caused non-invasive mucosal disease among children.

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

Molecular Characterization of Penicillin-Binding Protein2x, 2b and 1a of Streptococcus pneumoniae Causing Invasive Pneumococcal Diseases in China: A Multicenter Study.

Streptococcus pneumoniae is a common human pathogen that can cause severe invasive pneumococcal diseases (IPDs). Penicillin-binding proteins (PBPs) are the targets for β-lactam antibiotics (BLAs), which are the common empirical drugs for treatment of pneumococcal infection. This study investigated the serotype distribution and antibiotic resistance patterns of S. pneumoniae strains causing IPD in China, including exploring the association between penicillin (PEN) susceptibility and PBPs variations. A total of 300 invasive S. pneumoniae isolates were collected from 27 teaching hospitals in China (2010-2015). Serotypes were determined by Quellung reaction. Serotypes 23F and 19F were the commonest serotypes in isolates from cerebrospinal fluid (CSF), whilst serotypes 19A and 23F were most commonly seen in non-CSF specimens. Among the 300 invasive S. pneumoniae strains, only one strain (serotype 6A, MIC = 0.25 μg/ml) with PEN MIC value ≤ 0.25 μg/ml did not have any substitutions in the PBPs active sites. All the strains with PEN MIC value ≥ 0.5 μg/ml had different substitutions within PBPs active sites. Substitutions in PBP2b and PBP2x active sites were common in low-level penicillin-resistant S. pneumoniae (PRSP) strains (MIC = 0.5 μg/ml), with or without PBP1a substitution, while all strains with PEN MIC ≥ 1 μg/ml had substitutions in PBP1a active sites, accompanied by PBP2b and PBP2x active site substitutions. Based on the three PBPs substitution combinations, a high degree of diversity was observed amongst the isolates. This study provides some new insights for understanding the serology and antibiotic resistance dynamics of S. pneumoniae causing IPD in China. However, further genomic studies are needed to facilitate a comprehensive understanding of antibiotic resistance mechanisms of S. pneumoniae.