Invasive Pneumococcal Disease Isolates Research Articles

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

Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). 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. 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. 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.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to β-lactam antibiotics in a Chinese metropolitan city

ObjectivesWe characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. MethodsSeventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. ResultsThese IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to β-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. ConclusionA novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Antimicrobial resistance of Streptococcus pneumoniae from invasive pneumococcal diseases in Latin American countries: a systematic review and meta-analysis.

Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed. We conducted a systematic review to evaluate the frequency of antimicrobial resistance of Streptococcus pneumoniae from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097). From 8,600 records identified, 103 studies were included, with 49,660 positive samples of S. pneumoniae for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7-25.0, I2: 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2-6.9, I2: 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2-36.4, I2: 87.7], and 9.7% [95%IC 5.9-15.6, I2: 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime. Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction.

Clonal diversity of Streptococcus pneumoniae serotype 19A collected from children < 5 years old in Québec, Canada, 2016–2021

Streptococcus pneumoniae serotype 19A is a highly diverse, often antimicrobial-resistant Gram-positive bacterium which can cause invasive pneumococcal disease (IPD). In 2021, public health authorities in the Canadian province of Québec observed an increase of serotype 19A IPD in children <5 years. The purpose of this study was to determine the clonal composition of serotype 19A isolates collected from this age group in Québec, from 2016 to 2021. Forty-one and 37 IPD isolates from children <5 years from Québec and the remainder of Canada, respectively, were sequenced using the Illumina NextSeq platform. Phylogenetic analysis using SNVPhyl identified three clusters, corresponding to three common clones of serotype 19A: CC199, CC320 and ST695. CC199, predominantly represented by ST416, accounted for similar proportions of serotype 19A isolates collected from children in Québec (19.5 %) and other Canadian jurisdictions (OCJs, 21.6 %), with significant presence of ermB (62.5 % and 60 % of ST416 isolates, respectively). CC320 was more commonly identified from OCJs in comparison to Québec (18.9 % vs. 7.3 %, respectively), but were highly antimicrobial-resistant regardless of region. ST695 was the most common clone of serotype 19A collected in Québec from children <5 years, representing 65.9 % of isolates collected over the study period (40.5 % of isolates collected in OCJs). Phylogenetic analysis identified geographical differences in ST695 across Canada; including a large clade specific to Québec (with both susceptible and macrolide-resistant [ermB] subclades), and a separate macrolide-resistant (mefA) clade associated with OCJs. The Québec-specific ermB-ST695 clone represented 48.1 % of ST695 collected from the province. Continued genomic surveillance of S. pneumoniae serotype 19A is required to: i) track the prevalence and clonal composition of serotype 19A in Québec in future years; ii) characterize the clonal distribution of serotype 19A in adult populations; and iii) monitor whether the currently geographically restricted ermB-ST695 clone observed in Québec expands to OCJs.

Comparison of PCV10, PCV13, PCV15, PCV20 and PPSV23 vaccine coverage of invasive Streptococcus pneumoniae isolate serotypes in Canada: the SAVE study, 2011-20.

As pneumococci evolve under vaccine, antimicrobial and other selective pressures, it is important to track isolates covered by established (PCV10, PCV13 and PPSV23) and new (PCV15 and PCV20) vaccine formulations. To compare invasive pneumococcal disease (IPD) isolates from serotypes covered by PCV10, PCV13, PCV15, PCV20 and PPSV23, collected in Canada from 2011 to 2020, by demographic category and antimicrobial resistance phenotype. IPD isolates from the SAVE study were initially collected by members of the Canadian Public Health Laboratory Network (CPHLN) as part of a collaboration between the Canadian Antimicrobial Resistance Alliance (CARA) and the Public Health Agency of Canada (PHAC). Serotypes were determined by quellung reaction, and antimicrobial susceptibility testing was performed using the CLSI broth microdilution method. A total of 14 138 invasive isolates were collected from 2011 to 2020, with 30.7% of isolates covered by the PCV13 vaccine, 43.6% of isolates covered by the PCV15 vaccine (including 12.9% non-PCV13 serotypes 22F and 33F), and 62.6% of isolates covered by the PCV20 vaccine (including 19.0% non-PCV15 serotypes 8, 10A, 11A, 12F and 15B/C). Non-PCV20 serotypes 2, 9N, 17F and 20, but not 6A (present in PPSV23) represented 8.8% of all IPD isolates. Higher-valency vaccine formulations covered significantly more isolates by age, sex, region and resistance phenotype including MDR isolates. Coverage of XDR isolates did not significantly differ between vaccine formulations. When compared with PCV13 and PCV15, PCV20 covered significantly more IPD isolates stratified by patient age, region, sex, individual antimicrobial resistance phenotypes and MDR phenotype.

Comparative genomic epidemiology of serotype 3 IPD and carriage isolates from Southampton, UK between 2005 and 2017.

Serotype 3 pneumococci remains a significant cause of disease despite its inclusion in PCV13. Whilst clonal complex 180 (CC180) represents the major clone, recent studies have refined the population structure into three clades: Iα, Iβ and II, with the last being a recent divergent and more antibiotic-resistant. We present a genomic analysis of serotype 3 isolates from paediatric carriage and all-age invasive disease, collected between 2005 and 2017 in Southampton, UK. Forty-one isolates were available for analysis. Eighteen were isolated during the annual cross-sectional surveillance of paediatric pneumococcal carriage. The remaining 23 were isolated from blood/cerebrospinal fluid specimens at the University Hospital Southampton NHS Foundation Trust laboratory. All carriage isolates were CC180 GPSC12. Greater diversity was seen with invasive pneumococcal disease (IPD) with three GPSC83 (ST1377: n=2, ST260: n=1) and one GPSC3 (ST1716). For both carriage and IPD, Clade Iα was dominant (94.4 and 73.9 % respectively). Two isolates were Clade II with one from carriage (a 34-month-old, October 2017) and one invasive isolate (49-year-old, August 2015). Four IPD isolates were outside the CC180 clade. All isolates were genotypically susceptible to penicillin, erythromycin, tetracycline, co-trimoxazole and chloramphenicol. Two isolates (one each from carriage and IPD; both CC180 GPSC12) were phenotypically resistant to erythromycin and tetracycline; the IPD isolate was also resistant to oxacillin.In the Southampton area, carriage and invasive disease associated with serotype 3 is predominantly caused by Clade Iα CC180 GPSC12.

Streptococcus pneumoniae serotype 19A from carriers and invasive disease: virulence gene profile and pathogenicity in a Galleria mellonella model.

This study aimed to evaluate and compare the presence of genes related to surface proteins between isolates of Streptococcus pneumoniae from healthy carriers (HC) and invasive pneumococcal disease (IPD) with a particular focus on serotype 19A. The presence of these genes was identified by real-time PCR. Subsequently, we employed the Galleria mellonella larval infection model to study their effect on pathogenicity in vivo. The percentage of selected virulence genes was similar between the HC and IPD groups (p > 0.05), and the genes lytA, nanB, pavA, pcpA, phtA, phtB, phtE, rrgA, and sipA were all present in both groups. However, the virulence profile of the isolates differed individually between HC and IPD groups. The highest lethality in G. mellonella was for IPD isolates (p < 0.01), even when the virulence profile was the same as compared to the HC isolates or when the nanA, pspA, pspA-fam1, and pspC genes were not present. The occurrence of the investigated virulence genes was similar between HC and IPD S. pneumoniae serotype 19A groups. However, the IPD isolates showed a higher lethality in the alternative G. mellonella model than the HC isolates, regardless of the virulence gene composition, indicating that other virulence factors may play a decisive role in virulence. Currently, this is the first report using the in vivo G. mellonella model to study the virulence of clinical isolates of S. pneumoniae.

Antimicrobial resistance in Streptococcus pneumoniae: a retrospective analysis of emerging trends in the United Arab Emirates from 2010 to 2021.

Although pneumococcal conjugate vaccines (PCV) have been effective in reducing the burden of Streptococcus pneumoniae infections, there is a paucity of data on the relationship with antimicrobial resistance (AMR) trends in the Arabian Gulf region. This study was carried out to assess S. pneumoniae resistance trends in the United Arab Emirates (UAE) where PCV-13 vaccination was introduced in 2011. Retrospective analysis of S. pneumoniae demographic and microbiological data collected as part of the national AMR surveillance program from 2010 to 2021 was carried out. A survey of reporting sites and hand searching of annual reports of local health authorities was carried out to identify data on S. pneumoniae serotypes as this is not included in the AMR surveillance database. From 2010 to 2021, 11,242 non-duplicate S. pneumoniae isolates were reported, increasing from 324 in 2010 to 1,115 in 2021. Factoring in annual increment in the number of surveillance sites, the number of isolates per site showed an upward trajectory from 2015 to 2018 and declined in 2020 with the onset of the pandemic. The majority of isolates (n/N = 5,751/11,242; 51.2%) were from respiratory tract specimens with 44.5% (n/N = 2,557/5,751) being nasal colonizers. Up to 11.9% (n/N = 1,337/11,242) were invasive pneumococcal disease (IPD) isolates obtained from sterile site specimens including blood (n = 1,262), cerebrospinal (n = 52), pleural (n = 19) and joint (n = 4) fluid; and were predominantly from pediatric patients. The downward trend for amoxicillin and for penicillin G at the non-meningitis and meningitis as well as oral penicillin breakpoints was statistically significant. In contrast, increasing trends of resistance were seen for levofloxacin, moxifloxacin, trimethoprim/sulfamethoxazole and erythromycin. IPD and non-IPD isolates showed similar demographic and AMR trends. None of the surveillance sites carried out S. pneumoniae serotyping and handsearching of annual reports did not yield this information. The increasing trend of pneumococcal disease and AMR with emergence of isolates with MDR phenotype despite is of concern. In the absence of S. pneumoniae serotyping the role of non-vaccine serotypes in driving this pattern remains unknown. There is an urgent need for serotype, genomic and AMR surveillance of S. pneumoniae isolates in the UAE.

Characterization of Emerging Serotype 19A Pneumococcal Strains in Invasive Disease and Carriage, Belgium.

After switching from 13-valent to 10-valent pneumococcal conjugate vaccine (PCV10) (2015–2016) for children in Belgium, we observed rapid reemergence of serotype 19A invasive pneumococcal disease (IPD). Whole-genome sequencing of 166 serotype 19A IPD isolates from children (n = 54) and older adults (n = 56) and carriage isolates from healthy children (n = 56) collected after the vaccine switch (2017–2018) showed 24 sequence types (STs). ST416 (global pneumococcal sequence cluster [GPSC] 4) and ST994 (GPSC146) accounted for 75.9% of IPD strains from children and 65.7% of IPD (children and older adults) and carriage isolates in the PCV10 period (2017–2018). These STs differed from predominant 19A IPD STs after introduction of PCV7 (2011) in Belgium (ST193 [GPSC11] and ST276 [GPSC10]), which indicates that prediction of emerging strains cannot be based solely on historical emerging strains. Despite their susceptible antimicrobial drug profiles, these clones spread in carriage and IPD during PCV10 use.

Molecular characterization and epidemiology of Streptococcus pneumoniae serotype 8 in Denmark

BackgroundStreptococcus pneumoniae serotype 8 incidence has increased in Denmark after the introduction of pneumococcal conjugated vaccines (PCV). The mechanism behind the serotype 8 replacement is not well understood. In this study, we aimed to present epidemiological data on invasive pneumococcal disease (IPD) and molecular characterization of 96 serotype 8 clinical isolates.MethodsIPD data from 1999 to 2019 were used to calculate the incidence and age distribution. Whole-genome sequencing (WGS) analysis was performed on 96 isolates (6.8% of the total serotype 8 IPD isolates in the period) to characterize the isolates with respect to pneumococcal lineage traits, a range of genes with potential species discrimination, presence of colonization and virulence factors, and molecular resistance pattern.ResultsThe serotype 8 IPD incidence increased significantly (P < 0.05) for the age groups above 15 years after the introduction of PCV13, primarily affecting the elderly (65+). All isolates were phenotypically susceptible to penicillin, erythromycin and clindamycin.Molecular characterization revealed seven different MLST profiles with ST53 as the most prevalent lineage (87.5%) among the analyzed serotype 8 isolates. The genes covering the cell-surface proteins: lytA, rspB, pspA, psaA & Xisco and the pneumococcal toxin pneumolysin = ply were present in all isolates, while genes for the membrane transporter proteins: piaA/piaB/piaC; the capsular genes: cpsA (wzg) & psrP; the metallo-binding proteins zmpB & zmpC; and the neuroamidase proteins: nanA/nanB were variably present. Surprisingly, the putative transcriptional regulator gene SP2020 was not present in all isolates (98%). Susceptibility to penicillin, erythromycin and clindamycin was molecularly confirmed.ConclusionThe observed serotype 8 replacement was not significantly reflected with a change in the MLST profile or changes in antibiotic resistance- or virulence determinants.

176. Selected Impact of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Invasive Pneumococcal Disease (IPD) at Eight Children’s Hospitals in the United States. 2014–2019

BackgroundThe 2011 IDSA/PIDS Clinical Practice Guidelines for the Management of Community-acquired Pneumonia (CAP) in Children Older than 3 months recommended empiric treatment with either ampicillin/penicillin or ceftriaxone based on PCV13 vaccine status and the local antibiotic susceptibilities of IPD isolates. No study has addressed differences in antibiotic susceptibilities for isolates from children with pneumococcal pneumonia (PP) based on PCV13 status.MethodsInvestigators from 8 US children’s hospitals identified infants and children with IPD between 1/1/2014 and 12/31/2019. IPD was documented by positive cultures from a normally sterile site. PP diagnosis required an abnormal chest radiograph. Clinical data were recorded and isolates analyzed for serotype (ST) by the capsular swelling method and antimicrobial susceptibilities by standard methods. Administration of PCV7/13 was documented through the patient’s medical records, health care provider or a vaccine registry. Fisher Exact was performed; p< 0.05 was significant.Results690 IPD patients with isolates were available (0–18 y); 24% (166/690) of the isolates were PCV13 STs (ST3-75, ST19F-45, ST19A-36, ST7F-5, other STs-5). The most common non-PCV13 ST isolates were ST35B-60, ST23B-59, ST33F-47, ST22F-43, ST15C-35, ST23A-27, ST15B-26, ST10A-26, ST15A-23. Of non-PCV13 isolates, 41% (217/524) were among the 7 additional STs in PCV20. For children with PP (n=157), the distributions of penicillin (Table) (p=0.8) and ceftriaxone MICs were no different for isolates obtained from children regardless of prior PCV13 doses. Less than 7% of PP isolates were resistant to penicillin (MIC >2 µg/mL). Table. Minimal inhibitory concentrations (MIC) of pneumococcal isolates related to the number of PCV13 doses each patient received prior to pneumococcal pneumonia (PP).Number of PCV13 doses Penicillin MIC (µg/mL) 0 1 2 3 4 ≤ 0.125 26*1281743 0.25–0.5 42115 1 10031 2 40025 ≥4 12124*Number of pneumococcal pneumonia patients/isolates. 145/157 patients had immunization and isolate susceptibility data available for analysis.ConclusionPCV13 status should not modify empiric antibiotics for children with suspected pneumococcal CAP. 41% of non-PCV13 IPD isolates were among the 7 additional PCV20 STs.Disclosures Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support) Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member)

911. Assessment of Representativeness of IPD Surveillance Conducted by the National Microbiology Laboratory of Canada

BackgroundUnderstanding the evolving epidemiology of Streptococcus pneumoniae serotypes is important for assessing the current and potential future immunization programs. In Canada, Invasive pneumococcal disease (IPD) is mandatory reportable to provincial/territorial public health. Provinces and territories voluntarily submit annual IPD data to the Canadian Notifiable Disease Surveillance System (CNDSS), which publishes information on IPD cases and incidence rates, however serotype data are not available. Provinces/territories also voluntarily submit IPD isolates to the National Microbiology laboratory (NML) for serotyping; provinces that conduct their own serotyping submit this information. The NML produces comprehensive IPD surveillance reports including serotype distribution; due to lack of population denominator, no incidence rates are available. The two surveillance programs are not linked. The objective of the study is to assess the representativeness of the NML surveillance as compared to the CNDSS and provincial reportable diseases databases.MethodsOver the study time period (2010-2017), we compared annual IPD case counts between the NML and CNDSS reports. Due to the difference in age grouping between CNDSS and NML, comparison was limited to these groups: all age, < 5, 5-14 and > 15 years. In addition, the IPD counts from NML were compared to data from four largest provinces.ResultsFor < 5 group, NML reported 91% of CNDSS case count whereas for 5-14 and > 15 years of age, it was 81% and 79%, respectively. Compared to the corresponding provincial databases, NML reported 91%, 97%, and 93% case counts for Ontario, British Columbia, and Alberta, respectively, while it was only 47% for Quebec. Further analysis revealed that the discrepancy in Quebec is the result of under-representation of >5 populations.Figure 1: Comparison of age stratified IPD case counts between CNDSS and NML Figure 2. Comparison of all age IPD case counts between NML and provincial databases ConclusionIPD surveillance conducted by NML has been instrumental to gain insight into the evolving epidemiology of S. pneumoniae serotypes in Canada. Comparisons of IPD counts from NML surveillance reports with reportable disease databases revealed different levels of concordance across provinces and age groups. The limitations of NML surveillance including incomplete or inconsistent reporting should be taken into consideration when interpreting the data.DisclosuresRajeev M. Nepal, PhD, Pfizer (Employee) Stephane B. Dion, PhD, Pfizer (Employee) Ana Gabriela Grajales, MD, Pfizer (Employee) Maria Major, B.Sc., MPH, Pfizer (Employee) Alejandro Cane, MD, Pfizer (Employee) Jelena Vojicic, MD, Pfizer (Employee)

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

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. 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. 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. 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.

Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004–2016

Changes in pneumococcal antimicrobial resistance (AMR) have been reported following use of pneumococcal conjugate vaccines (PCVs) in childhood vaccination programmes. We describe AMR trends and clonality in Norway during 2004–2016; we studied 10,239 invasive pneumococcal disease (IPD) isolates in terms of serotypes, antimicrobial susceptibility, and for a systematically collected subset of 2473 isolates, multilocus sequence types (ST). The IPD cases were notified to the Norwegian Surveillance System for Communicable Diseases and pneumococcal isolates were collected through the National Reference Laboratory for Pneumococci. The cases are sourced from the entire Norwegian population. We supplemented the IPD isolates with isolates from carriage studies in children attending day-care, performed in 2006 (before mass childhood vaccination with PCV7), 2008 (2 years after PCV7 introduction), 2013 (2 years after the transition to PCV13), and 2015. IPD cases were 0–102 years old; median 64 years. Carriage study participants were typically aged 1–5 years. Overall, AMR was low; a maximum of 7% of IPD isolates were resistant, depending on the antimicrobial. Erythromycin and trimethoprim/sulfamethoxazole resistant IPD (ERY-R and SXT-R, respectively) decreased in the PCV7 period (2006–2010). In the PCV13 period (2011–2016) however, we saw an indication of increased non-susceptibility among IPD isolates. This increase was mainly due to non-vaccine serotypes 15A-ST63 (multidrug resistant), 24F-ST162 (SXT-R), 23B-ST2372 (penicillin non-susceptible and SXT-R) and 33F (ERY-R and clindamycin resistant). Resistant or non-susceptible IPD isolates were often clones introduced into Norway during the study period. The exception was ERY-R isolates; initially, these largely consisted of an established serotype 14-ST9 clone, which disappeared after introducing PCV7. The carriage study results mostly resembled the changes seen in IPD with a maximum of 9% of the participants per study carrying resistant pneumococci. As actual PCVs are not fully limiting AMR, higher-valency vaccines and prudent use of antimicrobials are still needed to temper pneumococcal AMR.

Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015–2017

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages.

Serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease isolates from children in mainland China-a systematic review.

This study aimed to review and report the serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease (IPD) isolates, as this information is important for policy making since China has not adopted any pneumococcal vaccines in the national immunization schedule. A systematic review of the published literature from January 2000 to December 2018 was performed to identify articles that describe the serotype and/or antimicrobial resistance patterns of IPD cases in children in mainland China. Analysis of the extracted data was performed with the Microsoft Excel spreadsheet program. The percentage of the serotypes was calculated by dividing the number of isolates for each serotype with the total number of isolates included in all the studies. The theoretical impact of the vaccine was estimated by calculating the percentage of isolates that exhibited the serotypes included in the vaccines. The prevalence of antimicrobial resistance was defined as the number of isolates that were resistant divided by the total number of isolates tested for resistance to the specific antimicrobial agent. Forty-two articles were screened in the preliminary search, of which sixteen fulfilled inclusion criteria and were included in the final analysis. The predominant serotypes were 19A, 19F, 14, 23F, and 6B, and the estimated impact of PCV13 was 90.4%. The isolates exhibited a high frequency of resistance to cefuroxime, cefaclor, and erythromycin. It is necessary for Chinese children to receive PCV13. Clinical workers should pay attention to the high frequency of resistance to antimicrobial agents.

1888. A Nationwide Outbreak of Invasive Pneumococcal Disease (IPD) Caused by a Novel Streptococcus Pneumoniae Serotype 2 (SP2) Clone in the PCV13 Era, in Israel

BackgroundIPD caused by Sp2 (non-PCV13 serotype) is relatively rare. However, Sp2 has a high potential for causing IPD including meningitis. Large-scale outbreaks of Sp2 IPD are rare and were not reported post-PCV implementation. We describe Sp2 IPD outbreak in Israel, in the PCV13 era, caused by a novel clone. Additionally, we analyzed the population structure and evolutionary dynamics of Sp2 during 2006–2018.MethodsAn ongoing, population-based, nationwide active surveillance, conducted since July 2009. PCV7/PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All isolates were tested for antimicrobial susceptibility, PFGE, MLST and whole-genome sequencing (WGS). Results. Overall, 173 Sp2 IPD cases were identified; all isolates were analyzed by MLST (Figure 1). During 2016–2017, Sp2 caused 7.6% of all-IPD, a 7-fold increase compared with 2006–2015, and ranked second (after serotype 12F causing 12%) among IPD isolates. During 2006–2015, 98% (40/41) Sp2 IPD were caused by the previously reported global ST-1504 clone. The outbreak was caused by a novel clone ST-13578, not previously reported (Figure 2). WGS analysis confirmed that ST-13578 was related, but genetically distinct from ST-1504, observed exclusively before the outbreak. A single strain of clone ST-74 previously globally reported was identified in 2017–2018. An additional case was identified in an adult in the UK, following a family visit from Israel. The ST-13578 clone was identified only in the Jewish population and was mainly distributed in 3 of the 7 Israeli districts. All tested strains were penicillin-susceptible (MIC < 0.06 μg/mL).ConclusionTo the best of our knowledge, this is the first widespread Sp2 outbreak since PCV13 introduction worldwide, caused by a novel clone ST-13578. The outbreak is still ongoing, although a declining trend was noted since 2017. Disclosures All Authors: No reported Disclosures.

Incidence and Risk Factors for Invasive Pneumococcal Disease and Community-acquired Pneumonia in Human Immunodeficiency Virus-Infected Individuals in a High-income Setting.

BackgroundAlthough people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations.MethodsWe identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART.ResultsIncidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts <500 cells/μL (incidence rate ratio [IRR], 6.1 [95% confidence interval, 2.2–17] and IRR, 2.4 [95% confidence interval, 1.9–3.0]), the incidence rate in patients with CD4 counts >500 cells/μL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts <500 cells/μL, smoking, drug use, and chronic obstructive pulmonary disease.ConclusionsThe incidence of IPD and CAP among PLWH remains higher compared with the general population, even in those who are virally suppressed and have high CD4 counts. With all serotyped IPD isolates covered by pneumococcal vaccines, our study provides additional argumentation against the poor current adherence to international recommendations to vaccinate PLWH.

Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017

ObjectivesWe aimed to provide population-based and whole-genome sequence (WGS) -based characterization of invasive pneumococcal disease isolates collected from multistate surveillance in the USA during 2017. MethodsWe obtained short-read WGS from 2881 isolates with associated bioinformatics pipeline strain feature predictions. For quality control, capsular serotypes and antimicrobial MICs were also obtained conventionally from 442 isolates. Annotated WGS were provided (inclusive of serotypes, MICs, multilocus sequence types, pilus type(s)) from 2723 isolates. For 158 isolates with suboptimal WGS, antimicrobial MICs were obtained conventionally. ResultsThere were 127 isolates from children <5 years of age and 2754 isolates from those ≥5 years old in 2017. One of 43 different serotypes was predicted for 2877 of the 2881 isolates. Serotypes in the 13-valent conjugate vaccine together with 6C (PCV13+6C) accounted for 816 (28.3%) isolates, with PCV13 serotype 3 being the most common serotype overall. Non-PCV13–6C– serotypes accounted for 2065 (71.7%) isolates, comprising 96 (75.6%) isolates from children < 5 years old and 1969 (61.4%) isolates from those aged ≥5 years. Of 36 different categories of recently emerged serotype-switch variants, three showed marked increases relative to 2015–2016 in that the number from 2017 surpassed the number from 2015–2016 combined. Two of these included antimicrobial-resistant serotype 11A and 35B serotype-switch variants of the ST156 clonal complex. ConclusionsPCV13+6C strains are still identified in 2017 but non-PCV13-type strains impose a considerable burden. This well-annotated year 2017 WGS/strain data set will prove useful for a broad variety of analyses and improved our understanding of invasive pneumococcal disease-causing strains in the post-PCV13 era.

Invasive Pneumococcal Disease in Children's Hospitals: 2014-2017.

The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in the United States in 2010. We describe invasive pneumococcal disease (IPD) in children at 8 children's hospitals in the US from 2014 to 2017. Children with IPD occurring from 2014 to 2017 were identified from a prospective study. Demographic and clinical data, including results of any immune evaluation along with the number and dates of previous pneumococcal conjugate vaccines administered, were recorded on case report forms. Isolate serotypes were determined in a central laboratory. Pneumococcal conjugate vaccine doses were counted if IPD occurred ≥2 weeks after a dose. PCV13 serotypes accounted for 23.9% (115 out of 482) of IPD isolates from 2014 to 2017. Serotypes 3, 19A, and 19F accounted for 91% of PCV13 serotypes. The most common non-PCV13 serotypes were 35B, 23B, 33F, and 22F. An underlying condition was significantly (P < .0001) more common in children with IPD due to non-PCV13 serotypes (200 out of 367, 54.5%) than for children with PCV13 serotypes (27 out of 115, 23.5%). An immune evaluation was undertaken in 28 children who received ≥2 PCV13 doses before IPD caused by a PCV13 serotype. Only 1 was found to have an immunodeficiency. PCV13 serotypes (especially serotypes 3, 19A, and 19F) continue to account for nearly a quarter of IPD in US children 4 to 7 years after PCV13 was introduced. Underlying conditions are more common in children with non-PCV13 serotype IPD. Immune evaluations in otherwise healthy children with PCV13 serotype IPD despite receiving ≥2 PCV13 doses did not identify an immunodeficiency.