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Streptococcus agalactiae (group B Streptococcus) colonizes the genital tract of approximately 20% of pregnant women. In the absence of intervention, approximately 1% of infants born to colonized mothers exhibit a clinical infection. This has led to implementation of screening and intervention in the form of intrapartum antibiotic prophylaxis in many countries, including the United States. However, screening has not been introduced in a substantial minority of other countries because of the absence of supportive level 1 evidence, the very large number needed to treat to prevent 1 case, and concerns about antimicrobial resistance. Optimal screening would involve rapid turnaround (to facilitate intrapartum testing) and report antibiotic sensitivity, but no such method exists. There is significant scope for a personalized medicine approach, targeting intrapartum antibiotic prophylaxis to cases at greatest risk, but the pathogen and host factors determining the risk of invasive disease are incompletely understood. Epidemiologic data have indicated the potential of prelabor invasion of the uterus by group B Streptococcus, and metagenomic analysis revealed the presence of group B Streptococcus in the placenta in approximately 5% of pregnant women at term before onset of labor and membrane rupture. However, the determinants and consequences of prelabor invasion of the uterus by group B Streptococcus remain to be established. The vast majority (98%) of invasive neonatal disease is caused by 6 serotypes, and hexavalent vaccines against these serotypes have completed phase 2 trials. However, an obstacle to phase 3 studies is conducting an adequately powered trial to demonstrate clinical effectiveness given that early-onset disease affects approximately 1 in 1000 births in the absence of vaccination.

Streptokoki skupine B (GBS) so vodilni vzrok obolevnosti in umrljivosti nosečnic, ploda in novorojenčkov po vsem svetu. Preklop med asimptomatskim kolonizatorjem v invazivnega patogena še ni popolnoma znan, zagotovo pa korelira z naborom številnih virulentnih dejavnikov. Enega izmed glavnih predstavlja kapsula, s pomočjo katere GBS vežejo regulatorne komponente komplementa in se izognejo prepoznavi z imunskim sistemom gostitelja. Nadalje je dokazano, da površinski protein β z vezavo faktorja H (FH) preprečuje opsonizacijo s C3b. Slednje smo v našem poskusu preverili z označevanjem s protitelesi anti-C3b/iC3b in anti-FH ter opazovali vezavo le-teh na kapsulo bakterij, ki smo jih predhodno izpostavili humanemu serumu. Pri tem smo spremljali tudi samo preživetje bakterij v serumu. Namen raziskave je bilo ugotoviti, če in kako sevi GBS, ki pripadajo različnim serotipom in vsebujejo različne virulentne dejavnike, vežejo in aktivirajo komplement. V študiji smo uporabili virulentno različne izolate GBS ter kontrolne seve E. coli z različnim tipom LPS. Vezavo komponent C3b/iC3b in FH smo interpretirali skupaj z rezultati viabilnosti. Razlike v vezavi C3b/iC3b in FH so bile opazne tako med sevi različnih serotipov kot tudi med sevi istega kapsularnega serotipa. Vendar pa smo ugotovili, da količina vezanega FH in C3b/iC3b ne vpliva vedno na povečano možnost preživetja. Prav tako nismo dokazali močne korelacije med izražanjem β proteina ter povečano viabilnostjo. Group B Streptococcus (GBS) is a major cause of maternal, fetal and neonatal morbidity and mortality worldwide. The transition from asymptomatic colonizer to invasive pathogen is not yet known, but it certainly correlates with a number of virulence factors. One of the most important is the capsule by which GBS binds regulatory components of the complement and thereby avoids recognition by the host immune system. In addition, the surface protein β has been shown to prevent opsonization by C3b by binding factor H (FH). In our experiment, we verified the latter by labeling with anti-C3b/iC3b and anti-FH antibodies and observed their binding to the capsule of bacteria previously exposed to the human serum. We also observed the survival of the bacteria in serum. The aim of the studywas to determine whether and how GBS strains, belonging to different serotypes and containing different virulence factors, bind and activate the complement system. In the study, virulently different GBS strains and control E. coli strains with different types of LPS were used. Binding of C3b/iC3b and FH was interpreted along with viability results. Differences in C3b/iC3b and FH binding were found between different GBS serotypes as well as between strains of the same capsular serotype. However, we found that the amount of FH and C3b/iC3b bound did not always increased survival. We also did not find a strong correlation between the expression of β protein and increased viability.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

Central nervous system infections caused by pathogens crossing the blood–brain barrier are extremely damaging and trigger cellular alterations and neuroinflammation. Bacterial brain infection, in particular, is a major cause of hippocampal neuronal degeneration. Hippocampal neurogenesis, a continuous multistep process occurring throughout life in the adult brain, could compensate for such neuronal loss. However, the high rates of cognitive and other sequelae from bacterial meningitis/encephalitis suggest that endogenous repair mechanisms might be severely affected. In the current study, we used Group B Streptococcus (GBS) strain NEM316, to establish an adult mouse model of brain infection and determine its impact on adult neurogenesis. Experimental encephalitis elicited neurological deficits and death, induced inflammation, and affected neurogenesis in the dentate gyrus of the adult hippocampus by suppressing the proliferation of progenitor cells and the generation of newborn neurons. These effects were specifically associated with hippocampal neurogenesis while subventricular zone neurogenesis was not affected. Overall, our data provide new insights regarding the effect of GBS infection on adult brain neurogenesis.

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.

Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis but has been recently isolated from non-pregnant adults with underlying medical conditions like diabetes. Despite diabetes being a key risk factor for invasive disease, the pathological consequences during GBS infection remain poorly characterized. Here, we demonstrate the pathogenicity of the GBS90356-ST17 and COH1-ST17 strains in streptozotocin-induced diabetic mice. We show that GBS can spread through the bloodstream and colonize several tissues, presenting a higher bacterial count in diabetic-infected mice when compared to non-diabetic-infected mice. Histological sections of the lungs showed inflammatory cell infiltration, collapsed septa, and red blood cell extravasation in the diabetic-infected group. A significant increase in collagen deposition and elastic fibers were also observed in the lungs. Moreover, the diabetic group presented red blood cells that adhered to the valve wall and disorganized cardiac muscle fibers. An increased expression of KC protein, IL-1β, genes encoding immune cell markers, and ROS (reactive oxygen species) production was observed in diabetic-infected mice, suggesting GBS promotes high levels of inflammation when compared to non-diabetic animals. Our data indicate that efforts to reverse the epidemic of diabetes could considerably reduce the incidence of invasive infection, morbidity and mortality due to GBS.

The difficulty in recognizing early-onset neonatal sepsis (EONS) in a timely manner due to non-specific symptoms and the limitations of diagnostic tests, combined with the risk of serious consequences if EONS is not treated in a timely manner, has resulted in a low threshold for starting empirical antibiotic treatment. New guideline strategies, such as the neonatal sepsis calculator, have been proven to reduce the antibiotic burden related to EONS, but lack sensitivity for detecting EONS. In this review, the potential of novel, targeted preventive and diagnostic methods for EONS is discussed from three different perspectives: maternal, umbilical cord and newborn perspectives. Promising strategies from the maternal perspective include Group B Streptococcus (GBS) prevention, exploring the virulence factors of GBS, maternal immunization and antepartum biomarkers. The diagnostic methods obtained from the umbilical cord are preliminary but promising. Finally, promising fields from the newborn perspective include biomarkers, new microbiological techniques and clinical prediction and monitoring strategies. Consensus on the definition of EONS and the standardization of research on novel diagnostic biomarkers are crucial for future implementation and to reduce current antibiotic overexposure in newborns.

We report a Case of a mycotic abdominal aortic aneurysm caused by invasive group B streptococcus. Given the anatomical suitability with healthy segments of aortoiliac vessels, in-situ repair was performed. A cryopreserved femoral vein graft was chosen due to risks of graft reinfection and negated the need for bilateral femoral vein harvest. The patient remained clinically well and the graft patent with no concerns at 6 months follow-up. A review of literature on group B streptococcus aortitis was performed.

The objective of this study was to develop a structural-cognitive-behavioral model for error analysis of group B streptococcus (GBS) prophylaxis failure, classify delivery cases into this model, and examine compliance with treatment guidelines. A retrospective, cohort study was conducted of women with liveborn pregnancies greater than 24 weeks in April 2018 at a single hospital. We created a structural-cognitive-behavioral model of five assessments for adherence to GBS prophylaxis guidelines and then classified these into four distinct error stages. A descriptive analysis was performed to determine if the pregnancy had a perfect process, a GBS prophylaxis failure, or a fortuitous outcome. There were 313 women who met the study criteria. The rate of GBS positive was 12.8%, negative 37.4%, and unknown 49.8%. The most common errors were cognitive perception errors related to incorrectly documenting GBS status, 57.7% (N = 79). Of these errors, 15.2% (N = 12) led to GBS prophylaxis failure. Perfect outcomes occurred in 62.7% (N = 196) women, GBS prophylaxis failure occurred in 13.7% (N = 43), and fortuitous outcomes occurred in 23.6% (N = 74). In our study, we were able to identify structural, cognitive, and behavioral errors that contribute to GBS prophylaxis failures. In other cases, these errors may contribute to fortuitous outcomes.

Background Infective endocarditis (IE) caused by Streptococcus agalactiae (GBS) is increasingly reported and associated with an aggressive course and high mortality rate. Existing literature on GBS IE is limited to case series; we compared the characteristics of patients with GBS IE to patients with GBS bacteremia without IE to identify risk factors for development of IE. Methods A nested case–control study in a cohort of adult patients with GBS bacteremia over a 18-year period was conducted across seven centres in three Canadian cities. A chart review identified patients with possible or definite IE (per Modified Duke Criteria) and patients with IE were matched to those without endocarditis in a 1:3 fashion. Multivariate analyses were completed using logistic regression. Results Of 520 patients with GBS bacteremia, 28 cases of possible or definite IE were identified (5.4%). 68% (19/28) met criteria for definite IE, surgery was performed in 29% (8/28), and the overall in-hospital mortality rate was 29% (8/28). Multivariate analysis demonstrated that IE was associated with injection drug use (OR = 19.6, 95% CI = 3.39–111.11, p = 0.001), prosthetic valve (OR = 11.5, 95% CI = 1.73–76.92, p = 0.011) and lack of identified source of bacteremia (OR = 3.81, 95% CI = 1.24–11.65, p = 0.019). Conclusions GBS bacteremia, especially amongst people who inject drugs, those with prosthetic valves, and those with no apparent source of infection, should increase clinical suspicion for IE.

Vaccination during pregnancy could protect women and their infants from invasive Group B Streptococcus (GBS) disease. To understand if neonatal dried blood spots (DBS) can be used to determine the amount of maternally derived antibody that protects infants against invasive GBS disease, a retrospective case-control study was conducted in England between 1 April 2014 and 30 April 2015. The DBS of cases with invasive GBS disease (n = 61) were matched with healthy controls (n = 125). The haematocrit, DBS storage temperature, freeze-thaw cycle, and paired serum/DBS studies were set up to optimise the antibody assessment. The samples were analysed using a multiplex immunoassay, and the results were assessed using parametric and nonparametric tests. Antibody concentrations were stable at haematocrits of up to 50% but declined at 75%. DBS storage at room temperature was stable for three months compared with storage from collection at −20 °C and rapidly degraded thereafter. Total IgG levels measured in DBS and paired serum showed a good correlation (r2 = 0.99). However, due to suboptimal storage conditions, no difference was found in the GBS IgG levels between DBS samples from cases and controls. We have demonstrated a proof of concept that assays utilising DBS for assessing GBS serotype-specific antibodies in infants is viable. This method could be used to facilitate future large sero-correlate studies, but DBS samples must be stored at −20 °C for long term preservation of antibody.

Despite effective prevention and control efforts over the past few decades, infectious diseases continue to pose a serious threat to global public health, causing millions of deaths annually. Numerous antibiotics can treat bacterial infections. However, practically almost all antimicrobial drugs now have some level of resistance, creating a severe global health issue and the urgent and rapid development of antibiotic alternatives. It has been demonstrated that NDOs are significant inhibitors of the development of pathogenic infections. Several anti-pathogenic effects can be achieved by NDOs, depending on their type and structural characteristics. This thesis suggests that Non-digestible oligosaccharides (NDOs) may serve as an alternative to antibiotics in treating bacterial infections. In our studies we investigated the effects of NDOs (AOS, COS, FOS and GOS) on the defense against several common bacterial pathogens (E. coli, S. agalactia, S. aureus, and C. difficile) in different steps of the pathogenesis: bacterial growth, bacterial adhesion, biofilm formation, inflammation and bacterial toxin activity. Each of these NDOs had some unique potentials against particular pathogens. Likewise, COS can be described as a potent biofilm inhibitor against S. aureus, a strong inhibitor of shiga toxin binding to its receptor (Gb3), a great inhibitor of cytotoxicity and cytopathogenicity of TcdA, an effective anti-inflammatory agent against inflammation caused by E. coli with intestinal barrier-protective properties and an enhancer of human intestinal epithelial cell integrity. Besides, AOS can be defined as a powerful inhibitor of the growth of both GBS and E. coli, an effective inhibitor of the adhesion of E. coli to intestinal epithelial cells, a potent anti-inflammatory agent against inflammation induced by E. coli, and an effective mediator on TcdA's ability to disrupt the intestinal barrier. The knowledge about the antimicrobial strategies of NDOs was used to further investigate in combination therapy by combining NDO with antibiotics to increase bacterial sensitivity to specific antibiotics. Likewise, a combination of COS and clindamycin was successful in preventing the growth of a S. aureus biofilm, as was a combination of AOS and ampicillin in the case of E. coli growth. AOS and trimethoprim were also successful in treating GBS when combined. NDOs are a desirable weapon in the fight against pathogens and antibiotic resistance due to their variety of antibacterial capabilities and minimal reported adverse effects. Moreover, a healthy microbiota plays a vital role in infection prevention by inhibiting pathogenic bacteria and/or coordinating proper immune responses, therefore the effect of NDOs on promoting beneficial bacteria in the gut should not be ignored.

Despite effective prevention and control efforts over the past few decades, infectious diseases continue to pose a serious threat to global public health, causing millions of deaths annually. Numerous antibiotics can treat bacterial infections. However, practically almost all antimicrobial drugs now have some level of resistance, creating a severe global health issue and the urgent and rapid development of antibiotic alternatives. It has been demonstrated that NDOs are significant inhibitors of the development of pathogenic infections. Several anti-pathogenic effects can be achieved by NDOs, depending on their type and structural characteristics. This thesis suggests that Non-digestible oligosaccharides (NDOs) may serve as an alternative to antibiotics in treating bacterial infections. In our studies we investigated the effects of NDOs (AOS, COS, FOS and GOS) on the defense against several common bacterial pathogens (E. coli, S. agalactia, S. aureus, and C. difficile) in different steps of the pathogenesis: bacterial growth, bacterial adhesion, biofilm formation, inflammation and bacterial toxin activity. Each of these NDOs had some unique potentials against particular pathogens. Likewise, COS can be described as a potent biofilm inhibitor against S. aureus, a strong inhibitor of shiga toxin binding to its receptor (Gb3), a great inhibitor of cytotoxicity and cytopathogenicity of TcdA, an effective anti-inflammatory agent against inflammation caused by E. coli with intestinal barrier-protective properties and an enhancer of human intestinal epithelial cell integrity. Besides, AOS can be defined as a powerful inhibitor of the growth of both GBS and E. coli, an effective inhibitor of the adhesion of E. coli to intestinal epithelial cells, a potent anti-inflammatory agent against inflammation induced by E. coli, and an effective mediator on TcdA's ability to disrupt the intestinal barrier. The knowledge about the antimicrobial strategies of NDOs was used to further investigate in combination therapy by combining NDO with antibiotics to increase bacterial sensitivity to specific antibiotics. Likewise, a combination of COS and clindamycin was successful in preventing the growth of a S. aureus biofilm, as was a combination of AOS and ampicillin in the case of E. coli growth. AOS and trimethoprim were also successful in treating GBS when combined. NDOs are a desirable weapon in the fight against pathogens and antibiotic resistance due to their variety of antibacterial capabilities and minimal reported adverse effects. Moreover, a healthy microbiota plays a vital role in infection prevention by inhibiting pathogenic bacteria and/or coordinating proper immune responses, therefore the effect of NDOs on promoting beneficial bacteria in the gut should not be ignored.

Despite effective prevention and control efforts over the past few decades, infectious diseases continue to pose a serious threat to global public health, causing millions of deaths annually. Numerous antibiotics can treat bacterial infections. However, practically almost all antimicrobial drugs now have some level of resistance, creating a severe global health issue and the urgent and rapid development of antibiotic alternatives. It has been demonstrated that NDOs are significant inhibitors of the development of pathogenic infections. Several anti-pathogenic effects can be achieved by NDOs, depending on their type and structural characteristics. This thesis suggests that Non-digestible oligosaccharides (NDOs) may serve as an alternative to antibiotics in treating bacterial infections. In our studies we investigated the effects of NDOs (AOS, COS, FOS and GOS) on the defense against several common bacterial pathogens (E. coli, S. agalactia, S. aureus, and C. difficile) in different steps of the pathogenesis: bacterial growth, bacterial adhesion, biofilm formation, inflammation and bacterial toxin activity. Each of these NDOs had some unique potentials against particular pathogens. Likewise, COS can be described as a potent biofilm inhibitor against S. aureus, a strong inhibitor of shiga toxin binding to its receptor (Gb3), a great inhibitor of cytotoxicity and cytopathogenicity of TcdA, an effective anti-inflammatory agent against inflammation caused by E. coli with intestinal barrier-protective properties and an enhancer of human intestinal epithelial cell integrity. Besides, AOS can be defined as a powerful inhibitor of the growth of both GBS and E. coli, an effective inhibitor of the adhesion of E. coli to intestinal epithelial cells, a potent anti-inflammatory agent against inflammation induced by E. coli, and an effective mediator on TcdA's ability to disrupt the intestinal barrier. The knowledge about the antimicrobial strategies of NDOs was used to further investigate in combination therapy by combining NDO with antibiotics to increase bacterial sensitivity to specific antibiotics. Likewise, a combination of COS and clindamycin was successful in preventing the growth of a S. aureus biofilm, as was a combination of AOS and ampicillin in the case of E. coli growth. AOS and trimethoprim were also successful in treating GBS when combined. NDOs are a desirable weapon in the fight against pathogens and antibiotic resistance due to their variety of antibacterial capabilities and minimal reported adverse effects. Moreover, a healthy microbiota plays a vital role in infection prevention by inhibiting pathogenic bacteria and/or coordinating proper immune responses, therefore the effect of NDOs on promoting beneficial bacteria in the gut should not be ignored.

Purpose In developed countries, data on the frequency of antibiotics given to mothers during childbirth are limited beyond the overall effect of all various prophylactic indications. Also, data on the impact of such antibiotics to the well-being of term babies are scarce. We aimed to characterize the frequency of antibiotic use during childbirth of term pregnancy. Secondly, we assessed whether the use of antibiotics was associated with any symptoms in infants. Methods This was a cross-sectional study of 1019 term deliveries of women participating in the prospective Health and Early Life Microbiota (HELMi) birth cohort study between March 2016 and March 2018 in the capital region of Finland. The data on antibiotic use were collected from the hospital records. Results In total, 37% of the mothers received antibiotics during childbirth and 100% in Caesarean Sects. (17% of the deliveries). Less than 5% of antibiotics were non-prophylactic. In vaginal deliveries, the most common indication (18%) was prophylaxis for Group B Streptococcus. The most frequently used antibiotics were cefuroxime (22%) and benzylpenicillin (15%), and 56% received only one dose. In infants exposed to antibiotics during delivery, defecation frequency was higher during the first months (p-value p-value 0.0371). Conclusion More than every third new-born in a developed country is exposed to antibiotics during birth. Our findings support the hypothesis that maternal antibiotics given during birth have an impact on the well-being of the infants. These findings should inform current policies for prophylactic antibiotics in childbirth.

Group B Streptococcus (GBS) is a Gram-positive bacteria known for causing a wide range of illnesses in neonates, pregnant woman, elderly, and immunocompromised people. Intrapartum antibiotic prophylaxis is the current prevention measure for pregnant women used worldwide and has been highly successful thus far. However, it is a dangerous long-term approach with the rising antimicrobial resistance crisis. Vaccine development has been ongoing for several decades and remains a key area of study for GBS researchers worldwide. Finding an effective vaccine target candidate that can be packaged in a safe and inexpensive manner is a continuous challenge. The use of metal ions, such as zinc, as an antibacterial has dated back centuries. Its potential to be harnessed against GBS shows promise as an alternative treatment and prevention option, leading to recent characterisation of GBS zinc efflux machinery. It has been established that GBS employs robust strategies to overcome zinc stress and mediate survival. While bacteria require essential nutrient metals for survival, it is presented with nutritional challenges imposed by the vertebrate host during infection. One such strategy is intoxication of invading bacterial pathogens with transition metals. This work assessed 16 strains of GBS from diverse capsular serotypes, sequence types and isolation sources for susceptibility or resistance toward zinc intoxication. The findings show that strains of a variety of clinical backgrounds, capsular types and sequence-types differ in their resistance phenotypes toward zinc intoxication. For example, cpsV and ST-19 were found to be highly resistant to zinc stress, whereas cpsIII and ST-7 and ST-17 were most sensitive to metal intoxication. It is also first reported here that IS1381, a previously identified transposon, has been found in the main zinc export gene, czcD, of strain 834. Investigation of its possible involvement in strain 834’s increased resistance phenotype was inconclusive.

Brojni mikrobiološki agensi koloniziraju donje dijelove genitalnog sustava žena, kako tijekom cijelog života, tako i u trudnoći. Iako mnoge vaginalne infekcije u žena prolaze asimptomatski i bez ozbiljnijih posljedica, u trudnoći ti patogeni posebno dobivaju na značaju, s obzirom na to da predstavljaju potencijalnu ugrozu trudnice i ploda. Od značajnih patogena potrebno je izdvojiti beta-hemolitički streptokok skupine B (BHSB) koji ima velik doprinos u morbiditetu i mortalitetu novorođenčadi, ali za koji također postoji vrlo efikasna profilaksa intrapartalnom primjenom antibiotika. Mehanizmima ascendentnog širenja infekcije dolazi do komplikacija poput korioamnionitisa, prijevremene rupture plodovih ovoja i intrauterine infekcije ploda koja može dovesti do sindroma fetalnog upalnog odgovora, a cjelokupna kaskada koju pokreće širenje infekcije nerijetko dovodi do prijevremenog porođaja te posljedično do komplikacija prematuriteta. Osim navedenog, ascendentne infekcije tijekom trudnoće mogu dovesti i do neželjnih perinatalnih ishoda u vidu rane novorođenačke sepse, pneumonije i meningitisa koji predstavljaju značajan rizik za nastanak trajnih ireverzibilnih posljedica na zdravlje djeteta. Ne treba zanemariti ni ostale česte uzročnike poput Ureaplasma spp. koji katkada, zbog dijagnostičkog pristupa i metode kultivacije uzorka brisa cerviksa koja je različita nego u slučaju BHSB-a, ostaje neporepoznat. Cilj ovog rada je predstaviti potencijalno štetne biološke agense koji koloniziraju rodnicu, navesti loše perinatalne ishode do kojih isti dovode te na taj način naglasiti važnost preventivnih metoda poput rutinskog provođenja cervikalnih briseva u trudnoći („screening“, eng.) te primjene intrapartalne antibiotske profilakse., A number of microbial agents colonize the female lower genital tract throughout the whole life as well as in pregnancy. Even though many vaginal infections in women are asymptomatic and don’t leave any serious consequences, in pregnancy, those pathogens are considered especially harmful, because they represent a potential threat for the fetus and the mother. One of the more notable pathogens is group B Streptococcus (GBS), which plays a big role in neonatal morbidity and mortality, but has a very efficient prophylaxis method using intrapartum antibiotics. The ascension of the infection may lead to complications like chorioamnionitis, premature rupture of membranes and intrauterine fetal infection leading to fetal inflammatory response syndrome. This whole cascade can often end with premature birth and thus, prematurity. Apart from this, the ascension of infections may also result in unwanted perinatal outcomes such as early onset neonatal sepsis, pneumonia and meningitis, which carry the risk of irreversible consequences. Other pathogens should not be disregarded, particularly Ureaplasma spp., as the diagnostic approach and the method of cultivation of the cervical swab is different than the one for group B Streptococcus and can sometimes remain undiagnosed. The objective of this paper is to present the potentially harmful biological agents, determine unwanted perinatal outcomes which they may lead to and to emphasize the importance of preventive measures, namely routine cervical screening as well as the use of intrapartum antibiotic prophylaxis.

IntroductionMaternal immunization against Group B Streptococcus (GBS) has the potential to significantly reduce the burden of neonatal GBS infections. Population genetics of GBS from maternal carriage can offer key insights into vaccine target distribution.MethodsIn this study we characterized the population structure of GBS isolates from maternal carriage (n = 535) in an ethnically diverse community in London, using whole genome sequencing.ResultsThe isolates clustered into nine clonal complexes (CCs) but the majority (95%) belonged to five lineages: CC1 (26%), CC19 (26%), CC23 (20%), CC17 (13%) and CC8/10 (10%). Nine serotypes were identified, the most common were serotypes III (26%), V (21%), II (19%) and Ia (19%). Other serotypes (Ib, IV, VI, VII, IX) represented less than 10% of all isolates each. Intra-lineage serotype diversity was observed in all major CCs but was highest in CC1, which revealed nine serotypes. Nearly all isolates (99%) carried at least one of the four alpha family protein genes (alpha, alp1, alp23, and rib). All isolates were susceptible to penicillin. We found 21% and 13% of isolates to be resistant to clarithromycin and clindamycin, respectively. Prevalence of macrolide-lincosamide-streptogramin B (MLSB) resistance genes was 22% and they were most common in CC19 (37%) and CC1 (28%), and isolates with serotypes V (38%) and IV (32%). We identified some associations between maternal ethnicity and GBS population structure. Serotype Ib was significantly less common among the South Asian compared to Black women (S. Asian: 3/142, Black: 15/135, p = 0.03). There was also a significantly lower proportion of CC1 isolates among the White other (24/142) in comparison to Black (43/135) and S. Asian (44/142) women (p = 0.04). We found a significantly higher proportion of CC17 isolates among the White other compared to S. Asian women (White other: 32/142, S. Asian: 10/142, p = 0.004).ConclusionOur study showed high prevalence of GBS vaccine targets among isolates from pregnant women in London. However, the observed serotype diversity in CC1 and high prevalence of MLSB resistance genes in CC19 demonstrates presence of high risk lineages, which might act as a reservoir of non-vaccine strains and antimicrobial resistance determinants.

The effectiveness of “inadequate” intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003–2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined “active” when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an “inactive” IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP “adequate” seems the pathogen’s antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Introduction. Group B Streptococcus (GBS) is the most frequent cause of early onset neonatal sepsis. The objective of the study was to assess antibiotic resistance of GBS in pregnant women at 35-37 weeks of gestation in South Vietnam. Materials and methods. A descriptive cross-sectional study was conducted between April 2018 and May 2019 in Can Tho University of Medicine and Pharmacy Hospital and Can Tho Maternity Hospital (Vietnam) to determine the incidence of GBS infection. Anorectal and vaginal samples were taken from 203 pregnant women attending an antenatal examination at 35-37 weeks of gestation. Specimens showing a positive result for GBS were evaluated to identify antibiotic resistance using the Kirby-Bauer test. Results. The positive GBS rate in pregnant women was 16.3%. The rate of antibiotic resistance in the GBS-positive samples analysed was as follows: Vancomycin (resistant 18.2%, sensitive 81.8%), Cefazolin (resistant 30.3%, sensitive 69.7%), Erythromycin (resistant 24.2%, intermediate 9.1%, sensitive 63.7%), Clindamycin (resistant 63.7%, intermediate 3% and sensitive 33.3%), and Ampicillin (resistant 87.9%, sensitive 12.1%). In Vietnam, antibiotic prophylaxis for infection prevention in pregnant women with positive GBS includes Cefazolin and Vancomycin. Conclusions. Pregnant women should be tested for GBS infection, ideally between weeks 35 and 37 of pregnancy. During labour, antibiotics such as Cefazolin and Vancomycin are most effective for preventing infections.

(1) Background: Streptococcus agalactiae or Group B Streptococcus (GBS) causes severe neonatal infections with a high burden of disease, especially in Africa. Maternal vaginal colonization and perinatal transmissions represent the common mode of acquiring the infection. Development of an effective maternal vaccine against GBS relies on molecular surveillance of the maternal GBS population to better understand the global distribution of GBS clones and serotypes. (2) Methods: Here, we present genomic data from a collection of colonizing GBS strains from Ismailia, Egypt that were sequenced and characterized within the global JUNO project. (3) Results: A large proportion of serotype VI, ST14 strains was discovered, a serotype which is rarely found in strain collections from the US and Europe and typically not included in the current vaccine formulations. (4) Conclusions: The molecular epidemiology of these strains clearly points to the African origin with the detection of several sequence types (STs) that have only been observed in Africa. Our data underline the importance of continuous molecular surveillance of the GBS population for future vaccine implementations.

Background To inform the World Health Organization’s full value of vaccine assessment for group B Streptococcus (GBS) vaccines, a rapid literature appraisal was conducted to inform the operationalization of maternal GBS vaccination. We found limited published information on stakeholder perceptions of the public health importance of GBS disease and vaccination, and we therefore undertook a multicountry survey. Methods An online survey was conducted in late 2019 to collect information on stakeholders’ awareness of GBS disease and the priority accorded to vaccination. The survey was distributed by email to 395 representatives of national pediatric, gynecology, and obstetrics associations, national immunization technical advisory groups (NITAGs), national regulatory agencies, academia, and United Nations organizations. Results Among 101 survey respondents from 66 countries, 36% were pediatricians, 25% obstetricians/gynecologists, 21% immunization specialists, and 18% other public health specialists. More than half (58%) of respondents reported being familiar with GBS disease as a public health problem; familiarity decreased by country income level. Knowledge of GBS disease was greatest in the Americas (68%) and Europe (66%) and lowest in Asia (13%–38%). Perception of GBS disease as a public health problem was highest among pediatricians (71%) and lowest among public health policy makers and NITAG members (30%) across country groupings. Approximately half of respondents (49%) considered the introduction of a GBS vaccine as a priority. Conclusions The information obtained will inform the appropriate packaging and presentation of information to address stakeholder perceptions and promote evidence-based decision making on GBS vaccination.

BACKGROUND Despite Group B streptococcus being a leading cause of maternal and infant morbidity and mortality, no vaccine is currently available to prevent this disease. To inform vaccine developers, countries, and funders, we analyse in this paper the key factors likely to influence the demand for a GBS vaccine and the long-term financial sustainability for a commercial entity considering the development of such a vaccine. METHODS By using population-based forecasting, we estimated the demand for a GBS vaccine based on the burden of disease, the strength of the maternal immunisation systems, the fiscal space, and the track record in introducing new vaccines. Furthermore, we estimated the financial viability for a vaccine developer by estimating the Net Present Value of the vaccine development project using a Discounted Cash Flow model. RESULTS Demand for this vaccine can be significant if policy recommendations for use are adopted by countries, in particular the largest ones, most of which have a burden that justifies the use of the vaccine and if financing for the vaccine will be made available either by countries themselves or by funding mechanisms such as Gavi, the Vaccine Alliance. Different administration schedules may result in even larger demand. With a widespread policy recommendation, the commercial viability of this vaccine can be achieved. The cost of clinical development - particularly the type of pivotal trial required - and the number of competitors are the factors that can strongly influence the long-term financial sustainability and hence the interest of vaccine developers. CONCLUSIONS This analysis suggests the potential for full financial and commercial viability for a manufacturer pursuing the development and commercialization of a GBS vaccine. Risks exists in relation to the clinical trial design and costs, the level of competition, countries' ability to pay, the administration schedule and the availability of policies that encourage use of the vaccine. To reduce those risks and ensure equitable access to a GBS vaccine, the role of donors or financers can prove very important; as can a coordinated operational research agenda that aims at clarifying those areas of uncertainty.

Background Invasive group B Streptococcus disease (iGBS) in infancy, including meningitis or sepsis, carries a high risk of mortality and neurodevelopmental impairment (NDI). We present data on iGBS from 2 decades of surveillance in Manhiça, Mozambique, with a focus on NDI. Methods Morbidity surveillance databases in a rural Mozambican district hospital were screened for iGBS cases. From February 2020 to March 2021, surviving iGBS patients (n = 39) plus age- and sex-matched children without iGBS (n = 119) were assessed for neurocognitive development, vision, and hearing. The role of GBS in stillbirths and infant deaths was investigated using minimally invasive tissue sampling (MITS). Results Ninety iGBS cases were included, with most children being Conclusions In absence of preventive strategies, such as intrapartum antibiotics, iGBS remains a significant cause of perinatal and infant disease and death. GBS also causes major longer-term neurodevelopmental sequelae, altogether justifying the need for maternal GBS vaccination strategies to increase perinatal and infant survival.

The global burden of Group B Streptococcus (GBS) was estimated for 2015 prompting inclusion of GBS as a priority in the Global Meningitis Roadmap. New estimates for the year 2020 and a WHO report analysing the full value of GBS maternal vaccines has been launched to advance evidence based decision making for multiple stakeholders. In this first of a 10-article supplement, we discuss the following (1) gaps in evidence and action, (2) new evidence in this supplement, and (3) what actions can be taken now and key research gaps ahead. We call for investment in the research pipeline, notably description, development, and delivery, in order to accelerate progress and address the large burden of GBS for every family in every country.

Objective Pregnant women with bacterial vaginosis due to Gardnerella vaginalis (GV) infection presents with a wide-ranging disease symptomatology. We speculate this may be due to interaction that varies between host immune response and the pathogen. We studied the oxidative burst in polymorphonuclear leukocytes (PMNL)s from maternal blood (MB) and cord blood (CB) upon phagocytosis of GV and compared against E. coli and Group B Streptococcus (GBS). Results The PHAGOBURST™ assay detects fluorescence from oxidized dihydrorhodamine during oxidative burst. The average percentage of PMNL showing oxidative burst was almost two-fold greater with GBS (99.5%) and E. coli (98.2%) than GV (56.9%) (p E. coli but comparable to GBS. The MFI of CB PMNL (1580 ± 245.8) was significantly higher than MB PMNL (1198 ± 262.1) with GV, p = 0.031. The live-cell imaging showed neutrophil oxidative burst upon phagocytosis of GV produces hypochlorous acid (HOCl). Overall, the HOCL-mediated microbicidal activity against GV is more variable and less robust than E. coli and GBS, especially in maternal than CB PMNL.

Background Nationwide group B Streptococcus agalactiae (GBS) antepartum screening was instituted in Taiwan in 2012. The impact of the policy on early-onset sepsis (EOS) has not been evaluated. This study aimed to examine the impact of the policy on the incidence of neonatal EOS. Methods This was a retrospective study conducted at MacKay Children's Hospital. Patients with culture-proven neonatal EOS were enrolled and divided by birth year in relation to the implementation of GBS prevention policy: Epoch 1, 2001–2004 pre-GBS screening; Epoch 2, 2005–2011 elective GBS screening; and Epoch 3, 2012–2018 universal GBS screening. The pathogens and antimicrobial resistance patterns were reviewed and analyzed. The incidence was modeled using Poisson regression. Results A total of 128 neonates met the enrollment criteria. The observed incidence of EOS was 1.52‰. The incidence rates of EOS, GBS, and Escherichia coli (E. coli) sepsis were similar in Epoch 1 and Epoch 3. E. coli and non-Enterococcal group D Streptococcus (GDS) infection increased significantly in term infants, whereas the EOS-related mortality rate declined in preterm infants. Approximately 72% of the isolated E. coli were ampicillin-resistant, and the antimicrobial sensitivity remained unaltered during the studied period. Conclusions The overall EOS incidence has not changed from 2001 to 2018. However, changes in the causative pathogens were observed in both term and preterm infants. Clinicians should be aware of this evolving epidemiology to provide prompt appropriate perinatal management.

International audience; Abstract : Streptococcus agalactiae is a leading cause of infections in neonates. This opportunistic pathogen colonizes the vagina, where it has to cope with acidic pH and hydrogen peroxide produced by lactobacilli. Thus, in the host, this bacterium possesses numerous adaptation mechanisms in which the pleiotropic regulators play a major role. The transcriptional regulator CcpA (catabolite control protein A) has previously been shown to be the major regulator involved in carbon catabolite repression in Gram-positive bacteria but is also involved in other functions. By transcriptomic analysis, we characterized the CcpA-dependent gene regulation in S. agalactiae. Approximately 13.5% of the genome of S. agalactiae depends on CcpA for regulation and comprises genes involved in sugar uptake and fermentation, confirming the role of CcpA in carbon metabolism. We confirmed by electrophoretic mobility shift assays (EMSAs) that the DNA binding site called cis-acting catabolite responsive element (cre) determined for other streptococci was effective in S. agalactiae. We also showed that CcpA is of capital importance for survival under acidic and oxidative stresses and is implicated in macrophage survival by regulating several genes putatively or already described as involved in stress response. Among them, we focused our study on SAK_1689, which codes a putative UspA protein. We demonstrated that SAK_1689, highly downregulated by CcpA, is overexpressed under oxidative stress conditions, this overexpression being harmful for the bacterium in a ΔccpA mutant.Importance : Streptococcus agalactiae is a major cause of disease burden leading to morbidity and mortality in neonates worldwide. Deciphering its adaptation mechanisms is essential to understand how this bacterium manages to colonize its host. Here, we determined the regulon of the pleiotropic regulator CcpA in S. agalactiae . Our findings reveal that CcpA is not only involved in carbon catabolite repression, but is also important for acidic and oxidative stress resistance and survival in macrophages.

Group B Streptococcus (GBS) is a gram-positive bacterium that is harmless for healthy individuals but may provoke invasive disease in young infants and immunocompromised hosts. GBS invades the epithelial barriers to enter the bloodstream, and thus strategies that enhance epithelial cell responses may hamper GBS invasion. In the present study, we sought to investigate whether the inhibition of Akt, a kinase that regulates host inflammatory responses and autophagy via suppression of mTOR, can enhance the response of non-phagocytic alveolar epithelial cells against GBS. Treatment of the alveolar epithelial cell line A549 with the Akt inhibitor MK-2206 resulted in the enhanced production of reactive oxygen species and inflammatory mediators in response to GBS. Additionally, Akt inhibition via MK-2206 resulted in elevated LC3II/I ratios and increased autophagic flux in alveolar epithelial cells. Importantly, the inhibition of Akt promoted GBS clearance both in alveolar epithelial cells in vitro and in lung tissue in vivo in a murine model of GBS pneumonia. The induction of autophagy was essential for GBS clearance in MK-2206 treated cells, as knockdown of ATG5, a critical component of autophagy, abrogated the effect of Akt inhibition on GBS clearance. Our findings highlight the role of Akt kinase inhibition in promoting autophagy and GBS clearance in the alveolar epithelium. The inhibition of Akt may serve as a promising measure to strengthen epithelial barriers and prevent GBS invasion in susceptible hosts.

Intrauterine infection, or chorioamnionitis, due to group B Streptococcus (GBS) is a common cause of miscarriage and preterm birth. To cause chorioamnionitis, GBS must bypass maternal-fetal innate immune defenses including nitric oxide (NO), a microbicidal gas produced by nitric oxide synthases (NOS). This study examined placental NO production and its role in host-pathogen interactions in GBS chorioamnionitis. In a murine model of ascending GBS chorioamnionitis, placental NOS isoform expression quantified by RT-qPCR revealed a four-fold expression increase in inducible NOS, no significant change in expression of endothelial NOS, and decreased expression of neuronal NOS. These NOS expression results were recapitulated ex vivo in freshly collected human placental samples that were co-incubated with GBS. Immunohistochemistry of wild type C57BL/6 murine placentas with GBS chorioamnionitis demonstrated diffuse inducible NOS expression with high-expression foci in the junctional zone and areas of abscess. Pregnancy outcomes between wild type and inducible NOS-deficient mice did not differ significantly although wild type dams had a trend toward more frequent preterm delivery. We also identified possible molecular mechanisms that GBS uses to survive in a NO-rich environment. In vitro exposure of GBS to NO resulted in dose-dependent growth inhibition that varied by serovar. RNA-seq on two GBS strains with distinct NO resistance phenotypes revealed that both GBS strains shared several detoxification pathways that were differentially expressed during NO exposure. These results demonstrate that the placental immune response to GBS chorioamnionitis includes induced NO production and indicate that GBS activates conserved stress pathways in response to NO exposure.

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.

Background The main purpose of this study was to investigate the prevalence rate, antimicrobial susceptibility patterns and molecular characteristics of Streptococcus agalactiae isolated from pregnant women at 35 weeks of gestation and above, who attended antenatal screening at selected hospitals in Ohangwena and Oshikoto regions of Namibia. Results Out of 210 women screened for Group B Streptococcus (GBS), 12 (5.7%) were colonised of which 25.0% were colonised rectovaginally, 58.0% vaginally and 17.0% rectally. No significant association was reported between GBS colonisation and maternal age, geographic location, marital status, education, employment, parity, still births and miscarriages (P values > 0.05). Antimicrobial susceptibility was reported at 100% for ampicillin, penicillin & ceftriaxone which are commonly used for empiric treatment of infection with GBS. Resistance to tetracycline was reported at 100%. Tetracycline resistance gene tet(M) was present in 88.9% of the isolates only and none of the isolates presented with tet(O). Polysaccharide capsular type Ia was found in 9(50%) and Ib was found in 1(5.5%) of the total isolates. The remaining isolates were not typeable using PCR. Conclusion Streptococcus agalactiae’s positive rate was 5.7% among the pregnant women examined. Socio-demographic and obstetric factors had no influence on GBS colonisation (P values > 0.05). No resistance was reported to ampicillin, penicillin and ceftriaxone. No sensitivity was reported to tetracycline. Fifty percent of the isolates were capsular type Ia, 5.5% were type Ib and 44.4% were not typeable using PCR. The study provides crucial information for informing policy in screening of GBS in pregnant women.

Background Growing concerns regarding the adverse effects of antibiotics during the first days of life and the marked reduction in the incidence of early-onset sepsis (EOS) are changing the clinical practice for managing neonates at risk of EOS. Strategies avoiding unnecessary antibiotics while promoting mother-infant bonding and breastfeeding deserve to be considered. Main body We compare strategies for managing newborns at risk of EOS recommended by the American Academy of Pediatrics, which are among the most followed recommendations worldwide. Currently three different approaches are suggested in asymptomatic full-term or late preterm neonates: i) the conventional management, based on standard perinatal risk factors for EOS alone, ii) the neonatal sepsis calculator, a multivariate risk assessment based on individualized, quantitative risk estimates (relying on maternal risk factors for EOS) combined with physical examination findings at birth and in the following hours and iii) an approach entirely based on newborn clinical condition (serial clinical observation) during the first 48 h of life. We discuss advantages and limitations of these approaches, by analyzing studies supporting each strategy. Approximately 40% of infants who develop EOS cannot be identified on the basis of maternal RFs or laboratory tests, therefore close monitoring of the asymptomatic but at-risk infant remains crucial. A key question is to know what proportion of babies with mild, unspecific symptoms at birth can be managed safely without giving antibiotics. Conclusions Both neonatal sepsis calculator and serial clinical observation may miss cases of EOS, and clinical vigilance for all neonates is essential There is a need to assess which symptoms at birth are more predictive of EOS, and therefore require immediate interventions, or symptoms that can be carefully reevaluated without necessarily treat immediately the neonate with antibiotics. Studies comparing strategies for managing neonates are recommended.

Background: Colonization and transmission precede invasive group B streptococcal (GBS) disease. Data on GBS colonization prevalence, detection methods and risk factors for carriage are relevant for vaccine development and to understand GBS pathogenesis. Objectives: To evaluate GBS colonization prevalence after the first week of life in the healthy non-pregnant population. Data sources: Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature, World Health Organization Library Information System, and Scopus. Search performed 12 January 2021 with search terms related to ‘GBS’ and ‘colonization, epidemiology, prevalence or screening’ without restrictions. Study eligibility criteria: All studies that reported prevalence of GBS colonization (any site) in the healthy population. Participants: All individuals (>6 days of age), with no indication of pregnancy, invasive disease or severe underlying immunological co-morbidities. Methods: Logit transformation and a random effects model (DerSimonian and Laird) were used to pool colonization estimates. Subgroup analysis and meta-regression on a priori determined subgroups were performed. Results: We included 98 studies with 43 112 participants. Our search identified 9309 studies of which 8831 were excluded based on title and abstract and 380 after reading the full text. Colonization rates varied considerably between studies (I2 = 97%), which could be partly explained by differences in culture methods (R2 = 27%), culture sites (R2 = 24%), continent (R2 = 10%) and participant's age (R2 = 6%). Higher prevalence was found with selective culture methods (19%, 95% CI 16%–23% versus non-selective methods 8%, 95% CI 6%–9%; p < 0.0001). Colonization rates were highest in rectum (19%, 95% CI 15%–24%), vagina (14%, 95% CI 12%–17%) and urethra (9%, 95% CI 5%–18%). In participants with negative rectal cultures, 7% (95% CI 5%–9%) had GBS cultured from another niche. Colonization prevalence was lower in children (6 months to 16 years; 3%, 95% CI 2%–5%) compared with adults (16%, 95% CI 14%–20%; p < 0.0001). Using selective culture methods in adults resulted in a prevalence of 26% (95% CI 19%–33%) rectal, 21% (95% CI 17%–25%) vaginal and 9% (95% CI 6%–14%) urethral colonization. Conclusion: The rectum is the most common body site colonized by GBS. The best approach to screen for any GBS colonization is to screen multiple body sites using selective culture methods.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of neonatal infections. Yet, detailed assessment of the genotypic and phenotypic factors associated with GBS carriage, mother-to-baby transmission, and GBS infection in neonates and adults is lacking. Understanding the distribution of GBS genotypes, including the predominance of different serotypes, antimicrobial resistance (AMR) genes, and virulence factors, is likely to help to prevent GBS diseases, as well as inform estimates of the efficacy of future GBS vaccines. To this end, we set out to characterise GBS isolates collected from pregnant and non-pregnant women in Kaunas region in Lithuania. Whole genome sequences of 42 GBS isolates were analysed to determine multi-locus sequence typing (MLST), the presence of acquired AMR and surface protein genes, and the phylogenetic relatedness of isolates. We identified serotypes Ia (42.9%, 18/42), III (33.3%, 14/42), V (21.4%, 9/42), and a single isolate of serotype Ib. Genomic analyses revealed high diversity among the isolates, with 18 sequence types (STs) identified, including three novel STs. 85.7% (36/42) of isolates carried at least one AMR gene: tetM or tetO (35/42), ermB or lsaC (8/42) and ant6-Ia and aph3-III (2/42). This study represents the first genomic analysis of GBS isolated from women in Lithuania and contributes to an improved understanding of the global spread of GBS genotypes and phenotypes, laying the foundations for future GBS surveillance in Lithuania.

Background Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease. Methods A multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5–18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator. Findings Amongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% – 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 – 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77)). Interpretation Our findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice. Funding This work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene & Tropical Medicine.

Group B streptococcus (GBS) late-onset disease (LOD, occurring from 7 through 89 days of life) is an important cause of sepsis and meningitis in infants. The pathogenesis and modes of transmission of LOD to neonates are yet to be elucidated. Established risk factors for the incidence of LOD include maternal GBS colonisation, young maternal age, preterm birth, HIV exposure and African ethnicity. The mucosal colonisation by GBS may be acquired perinatally or in the postpartum period from maternal or other sources. Growing evidence has demonstrated the predominant role of maternal sources in the transmission of LOD. Intrapartum antibiotic prophylaxis (IAP) to prevent early-onset disease reduces neonatal GBS colonisation during delivery; however, a significant proportion of IAP-exposed neonates born to GBS-carrier mothers acquire the pathogen at mucosal sites in the first weeks of life. GBS-infected breast milk, with or without presence of mastitis, is considered a potential vehicle for transmitting GBS. Furthermore, horizontal transmission is possible from nosocomial and other community sources. Although unfrequently reported, nosocomial transmission of GBS in the neonatal intensive care unit is probably less rare than is usually believed. GBS disease can sometime recur and is usually caused by the same GBS serotype that caused the primary infection. This review aims to discuss the dynamics of transmission of GBS in the neonatal LOD.

INTRODUCTION Labor induction rates are increasing and, in Finland today, one of three labors is induced. Group B streptococcus (GBS) is a bacterium found in 10%-30% of pregnant women and it can be transmitted to the neonate during vaginal delivery. Although GBS is rarely harmful in the general population, it is the leading cause of severe neonatal infections such as sepsis, pneumonia, and meningitis. In addition, GBS can cause maternal morbidity. Labor induction in GBS-positive women has not yet been investigated but concerns of infectious morbidity associated with balloon catheters have been raised. MATERIAL AND METHODS A historical cohort study of 1959 women undergoing labor induction by balloon catheter in Helsinki University Hospital, Finland, between January 1, 2014 and December 31, 2017. Women with viable singleton term pregnancy in cephalic presentation, unfavorable cervix (Bishop score

الملخص: يهدف هذا التقرير إلى تنبيه الأطباء حول النزيف المتأخر داخل المخ باعتباره مظهر نادر لمرض المكورات العقدية من المجموعة ب لدى حديثي الولادة، وتسليط الضوء على الحاجة إلى إرشادات علاجية فاعلة. نقدم هنا حالة مرض نزيف متأخر داخل المخ ناتج عن مرض المكورات العقدية من المجموعة ب لدى طفلة حديثة ولادة تبلغ من العمر ١٧ يوما، وكانت الحالة معقدة مع نزيف ثنائي تحت العنكبوتية أكده التصوير بالرنين المغناطيسي، من خلال مراجعة الملف الطبي. تأخرت الأعراض لهذه المريضة مع أعراض الحمى والخمول والتشنجات والتأكيد الميكروبيولوجي للمكورات العقدية في مزرعة الدم، إضافة إلى وجود نزيف ثنائي تحت العنكبوتية ونقص التروية الدماغي المنتشر الذي أكده التصوير بالرنين المغناطيسي للدماغ، يشير إلى حدوث مضاعفات شديدة، مع عدد قليل جدا من الحالات المبلغ عنها من نزيف داخل المخ. وقد أظهرت المتابعة على المدى القصير تأخرا ملحوظا في النمو.يعد الفحص المبكر لعدوى المكورات العقدية من المجموعة ب بين النساء الحوامل أمرا مهما لمنع الحالات الشديدة من مرض النزيف المتأخر داخل المخ الناتج عن مرض المكورات العقدية من المجموعة ب. وهناك حاجة إلى مزيد من الأدلة لدعم الصلة الوثيقة بين مرض النزيف المتأخر داخل المخ الناتج عن مرض المكورات العقدية من المجموعة ب والنزيف داخل المخ. Abstract: This report aims to alert clinicians to the possibility of intracerebral haemorrhage as a rare manifestation of late-onset neonatal group B streptococcal (LOGBS) disease. This case also highlights the need for effective treatment guidelines for LOGBS disease. We report a case of LOGBS disease in a 17-day-old full-term female neonate, complicated by bilateral subarachnoid haemorrhage confirmed on magnetic resonance imaging (MRI). The patient presented with fever, lethargy, and convulsions. Microbiological examination confirmed the presence of Streptococcus agalactiae in the blood culture. Brain MRI showed bilateral subarachnoid haemorrhage and diffuse cerebral ischaemia, suggesting a severe complication of LOGBS disease. Short-term follow-up of the patient showed marked developmental delay. Early screening for group B streptococcus infection in pregnant women is essential to prevent severe cases of LOGBS disease. Very few cases of intracerebral haemorrhage in LOGBS disease have been reported. Further evidence is required to support a pertinent link between LOGBS disease and intracerebral haemorrhage.

Background: Group B Streptococcus (GBS) is a significant cause of invasive disease among adult non-pregnant patients with increasing incidence and mortality rates. Although non-alcoholic fatty liver disease (NAFLD) is associated with components of metabolic syndrome previously recognized as risk factors for GBS, the impact of NAFLD on GBS course and outcomes is unknown. Methods: We conducted a retrospective cohort study of all non-pregnant adult patients diagnosed with invasive GBS infection during a 15-year period. Results: 102 patients were included in the study (46.1% males; median age 69, IQR 58-78 years). Disease primarily presented as bacteremia without a defined source (37; 36.3%), cellulitis/erysipelas (35; 34.3%), pneumonia (13; 12.7%) and endocarditis (8; 7.8%). The most common comorbidities were diabetes (42; 41.2%), dyslipidemia (39; 38.2%), cardiovascular disease (34; 33.3%), peripheral vascular disease (21; 20.6%), obesity (21; 20.6%) and malignancy (10; 9.8%). Based upon the results of abdominal ultrasound, the patients were divided into two groups: the ones with steatosis (44; 43.1%) and the ones without steatosis (58; 56.9%). There were no significant differences in clinical presentations and comorbidities between groups. In-hospital mortality was 29.5% (13/44) in patients with NAFLD and 10.3% (6/58) in the control group (p=0.0200). Endocarditis (OR 6.69; 95%CI 1.045-44.46, p=0.0410), acute renal failure (OR 13.92; 95%CI 3.00-77.71, p=0.0013), qSOFA > 2 (OR 23.93; 95%CI 4.66-171.2) and NAFLD (OR 6.64; 95%CI 1.23-47.88, p=0.0258) were independently associated with in-hospital mortality. Conclusions: NAFLD is associated with higher mortality in patients suffering from invasive GBS disease which appears to be independent of other components of the metabolic syndrome, such as obesity and diabetes mellitus., Uvod: Streptokok grupe B (GBS) značajan je uzrok invazivne bolesti kod odraslih bolesnika s porastom incidencije i smrtnosti. Iako je nealkoholna masna bolest jetre – NAFLD (engl. non-alcoholic fatty liver disease) povezana s komponentama metaboličkog sindroma koji su prepoznati kao čimbenici rizika za GBS, utjecaj NAFLD na tijek i ishode invazivne GBS bolesti još uvijek nije poznat. Metode: Proveli smo retrospektivno kohortno istraživanje svih odraslih bolesnika koji nisu trudni, a kojima je dijagnosticirana invazivna GBS infekcija tijekom 15-godišnjeg razdoblja. Rezultati: U istraživanje je uključeno 102 bolesnika (46,1% muškaraca; srednja dob 69, IQR 58-78 godina). Bolest se primarno prezentirala kao bakterijemija nepoznatog ishodišta (37; 36,3%), celulitis/erizipel (35; 34,3%), pneumonija (13; 12,7%) i endokarditis (8; 7,8%). Najčešći komorbiditeti bili su dijabetes (42; 41,2%), dislipidemija (39; 38,2%), kardiovaskularne bolesti (34; 33,3%), periferne vaskularne bolesti (21; 20,6%), pretilost (21; 20,6%) i maligna bolest (10; 9,8%). Prema nalazu ultrazvuka abdomena, bolesnici su podijeljeni u dvije skupine: bolesnici s NAFLD (44; 43,1%) i bolesnici bez steatoze jetre (58; 56,9%). Nije bilo značajnih razlika u kliničkoj prezentaciji i komorbiditetima među skupinama. Smrtnost za vrijeme hospitalizacije iznosila je 29,5% (13/44) kod bolesnika s NAFLD i 10,3% (6/58) u kontrolnoj skupini (p = 0,0200). Endokarditis (OR 6,69; 95% CI 1,045-44,46, p = 0,0410), akutno zatajenje bubrega (OR 13,92; 95% CI 3,00-77,71, p = 0,0013), qSOFA> 2 (OR 23,93; 95% CI 4,66-171,2) i NAFLD (OR 6,64; 95% CI 1,23-47,88, p = 0,0258) bili su neovisno povezani sa smrtnošću. Zaključci: NAFLD je povezan s većom smrtnošću kod bolesnika s invazivnom GBS bolešću i čini se da je to neovisno o drugim komponentama metaboličkog sindroma, kao što su pretilost i dijabetes melitus.

Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of neonatal sepsis and increasingly found as an invasive pathogen in older patient populations. Beta-lactam antibiotics remain the most effective therapeutic with resistance rarely reported, while the majority of GBS isolates carry the tetracycline resistance gene tet(M) in fixed genomic positions amongst five predominant clonal clades. In the UK, GBS resistance to clindamycin and erythromycin has increased from 3% in 1991 to 11.9% (clindamycin) and 20.2% (erythromycin), as reported in this study. Here, a systematic investigation of antimicrobial resistance genomic content sought to fully characterise the associated mobile genetic elements within phenotypically resistant GBS isolates from 193 invasive and non-invasive infections of UK adult patients collected during 2014 and 2015. Resistance to erythromycin and clindamycin was mediated by erm(A) (16/193, 8.2%), erm(B) (16/193, 8.2%), mef(A)/msr(D) (10/193, 5.1%), lsa(C) (3/193, 1.5%), lnu(C) (1/193, 0.5%), and erm(T) (1/193, 0.5%) genes. The integrative conjugative elements (ICEs) carrying these genes were occasionally found in combination with high gentamicin resistance mediating genes aac(6′)-aph(2″), aminoglycoside resistance genes (ant(6-Ia), aph(3′-III), and/or aad(E)), alternative tetracycline resistance genes (tet(O) and tet(S)), and/or chloramphenicol resistance gene cat(Q), mediating resistance to multiple classes of antibiotics. This study provides evidence of the retention of previously reported ICESag37 (n = 4), ICESag236 (n = 2), and ICESpy009 (n = 3), as well as the definition of sixteen novel ICEs and three novel transposons within the GBS lineage, with no evidence of horizontal transfer.

Background Although infection and inflammation within the genital tract during pregnancy is considered a major risk factor for spontaneous preterm birth (PTB), there are few studies on association between vaginal microorganisms in the early stage of pregnancy and PTB. The aim of this study was to investigate relationship between vaginal Group B streptococcus (GBS) colonization, a leading cause of infection during pregnancy, in the early stage of pregnancy and PTB. Methods This single-center, retrospective cohort study utilized data from 2009 to 2017 obtained at TOYOTA Memorial Hospital. Women with singleton pregnancies who underwent vaginal culture around 14 weeks of gestation during their routine prenatal check-up were included. Vaginal sampling for Gram staining and culture was performed regardless of symptoms. GBS colonization was defined as positive for GBS latex agglutination assay. Statistical analysis was performed to determine the factors associated with PTB. Results Overall 1079 singleton pregnancies were included. GBS (5.7%) and Candida albicans (5.5%) were the most frequently observed microorganisms. The incidence of PTB (before 34 and before 37 weeks of gestation) were significantly higher in the GBS-positive group than in the GBS-negative group (6.6% vs 0.5%, p = 0.001 and 9.8% vs 4.3%, p = 0.047). Our multivariable logistic regression analysis revealed that GBS colonization was a factor associated with PTB before 34 and before 37 weeks of gestation (Odds ratio [OR] 15.17; 95% confidence interval [CI] 3.73–61.74), and OR 2.42; 95%CI 1.01–5.91, respectively). Conclusions The present study found that vaginal GBS colonization in the early stage of pregnancy was associated with PTB. Our study indicates that patients at a high risk for PTB can be extracted by a simple method using conventional culture method.

Objectives: to estimate the prevalence and the factors associated with the colonization by group B streptococcus (GBS) in pregnant women from the urban area attended at health units in a municipality in northeastern Brazil. Methods: it is a cross-sectional study conducted from January 2017 to March 2018. Vagino-rectal swabs were collected from 210 pregnant women between 32 and 40 weeks of gestation. The swabs were seeded on 5% sheep blood agar and on chromogenic agar. For confirmatory identification of GBS, the CAMP test and latex agglutination were used. Descriptive analysis and univariate and multivariate association analysis were performed using a multinomial logistic model. Results: the prevalence of GBS colonization among pregnant women was 18.1% (n = 38), and a statistically significant association (p

International audience; Bone and joint infections (BJI) represent the second cause of invasive Group B Streptococcus (GBS) infections. Biofilm formation plays a major role in BJI. This study’s aim was to analyze the genetic features and biofilm production of GBS strains. In six French laboratories, 77 GBS strains isolated from BJI and 57 strains from vaginal human colonization (Hcol) were characterized and compared by Multi-Locus Sequence Typing (MLST). PCR was used to search for the adhesins (bsaB, lmb, scpB, fbsA, fbsB, hvgA, bibA, bca, srr-1, and srr-2) and Pilus Islands (PI) related genes (PI-1, PI-2a, PI-2b). Biofilm production was studied by crystal violet assay. Strains were categorized into three groups, based on Specific Biofilm Formation (SBF) values defined as: weak, moderate, or strong producers. Molecular study revealed three major clonal complexes (CC) in BJI strains: CC1 (42%), CC23 (22%) and CC10 (14%). Several associations between CC and adhesin/pili were identified: CC1 with srr2, PI-1 + 2a; CC10 with srr-1, bca, PI-1 + 2a; CC17 with fbsB, hvgA, srr-2, PI-1+PI-2b; CC19 with bibA, srr-1, PI-1 + 2a; CC23 with fbsB, bibA, srr-1, PI-2a. The biofilm production was significantly different according to CC, adhesins and pili gene detection. CC10, CC23 and strains harboring fbsB produce more biofilm than CC1, PI-1 + 2a (independently). Finally, SBF values were significantly stronger for Hcol strains rather than for BJI strains (76% versus 40%). This study revealed that Hcol strains appeared to produce stronger biofilm than BJI strains, though they belonged to similar CCs and had the same adhesin and pili content. IMPORTANCE Bone and joint infections (BJI) are pathologies that can be life-threatening and result in compromised functional prognosis for patients. Relapses are common and often related to biofilm formation. Group B streptococci (GBS) BJI increased since the last decade. However, few data are available on this subject in the literature. Our study aims to highlight genotype and biofilm production of GBS isolates from BJI. Seventy-seven GBS strains isolated from BJI and 57 from asymptomatic human vaginal colonization were characterized by multilocus sequence typing (MLST), adhesins content, nature of the pili and the ability to form biofilm. Our results revealed that vaginal human colonization strains produced stronger biofilm than BJI strains, despite belonging to the same phylogenetic lineage and having the same adhesin and pili content.

Group B Streptococci (GBS) are important causes of neonatal sepsis and meningitis globally. To elucidate the potential benefits of maternal GBS vaccines, data is needed on the epidemiology of maternal GBS rectovaginal colonization, distribution of serotypes, and resistance to intrapartum antibiotic prophylaxis (IAP). We collected rectal and vaginal samples from 305 pregnant women in León, Nicaragua between 35 and 40 weeks gestation. Samples were cultured for GBS and confirmed using latex agglutination. GBS isolates underwent serotyping by quantitative polymerase chain reaction, and antimicrobial susceptibility testing by disk diffusion and microdilution following Clinical Laboratory Standard Institute guidelines. Sixty-three women (20.7%) were colonized with GBS in either the rectum or the vagina. Of 91 GBS isolates collected from positive cultures, most were serotypes II (28.6%), Ia (27.5%), and III (20.9%). Most GBS isolates (52.9%) were resistant to penicillin, the first-line prophylactic antibiotic. Penicillin resistance was highly correlated with resistance to vancomycin, ceftriaxone, and meropenem. The results of our study suggest that one-fifth of pregnant women in the urban area of León, Nicaragua are colonized with GBS and risk transmitting GBS to their offspring during labor. High resistance to commonly available antibiotics in the region suggests that prophylactic maternal GBS vaccination would be an effective alternative to IAP.

Background Group B Streptococcus (GBS) remains a significant cause of neonatal infection, but the maternal risk factors for GBS colonization remain poorly defined. We hypothesized that there may be an association between antibiotic exposure during pregnancy and GBS colonization and/or the presence of inducible clindamycin resistance (iCLI-R) in GBS isolates from GBS-colonized pregnant women. Methods A retrospective cohort study was performed at Louisiana State University Health Sciences Center – Shreveport including demographic and clinical data from 1513 pregnant women who were screened for GBS between July 1, 2009 and December 31, 2010. Results Among 526 (34.8%) women who screened positive for GBS, 124 (23.6%) carried GBS strains with iCLI-R (GBS-iCLI-R). While antibiotic exposure, race, sexually-transmitted infection (STI) in pregnancy, GBS colonization in prior pregnancy and BMI were identified as risk factors for GBS colonization in univariate analyses, the only independent risk factors for GBS colonization were African–American race (AOR = 2.142; 95% CI = 2.092–3.861) and STI during pregnancy (AOR = 1.309; 95% CI = 1.035–1.653). Independent risk factors for GBS-iCLI-R among women colonized with GBS were non-African–American race (AOR = 2.13; 95% CI = 1.20–3.78) and younger age (AOR = 0.94; 95% CI = 0.91–0.98). Among GBS-colonized women with an STI in the current pregnancy, the only independent risk factor for iCLI-R was Chlamydia trachomatis infection (AOR = 4.31; 95% CI = 1.78–10.41). Conclusions This study identified novel associations for GBS colonization and colonization with GBS-iCLI-R. Prospective studies will improve our understanding of the epidemiology of GBS colonization during pregnancy and the role of antibiotic exposure in alterations of the maternal microbiome.

Neonatal sepsis (NS) kills 750,000 infants every year. Effectively treating NS requires timely diagnosis and antimicrobial therapy matched to the causative pathogens, but most blood cultures for suspected NS do not recover a causative pathogen. We refer to these suspected but unidentified pathogens as microbial dark matter. Given these low culture recovery rates, many non-culture-based technologies are being explored to diagnose NS, including PCR, 16S amplicon sequencing, and whole metagenomic sequencing. However, few of these newer technologies are scalable or sustainable globally. To reduce worldwide deaths from NS, one possibility may be performing population-wide pathogen discovery. Because pathogen transmission patterns can vary across space and time, computational models can be built to predict the pathogens responsible for NS by region and season. This approach could help to optimally treat patients, decreasing deaths from NS and increasing antimicrobial stewardship until effective diagnostics that are scalable become available globally.

Background: Group A β-hemolytic streptococcus (GAS) and Group B streptococcus (GBS) are two common pathogens that are associated with many diseases in children. Severe infections as a result of these two streptococci are albeit uncommon but associated with high mortality and morbidity, and often necessitate intensive care support. This paper aims to review mortality and morbidity severe infection associated with GAS and GBS isolations at a Pediatric Intensive Care Unit (PICU). Methods: All children admitted to PICU of a teaching hospital between October 2002 and May 2018 with laboratory-proven GAS and GBS isolations were included. Results: There were 19 patients (0.7% PICU admissions) with streptococcal isolations (GAS, n=11 and GBS, n=8). Comparing to GAS, GBS affected infants were younger (median age 0.13 versus 5.47 years, 95% CI, 1.7-8.5, p=0.0003), and cerebrospinal fluids more likely positive (p = 0.0181). All GAS and GBS were sensitive to penicillin (CLSI: MICs 0.06 – 2.0 μg/mL), with majority of GAS sensitive to clindamycin and erythromycin, and half of the GBS resistant to clindamycin and erythromycin. Co-infections were prevalent, but viruses were only isolated with GAS (p=0.024). Isolation of GAS and GBS was associated with nearly 40% mortality and high rates of mechanical ventilation and inotropic supports. All non-survivors had high mortality (PIM2) and sepsis scores. Conclusions: Severe GAS and GBS are rare but associated with high mortality and rates of mechanical ventilation and inotropic supports in PICU. The streptococci are invariably sensitive to penicillin. The high PIM2 and Sepsis scores suggest that prompt recognition of sepsis and timely judicious institution of antibiotics and intensive care support may be life-saving for these devastating infections.

Group B streptococcus (GBS) is a rare cause of meningitis in adults that commonly affects patients with multiple underlying comorbidities. Although it is uncommon, it typically progresses very rapidly and has a high mortality rate as compared to other causes of bacterial meningitis. Here, we report a patient with GBS meningitis who had no underlying medical illness and presented with multiple episodes of seizure within hours of developing fever. Cerebrospinal fluid analysis results were consistent with bacterial meningitis, and blood cultures grew GBS. She was treated with intravenous ceftriaxone for 2 weeks and made a great recovery without any sequalae. In conclusion, although GBS meningitis is uncommon in adults, it is a serious medical disease and associated with a high mortality rate. To the best of our knowledge, this patient represents one of the few reported cases of GBS meningitis in a previously healthy young adult., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/hooqOJvn3cc

Alvin Oliver Payus,1 Clarita Clarence,2 Raymond Azman Ali2 1Faculty of Medicine and Health Science, Universiti Malaysia Sabah (UMS), Sabah, Malaysia; 2Department of Internal Medicine, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, MalaysiaCorrespondence: Alvin Oliver PayusFaculty of Medicine and Health Science, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, MalaysiaTel +6018-8703503Fax +6088-320 000Email dralvinpayus@ums.edu.myAbstract: Group B streptococcus (GBS) is a rare cause of meningitis in adults that commonly affects patients with multiple underlying comorbidities. Although it is uncommon, it typically progresses very rapidly and has a high mortality rate as compared to other causes of bacterial meningitis. Here, we report a patient with GBS meningitis who had no underlying medical illness and presented with multiple episodes of seizure within hours of developing fever. Cerebrospinal fluid analysis results were consistent with bacterial meningitis, and blood cultures grew GBS. She was treated with intravenous ceftriaxone for 2 weeks and made a great recovery without any sequalae. In conclusion, although GBS meningitis is uncommon in adults, it is a serious medical disease and associated with a high mortality rate. To the best of our knowledge, this patient represents one of the few reported cases of GBS meningitis in a previously healthy young adult.Keywords: group B streptococcus, meningitis, young adult, seizure, ceftriaxone