Invasive Group B Streptococcus Infection Research Articles

Burden of Invasive Group B Streptococcus Infection Among Omani Infants Less Than 90 Days Old: A Multicenter Study.

Group B Streptococcus (GBS) infection is the leading cause of neonatal morbidity and mortality worldwide. This study aims to investigate the incidence of invasive GBS disease among infants less than 90 days old in Oman and to describe their risk factors, clinical presentations and clinical outcomes. We retrospectively collected the data of less than 90-day-old Omani infants with culture-positive GBS from sterile samples. This study was conducted in 3 tertiary hospitals in Oman from 2009 to 2018. Over 10 years, we identified 92 cases of culture-confirmed invasive GBS infection from 178,285 live births in the 3 hospitals, giving an overall incidence of 0.53 per 1000 live births [95% confidence interval (CI): 0.4-0.7)]. Of those, 59 (64.1%) had early-onset neonatal GBS disease and 33 (35.9%) had late-onset neonatal GBS disease. The incidence of invasive GBS disease was significantly higher in the last 5 years from 2014 to 2018 (0.69 per 1000 live births, 95% CI: 0.5-0.9) compared to the previous years from 2009 to 2013 (0.36 per 1000 live births, 95% CI: 0.2‒0.5), (P = 0.004). Infants with late-onset neonatal GBS disease had a higher risk of meningitis compared to infants with early-onset neonatal GBS disease (30.3% vs. 10.2%, P = 0.021). The mortality rate was 13.5%. The incidence of invasive GBS disease in Oman is similar to what was reported worldwide, however, the burden of the disease in terms of mortality is high. In addition, a significant increase in the annual incidence of invasive GBS disease in Omani infants was found over the study period.

GBS vaccines in the UK: a round table discussion

Background Group B streptococcus (GBS) remains a leading cause of infant sepsis, meningitis and death despite intrapartum antibiotic prophylaxis. A vaccine is urgently required, and two candidates are in advanced clinical trials. For successful GBS vaccine implementation, especially if a vaccine is licensed based on an immunological threshold, there must be cross-sector engagement, effective advocacy, robust plans for phase IV studies and equitable access. Meeting A round-table discussion, held at St George’s University of London, reviewed the current position of GBS vaccines in the UK context, focusing on phase IV plans, convening a diverse group of stakeholders from across the UK, with a role in GBS vaccine licensure, advocacy, implementation or effectiveness evaluation. Presentations outlined the latest UK epidemiology, noting the rising infant invasive GBS (iGBS) infection rates from 1996 to 2021 for both early and late onset disease, with the highest disease rates in Black infants (1.1/1000 livebirths vs white infants (0.81/1000 livebirths). Potential coverage of the candidate vaccines was high (>95%). Regulatory input suggested that EU regulators would consider waiving the need for a pre-licensure efficacy study if a putative correlate of protection could be adequately justified. Phase IV study methodologies for a GBS vaccine were considered, largely based on previous UK maternal vaccine assessments, such as a nationwide cohort study design using a vaccine register and a maternal services dataset. Other strategies were also discussed such as a cluster or stepped-wedge randomised trial to evaluate implementation outcomes. Opportunities for advocacy, education and engagement with additional key partners were discussed and identified. Conclusions With an approved GBS vaccine a near possibility, planning of phase IV studies and identification of critical barriers to implementation are urgently needed. Cross-sector engagement is essential and will facilitate a successful pathway.

Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway. We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population. A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes. The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease.

Clinical Disease and Outcomes of Group B Streptococcus Bloodstream Infections at a Teaching Hospital in Saudi Arabia From 2015 to 2022.

Background Invasive disease due to group B Streptococcus (GBS) infection in adult males and nonpregnant females can cause various diseases, such as primary bacteremia, endocarditis, skin and soft tissue infection (SSTI), and meningitis. Especially in older people, invasive GBS infection has a high case fatality rate. In Saudi Arabia, little is known about the clinical signs and symptoms of GBS bacteremia and the associated risk factors and mortality rate. Methodology We performed a retrospective study at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, a large tertiary hospital, to investigate clinical disease, potential risk factors, susceptibility patterns, and mortality related to GBS in adult males and nonpregnant females diagnosed with GBS bacteremia. All patients ≥14 years of age with GBS-positive blood cultures from January 1, 2015, until December 31, 2022, were included. Patient data such as age, sex, comorbidities, hospital ward, length of hospital stay, monomicrobial versus polymicrobial bloodstream infection, antimicrobials used for treatment, complications, whether an infectious disease specialist had seen them, and outcomes were extracted from the electronic health records. Results A total of 50 patients with GBS bacteremia met the inclusion criteria. The mean age of these patients was 57.0 years (SD = 16.0), and 27 (54%) were female. The 90-day mortality was 11 (22%). In total, 34 (68%) patients had a monomicrobial infection, and among those with polymicrobial infection, methicillin-resistant Staphylococcus aureus was the most common co-infection (56%, n = 9/16). The most common source of infection was SSTI and wound infection in 24 (48%) patients. Most patients had one or more comorbidities; the mean Charlson comorbidity index was 3.8 (SD = 2.4). The most prevalent comorbidity was diabetes mellitus in 35 (70%) patients. Of all variables analyzed, only age was significantly associated with mortality (p = 0.016), and age had a predictive value for mortality (p = 0.035). Conclusions In Saudi Arabia, as in other countries, GBS is an important pathogen, especially in older people, that should be considered when encountering a patient with bacteremia. In addition, in patients over 65 years old, GBS bacteremia carries a high risk for mortality.

207. The increased frequency and clinical characteristics of Streptococcus agalactiae serotype VIII from blood isolates at two tertiary care hospital in South Korea over 14 years

Abstract Background Invasive group B Streptococcus (GBS) infections are increasing among non-pregnant adults with underlying diseases. Previous studies have shown that the proportion of GBS serotype of pregnant women were differed from geographic regions. However, studies on the serotype of invasive GBS infection in non-pregnant adults are sparse. This study aimed to evaluate epidemiology and clinical characteristics of strains caused GBS bloodstream infection according to serotypes. Methods S. agalactiae blood isolates were collected between March 2007 and December 2021, and their clinical data were obtained from two tertiary hospital of South Korea. Species identification was performed using MALDI-TOF MS and serotyping test was performed using commercial latex particle agglutination kit. Antimicrobial susceptibility tests are conducted using automated equipment. Results A total of 130 patients with GBS bacteremia were identified and among them 125 isolates were serotypeable. The median age were 66 years and 46% were male. Serotype VIII was most dominant (31.5%) and Ib, III, Ia, V were as follows (20.8%, 13.8%, 12.3%, 11.5% retrospectively). The proportion of serotype VIII increased from 27.3% to 53.3% from 2015 to 2021. Most common source of GBS bloodstream infection were primary bacteremia (34.4%), followed by bone and joint infections (16.8%) and skin and soft tissue infections (13.6%). Cardiovascular disease (79.2%) was most frequently reported in GBS bacteremia patients, followed by malignancy (44.6%) and diabetes mellitus (40%). The 30-day mortality rate was 12.3% and there was no difference in 30-day mortality according to serotypes (log rank test P=0.39). In logistic regression analysis, high SOFA score was significantly associated with 30-day mortality (odd ratio 1.28, 95% C.I. 1.28-2.53, P< 0.01). All isolated GBS were susceptible to penicillin and resistances were identified against clindamycin, erythromycin and levofloxacin as 30%, 26.9%, 24.6% of the isolates, respectively. Conclusion We found the most common capsular serotype was VIII (31.5%) in Korea and the proportion of type VIII increasing over time. It is necessary to consider GBS vaccine in adults with underlying disease and its composition for serotype VIII according to epidemiologic characteristics. Disclosures All Authors: No reported disclosures

Clinical characteristics of infants younger than 90 days diagnosed with invasive group B streptococcal infection in the emergency department

Purpose: We aimed to characterize invasive group B streptococcal infection (IGBSI) in young infants hospitalized through the emergency department.Methods: We analyzed medical records of infants younger than 90 days with IGBSI, defined as group B streptococcus bacteremia or meningitis, who visited the emergency department from January 2009 through December 2021. Their clinical features were compared as per 2 criteria, neonates and meningitis. For the comparisons, we defined 2 composite outcomes, “clinically important abnormality (any of the followings: temperature > 38.5℃, leukocytes < 5,000/mm<sup>3</sup> or > 15,000/mm<sup>3</sup>, absolute neutrophils > 4,000/mm<sup>3</sup> or C-reactive protein > 2.0 mg/dL)”and “poor outcomes (any of the followings: intensive care unit, transfer, seizure or complications).”Percentages are rounded to the first decimal places.Results: A total of 35 infants, of whom 15 (43%) were neonates and 17 (49%) were boys, had IGBSIs, including 23 infants (66%) with isolated bacteremia, 11 (31%) with bacteremia with meningitis, and 1 (3%) with isolated meningitis. Ill appearances were noted in 27 infants (77%) who encompassed all with meningitis. The other 8 infants (23%) looking well had 1 or more components of the clinically important abnormality. The neonates showed a higher frequency of vaginal delivery (87% vs. 35%; P = 0.002) and a lower frequency of a temperature > 38.5℃, compared to their counterparts (47% vs. 80%; P = 0.040). The infants with meningitis had a longer median time required to visit (5.0 vs. 2.0 hours; P = 0.011), and higher frequencies of ill appearance (100% vs. 65%; P = 0.032), leukocytes < 5,000/mm3 (67% vs. 13%; P = 0.002), and the poor outcomes (75% vs. 0%; P < 0.001).Conclusion: Young infants with ill-looking appearance or abnormality in any of the fever or inflammatory markers may have IGBSIs, particularly meningitis.

Gamma-Irradiated Non-Capsule Group B Streptococcus Promotes T-Cell Dependent Immunity and Provides a Cross-Protective Reaction.

Group B Streptococcus (GBS) is a Gram-positive bacterium commonly found in the genitourinary tract and is also a leading cause of neonatal sepsis and pneumonia. Despite the current antibiotic prophylaxis (IAP), the disease burdens of late-onset disease in newborns and non-pregnant adult infections are increasing. Recently, inactivation of the pathogens via gamma radiation has been proven to eliminate their replication ability but cause less damage to the antigenicity of the key epitopes. In this study, the non-capsule GBS strain was inactivated via radiation (Rad-GBS) or formalin (Che-GBS), and we further determined its immunogenicity and protective efficacy as vaccines. Notably, Rad-GBS was more immunogenic and gave rise to higher expression of costimulatory molecules in BMDCs in comparison with Che-GBS. Flow cytometric analysis revealed that Rad-GBS induced a stronger CD4+ IFN-γ+ and CD4+IL-17A+ population in mice. The protective efficacy was measured through challenge with the highly virulent strain CNCTC 10/84, and the adoptive transfer results further showed that the protective role is reversed by functionally neutralizing antibodies and T cells. Finally, cross-protection against challenges with prevalent serotypes of GBS was induced by Rad-GBS. The higher opsonophagocytic killing activity of sera against multiple serotypes was determined in sera from mice immunized with Rad-GBS. Overall, our results showed that the inactivated whole-cell encapsulated GBS could be an alternative strategy for universal vaccine development against invasive GBS infections.

Invasive Group B Streptococcus Infection and Early Complement Deficiency

Group B Streptococcus (GBS) is a well-known cause of invasive disease in newborns. Although neonatal GBS infection does not often prompt immunologic work-up, history of invasive GBS infection may suggest an underlying early complement deficiency.

Streptococcus agalactiae npx Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy.

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a Gram-positive encapsulated bacterium that colonizes the gastrointestinal tract of 30 to 50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues. Once phagocytosed by macrophages, GBS upregulates the expression of the gene npx, which encodes an NADH peroxidase. GBS mutants with an npx deletion (Δnpx) are exquisitely sensitive to reactive oxygen stress. Furthermore, we have shown that npx is required for GBS survival in both THP-1 and placental macrophages. In an in vivo murine model of ascending GBS vaginal infection during pregnancy, npx is required for invading reproductive tissues and is critical for inducing disease progression, including PPROM and preterm birth. Reproductive tissue cytokine production was also significantly diminished in Δnpx mutant-infected animals compared to that in animals infected with wild-type (WT) GBS. Complementation in trans reversed this phenotype, indicating that npx is critical for GBS survival and the initiation of proinflammatory signaling in the gravid host. IMPORTANCE This study sheds new light on the way that group B Streptococcus (GBS) defends itself against oxidative stress in the infected host. The enzyme encoded by the GBS gene npx is an NADH peroxidase that, our study reveals, provides defense against macrophage-derived reactive oxygen stress and facilitates infections of the uterus during pregnancy. This enzyme could represent a tractable target for future treatment strategies against invasive GBS infections.

MULTIPLE CAVITATORY LUNG LESIONS DUE TO GROUP B STREPTOCOCCUS IN A HEALTHY ADULT

MULTIPLE CAVITATORY LUNG LESIONS DUE TO GROUP B STREPTOCOCCUS IN A HEALTHY ADULT

Group B streptococcus — a pathogen not restricted to neonates

ObjectivesThis was a retropective study of invasive group B streptococcal (GBS) infections isolated from blood, cerebrospinal fluid (CSF), synovial fluid, peritoneal fluid, pleural fluid, pericardial fluid and corpus vitreum in a defined region in southwest Sweden over a 14-year period. DesignInformation on all invasive GBS infections was obtained from all four bacteriological laboratories in the region, with data obtained from individual patient records. ResultsGBS was isolated from normally sterile body fluids in 1244 samples (579 from females and 665 from males) from 1101 patients. Of these patients, 196 were neonates. The incidence in neonates (0–27 days) was 7.3 per 100 000 live births per year, but there was a significant decrease from 2012 when risk-factor-based intrapartum antibibiotic prophylaxis was implemented. The great majority of neonatal infections were very early-onset infections. The incidence rates in children (28 days to 17 years), adults (18–64 years) and elderly patients (≥ 65 years) were 1.3, 3.6, and 12.9 per 100 000 per year, respectively. The majority of children and adults had severe underlying diseases, but severe infections were also seen in individuals with no risk factors. ConclusionsGBS is an important pathogen in all age groups. Intrapartum antibiotic prophylaxis significantly decreases very early-onset infections.

Genomic Traits Associated with Virulence and Antimicrobial Resistance of Invasive Group B Streptococcus Isolates with Reduced Penicillin Susceptibility from Elderly Adults.

ABSTRACTThis study aimed to investigate genomic traits underlying the antimicrobial resistance and virulence of multidrug-resistant (MDR) group B streptococci with reduced penicillin susceptibility (PRGBS) recovered from elderly patients with bloodstream infections, which remain poorly characterized. The pangenome was found to be open, with the predicted pan- and core genome sizes being 3,531 and 1,694 genes, respectively. Accessory and unique genes were enriched for the Clusters of Orthologous Groups (COG) categories L, Replication, recombination, and repair, and K, Transcription. All MDR PRGBS isolates retained a core virulence gene repertoire (bibA, fbsA/-B/-C, cspA, cfb, hylB, scpB, lmb, and the cyl operon), supporting an invasive ability similar to that of the other invasive GBS, penicillin-susceptible GBS (PSGBS), and noninvasive PRGBS isolates. The putative sequence type 1 (ST1)-specific AlpST-1 virulence gene was also retained among the serotype Ia/ST1 PRGBS isolates. In addition to tet(M) and erm(B), mef(A)-msr(D) elements or the high-level gentamicin resistance gene aac(6′)-aph(2″), which are both rare in PSGBS, were detected among those MDR PRGBS isolates. In the core single-nucleotide polymorphism (SNP) phylogenetic tree, all invasive ST1 PRGBS isolates with serotypes Ia and III were placed together in a clade with a recombination rate of 3.97, which was 36 times higher than the value found for a clade formed by serotype V/ST1 PSGBS isolates derived mostly from human blood. ST1 has been the predominant sequence type among the PRGBS isolates in Japan, and serotypes Ia and III have been very rare among the ST1 PSGBS isolates. Thus, these lineages that mostly consisted of serotypes Ia/ST1 and III/ST1 PRGBS could possibly emerge through recombination within the ST1 populations.IMPORTANCE Streptococcus agalactiae, or group B Streptococcus (GBS), is recognized as the leading cause of neonatal invasive infections. However, an increasing incidence of invasive GBS infections among nonpregnant adults, particularly the elderly and those with underlying diseases, has been observed. There is a trend toward the increasing occurrence of penicillin nonsusceptibility among GBS clinical isolates, from 4.8% in 2008 to 5.8% in 2020 in Japan. Also, in the United States, the frequency of adult invasive GBS isolates suggestive of β-lactam nonsusceptibility increased from 0.7% in 2015 to 1.0% in 2016. In adults, mortality has been significantly higher among patients with bacteremia than among those without bacteremia. Our study revealed that invasive GBS with reduced penicillin susceptibility (PRGBS) isolates harbor major virulence and resistance genes known among GBS, highlighting the need for large population-based genomic surveillance studies to better understand the clinical relevance of invasive PRGBS isolates.

Group B Streptococcal Colonisation among Antenatal Women from a Tertiary Care Centre, Northern Kerala: A Cross-sectional Study

Introduction: Group B Streptococcus (GBS) is the leading cause of neonatal sepsis all over the world. Maternal colonisation of GBS in vaginal and anorectal area poses risk for subsequent invasive disease. The prevalence of maternal colonisation varies with geographical, biological and socio-economical factors. Current recommendations consider maternal screening and antibiotic therapy to prevent GBS neonatal disease with a potential of alteration of infant gut flora. Aim: To find out the prevalence, outcome and antimicrobial susceptibility pattern of the GBS colonisation in antenatal women. Materials and Methods: A hospital-based descriptive crosssectional study was conducted in Government Medical College, Kozhikode, Kerala, India, during December 2017 to May 2019 including 300 antenatal women of 35-37 weeks gestational age. Vaginal and rectal swabs were taken and were subjected to microbiological examination and culture. Data analysis was done by Statistical Package for the Social Sciences (SPSS) version 16.0. The Chi-square test and Fisher’s exact test were used wherever applicable and p-value <0.05 is considered significant. Results: Among the 300 antenatal women, 8 (2.7%) were colonised with GBS. Higher rate of colonisation was observed in women of 21-25 years, higher parity, rural dwelling and in women with poor glycaemic control. All the colonised women received antibiotic prophylaxis with intravenous ampicillin. None of the colonised women or the neonates born to them developed any invasive GBS infection. Antibiotic susceptibility testing showed that all the isolates were sensitive to penicillin, ampicillin and vancomycin but only 62.5% of the isolates were susceptible to clindamycin and 37.5% of the isolates were susceptible to erythromycin. Conclusion: The prevalence of GBS colonisation is low in Asian countries, compared to the data from western countries. Evidence based usage of narrow spectrum antibiotics should be considered. Further studies regarding prevalence, antibiotic susceptibility pattern, cost benefit analysis of the antibiotic usage and its effect on neonatal gut flora etc, including a wider population, is a need of the hour in the setting of emergence of resistance.

Serotype distribution and incidence of invasive early onset and late onset group B streptococcal disease amongst infants in Singapore

BackgroundThe current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD.MethodsA retrospective study of infants ≤ 90-day-old over an 8-year period (2010–2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared.ResultsA total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0–243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0–250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD.ConclusionsThe LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.

Group B streptococcal infection of the genitourinary tract in pregnant and non-pregnant patients with diabetes mellitus: An immunocompromised host or something more?

Group B Streptococcus (GBS), also known as Streptococcus agalactiae is a Gram-positive bacterium commonly encountered as part of the microbiota within the human gastrointestinal tract. A common cause of infections during pregnancy, GBS is responsible for invasive diseases ranging from urinary tract infections to chorioamnionitis and neonatal sepsis. Diabetes mellitus (DM) is a chronic disease resulting from impaired regulation of blood glucose levels. The incidence of DM has steadily increased worldwide to affecting over 450 million people. Poorly controlled DM is associated with multiple health comorbidities including an increased risk for infection. Epidemiologic studies have clearly demonstrated that DM correlates with an increased risk for invasive GBS infections, including skin and soft tissue infections and sepsis in non-pregnant adults. However, the impact of DM on risk for invasive GBS urogenital infections, particularly during the already vulnerable time of pregnancy, is less clear. We review the evolving epidemiology, immunology, and pathophysiology of GBS urogenital infections including rectovaginal colonization during pregnancy, neonatal infections of infants exposed to DM in utero, and urinary tract infections in pregnant and non-pregnant adults in the context of DM and highlight in vitro studies examining why DM might increase risk for GBS urogenital infection.

Group B streptococcal infections in infants in Iceland: clinical and microbiological factors.

IntroductionGroup B streptococcus (GBS) is a leading cause of invasive neonatal infections. These have been divided into early-onset disease (EOD; <7 days) and late-onset disease (LOD; 7–89 days), with different GBS clonal complexes (CCs) associated with different disease presentations.Hypothesis/Gap StatementDifferent GBS CCs are associated with timing of infection (EOD or LOD) and clinical presentation (sepsis, meningitis or pneumonia).AimTo study infant GBS infections in Iceland from 1975 to 2019. Are specific GBS CCs related to disease presentation? Is CC17 overrepresented in infant GBS infections in Iceland?MethodologyAll culture-confirmed invasive GBS infections in infants (<90 days) in Iceland from 1975 to 2019 were included. Clinical information was gathered from medical records.ResultsA total of 127 invasive GBS infections in infants were diagnosed, but 105 infants were included in the study. Of these, 56 had EOD and 49 had LOD. The incidence of GBS infections declined from 2000 onwards but increased again at the end of the study period. Furthermore, there was a significant increase in LOD over the study period (P=0.0001). The most common presenting symptoms were respiratory difficulties and fever and the most common presentation was sepsis alone. Approximately one-third of the cases were caused by GBS CC17 of serotype III with surface protein RIB and pili PI-1+PI-2b or PI-2b. CC17 was significantly associated with LOD (P<0.001).ConclusionCC17 is a major cause of GBS infection in infants in Iceland. This clone is associated with LOD, which has been increasing in incidence. Because intrapartum antibiotic prophylaxis only prevents EOD, it is important to continue the development of a GBS vaccine in order to prevent LOD infections.

Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy.

Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.

Trends in molecular characteristics and antimicrobial resistance of group B streptococci: a multicenter study in Serbia, 2015\u20132020

Group B Streptococcus (GBS) is a major cause of neonatal morbidity and mortality. Serbia has not fully implemented preventive measures against GBS neonatal diseases. Therefore, we aimed to assess the maternal GBS colonisation and invasive neonatal disease rate, to reveal the trends of antimicrobial resistance and serotype distribution of GBS from various patient groups. Randomly selected non-invasive (n = 991) and all invasive GBS (n = 80) collected throughout Serbia from 2015 to 2020 were tested for antimicrobial susceptibility, capsular typing, and hvgA detection. Overall, 877/5621 (15.6%) pregnant women were colonised with GBS. Invasive GBS infections incidence in infants (0.18/1000 live births) showed a decreasing trend (0.3 to 0.1/1000 live births). Type III was overrepresented in infants with invasive infections (n = 35, 58.3%), whereas type V predominated among colonised adults (n = 224, 25.5%) and those with noninvasive (n = 37, 32.5%) and invasive infections (n = 8, 40%). The hypervirulent clone III/ST17 was highly associated with invasive infections (n = 28, 35%), particularly late-onset disease (n = 9, 47.4%), showing an increase from 12.3 to 14.8%. The GBS resistance to erythromycin and clindamycin was 26.7% and 22.1%, respectively, with an upward trend. The emergence of the hypervirulent clone III/ST17 and the escalation in GBS resistance highlight an urgent need for continuous monitoring of GBS infections.

Hypoxia-Inducible Factor 1 Alpha Is Dispensable for Host Defense of Group B Streptococcus Colonization and Infection

Group B Streptococcus (GBS) is a leading cause of neonatal morbidity and mortality, and the primary source of exposure is the maternal vagina. Intrapartum antibiotic prophylaxis for GBS-positive mothers has reduced the incidence of GBS early-onset disease, however, potential long-lasting influence of an antibiotic-altered neonatal microbiota, and the frequent clinical sequelae in survivors of invasive GBS infection, compels alternative treatment options for GBS. Here, we examined the role of transcription factor hypoxia-inducible factor 1 alpha (HIF-1α), widely recognized as a regulator of immune activation during infection, in the host response to GBS. Given the importance of endogenous HIF-1α for innate immune defense, and the potential utility of HIF-1α stabilization in promoting bacterial clearance, we hypothesized that HIF-1α could play an important role in coordinating host responses to GBS in colonization and systemic disease. Counter to our hypothesis, we found that GBS infection did not induce HIF-1α expression in vaginal epithelial cells or murine macrophages, nor did HIF-1α deficiency alter GBS colonization or pathogenesis in vivo. Furthermore, pharmacological enhancement of HIF-1α did not improve control of GBS in pathogenesis and colonization models, while displaying inhibitory effects in vaginal epithelial cytokines and immune cell killing in vitro. Taken together, we conclude that HIF-1α is not a prominent aspect of the host response to GBS colonization or invasive disease, and its pharmacological modulation is unlikely to provide significant benefit against this important neonatal pathogen.

260. A Rare Case of Severe Group B Streptococcal Infection with Toxic Shock-like Syndrome and Diffuse Metastatic Infection

BackgroundThe incidence of invasive Group B streptococcal (GBS) infection has been increasing in the past decade and is currently at 10.9 cases per 100,000 population. GBS toxic shock-like syndrome is rare, with few cases reported over the past decade. The presumed etiology is the production of an uncharacterized pyrogenic toxin by certain strains.MethodsWe present a unique case of invasive GBS infection complicated by severe GBS-mediated toxic shock-like syndrome (TSLS) and diffuse metastatic infection.ResultsA 62-year-old obese male with diabetes mellitus presented with pain, swelling, and redness of the right shoulder and ankle for one week after a fall. Vitals were remarkable for tachycardia to 106 BPM and fever of 101°F with labs showing a leukocytosis to 23,500 u/L. The patient was started on ceftriaxone IV but continued to develop worsening fever, leukocytosis, encephalopathy, diffuse extremity pain, and whole-body macular erythema at 48 hours. Blood cultures grew GBS and TSLS was suspected. Adjunct clindamycin was started. MRI of the extremities demonstrated abscesses of the right levator scapulae, posterior scalene, brachioradialis, and right ankle. MRI of the spine showed epidural abscesses at L3-L5 and septic arthritis of the spinal facets at L4-L5. Operative abscess removal with joint washouts were performed by neurosurgery and orthopedics, and the patient symptomatically improved within 2 weeks on IV ceftriaxone. He was subsequently continued on cefazolin for 10 weeks and did well at follow-up.Right elbow showing a characteristic flat, macular erythema of toxic shock-like syndrome. Left arm with macular erythema. MRI showing spinal epidural abscesses at L3-L5 spinal levels (arrows). ConclusionInvasive metastatic Group B Streptococcus infection in non-pregnant adults presenting with TSLS is rare. To our knowledge, there has never been a case of GBS infection causing TSLS with rapidly developing florid metastatic infection including epidural abscess development, septic arthritis, and musculoskeletal abscesses. This case highlights the wide range of infectious possibilities associated with severe GBS infection.Disclosures All Authors: No reported disclosures