Intrapartum Prophylaxis Research Articles

The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome.

Group B Streptococcus (GBS, S. agalactiae) is a human commensal and occasional pathogen that remains a leading cause of neonatal sepsis and meningitis with increasing disease burden in adult populations. Although programs for universal screening in pregnancy to guide intrapartum prophylaxis have reduced GBS invasive disease burden resulting from mother-to-newborn transfer during birth, better knowledge of disease mechanisms may elucidate new strategies to reduce antibiotic exposure. In our efforts to expand the knowledge base required for targeted anti-virulence therapies, we identified a GBS homolog for a recently identified virulence determinant of group A Streptococcus, S protein, and evaluated its role in GBS pathogenesis. A GBS S protein deletion mutant, Δess, showed altered cell-surface properties compared to the WT parent strain, including defective retention of its surface polysaccharide. Quantitative proteome analysis of enzymatically shaved surface epitopes of the GBS Δess mutant revealed a dysregulated cell surface virulome, with reduced abundance of several protein and glycoprotein components. The Δess mutant showed markedly attenuated virulence in a murine model of GBS systemic infection, with increased proteasome activity detected in the spleens of animals infected with the Δess mutant. These results expand the key roles S protein plays in streptococcal pathogenesis and introduces a new GBS virulence determinant and potential target for therapy development.

Effect of Intrapartum Antibiotics Prophylaxis on the Bifidobacterial Establishment within the Neonatal Gut.

Antibiotics are important disruptors of the intestinal microbiota establishment, linked to immune and metabolic alterations. The intrapartum antibiotics prophylaxis (IAP) is a common clinical practice that is present in more than 30% of labours, and is known to negatively affect the gut microbiota composition. However, little is known about how it affects to Bifidobacterium (sub)species level, which is one of the most important intestinal microbial genera early in life. This study presents qualitative and quantitative analyses of the bifidobacterial (sub)species populations in faecal samples, collected at 2, 10, 30 and 90 days of life, from 43 healthy full-term babies, sixteen of them delivered after IAP use. This study uses both 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing and q-PCR techniques for the analyses of the relative proportions and absolute levels, respectively, of the bifidobacterial populations. Our results show that the bifidobacterial populations establishment is affected by the IAP at both quantitative and qualitative levels. This practice can promote higher bifidobacterial diversity and several changes at a compositional level. This study underlines specific targets for developing gut microbiota-based products for favouring a proper bifidobacterial microbiota development when IAP is required.

GROUP B STREPTOCOCCAL INFECTIONS DURING PREGNANCY AND PERINATAL CONSEQUENCES: WHAT DO WE NEED TO DETERMINE MORE THAN A BACTERIOLOGICAL ANALYSIS?

Group B of streptococcal infection is responsible for maternal and fetal morbidity and mortality. Fetal consequences of streptococcal B infection may lead to puerperal sepsis, meningitis, encephalitis or pneumonia. Long-term consequences may determine neurological sequelae and mental disabilities, and very rare are reported cases for the late death of the child. Maternal consequences of streptococcal B infection are endometritis and sepsis. Universal screening and antibioprophylaxy during labour are safe and effective. But, systematic intrapartum prophylaxis for carriers of SGB does not appear to have effects on long-term complications. Also, systematic cultures in neonates do not appear to detect antenatally all carriers of streptococcus B. Herein, we present the particularity of streptococcal infection in pregnancy that may contribute to further strategy. Better laboratory tests for identifying serotypes, genotypes and phenotypes must be available, significantly to differentiate between dtreptococcal high- and low-risk regarding materno-fetal consequences.Immunization remains a promising way to eradicate this infection.

Microbiologic Etiology and Infant Factors Associated with Early Onset Neonatal Bacteremia at the Mount Sinai Hospital

Background/Rationale: Early-onset neonatal sepsis (EOS) is often acquired through vertical transmission and is an important cause of morbidity and mortality in infants. The etiology of neonatal sepsis has changed over time, and the intrapartum management of women at risk for infection has been shown to improve neonatal outcomes. Hypothesis or Research Question: To identify the microbiologic etiology of organisms causing EOS and evaluate the impact of maternal illness, labor and delivery practices, and postnatal factors on EOS rates at Mount Sinai Hospital (MSH). Study Design/Methods: An IRB approved descriptive retrospective chart review of cases of EOS in infants less than 7 days of age at MSH from 2015–2018 was conducted. A total of 41 infants were identified. Clinical charts were reviewed and classified into two groups based on age at time of presentation: very early onset sepsis (VEOS) (age days 0–2) and delayed early onset sepsis (DEOS) (age days 3–7). Corresponding maternal charts were also reviewed to identify obstetric risk factors and whether at-risk mothers received appropriate intrapartum prophylaxis. Results: In the VEOS group, 41% of cases were caused by Group B Streptococcus (GBS), 30% by E.coli, and 18% by other Streptococci. In the DEOS group, 33% of cases were coagulase-negative Staphylococci, 27% E.coli, and 20% S. aureus. There were no cases of GBS among the DEOS group. On average, VEOS occurred in term infants (37.40 ± 4.41 weeks) with a normal weight (2840 ± 88g), while DEOS occurred in preterm infants (30.74 ± 6.08 weeks) with a low birth weight (1550 ± 104g). 36.4% of GBS isolates demonstrated resistance to clindamycin. E.coli isolates demonstrated resistance to ampicillin/sulbactam (66.7%), co-trimoxazole (41.7%), and gentamicin (35%). No extended spectrum beta-lactamase-producing E.coli isolates were found in the VEOS or DEOS groups. Within the GBS EOS cases, 63.6% of infants who developed GBS EOS were born to women with a documented GBS negative screening test. Conclusions/Future Plans: The microbiologic etiology of VEOS and DEOS varied, with GBS only identified in the VEOS group and E.coli common in both the VEOS and DEOS groups. The failure to identify GBS colonization in women who give birth to infants that develop GBS EOS requires further exploration. Our study demonstrates the need for both strategies to reduce the risk of E.coli EOS among preterm, low birth weight neonates, as well as further investigation into E.coli EOS resistance patterns.

The Epidemiology of Meningitis in Infants under 90 Days of Age in a Large Pediatric Hospital.

Background: Meningitis is associated with substantial morbidity and mortality, particularly in the first three months of life. Methods: We conducted a retrospective review of patients <90 days of age with meningitis at Texas Children’s Hospital from 2010–2017. Cases were confirmed using the National Healthcare Safety Network (NHSN) definition of meningitis. Results: Among 694 infants with meningitis, the most common etiology was viral (n = 351; 51%), primarily caused by enterovirus (n = 332; 95%). A quarter of cases were caused by bacterial infections (n = 190; 27%). The most common cause of bacterial meningitis was group B Streptococcus (GBS, n = 60; 32%), followed by Gram-negative rods other than E. coli (n = 40; 21%), and E. coli (n = 37; 19%). The majority of Gram-negative organisms (63%) were resistant to ampicillin, and nearly one-fourth of Gram-negative rods (23%) other than E. coli and 2 (6%) E. coli isolates were resistant to third-generation cephalosporins. Significant risk factors for bacterial meningitis were early preterm birth and the Black race. Conclusions: Enteroviruses most commonly caused viral meningitis in infants; GBS was the most common bacterial cause despite universal screening and intrapartum prophylaxis. The emergence of MRSA and resistance to third-generation cephalosporins in Gram-negative bacterial meningitis challenges the options for empirical antimicrobial therapy.

HIV in Canada-surveillance report, 2019.

Human immunodeficiency virus (HIV) is a global public health issue. HIV has been nationally notifiable in Canada since 1985. The Public Health Agency of Canada (PHAC) monitors trends in new HIV diagnoses. The objective of this surveillance report is to provide an overview of the epidemiology of reported HIV cases in 2019 in Canada. The report highlights 10-year trends (2010-2019). Data on HIV diagnosed through Immigration Medical Exams (IME) and trends in perinatal transmission of HIV are also presented. PHAC monitors HIV through the HIV/AIDS Surveillance System, a passive, case-based system that collates non-nominal data submitted voluntarily by all Canadian provinces and territories. Descriptive analyses were conducted on national data. IME data were obtained from Immigration, Refugees and Citizenship Canada (IRCC), and data on HIV-exposed pregnancies were obtained through the Canadian Perinatal HIV Surveillance Program. In 2019, a total of 2,122 HIV diagnoses were reported in Canada (5.6 per 100,000 population). Saskatchewan reported the highest provincial diagnosis rate at 16.9 per 100,000 population. The 30 to 39-year age group had the highest HIV diagnosis rate at 12.7 per 100,000 population. While the rates for both males and females fluctuated in the past decade, since 2010 the rates among males decreased overall, while the rate among females increased slightly. As in previous years, the diagnosis rate for males in 2019 was higher than that for females (7.9 versus 3.4 per 100,000 population, respectively). The highest proportion of all reported adult cases with known exposure were gay, bisexual and other men who have sex with men (gbMSM, 39.7%), followed by cases attributed to heterosexual contact (28.3%) and among people who inject drugs (PWID, 21.5%). The number of migrants who tested positive for HIV during an IME conducted in Canada was 626. The one documented perinatal HIV transmission related to a mother who had not received antepartum or intrapartum antiretroviral therapy prophylaxis. The number and rate of reported HIV cases in Canada has remained relatively stable over the last decade, with minor year-to-year variations. As in previous years, the gbMSM and PWID populations represent a high proportion of HIV diagnoses, although a sizable number of cases were attributed to heterosexual contact. It is important to routinely monitor trends in HIV in light of pan-Canadian commitments to reduce the health impact of sexually transmitted and blood-borne infections by 2030.

Determination of Capsular Serotypes, Antibiotic Susceptibility Pattern, and Molecular Mechanism of Erythromycin Resistance among Clinical Isolates of Group B Streptococcus in Isfahan, Iran.

Background:Documented streptococcal resistance to erythromycin has recently been raised. The aim of this study is to identify the molecular mechanism of erythromycin resistance among group B Streptococcus (GBS) strains and to correlate with the clinical origin of strains.Materials and Methods:A total number of 134 colonizing (n = 36), invasive (n = 36), noninvasive (n = 46), and asymptomatic (n = 16) GBS isolates were characterized by the detection of dltS gene, capsular serotyping, antibiotic susceptibility profiles using disc diffusion method, and screening of the ermB, ermTR, and mefA resistance genes.Results:The distribution of capsular serotypes was as follow: serotype III (24.6%), Ia (21.6%), V (17.9%), Ib (14.9%), II (8.9%), IV (8.9%), VI (1.5%), and VII (1.5%). From 134 GBS isolates, 51 (38%) isolates were resistant to erythromycin. The constitutive macrolide lincosamide streptogrmin B (MLSB) was the most common resistance phenotype (62.7%), followed by inducible MLSB (27.4%) and M phenotype (9.8%). Erythromycin resistance rate was higher among asymptomatic GBS strains (13/16, 81.2%). Serotype III was the most prevalent type among resistant isolates (41.1%). The ermB gene highly distributed among resistant strains (64.7%), followed by ermTR (21.5%) and mefA (9.8%). The ermB gene was related to constitutive MLSB phenotype (84.3%, P < 0.05) and serotypes III (61.9%), Ib (87.5%), and V (83.3%). All M phenotype strains harbored mefA gene and were in association with serotype Ia (90%).Conclusion:The current study suggests that ribosomal modification with erm genes is the main mechanism of erythromycin resistance. Because of relatively high prevalence of erythromycin resistance, double disc test highly recommended for GBS disease treatment and intrapartum prophylaxis among penicillin intolerant patients in our region.

Human Immunodeficiency Virus infection associated with crack cocaine use: the impact on perinatal transmission among 890 pregnancies in Brazil

Introduction: Human Immunodeficiency Virus infection is a prevalent infection occurring during pregnancy. The implementation of a program to screen and prevent vertical transmission is highly important in Public Healthcare. Pregnant crack users could face difficulties to test and adhere to the Highly Active Antiretroviral Therapy. Objective: The purpose of this research paper was to investigate whether crack cocaine abuse increases Human Immunodeficiency Virus perinatal transmission rates, as well as to evaluate the risk factors associated with such an increase. Methods: Design: A retrospective study. Setting: Department of Obstetrics and Gynecology, General Hospital of Universidade Federal do Paraná. Population: pregnancies of Human Immunodeficiency Virus-positive women who were using crack cocaine (n=64) were compared with that of non-users (n=826) from 2005 to 2013. Prenatal medical records, delivery records, and newborn records were analyzed. Main Outcome Measures: The vertical transmission of Human Immunodeficiency Virus in the group of crack cocaine users was 9.37% (6) versus 2.54% (21) among non-users (p=0.009744). Results: Over the years of the study, there was a decrease in the vertical transmission rate in non-users, while this number remained constant in the group of users. When analyzing the cases of perinatal transmission, it was found that 83.34% (5) had inadequate prenatal care, and 100% (6) had inadequate Human Immunodeficiency Virus treatment, compared to the group in which there was no vertical transmission, where 65.52% (38) had inadequate prenatal care and 70.86% (41) had inadequate treatment. Conclusion: Vertical transmission is higher among crack cocaine users and did not decrease over the years of the study, as occurred among non-users. Trends that explain this increase were non-adherence to adequate prenatal care, Human Immunodeficiency Virus diagnosis during pregnancy, irregular treatment, absence of intrapartum antiretroviral prophylaxis, and vaginal delivery route.

1300. ACOG Committee Opinion #797 and the Dose of Intrapartum Vancomycin: a Potential Danger to Mother and Newborn Alike

BackgroundIntra-partum (IP) IV vancomycin (VAN) 20 mg/kg every 8 hours is proposed by #797 for the prevention of early onset neonatal group B streptococcal disease (GBS), a recommendation for which the basis of scientific merit is poor. The goal of our study was to analyze the sparsely sampled published data and raise awareness about the underlying risk of VAN toxicity with this dosing approach.MethodsPlasma and cord-blood concentration-time data of IV VAN given to mothers in the IP period was analyzed. 5000 Monte Carlo runs were conducted to simulate maternal/fetal exposure (AUC0-24; 24-48) for doses of 1500, 1750 and 2000 mgs q8h and for possible birth times at two-hour intervals. Neonatal VAN clearance was not possible to determine; hence, we used a validated PK model to calculate exposure for the first 24h of life for gestational ages (GA) of 33 to 40 weeks. The AUC range of 400 – 600, and > 600 mg*h/L were considered for indices of efficacy and toxicity, respectively.ResultsEstimates from 30 pairs of serum and cord-blood concentrations analyzed with a 2-compartment model are shown in Table 1. Maternal VAN exposures seem acceptable up to 2 IP doses given with mean (SD) AUC0-24 of 394 (140), 474 (167), and 540 (193) mg*h/L for the 1500, 1750 and 2000 mg regimens. Most mothers (up to 83%) who receive three or more doses will be subjected to nephrotoxic exposures (Figure 1.). Neonatal evaluations indicate similarly low PTAs for the three dosing regimens when the efficacy target is considered (Figure 2. A). On the other hand, the PTAs for potentially nephrotoxic exposure is expected to reach undesirable levels when three or more doses were to be administered. The risk is profoundly high in GA of 33 to 35 weeks and birth times beyond 20 hours after the initiation of intra-partum prophylaxis (Figure 2. B).Figure 1. Figure 2.A Figure 2.B ConclusionCurrent recommendations by #797 for dosing of vancomycin pose significant risk to mother and newborn alike, especially in cases with lengthy duration of labor. Based on our results, maternal therapeutic drug monitoring for all cases requiring more than two doses should be considered. With the proposed dosing regimen going un-adjusted, 1 out of 4 newborns and 4 out of 5 mothers may be subjected to nephrotoxic exposures in prolonged labor.Table 1. Disclosures All Authors: No reported disclosures

Association of Obesity With Maternal and Cord Blood Penicillin Levels in Women With Group B Streptococcus Colonization.

To compare maternal and cord blood penicillin concentrations in women with and without obesity who are receiving intrapartum group B streptococcus (GBS) prophylaxis. We performed a prospective cohort study of term women receiving intrapartum penicillin prophylaxis for GBS colonization (determined by antenatal rectovaginal culture). The following outcomes were compared between obese (body mass index [BMI] 35 or higher at delivery) and nonobese (BMI less than 30 at delivery) groups: penicillin concentration in maternal blood (after two penicillin doses) and umbilical cord blood, GBS rectovaginal colonization status on admission and after two completed doses, and neonatal GBS colonization (using a postnatal ear swab). Fifty-five women were needed to detect a 0.75 SD difference in cord blood penicillin concentrations. Fifty-five women were enrolled and had all specimens collected; 49 had complete data for analysis (obese n=25, nonobese n=24). There was no difference in the median maternal penicillin concentration between groups (obese 4.2 micrograms/mL vs nonobese 4.0 micrograms/mL, P=.58). There was, however, a 60% lower median cord blood penicillin concentration in the obese compared with the nonobese group (2.7 micrograms/mL vs 6.7 micrograms/mL, respectively, P<.01), with no significant difference in time from last penicillin dose to delivery (obese 2.9 hours vs nonobese 1.7 hours, P=.07). The difference in cord blood concentrations remained significant after adjustment for nulliparity, hypertensive disorders, and time from last penicillin dose to delivery. Only 59.6% of women tested positive for GBS by rectovaginal culture on admission (obese 60.9% vs nonobese 58.3%, P=.86). The median cord blood penicillin concentration was 60% lower in neonates born to women with obesity compared with those born to women without obesity. However, all concentrations exceeded the minimum inhibitory concentration. Maternal penicillin levels were not significantly different between groups. More than 40% of women who previously tested positive for GBS by antenatal culture tested negative for GBS on admission for delivery.

Group B streptococcal disease in the mother and newborn—A review

Group B Streptococcus, a common commensal in the gut of humans and in the lower genital tract in women, remains an important cause of neonatal mortality and morbidity. The incidence of early onset disease has fallen markedly in countries that test women for carriage at 35–37 weeks of pregnancy and then offer intrapartum prophylaxis with penicillin during labour. Countries that do not test, but instead employ a risk factor approach, have not seen a similar fall. There are concerns about the effect on the neonatal microbiome of widespread use of antibiotic prophylaxis during labour, but so far the effects seem minor and temporary. Vaccination against GBS would be acceptable to most women and GBS vaccines are in the early stages of development.Tweetable abstract: Group B Strep is a key cause of infection, death and disability in young babies. Antibiotics given in labour remain the mainstay of prevention, until a vaccine is available.

Comparison of institutional guidelines with established early onset sepsis risk calculator in reducing antibiotic use in an inner-city NICU in US

ObjectivesEarly onset sepsis (EOS) incidence has decreased since national guidelines and intrapartum prophylaxis were introduced. However, there has been a rising concern in antibiotic overtreatment for suspicion of EOS. A web-based EOS calculator has recently been used to evaluate the risk in newborns ≥34 weeks. Our purpose was to compare local strategies with the EOS calculator in our setting with an EOS incidence of 2/1000 live births. MethodsA retrospective review of all newborns born ≥34 weeks from 1 January 2016 to 31 December 2017 was completed after receiving IRB approval. We applied the calculator to those eligible using an EOS incidence of 0.6/1000 and 2/1000 live births and divided the patients into four cohorts. The rate of antibiotic use was compared between local evidence-based guidelines and the EOS calculator. ResultsOf the 1367 newborns included in the study, 679 received antibiotics. Over the 2 years, antibiotic utilization decreased by 38%. The calculator would have recommended antibiotics for 468 patients (31% decrease) for an EOS incidence of 0.6/1000, but with a 2/1000 incidence rate the calculator recommended antibiotics for 673 patients (1% decrease). ConclusionsThe EOS calculator has been helpful in optimizing antibiotic use, but its use may result in suboptimal treatment without the knowledge of local EOS incidence. Our local antibiotic stewardship guidelines seemed to be comparable to the EOS calculator, especially by the last 6 months of the study period.

Vancomycin during delivery hospitalizations for women with group B streptococcus

Objective Vancomycin use for intrapartum GBS prophylaxis is not well characterized. The objective of this study was to describe trends in the use of vancomycin among women undergoing vaginal delivery with group B Streptococcus (GBS) colonization. Methods An administrative inpatient database that includes medications was analyzed to evaluate antibiotic use in women undergoing vaginal delivery hospitalizations complicated by GBS colonization from January 2006 to March 2015. Patients with other obstetric or infectious indications for antibiotics were excluded. Frequency of use of individual antibiotic agents was determined. The Cochran–Armitage test was used to assess temporal trends. An adjusted log-linear regression model accounting for demographic and hospital factors with vancomycin receipt as the outcome was performed with adjusted risk ratios (aRR) and 95% confidence intervals (CI) as the measure of effect. Hospital level variation in administration of vancomycin was also evaluated. Results 469,717 deliveries met inclusion criteria and were included in this analysis. Use of vancomycin increased from 0.8% of patients in 2006 to 3.8% of patients in the first quarter of 2015. Comparing 2015 to 2006 both the unadjusted (relative risk 4.89 95% CI 4.26–5.60) and adjusted (aRR 4.52 95% 3.94–5.19) models demonstrated significantly increased likelihood of vancomycin administration. In evaluating hospital level vancomycin use, variation was noted with 8.0% of centers administering vancomycin to ≥6.0% of patients. Conclusions Vancomycin is becoming increasingly commonly used for intrapartum GBS prophylaxis. Further research and quality improvements initiatives are indicated to optimize intrapartum GBS antibiotic prophylaxis.

Comparative study of Revogene GBS LB assay and GeneXpert GBS LB assay for the detection of group B Streptococcus in prenatal screening samples

BackgroundGroup B Streptococcal (GBS) infections in the United States are a leading cause of meningitis and sepsis in newborns. The CDC therefore recommends GBS screening for all pregnant women at 35–37 weeks of gestation and administration of intrapartum prophylaxis (in those that tested positive) as an effective means of controlling disease transmission. Several FDA approved molecular diagnostic tests are available for rapid and accurate detection of GBS in antepartum women.MethodIn this study, we report a clinical comparison of the Xpert GBS LB assay and a novel FDA-cleared test, Revogene GBS LB assay. A total of 250 vaginal-rectal swabs from women undergoing prenatal screening were submitted to the University of Wisconsin’s clinical microbiology laboratory for GBS testing.ResultsWe found 96.8% of samples were concordant between the two tests, while 3.2% were discordant with a positive percent agreement of 98.0% and a negative percent agreement of 96.5% between the Revogene GBS LB assay and the GeneXpert GBS LB assay.ConclusionOverall, we report that both assays perform well for the detection of GBS colonization in pregnant women.

Mobilome and Resistome Reconstruction from Genomes Belonging to Members of the Bifidobacterium Genus.

Specific members of the genus Bifidobacterium are among the first colonizers of the human/animal gut, where they act as important intestinal commensals associated with host health. As part of the gut microbiota, bifidobacteria may be exposed to antibiotics, used in particular for intrapartum prophylaxis, especially to prevent Streptococcus infections, or in the very early stages of life after the birth. In the current study, we reconstructed the in silico resistome of the Bifidobacterium genus, analyzing a database composed of 625 bifidobacterial genomes, including partial assembled strains with less than 100 genomic sequences. Furthermore, we screened bifidobacterial genomes for mobile genetic elements, such as transposases and prophage-like elements, in order to investigate the correlation between the bifido-mobilome and the bifido-resistome, also identifying genetic insertion hotspots that appear to be prone to horizontal gene transfer (HGT) events. These insertion hotspots were shown to be widely distributed among analyzed bifidobacterial genomes, and suggest the acquisition of antibiotic resistance genes through HGT events. These data were further corroborated by growth experiments directed to evaluate bacitracin A resistance in Bifidobacterium spp., a property that was predicted by in silico analyses to be part of the HGT-acquired resistome.

Joint synthesis of conditionally related multiple outcomes makes better use of data than separate meta-analyses.

BackgroundWhen there are structural relationships between outcomes reported in different trials, separate analyses of each outcome do not provide a single coherent analysis, which is required for decision‐making. For example, trials of intrapartum anti‐bacterial prophylaxis (IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS, and the effect on EOGBS conditional on newborn colonisation. These outcomes are conditionally related, or nested, in a multi‐state model.This paper shows how to exploit these structural relationships, providing a single coherent synthesis of all the available data, while checking to ensure that different sources of evidence are consistent.ResultsOverall, the use of IAP reduces the risk of EOGBS (RR: 0.03; 95% Credible Interval (CrI): 0.002–0.13). Most of the treatment effect is due to the prevention of colonisation in newborns of colonised mothers (RR: 0.08, 95% CrI: 0.04–0.14). Node‐splitting demonstrated that the treatment effect calculated using only direct evidence was consistent with that predicted from the remaining evidence (p = 0.15). The findings accorded with previously published separate meta‐analyses of the different outcomes, once these are re‐analysed correctly accounting for zero cells.ConclusionMultiple outcomes should be synthesised together where possible, taking account of their structural relationships. This generates an internally coherent analysis, suitable for decision making, in which estimates of each of the treatment effects are based on all available evidence (direct and indirect). Separate meta‐analyses of each outcome have none of these properties.

Rectovaginal group B streptococcus colonization among pregnant women in Nicaragua: a systematic review and meta-analysis

Background Maternal colonization with group B Streptococcus (GBS) is a predictor of neonatal sepsis. In Nicaragua, neonatal sepsis is a major cause of hospitalization, but it can be prevented with intrapartum antibiotic prophylaxis. We undertook this study to estimate the pooled prevalence of rectovaginal GBS colonization among pregnant women 35–40-week gestation in Nicaragua, and sensitivity of GBS isolates to various antibiotics. Methods We systematically searched electronic databases of peer-reviewed and unpublished literature using prespecified search terms. We included English- and Spanish-language studies of rectovaginal GBS colonization and/or antibiotic sensitivity of GBS isolates that followed internationally-recognized diagnostic standards, from various sites and years. Two reviewers independently abstracted data and assessed risk of study bias. We then meta-analyzed the pooled prevalence of rectovaginal GBS colonization and antibiotic sensitivity of GBS isolates. We performed subgroup analyses by geographic location, urbanicity, and study risk of bias. Main results Prevalence of rectovaginal GBS colonization from 13 samples in 11 studies was 0.14 (95% CI: 0.09, 0.21). Effect size heterogeneity was identified between coastal (0.12 [95% CI: 0.07, 0.19]) and central study sites (0.23 [95% CI: 0.18, 0.28]), and between predominantly rural (0.06 [95% CI: 0.02, 0.10]) and urban (0.28 [95% CI: 0.19, 0.37]) samples of pregnant women. GBS sensitivity to penicillin, the first-line antibiotic for intrapartum prophylaxis, was 0.89 (95% CI: 0.71, 1.00) based on seven studies. Conclusions Maternal GBS colonization was substantial in some study sites. Most GBS isolates are sensitive to recommended antibiotics, and intrapartum antibiotic prophylaxis may effectively prevent neonatal sepsis in Nicaragua.

Evolving a national preventive protocol for vertical transmission of group B streptococcus in a low-resource country: The culture-based approach

Abstract Objective: The study objective was to determine the role and applicability of the culture-based approach to Group B Streptococcus(GBS) screening and the effect on pregnancy outcome. Materials and Methods: This is a prospective cross-sectional study involving 166 consenting antenatal clinic attendees at 35–37 weeks' gestation using purposive sampling. All participants had vaginal and rectal swabs collected and cultured with the availability of culture results at the time of presentation in labor. All GBS-colonized mothers received intrapartum prophylaxis with parenteral antibiotics based on antibiotic sensitivity from the onset of labor or the rupture of membrane until delivery. Statistical analysis was conducted using SPSS software version 21.0, while P &lt; 0.05 was considered statistically significant. Results: The GBS maternal prevalence was 7.8%, and culture-positive women had both vaginal and rectal colonization. Marital status (P = 0.002), multiple sexual partners (P =0.001), previous sexually transmitted infections (P = 0.013), and low socioeconomic status (P = 0.012) were significantly associated with GBS colonization. GBS isolates were 100% sensitive to ampicillin, all participants had a minimum of two doses of intrapartum prophylaxis with parenteral ampicillin, there was no maternal morbidity, and the vertical transmission of GBS was 0%. Conclusions: The culture-based approach and the culture-based maternal intrapartum prophylaxis prevented both maternal and neonatal complications from GBS. Establishing regional- and national-level preventive protocols will be a central strategy for the prevention.

New Approaches to the Evaluation and Management of Well-Appearing Term and Late Preterm Neonates at Risk for Early-Onset Sepsis

We examine established guidelines for evaluating infants at risk for early-onset sepsis (EOS), as well as newer risk-based assessment strategies that may safely reduce unnecessary antibiotic exposure for well-appearing newborns. We highlight a new multivariate risk assessment tool (Neonatal Early-Onset Sepsis Calculator) that can reduce empirical antibiotic therapy, laboratory testing, maternal-infant separation, and healthcare costs, without increasing adverse events. In the era of intrapartum antimicrobial prophylaxis for group B Streptococcus (GBS), the incidence of EOS among term and late preterm infants has decreased substantially. Established guidelines recommend laboratory evaluation and empirical antibiotics for all infants exposed to maternal chorioamnionitis, regardless of the infant’s clinical condition. Since the publication of these guidelines, newer evidence suggests that well-appearing infants can safely be managed with close clinical observation alone. The Neonatal Early-Onset Sepsis Calculator is a useful tool that quantifies an individual newborn’s EOS risk based on perinatal risk factors and clinical examination and has been shown to decrease laboratory evaluations and antibiotic use.

Group B Streptococci: Declining Incidence in Infants in Germany.

Group B streptococcus (GBS) is a leading cause of morbidity and mortality in newborns worldwide. From 2000 to 2008, national guidelines in Germany recommended intrapartum antibiotic prophylaxis for pregnant women displaying risk factors (eg, perinatal anogenital GBS colonization, rupture of the membranes ≥18 hours before birth) for the vertical transmission of GBS to their children. In 2008, these guidelines were revised to advocate universal, culture-based screening for GBS colonization among all pregnant women between 35 and 37 weeks of gestation. For the period 2009-2010, our prospective active surveillance study assessed the incidence of invasive GBS infections in infants 0-90 days of age in Germany. We did this by means of a capture-recapture analysis of 2 separate, independent systems (pediatric reporting versus laboratory reporting). We compared our results with those from a previous study by employing an equivalent design (2001-2003). We detected a 32% reduction in GBS incidence, from 0.47 per 1000 live births (n = 679) in 2001-2003 to 0.34 per 1000 live births (n = 450) in 2009-2010. This decline primarily is tied to a reduced number of GBS cases in children under 1 week of age. In 2009-2010, the ratio of early-onset disease to late-onset disease reversed from 1.52 (206:136), as determined in 2001-2003, to 0.75 (92:122). This study is the first to assess changes in the incidence of invasive GBS in Germany after the implementation of the guidelines for intrapartum prophylaxis for pregnant women colonized with GBS.