Intrapartum Antimicrobial Prophylaxis Research Articles

Group B Streptococcus vaccines: progress and potential

Group B Streptococcus (GBS, Streptococcus agalactiae) is a pathogen that causes sepsis and meningitis, particularly in newborns, as well as severe infections in the elderly and those at high risk. For many years, the administration of intrapartum antimicrobial prophylaxis (IAP) has been a standard method to prevent neonatal GBS infection. However, IAP may be unsuitable in low-income settings due to its high cost and difficult accessibility to medical institutions. Additionally, IAP may lead to the emergence of antimicrobial-resistant bacteria. Hence, an alternative method for the control of GBS, such as a vaccine, is needed. An effective vaccine will likely prevent the further spread of GBS and be cost-effective compared with IAP. GBS vaccines have been under development for the past two decades, and several candidates have shown potential. In this review, we discuss the current development of GBS vaccines, including types and their implementation in different target populations.

Cost-effectiveness analysis of maternal vaccination against Group B streptococcus in Japan

BackgroundGroup B Streptococcus (GBS) is a leading pathogen causing life-threatening bacterial infections in neonates (early- or late-onset) and infants, and is associated with preterm and stillbirth. Japan introduced national guidelines to reduce early-onset neonatal GBS disease, with universal prenatal screening and intrapartum antimicrobial prophylaxis (IAP). However, screening/IAP does not prevent GBS associated late-onset disease, preterm or stillbirth. Maternal GBS vaccines in development are targeted at infant GBS disease but may provide benefit across perinatal outcomes. We aimed to assess cost-effectiveness of a future maternal GBS vaccine, for a base case prevention of infant GBS disease in combination with screening/IAP compared to screening/IAP alone. MethodsWe used a decision tree model to estimate cases of infant GBS disease, deaths, and neuro-developmental impairment (NDI), GBS-related stillbirths, and the associated costs and loss in Quality-Adjusted Life Years (QALYs). We calculate the threshold price at which a vaccine would be cost-effective assuming a cost-effectiveness threshold of ¥5 million/QALY. We explored the potential benefit of a maternal GBS vaccine that also prevents preterm birth in a scenario analysis. ResultsMaternal GBS vaccination in Japan could prevent an additional 142 infant GBS cases annually, including 5 deaths and 21 cases of NDI, and 13 stillbirths compared to screening/IAP alone. The incremental cost-effectiveness ratio (ICER) was ¥3.78 million/QALY with a vaccine cost of ¥5,000/dose. If the QALY lost for stillbirth is included, the ICER is reduced to ¥1.78 million/QALY. Median threshold vaccine price was ¥6,900 per dose (95 % uncertainty interval ¥5,100 to ¥9,200 per dose). If maternal GBS vaccination also prevented half of GBS-associated preterm, the ICER would be reduced to ¥1.88 million/QALY. ConclusionsAn effective maternal GBS vaccine is likely to be considered cost-effective in Japan at a price of ¥5,000/dose. Effectiveness against other adverse perinatal outcomes would increase health benefits and cost-effectiveness.

Cervicovaginal and rectal colonization by group B Streptococci in Mexican women with full-term pregnancies.

A pregnant woman rectally or vaginally colonized by group B Streptococcus can infect her newborn. Prospective, cross-sectional, analytical 24-month study in pregnant women. Women in labor with ≥ 36 weeks of gestation were included. Pregnancy was classified as normal or high-risk. Main risk factors of the pregnant women were analyzed. Rectal and vaginal samples were obtained, placed in Todd-Hewitt broth and subsequently inoculated in 5% sheep blood agar. Identification was carried out by biochemical tests and latex agglutination. 3,347 pregnant women were included. Mean age was 25.6 ± 5.3 years, 95.5% received antenatal care; 2,213 (66%) had normal-risk pregnancies, and in 1,370 (41%), delivery was by cesarean section. Overall colonization was 4.3% (145/3,347), and it was higher in the 30-34 years age group (6.8%). Serotype I (58%) was the most common. The percentage of colonization in this population was low. A routine cervicovaginal and rectal culture program in pregnant women and the intrapartum antimicrobial prophylaxis program are controversial in our region.

Impact of intrapartum antibiotics on the developing microbiota: a review.

The perinatal period sets the basis for the later physiological and immune homeostasis of the individual, with the intestinal microbiota being an important contributor to driving this homeostasis development. Therefore, the initial establishment and later development of the microbiota during early life may play a key role in later health. This early establishment of the intestinal microbiota is known to be affected by several factors, with gestational age, delivery mode, and feeding habits being extensively studied ones. Other factors are not so well understood, although knowledge has been accumulating in the last years. Among them, a factor of great relevance is the effect of perinatal exposure to antibiotics. Administration of intrapartum antimicrobial prophylaxis (IAP) to women during the delivery process represents the most common form of exposure to antibiotics during the perinatal period, present in around 30% of deliveries. During the last decade, evidence has accumulated demonstrating that IAP alters intestinal microbiota development in neonates. Moreover, recent evidence indicates that this practice may also be altering the infant intestinal resistome by increasing the levels of some antibiotic resistance genes. This evidence, as reviewed in this manuscript, suggests the interest in promoting the rational use of IAP. This practice has significantly reduced the risk of neonatal infections, but now the accumulating knowledge suggests the need for strategies to minimize its impact on the neonatal microbiota establishment.

Universal testing for group B streptococcus during pregnancy: need for a randomised trial.

A third of developed countries do not test for maternal group B streptococcus colonisation in pregnant women and follow a strategy of identifying maternal risk factors for EOGBS disease in the baby, and offering those 'higher risk groups' intrapartum antimicrobial prophylaxis. Hasperhoven et al (BJOG, 2020) present an updated systematic review of culture-based testing for group B streptococcus (GBS) colonisation in women or risk factor-based approach for prevention of newborn early-onset GBS (EOGBS) disease. The review identified 17 observational studies, of which 15 provided data for a meta-analysis and 11 directly compared screening protocols with risk-based strategies.

To screen or not to screen women for Group B Streptococcus (Streptococcus agalactiae) to prevent early onset sepsis in newborns: recent advances in the unresolved debate.

Streptococcus agalactiae, also known as Group B streptococcus (GBS) is the commonest cause of early onset sepsis in newborns in developed high-income countries. Intrapartum antimicrobial (antibiotic) prophylaxis (IAP) is recognized to be highly effective in preventing early onset Group B sepsis (EOGBS) in newborns. The key controversy is about the strategy that should be used to identify mothers who should receive IAP. There are two strategies that are followed in developed countries: screening-based or risk-factor-based identification of women requiring IAP. The debate regarding which of the two approaches is better has intensified in the recent years with concerns about antimicrobial resistance, effect on newborn’s microbiome and other adverse effects. In this review, we have discussed some of the key research papers published in the period 2015–2019 that have addressed the relative merits and disadvantages of screening versus risk-factor-based identification of women requiring IAP. Although screening-based IAP appears to be more efficacious than risk-based IAP, IAP-based prevention has several limitations including ineffectiveness in prevention of late-onset GBS infection in babies, premature and still births, impact of IAP on neonatal microbiota, emergence of antimicrobial resistance and difficulties in implementing IAP-based strategies in middle and low income countries. Alternative strategies, principally maternal immunization against GBS would circumvent use of IAP. However, no licensed vaccines are currently available for use.

Changes in incidence and etiology of early-onset neonatal infections 1997\u20132017 \u2013 a retrospective cohort study in western Sweden

BackgroundThe objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997–2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975.MethodsObservational epidemiological, retrospective study on infants 0–6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997–2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975.ResultsThe total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997–2007 to 0.9/1000 LB in 2008–2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997–2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987–1996 to 0.45/1000 live births 1997–2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge.ConclusionThere has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area.Key notesThis study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life.

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.

Risk factors for neonatal group B streptococcus vertical transmission: a prospective cohort study of 1815 mother-baby pairs.

The potential factors associated with group B streptococcus (GBS) vertical transmission have not been studied in detail. A prospective cohort study was conducted to recruit 1815 mother-neonate pairs for GBS analysis. Pearson's chi-squared tests and generalized linear models were used to explore the risk factors for neonatal GBS colonization. The rate of GBS vertical transmission was 14.1%. GBS colonization in all neonates was significantly associated with maternal GBS colonization, mode of delivery, episiotomy, number of prenatal vaginal exams, parity, and hypertension. For neonates born to GBS-positive mothers, GBS vertical transmission was associated with the mode of delivery, episiotomy, and sexually transmitted diseases. For neonates born to GBS-negative mothers, neonatal GBS colonization was associated with the number of prenatal vaginal exams, parity, and hypertension. These findings suggest the need for prenatal GBS screening for pregnant women and intrapartum antimicrobial prophylaxis for GBS-colonized women.

Development of a melting-curve based multiplex real-time PCR assay for simultaneous detection of Streptococcus agalactiae and genes encoding resistance to macrolides and lincosamides

BackgroundStreptococcus agalactiae or Group B Streptococcus (GBS) remains the leading cause of infections in newborns worldwilde. Prenatal GBS screening of pregnant women for vaginal-rectal colonization is recommended in many countries to manage appropriate intrapartum antimicrobial prophylaxis for those identified as carriers. In this study, a novel melting-curve based multiplex real-time PCR assay for the simultaneous detection of GBS and macrolide and lincosamide resistance markers was developed. The usefulness of the assay was evaluated for rapid and accurate prenatal GBS screening.MethodsOne hundred two pregnant women who were at 35–37 weeks of gestation were enrolled in this study. The analytical performance of the multiplex real-time PCR was first tested using a panel of reference and clinical bacterial and fungal strains. To test the clinical performance, vaginal-rectal swabs were obtained from pregnant women who were seen at the teaching hospital for regular prenatal care. The results of real-time were compared with those obtained from microbiological analyses.ResultsThe real-time PCR assay showed 100% specificity and a limit of detection of 104 colony forming units equivalent per reaction. The prevalence of GBS colonization among the population studied was 15.7% (16/102) based on a positive culture and the real-time PCR results. Agreement between the two assays was found for 11 (68.75%) GBS colonized women. Using the culture-based results as a reference, the multiplex real-time PCR had a sensitivity of 91.7% (11/12, CI 59.7–99.6%), a specificity of 95.5% (86/90, CI 89.8–98.7%), a positive predictive value of 73.3% (11/15, CI 44.8–91.1%) and a negative predictive value of 98.9% (86/87, CI 92.9–99.9%).ConclusionThe multiplex real-time PCR is a rapid, affordable and sensitive assay for direct detection of GBS in vaginal-rectal swabs.

Early-onset group B Streptococcus (EOGBS) infection subsequent to cessation of screening-based intrapartum prophylaxis: findings of an observational study in West London, UK

ObjectivesTo describe the impact on early-onset group B Streptococcus (EOGBS) infection rates following reversion from screening-based to risk-based intrapartum antimicrobial prophylaxis (IAP) for prevention.SettingMaternity services provided by secondary healthcare organisation...

Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates

BackgroundDisturbances in the early establishment of the intestinal microbiota may produce important implications for the infant’s health and for the risk of disease later on. Different perinatal conditions may be affecting the development of the gut microbiota. Some of them, such as delivery mode or feeding habits, have been extensively assessed whereas others remain to be studied, being critical to identify their impact on the microbiota and, if any, to minimize it. Antibiotics are among the drugs most frequently used in early life, the use of intrapartum antimicrobial prophylaxis (IAP), present in over 30% of deliveries, being the most frequent source of exposure. However, our knowledge on the effects of IAP on the microbiota establishment is still limited. The aim of the present work was to evaluate the impact of IAP investigating a cohort of 40 full-term vaginally delivered infants born after an uncomplicated pregnancy, 18 of which were born from mothers receiving IAP.ResultsFecal samples were collected at 2, 10, 30, and 90 days of age. We analyzed the composition of the fecal microbiota during the first 3 months of life by 16S rRNA gene sequencing and quantified fecal short chain fatty acids by gas chromatography. The presence of genes for resistance to antibiotics was determined by PCR in the samples from 1-month-old infants. Our results showed an altered pattern of intestinal microbiota establishment in IAP infants during the first weeks of life, with lower relative proportions of Actinobacteria and Bacteroidetes and increased of Preoteobacteria and Firmicutes. A delay in the increase on the levels of acetate was observed in IAP infants. The analyses of specific antibiotic resistance genes showed a higher occurrence of some β-lactamase coding genes in infants whose mothers received IAP.ConclusionsOur results indicate an effect of IAP on the establishing early microbiota during the first months of life, which represent a key moment for the development of the microbiota-induced host homeostasis. Understanding the impact of IAP in the gut microbiota development is essential for developing treatments to minimize it, favoring a proper gut microbiota development in IAP-exposed neonates.

C reactive protein in healthy term newborns during the first 48 hours of life

BackgroundEarly-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is...

Prevention of early onset group B streptococcal disease by universal antenatal culture-based screening in all public hospitals in Hong Kong

Objectives: To determine the prevalence of maternal colonization with group B streptococcus (GBS), and early onset GBS disease (EOGBSD) after implementation of universal screening.Methods: This was a three-year retrospective cohort study on universal antenatal rectovaginal culture-based screening and intrapartum antimicrobial prophylaxis (IAP) to colonized women in the public sector in Hong Kong. Routinely collected data including maternal colonization and EOGBSD were retrieved.Results: Of 113,989 GBS screening performed, 21.8% were positive. The colonization rate was higher in the public hospitals (higher risk) than in the Maternal and Child Health Centers (lower risk) (23.7% vs 18.1%, p < .001), while their false negative rates were not greater than expected. Majority of eligible women opted for screening, and colonized women received IAP. There were 29 cases of EOGBSD with clinical signs and a positive blood or cerebrospinal fluid culture. Compared to clinical risk-based screening, EOGBSD incidence decreased after universal screening (1 vs 0.24 per 1000 births, p < .001). Although EOGBSD occurred at a higher rate in preterm than term infants, 86.7% occurred in the latter, and were associated with a false negative screening result (41.3%), lack of screening (20.7%) or unavailability of a colonization result at labour (13.8%).Conclusions: Maternal GBS colonization rate was higher than previously reported, and varied with different risk populations. EOGBSD reduced after universal screening.

The prevalence of asymptomatic group B streptococcal infection and antimicrobial sensitivity pattern among parturients at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Background: Early-onset Group B Streptococcal (GBS) infection is an important cause of perinatal morbidity and mortality. Policy of active prevention by antepartum screening and treatment is not a popular practice in resource-constrained settings. Objectives: This study determined the prevalence of asymptomatic GBS infection and antimicrobial sensitivity pattern. It also determined the outcome of Intrapartum antimicrobial prophylaxis (IAP). Methodology: It was a prospective and longitudinal study done in Ahmadu Bello University Teaching Hospital, Zaria, between June 2014 and April 2015. Two hundred and twenty consenting pregnant women with gestational ages between 35 and 37 completed weeks were participated in the study. Vagina and rectum were swabbed using different rayon swab sticks. Swabs were placed in Amies, nonnutritive transport medium. Bacteriological procedures to culture GBS and confirmation with biochemical tests and serological test were done. Antibiotic sensitivity pattern was determined. Participants who had GBS rectovaginal colonization had intrapartum antibiotic prophylaxis with penicillin G. All participants were followed up till to a week after birth. Results: Out of the 220 pregnant participants, 19 (8.6%) had GBS rectovaginal colonization. Antibiotic sensitivity pattern revealed that GBS isolates were all sensitive to penicillin, ampicillin, and cefazolin while 4 (21.1%) were resistant to ceftriaxone and 6 (31.6%) were resistant to both erythromycin and clindamycin. None of the isolates were resistant to erythromycin and sensitive to clindamycin or vice versa. Of the 19 participants with GBS rectovaginal colonization, 2 (10.5%) delivered low birth weight baby, but there was no incidence of early-onset GBS disease. Conclusion: The prevalence of GBS rectovaginal colonization in this study is similar to figures from other parts of the country. The GBS sensitivity pattern to penicillin was similar to those reported elsewhere. Fetal outcome following intrapartum antibiotic prophylaxis was good.

Early-Onset Neonatal Sepsis: A Continuing Problem in Need of Novel Prevention Strategies.

* Abbreviations: ABC — : Active Bacterial Core surveillance EOS — : early-onset neonatal sepsis GBS — : group B streptococcus IAP — : intrapartum antimicrobial prophylaxis Early-onset neonatal sepsis (EOS) remains a feared cause of severe illness and death among infants of all birthweights and gestational ages, with particular impact among preterm infants. Centers for Disease Control and Prevention investigators have studied the changing epidemiology of invasive EOS for several decades. The Active Bacterial Core surveillance (ABCs) network, a collaboration between the Centers for Disease Control and Prevention, state health departments, and universities, was established in 1995 to address emerging infectious diseases of public health importance, including infections due to major neonatal pathogens.1,2 ABCs data are remarkable because of the geographic distribution and size of the population-based network, laboratory-based identification of cases, linked epidemiologic and laboratory data, and surveillance over many years. In this issue of Pediatrics , Schrag and colleagues3 present ABCs data on the epidemiology of early-onset neonatal sepsis collected over a recent 10-year period, with special attention to group B streptococcal (GBS) and Escherichia coli infections. Invasive GBS infection among neonates, identified in the 1960s,4 emerged as the most common cause of EOS, with high risk of morbidity and mortality. National guidelines … Address correspondence to Barbara J. Stoll, MD, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St, MSB G.150, Houston, TX 77030. E-mail: barbara.j.stoll{at}uth.tmc.edu

Maternal colonization of group B streptococcus: prevalence, associated factors and antimicrobial resistance.

BACKGROUND AND OBJECTIVESGroup B streptococcus (GBS, Streptococcus agalactiae) can be transferred during delivery to neonates from mothers who are colonized with GBS in the genital tract. GBS can cause sepsis and meningitis in newborns. This study was conducted to determine GBS colonization rates among pregnant women and the antibiotic sensitivity patterns.DESIGN AND SETTINGProspective descriptive study at the Maternity and Children Hospital, Makkah.PATIENTS AND METHODSVaginal swabs from 1328 pregnant women (≥35 weeks of gestation) attending antenatal clinic were cultured in Todd-Hewitt broth supplemented with gentamicin and nalidixic acid. After 36 hours of incubation, subculture was made onto sheep blood agar and incubated in 5% carbon dioxide for 18 to 24 hours. A Microscan Walk Away system was used for the identification and antibiotic susceptibility of GBS isolates. Each isolate was also tested for group B by using latex slide agglutination test. Information such as maternal age, gestational age and parity was collected using a predesigned questionnaire.RESULTSThe study population ranged between ages 17–47 years. The GBS colonization in all age groups was found to be 13.4%. A higher colonization rate was seen in pregnant women >40 years of age (27.4%). Women with gestational age >42 weeks were colonized (25%) more frequently that women with a gestational age from 41–42 weeks (20.2%). An increased rate of colonization was found in women who delivered >5 times and no colonization in women who delivered once. All GBS isolates were 100% sensitive to penicillin G, ampicillin and vancomycin. Erythromycin and clindamycin showed resistance −15.7% and 5.1%, respectively.CONCLUSIONThe high prevalence of GBS colonization in pregnant women demands for screening in women attending an antenatal clinic so that intrapartum antimicrobial prophylaxis can be offered to all women who are colonized with GBS, thus preventing its transfer to the newborn.

Intestinal Microbiota Development in Preterm Neonates and Effect of Perinatal Antibiotics

To assess the establishment of the intestinal microbiota in very low birthweight preterm infants and to evaluate the impact of perinatal factors, such as delivery mode and perinatal antibiotics. We used 16S ribosomal RNA gene sequence-based microbiota analysis and quantitative polymerase chain reaction to evaluate the establishment of the intestinal microbiota. We also evaluated factors affecting the microbiota, during the first 3 months of life in preterm infants (n = 27) compared with full-term babies (n = 13). Immaturity affects the microbiota as indicated by a reduced percentage of the family Bacteroidaceae during the first months of life and by a higher initial percentage of Lactobacillaceae in preterm infants compared with full term infants. Perinatal antibiotics, including intrapartum antimicrobial prophylaxis, affects the gut microbiota, as indicated by increased Enterobacteriaceae family organisms in the infants. Prematurity and perinatal antibiotic administration strongly affect the initial establishment of microbiota with potential consequences for later health.

Management of the neonate at risk for early-onset Group B streptococcal disease (GBS EOD): new paediatric guidelines in Belgium

Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source of neonatal morbidity and mortality especially in preterm neonates. The identification of neonates with early-onset sepsis is usually based on perinatal risk factors. Clinical signs are aspecific and laboratory tests are not sensitive. Therefore, many clinicians will overtreat at-risk infants. Inappropriate treatment with antibiotics increases the risk for late-onset sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and costs. In 2003, the Belgian Health Council published guidelines for the prevention of perinatal GBS infections. This report presents the Belgian paediatric management guidelines, which have been endorsed by the Belgian and Flemish societies of neonatology and paediatrics. The most imported changes in the 2014 guidelines are the following: recommendations for a lumbar puncture; clarification of normal spinal fluid parameters and blood neutrophil indices corrected for gestation age; specific timing for diagnostic testing after birth; no indication for diagnostic testing in asymptomatic newborns unless additional risk factors; a revised algorithm for management of neonates according to maternal and neonatal risk factors; and premature infants described as those below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the best evidence and on expert opinion when inadequate evidence exists.

Early-Onset Neonatal Sepsis

Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.