Geographical migration and fitness dynamics of Streptococcus pneumoniae.

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance.

BACKGROUND: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). METHODS: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. RESULTS: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. CONCLUSIONS: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD.

The emergent invasive serotype 4 ST10172 strain acquires vanG type vancomycin-resistance element: A case of a 66-year-old with bacteremic pneumococcal pneumonia.

We report a single case of invasive pneumococcal disease (IPD) by serotype 4, multilocus sequence type 10172 (serotype 4/ST10172) isolate with vanG-type resistance genes and reduced vancomycin susceptibility. The isolate was recovered during 2022 from a 66-year-old resident with bacteremic pneumococcal pneumonia within a CDC Active Bacterial Core surveillance (ABCs) site hospital. The patient had received 23-valent pneumococcal polysaccharide vaccine and there was no evidence of concurrent or prior receipt of vancomycin in the previous year. Serotype 4/ST10172 IPD has shown increases within western ABCs sites and the recent acquisition of a vanG element warrants close monitoring of this lineage.

Novel pneumococcal capsule type 33E results from the inactivation of glycosyltransferase WciE in vaccine type 33F.

The polysaccharide (PS) capsule is essential for immune evasion and virulence of Streptococcus pneumoniae. Existing pneumococcal vaccines are designed to elicit anticapsule antibodies; however, the effectiveness of these vaccines is being challenged by the emergence of new capsule types or variants. Herein, we characterize a newly discovered capsule type, 33E, that appears to have repeatedly emerged from vaccine type 33F via an inactivation mutation in the capsule glycosyltransferase gene, wciE. Structural analysis demonstrated that 33E and 33F share an identical repeat unit backbone [→5)-ß-D-Galf2Ac-(1→3)-ß-D-Galp-(1→3)-α-D-Galp-(1→3)-ß-D-Galf-(1→3)-ß-D-Glcp-(1→], except that a galactose (α-D-Galp) branch is present in 33F but not in 33E. Though the two capsule types were indistinguishable using conventional typing methods, the monoclonal antibody Hyp33FM1 selectively bound 33F but not 33E pneumococci. Further, we confirmed that wciE encodes a glycosyltransferase that catalyzes the addition of the branching α-D-Galp and that its inactivation in 33F strains results in the expression of the 33E capsule type. Though 33F and 33E share a structural and antigenic similarity, our pilot study suggested that immunization with a 23-valent pneumococcal PS vaccine containing 33F PS did not significantly elicit cross-opsonic antibodies to 33E. New conjugate vaccines that target capsule type 33F may not necessarily protect against 33E. Therefore, studies of new conjugate vaccines require knowledge of the newly identified capsule type 33E and reliable pneumococcal typing methods capable of distinguishing it from 33F.

Continued Increase of Erythromycin Nonsusceptibility and Clindamycin Nonsusceptibility Among Invasive Group A Streptococci Driven by Genomic Clusters, United States, 2018-2019.

We analyzed 9630 invasive GAS surveillance isolates in the USA. From 2015-2017 to 2018-2019, significant increases in erythromycin-nonsusceptibility (18% vs 25%) and clindamycin-nonsusceptibility (17% vs 24%) occurred, driven by rapid expansions of genomic subclones. Prevention and control of clustered infections appear key to containing antimicrobial resistance.

Expansion of Invasive Group A Streptococcus M1UK Lineage in Active Bacterial Core Surveillance, United States, 2019‒2021.

From 2015-2018 to 2019‒2021, hypertoxigenic M1UK lineage among invasive group A Streptococcus increased in the United States (1.7%, 21/1,230 to 11%, 65/603; p<0.001). M1UK was observed in 9 of 10 states, concentrated in Georgia (n = 41), Tennessee (n = 13), and New York (n = 13). Genomic cluster analysis indicated recent expansions.

Discovery and Characterization of Pneumococcal Serogroup 36 Capsule Subtypes, Serotypes 36A and 36B.

Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized. Prior sequence analysis of pneumococcal capsule synthesis (cps) loci suggested the existence of capsule subtypes among isolates identified as "serotype 36" according to conventional capsule typing methods. We discovered these subtypes represent two antigenically similar but distinguishable pneumococcal capsule serotypes, 36A and 36B. Biochemical analysis of their capsule PS structure reveals that both have the shared repeat unit backbone [→5)-α-d-Galf-(1→1)-d-Rib-ol-(5→P→6)-ß-d-ManpNAc-(1→4)-ß-d-Glcp-(1→] with two branching structures. Both serotypes have a ß-d-Galp branch to Ribitol. Serotypes 36A and 36B differ by the presence of a α-d-Glcp-(1→3)-ß-d-ManpNAc or α-d-Galp-(1→3)-ß-d-ManpNAc branch, respectively. Comparison of the phylogenetically distant serogroup 9 and 36 cps loci, which all encode this distinguishing glycosidic bond, revealed that the incorporation of Glcp (in types 9N and 36A) versus Galp (in types 9A, 9V, 9L, and 36B) is associated with the identity of four amino acids in the cps-encoded glycosyltransferase WcjA. Identifying functional determinants of cps-encoded enzymes and their impact on capsule PS structure is key to improving the resolution and reliability of sequencing-based capsule typing methods and discovering novel capsule variants indistinguishable by conventional serotyping methods.

Cluster Transmission Drives Invasive Group A Streptococcus Disease Within the United States and Is Focused on Communities Experiencing Disadvantage.

BACKGROUND: Group A streptococci (GAS), although usually responsible for mild infections, can sometimes spread into normally sterile sites and cause invasive GAS disease (iGAS). Because both the risk of iGAS disease and occurrence of outbreaks are elevated within certain communities, such as those comprising people who inject drugs (PWID) and people experiencing homelessness (PEH), understanding the transmission dynamics of GAS is of major relevance to public health. METHODS: We used a cluster detection tool to scan genomes of 7552 Streptococcus pyogenes isolates acquired through the population-based Active Bacterial Core surveillance (ABCs) during 2015-2018 to identify genomically related clusters representing previously unidentified iGAS outbreaks. RESULTS: We found that 64.6% of invasive isolates were included within clusters of at least 4 temporally related isolates. Calculating a cluster odds ratio (COR) for each emm type revealed that types vary widely in their propensity to form transmission clusters. By incorporating additional epidemiological metadata for each isolate, we found that emm types with a higher proportion of cases occurring among PEH and PWID were associated with higher CORs. Higher CORs were also correlated with emm types that are less geographically dispersed. CONCLUSIONS: Early identification of clusters with implementation of outbreak control measures could result in significant reduction of iGAS.

Invasive Pneumococcal Disease Clusters Disproportionally Impact Persons Experiencing Homelessness, Injecting Drug Users, and the Western United States.

BACKGROUND: Invasive pneumococcal disease (IPD) isolates forming genomic clusters can reflect rapid disease transmission between vulnerable individuals. METHODS: We performed whole genome sequencing of 2820 IPD isolates recovered during 2019 through Centers for Disease Control and Prevention's Active Bacterial Core surveillance to provide strain information (serotypes, resistance, genotypes), and 2778 of these genomes were analyzed to detect highly related genomic clusters. RESULTS: Isolates from persons experiencing homelessness (PEH) were more often within genomic clusters than those from persons not experiencing homelessness (PNEH) (105/198 [53.0%] vs 592/2551 [23.2%]; P < .001). The 4 western sites accounted for 33.4% (929/2778) of isolates subjected to cluster analysis yet accounted for 48.7% (343/705) of clustering isolates (P < .001) and 75.8% (150/198) of isolates recovered from PEH (P < .001). Serotypes most frequent among PEH were (in rank order) 12F, 4, 3, 9N, 8, 20, and 22F, all of which were among the 10 serotypes exhibiting the highest proportions of clustering isolates among all cases. These serotypes accounted for 44.9% (1265/2820) of all IPD cases and are included within available vaccines. CONCLUSIONS: We identified serotype-specific and geographic differences in IPD transmission. We show the vulnerability of PEH within different regions to rapidly spreading IPD transmission networks representing several pneumococcal serotypes included in available vaccines.

Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016- April 2017.

BACKGROUND: The genomic features and transmission link of circulating Group A Streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood. METHODS: We used whole-genome sequencing to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017. RESULTS: The GAS isolates were cultured from 236 invasive and 417 pharyngitis infections. Whole-genome sequencing identified 34 emm types. Compared with pharyngitis isolates, invasive isolates were more likely to carry the erm family genes (23% vs 7.4%, P<.001), which confer resistance to erythromycin and clindamycin (including inducible resistance), and covS gene inactivation (7% vs 0.5%, P<.001). Whole-genome sequencing identified 97 genomic clusters (433 isolates; 2-65 isolates per cluster) that consisted of genomically closely related isolates (median single-nucleotide polymorphism=3 [interquartile range, 1-4] within cluster). Thirty genomic clusters (200 isolates; 31% of all isolates) contained both pharyngitis and invasive isolates and were found in 11 emm types. CONCLUSIONS: In the Denver metropolitan population, mixed disease types were commonly seen in clusters of closely related isolates, indicative of overlapping transmission networks. Antibiotic-resistance and covS inactivation was disproportionally associated with invasive disease.

Invasive Group A Streptococcal Penicillin Binding Protein 2× Variants Associated with Reduced Susceptibility to ß-Lactam Antibiotics in the United States, 2015-2021.

All known group A streptococci [GAS] are susceptible to ß-lactam antibiotics. We recently identified an invasive GAS (iGAS) variant (emm43.4/PBP2x-T553K) with unusually high minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin, although clinically susceptible to ß-lactams. We aimed to quantitate PBP2x variants, small changes in ß-lactam MICs, and lineages within contemporary population-based iGAS. PBP2x substitutions were comprehensively identified among 13,727 iGAS recovered during 2015-2021, in the USA. Isolates were subjected to antimicrobial susceptibility testing employing low range agar diffusion and PBP2x variants were subjected to phylogenetic analyses. Fifty-five variants were defined based upon substitutions within an assigned PBP2x transpeptidase domain. Twenty-nine of these variants, representing 338/13,727 (2.5%) isolates and 16 emm types, exhibited slightly elevated ß-lactam MICs, none of which were above clinical breakpoints. The emm43.4/PBP2x-T553K variant, comprised of two isolates, displayed the most significant phenotype (ampicillin MIC 0.25 µg/ml) and harbored missense mutations within 3 non-PBP genes with known involvement in antibiotic efflux, membrane insertion of PBP2x, and peptidoglycan remodeling. The proportion of all PBP2x variants with elevated MICs remained stable throughout 2015-2021 (<3.0%). The predominant lineage (emm4/PBP2x-M593T/ermT) was resistant to macrolides/lincosamides and comprised 129/340 (37.9%) of isolates with elevated ß-lactam MICs. Continuing ß-lactam selective pressure is likely to have selected PBP2x variants that had escaped scrutiny due to MICs that remain below clinical cutoffs. Higher MICs exhibited by emm43.4/PBP2x-T553K are probably rare due to the requirement of additional mutations. Although elevated ß-lactam MICs remain uncommon, emm43.4/PBP2x-T553K and emm4/PBP2x-M593T/ermT lineages indicate that antibiotic stewardship and strain monitoring is necessary.

Pediatric Brain Abscesses, Epidural Empyemas, and Subdural Empyemas Associated with Streptococcus Species - United States, January 2016-August 2022.

In May 2022, CDC learned of three children in California hospitalized concurrently for brain abscess, epidural empyema, or subdural empyema caused by Streptococcus intermedius. Discussions with clinicians in multiple states raised concerns about a possible increase in pediatric intracranial infections, particularly those caused by Streptococcus bacteria, during the past year and the possible contributing role of SARS-CoV-2 infection (1). Pediatric bacterial brain abscesses, epidural empyemas, and subdural empyemas, rare complications of respiratory infections and sinusitis, are often caused by Streptococcus species but might also be polymicrobial or caused by other genera, such as Staphylococcus. On June 9, CDC asked clinicians and health departments to report possible cases of these conditions and to submit clinical specimens for laboratory testing. Through collaboration with the Children's Hospital Association (CHA), CDC analyzed nationally representative pediatric hospitalizations for brain abscess and empyema. Hospitalizations declined after the onset of the COVID-19 pandemic in March 2020, increased during summer 2021 to a peak in March 2022, and then declined to baseline levels. After the increase in summer 2021, no evidence of higher levels of intensive care unit (ICU) admission, mortality, genetic relatedness of isolates from different patients, or increased antimicrobial resistance of isolates was observed. The peak in cases in March 2022 was consistent with historical seasonal fluctuations observed since 2016. Based on these findings, initial reports from clinicians (1) are consistent with seasonal fluctuations and a redistribution of cases over time during the COVID-19 pandemic. CDC will continue to work with investigation partners to monitor ongoing trends in pediatric brain abscesses and empyemas.

Nasopharyngeal Carriage of Streptococcus pneumoniae Among Young Children in Haiti Before Pneumococcal Conjugate Vaccine Introduction.

BACKGROUND: Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13). METHODS: We conducted a cross-sectional study of children aged 6-24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression. RESULTS: Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers. CONCLUSIONS: Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.

Upsurge of Conjugate Vaccine Serotype 4 Invasive Pneumococcal Disease Clusters Among Adults Experiencing Homelessness in California, Colorado, and New Mexico.

After 7-valent pneumococcal conjugate vaccine introduction in the United States in 2000, invasive pneumococcal disease (IPD) due to serotype 4 greatly decreased in children and adults. Starting in 2013, serotype 4 IPD incidence increased among adults within 3 of 10 Active Bacterial Core surveillance sites. Of 325 serotype 4 cases among adults in 2010-2018, 36% were persons experiencing homelessness (PEH); incidence of serotype 4 IPD among PEH was 100-300 times higher than in the general population within these 3 areas. Genome sequencing for isolates recovered 2015-2018 (n = 246), revealed that increases in serotype 4 IPD were driven by lineages ST10172, ST244, and ST695. Within each lineage, clusters of near-identical isolates indicated close temporal relatedness. Increases in serotype 4 IPD were limited to Colorado, California, and New Mexico, with highest increases among PEH, who were at increased risk for exposure to and infections caused by these strains.

Pneumococcal Carriage in Burkina Faso After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Results From 2 Cross-sectional Population-Based Surveys.

BACKGROUND: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction. METHODS: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey. RESULTS: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed. CONCLUSION: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.

Triplex Direct Quantitative Polymerase Chain Reaction for the Identification of Streptococcus pneumoniae Serotypes.

The quantitative polymerase chain reaction (qPCR) method presented in this study allows the identification of pneumococcal capsular serotypes in cerebrospinal fluid without first performing DNA extraction. This testing approach, which saves time and resources, demonstrated similar sensitivity and a high level of agreement between cycle threshold values when it was compared side-by-side with the standard qPCR method with extracted DNA.

Invasive Pneumococcal Strain Distributions and Isolate Clusters Associated With Persons Experiencing Homelessness During 2018.

BACKGROUND: We aimed to characterize invasive pneumococcal disease (IPD) isolates collected from multistate surveillance in the United States during 2018 and examine within-serotype propensities of isolates to form related clusters. METHODS: We predicted strain features using whole genome sequencing obtained from 2885 IPD isolates obtained through the Center for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), which has a surveillance population of approximately 34.5 million individuals distributed among 10 states. Phylogenetic analysis was provided for serotypes accounting for ≥27 isolates. RESULTS: Thirteen-valent pneumococcal conjugate vaccine (PCV13) serotypes together with 6C accounted for 23 of 105 (21.9%) of isolates from children aged <5 years and 820 of 2780 (29.5%) isolates from those aged ≥5 years. The most common serotypes from adult IPD isolates were serotypes 3 (413/2780 [14.9%]), 22F (291/2780 [10.5%]), and 9N (191/2780 [6.9%]). Among child IPD isolates, serotypes 15BC (18/105 [17.1%]), 3 (11/105 [10.5%]), and 33F (10/105 [9.5%]) were most common. Serotypes 4, 12F, 20, and 7F had the highest proportions of isolates that formed related clusters together with the highest proportions of isolates from persons experiencing homelessness (PEH). Among 84 isolates from long-term care facilities, 2 instances of highly related isolate pairs from co-residents were identified. CONCLUSIONS: Non-PCV13 serotypes accounted for >70% of IPD in ABCs; however, PCV13 serotype 3 is the most common IPD serotype overall. Serotypes most common among PEH were more often associated with temporally related clusters identified both among PEH and among persons not reportedly experiencing homelessness.

A Nationwide Outbreak of Invasive Pneumococcal Disease in Israel Caused by Streptococcus pneumoniae Serotype 2.

BACKGROUND: Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 2 (Sp2) is infrequent. Large-scale outbreaks were not been reported following pneumococcal conjugate vaccine (PCV) implementation. We describe a Sp2 IPD outbreak in Israel, in the PCV13 era, with focus on Sp2 population structure and evolutionary dynamics. METHODS: The data were derived from a population-based, nationwide active surveillance of IPD since 2009. PCV7/PCV13 vaccines were introduced in July 2009 and November 2010, respectively. Sp2 isolates were tested for antimicrobial susceptibility, multilocus sequence typing, and whole-genome sequencing (WGS) analysis. RESULTS: Overall, 170 Sp2 IPD cases were identified during 2009-2019; Sp2 increased in 2015 and caused 6% of IPD during 2015-2019, a 7-fold increase compared with 2009-2014. The outbreak was caused by a previously unreported molecular type (ST-13578), initially observed in Israel in 2014. This clone caused 88% of Sp2 during 2015-2019. ST-13578 is a single-locus variant of ST-1504, previously reported globally including in Israel. WGS analysis confirmed clonality among the ST-13578 population. Single-nucleotide polymorphism-dense regions support a hypothesis that the ST-13578 outbreak clone evolved from ST-1504 by recombination. All tested strains were penicillin-susceptible (minimum inhibitory concentration <0.06 µg/mL). The ST-13578 clone was identified almost exclusively (99%) in the Jewish population and was mainly distributed in 3 of 7 Israeli districts. The outbreak is still ongoing, although it began declining in 2017. CONCLUSIONS: To the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by the emerging ST-13578 clone.

Multistate, Population-Based Distributions of Candidate Vaccine Targets, Clonal Complexes, and Resistance Features of Invasive Group B Streptococci Within the United States, 2015-2017.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS: Using whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states. RESULTS: Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more ß-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1-2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS: This first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The ß-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

Whole genome sequence based capsular typing and antimicrobial resistance prediction of Group B streptococcal isolates from colonized pregnant women in Nigeria.

BACKGROUND: Streptococcus agalactiae (Group B Streptococcus, GBS) is one of the major bacterial pathogens responsible for neonatal sepsis. Whole genome sequencing has, in recent years, emerged as a reliable tool for capsular typing and antimicrobial resistance prediction. This study characterized vaginal and rectal isolates of Group B Streptococcus obtained from pregnant women in Port Harcourt, Nigeria using a whole-genome sequence-based approach. RESULTS: Capsular types Ia, Ib, II, III, IV and V were detected among the 43 isolates sequenced. Twelve sequence types (STs) were identified, with ST19 (n = 9, 27.3 %) and ST486 (n = 5, 15.2 %) the most frequent among non-duplicated isolates. Of the alpha-like proteins (alp) identified, Alp1 was the most prevalent in 11 (33.3 %) isolates. Macrolide and lincosamide resistance determinants were present in 15 (45.5 %) isolates; ermB was detected in 1 (3 %), ermTR in 7 (21.2 %) isolates, lnu gene was detected in 6 (18.2 %) and mef was identified in 3 (9.1 %) isolates. Resistance of GBS to erythromycin and clindamycin (predicted from presence of erm or mef genes) was found to be 30.3 % and 24.2 %, respectively. All isolates were predicted resistant to tetracycline with only the tetM gene identified. Fluoroquinolone-resistance conferring substitutions in gyrA + parC were detected in 9 (27.3 %) isolates and chloramphenicol resistance was predicted from presence of aac6'-aph2 gene in 11 (33.3 %). CONCLUSIONS: The data available from the whole genome sequencing of these isolates offers a small but insightful description of common serotypes and resistance features within colonizing GBS in Nigeria.