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Objectives: To define bacterial aetiology of neonatal sepsis and estimate the prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs., Methods: We carried out a cross-sectional study of newborns with clinical sepsis admitted to three hospitals in the Gambia neonatal wards. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically-matched paired neonatal blood cultures and maternal genital tract bacterial isolates., Results: We enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0-6 after birth) of which 26% (36/137) were because of a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis because of Staphylococcus aureus (n = 5), Klebsiella pneumonia (n = 2), and Enterococcus faecalis (n = 1), phenotypically matched their maternal genital tract isolates. Pairwise single-nucleotide variants comparisons showed differences of 12 to 52 single-nucleotide variants only between maternal and newborn S. aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36)., Conclusions: We found a low prevalence of vertical transmission of maternal genital tract colonization in maternal-newborn pairs for early-onset neonatal sepsis in the West African context. Identifying infection acquisition pathways among newborns is essential to prioritize preventive interventions, which could be targeted at the mother or infection control in the hospital environment, depending on the major pathways of transmission., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Intrauterine infections are an urgent problem of modern neonatology. One of the causes of intrauterine infective foetal lesions is physiological immunosuppression. The purpose of this study is to investigate the cytokine status in newborns infected with perinatal infections, depending on their body weight. The study examined 145 newborns. Taking into account their body weight, they were divided into 2 groups: main and secondary. The study was conducted in the immunological laboratory of the Medical Centre of Marat Ospanov West Kazakhstan Medical University in the city of Aktobe, with the determination of the level of IgM and IgG to the herpes simplex virus (HSV) types 1, 2, cytomegalovirus (CMV), and chlamydia using the MULTISKANASCENT analyser with the "Chemo" T system. The main results of this study are the predominance of the anti-inflammatory component in both normal weight and underweight infants, which is evidence of the Th-cell-mediated immune response prevalence. The applied value of this study lies in the possibility of applying its results in practice to obtain effective methods to counteract the occurrence and development of intrauterine infections., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Listeriosis is caused by the foodborne pathogen Listeria monocytogenes. It can present as a maternal-neonatal infection. We implemented a nationwide prospective cohort and analyzed the features of neonatal listeriosis., Methods: We studied all neonates born alive from mothers with microbiologically proven maternal-neonatal listeriosis enrolled from November 2009 to December 2017. We analyzed presentation, neonatal outcome at discharge, and predictors of severe presentation and outcome., Results: We studied 189 infants; 133 of 189 (70%) had abnormal clinical status at birth, including acute respiratory distress in 106 of 189 (56%). There were 132 of 189 (70%) infants who developed early-onset listeriosis and 12 of 189 (6%) who developed late-onset listeriosis; all presented with acute meningitis. There were 17 of 189 (9%) infants who had major adverse outcomes: 3%, (5 of 189) death; 6% (12 of 189), severe brain injury; and 2% (3 of 189), severe bronchopulmonary dysplasia. Fifteen of 17 infants were born <34 weeks of gestation (P < .0001 vs infants born ≥34 weeks of gestation). Maternal antimicrobial treatment ≥1 day before delivery was associated with a significant decrease in presentation severity for the infant, resulting in significantly fewer inotropic drugs, fluid resuscitation, and mechanical ventilation requirement (odds ratio, 0.23; 95% confidence interval, 0.09-0.51; P < .0001)., Conclusions: Antenatal maternal antimicrobial treatment is associated with reduced neonatal listeriosis severity, justifying the prescription of preemptive maternal antimicrobial therapy when maternal-fetal listeriosis is suspected. Neonatal outcome is better than reported earlier, and its major determinant is gestational age at birth., Clinical Trials Registration: NCT01520597., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Invasive fungal infections remain the leading causes of morbidity and mortality in neonates, especially preterm and very low birth weight infants. Most invasive fungal infections are due to Candida or Aspergillus species, and other fungi are increasingly reported and described. Appropriate identification and treatment are required to augment activity and reduce the toxicity of antifungal drugs. Successful use of antifungals in the vulnerable neonatal population is important for both prevention and treatment of infection. Strategies for prevention, including prophylactic antifungal therapy as well as reducing exposure to modifiable risk factors, like limiting antibiotic exposure, discontinuation of central catheters, and hand hygiene are key techniques to prevent and decrease rates of invasive fungal infections. In conclusion, this is a review of the most common causes, prevention strategies, prophylaxis, and treatment of invasive fungal infections in neonates., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Loss of Paneth cell (PC) function is implicated in intestinal dysbiosis, mucosal inflammation, and numerous intestinal disorders, including necrotizing enterocolitis (NEC). Studies in mouse models show that zinc transporter ZnT2 ( SLC30A2 ) is critical for PC function, playing a role in granule formation, secretion, and antimicrobial activity; however, no studies have investigated whether loss of ZnT2 function is associated with dysbiosis, mucosal inflammation, or intestinal dysfunction in humans. SLC30A2 was sequenced in healthy preterm infants (26-37 wks; n = 75), and structural analysis and functional assays determined the impact of mutations. In human stool samples, 16S rRNA sequencing and RNAseq of bacterial and human transcripts were performed. Three ZnT2 variants were common (>5%) in this population: H 346 Q, f = 19%; L 293 R, f = 7%; and a previously identified compound substitution in Exon7, f = 16%). H 346 Q had no effect on ZnT2 function or beta-diversity. Exon7 impaired zinc transport and was associated with a fractured gut microbiome. Analysis of microbial pathways suggested diverse effects on nutrient metabolism, glycan biosynthesis and metabolism, and drug resistance, which were associated with increased expression of host genes involved in tissue remodeling. L 293 R caused profound ZnT2 dysfunction and was associated with overt gut dysbiosis. Microbial pathway analysis suggested effects on nucleotide, amino acid and vitamin metabolism, which were associated with the increased expression of host genes involved in inflammation and immune response. In addition, L 293 R was associated with reduced weight gain in the early postnatal period. This implicates ZnT2 as a novel modulator of mucosal homeostasis in humans and suggests that genetic variants in ZnT2 may affect the risk of mucosal inflammation and intestinal disease.

Infants admitted to the neonatal intensive care unit, particularly those born preterm, are at high risk for infection due to the combination of an immature immune system, prolonged hospitalization, and frequent use of invasive devices. Emerging evidence suggests that multidrug-resistant gram-negative (MDR-GN) infections are increasing in neonatal settings, which directly threatens recent and ongoing advances in contemporary neonatal care. A rising prevalence of antibiotic resistance among common neonatal pathogens compounds the challenge of optimal management of suspected and confirmed neonatal infection. We review the epidemiology of MDR-GN infections in neonates in the United States and internationally, with a focus on extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE). We include published single-center studies, neonatal collaborative reports, and national surveillance data. Risk factors for and mechanisms of resistance are discussed. In addition, we discuss current recommendations for empiric antibiotic therapy for suspected infections, as well as definitive treatment options for key MDR organisms. Finally, we review best practices for prevention and identify current knowledge gaps and areas for future research. IMPACT: Surveillance and prevention of MDR-GN infections is a pediatric research priority. A rising prevalence of MDR-GN neonatal infections, specifically ESBL-producing Enterobacterales and CRE, compounds the challenge of optimal management of suspected and confirmed neonatal infection. Future studies are needed to understand the impacts of MDR-GN infection on neonatal morbidity and mortality, and studies of current and novel antibiotic therapies should include a focus on the pharmacokinetics of such agents among neonates., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Group B Streptococcus (GBS) is a leading cause of invasive neonatal disease. Epidemiological surveillance of GBS is important to determine cumulative incidence, antimicrobial resistance rates, and maternal and neonatal disease prevention. In this study, we present an update on GBS epidemiology in Alberta, Canada, from 2014 to 2020. Over the 7-year period, 1,556 GBS isolates were submitted to the Alberta Public Health Laboratory for capsular polysaccharide (CPS) typing and antimicrobial susceptibility testing. We analyzed the distribution of CPS types in Alberta and found CPS types III (23.6%), Ia (16.0%), Ib (14.8%), II (13.3%), V (12.7%), IV (12.5%), and VI (2.38%) to be the most prevalent. Less than 1% each of CPS types VII, VIII, and IX were identified. In agreement with historical data, the presence of CPS type IV continued to rise across Alberta, particularly in cases of adult infection, where a 2-fold increase was observed. Cumulative incidences of GBS cases per 100,000 population and late-onset disease per 1,000 live births increased from 4.43 to 5.36 and 0.38 to 0.41, respectively, from 2014 to 2020. However, the incidence of early-onset disease decreased during the 7-year period from 0.2 to 0.07, suggestive of successful intrapartum chemoprophylaxis treatment programs. All GBS isolates were susceptible to penicillin and vancomycin. However, nonsusceptibility to erythromycin increased significantly, from 36.85% to 50.8%, from 2014 to 2020. Similarly, nonsusceptibility to clindamycin also increased significantly, from 21.0% to 45.8%. In comparison to historical data, the overall rates of GBS infection and antimicrobial resistance have increased and the predominant CPS types have changed. IMPORTANCE This work describes the epidemiology of invasive infections caused by the bacterium group B Streptococcus (GBS) in Alberta, Canada. We show that rates of invasive GBS disease have increased from 2014 to 2020 for both adult disease and late-onset disease in neonates, whereas the rate of early onset disease in neonates has decreased. We also show that the rate of resistance to erythromycin (an antibiotic used to treat GBS) has also increased in this time.

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy., (© 2021. The Author(s).)

Introduction: Neonatal septicaemia is one of the most common leading causes of neonatal morbidity and mortality in developing countries. It is estimated to affect more than 30 million people worldwide annually, potentially leading to 6 million deaths., Objective(s): To determine the prevalence, bacteriological profile, antibiotic susceptibility and factors associated with neonatal septicaemia among neonates suspected to sepsis at Kilembe mines hospital., Methods: We conducted a descriptive cross-sectional study, where purposive sampling technique was used and blood was drawn from 122 neonates suspected to sepsis attending Kilembe Mines Hospital during the period (July to November 2020). Specimens were inoculated in Brain heart infusion broth, transported to Fortportal Regional Referral Hospital, plated daily up to 7 days on blood, chocolate, MacConkey agar and incubated in aerobic and 5% carbondioxide. Pure colonies were identified by Gram stain, biochemical tests and antibiotic sensitivities obtained by Kirby Bauer disc diffusion method. Associations were tested using Chi square with Fisher's exact or Yates correction tests where necessary and statistical significance was set at P < 0.05. Stata (version 14) used for statistical analysis., Results: Blood cultures were positive in 59.0% cases with 55.5% male and 44.4% female. EOS was present in 56.9% and LOS 43.1% of the cases. Gram negative (56.9%) organisms were most implicated with neonatal septicaemia than Gram positives ones (43.1%). Gram positive organisms exhibited better susceptibility to amikacin, linezolid and vancomycin but more resistant to ampicillin and gentamicin. Of the aminoglycosides, amikacin exhibited a verge over netilmicin and gentamicin against Gram negative isolates. Risk factors of neonatal septicaemia were mother's age of ≥25 years, employed mothers, tertiary-level of education, SVD, ANC attendance of ≥4 times, UTI during pregnancy, PROMS, foul Smelling liquor, urban residence, neonatal birth weight of ≥2500 g, Apgar score 1st and 5th min ≥6 and resuscitation., Conclusion: Multi-drug resistant organisms were isolated. Therefore caution is required in selection of antibiotic therapy and avoid empirical treatment., (© 2021. The Author(s).)

Background: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257)., Methods: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events., Findings: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment., Interpretation: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome., Funding: Health Research Council of New Zealand, A Better Start - National Science Challenge., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning, and both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or lacking the IL-22 receptor in the intestine display a similar susceptibility to NEC, consistent with the lack of endogenous IL-22 during development. Strikingly, treatment with recombinant IL-22 during NEC substantially reduces inflammation and enhances epithelial regeneration. These findings may provide a new therapeutic strategy to attenuate NEC., Competing Interests: Drs. J.K.K. and M. Good have a patent pending on the use of IL-22 to prevent or treat NEC. Dr. M. Good has received sponsored research agreement funding from Astarte Medical, Evive Biotech, and Takeda Pharmaceuticals. Dr. M. Good also serves on the Scientific Advisory Council of the NEC Society and the Clinical and Technology Advisory Board of Astarte Medical. She also participated in a neonatal microbiome advisory board for Abbott Laboratories in 2019. None of these sources had any role in this study., (© 2021 The Author(s).)

Ureaplasma species are increasingly recognized as relevant pathogens in prenatal, perinatal and postnatal morbidity. They are commonly found as commensals on the mucous membranes of the lower urogenital tract of pregnant women, but when ascending, they can cause bacterial vaginosis, chorioamnionitis, premature birth and postnatal morbidities such as bronchopulmonary dysplasia, and early-onset neonatal sepsis and meningitis. The detection of Ureaplasma species is challenging and is not covered by routine diagnostics, and current empiric antibiotic treatment in neonates suspected of infection is not directed against Ureaplasma species. The aim of this review is to discuss the pathophysiology of Ureaplasma infections, the clinical consequences and the current difficulties in diagnosis and treatment by providing an overview of the current literature., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Neonatal infections contribute substantially to infant mortality in Nigeria and globally. Management requires hospitalization, which is not accessible to many in low resource settings. World Health Organization developed a guideline to manage possible serious bacterial infection (PSBI) in young infants up to two months of age when a referral is not feasible. We evaluated the feasibility of implementing this guideline to achieve high coverage of treatment., Methods: This implementation research was conducted in out-patient settings of eight primary health care centres (PHC) in Lagelu Local Government Area (LGA) of Ibadan, Oyo State, Nigeria. We conducted policy dialogue with the Federal and State officials to adopt the WHO guideline within the existing programme setting and held orientation and sensitization meetings with communities. We established a Technical Support Unit (TSU), built the capacity of health care providers, supervised and mentored them, monitored the quality of services and collected data for management and outcomes of sick young infants with PSBI signs. The Primary Health Care Directorate of the state ministry and the local government led the implementation and provided technical support. The enablers and barriers to implementation were documented., Results: From 1 April 2016 to 31 July 2017 we identified 5278 live births and of these, 1214 had a sign of PSBI. Assuming 30% of births were missed due to temporary migration to maternal homes for delivery care and approximately 45% cases came from outside the catchment area due to free availability of medicines, the treatment coverage was 97.3% (668 cases/6861 expected births) with an expected 10% PSBI prevalence within the first 2 months of life. Of 1214 infants with PSBI, 392 (32%) infants 7-59 days had only fast breathing (pneumonia), 338 (27.8%) infants 0-6 days had only fast breathing (severe pneumonia), 462 (38%) presented with signs of clinical severe infection (CSI) and 22 (1.8%) with signs of critical illness. All but two, 7-59 days old infants with pneumonia were treated with oral amoxicillin without a referral; 80% (312/390) adhered to full treatment; 97.7% (381/390) were cured, and no deaths were reported. Referral to the hospital was not accepted by 87.7% (721/822) families of infants presenting with signs of PSBI needing hospitalization (critical illness 5/22; clinical severe infection; 399/462 and severe pneumonia 317/338). They were treated on an outpatient basis with two days of injectable gentamicin and seven days of oral amoxicillin. Among these 81% (584/721) completed treatment; 97% (700/721) were cured, and three deaths were reported (two with critical illness and one with clinical severe infection). We identified health system gaps including lack of staff motivation and work strikes, medicines stockouts, sub-optimal home visits that affected implementation., Conclusions: When a referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing programme structures in Nigeria with high coverage and low case fatality. To scale up this intervention successfully, government commitment is needed to strengthen the health system, motivate and train health workers, provide necessary commodities, establish technical support for implementation and strengthen linkages with communities., Registration: Trial is registered on Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369., Competing Interests: No competing interest.

Background: Analysis of hospital-acquired bloodstream infection (HA-BSI) trends is important to monitor emerging antimicrobial resistance (AMR) threats and guide empiric antibiotic choices., Methods: A retrospective 10-year review of neonatal HA-BSI was performed at Tygerberg Hospital's neonatal unit in Cape Town, South Africa. Neonatal clinical and laboratory data from 2014 to 2018 (Period 2) was compared with published data from 2009 to 2013 (Period 1)., Results: The neonatal unit's HA-BSI rate declined between periods from 3.9/1000 inpatient-days in Period 1 to 3.3/1000 inpatient-days in Period 2 (p = 0.002). Pathogen yield and blood culture contamination rate were unchanged (11.0% to 10.4%, p = 0.233; 5.1% to 5.3%, p = 0.636 respectively). Gram-negative pathogens predominated (1047/1636; 64.0%); Klebsiella species, Staphylococcus aureus, Serratia marcescens, Enterococcus species and Acinetobacter baumannii were the most frequent pathogens. Extended spectrum beta-lactamase production was observed in 319/432 (73.8%) of Klebsiella species, methicillin resistance in 171/246 (69.5%) of Staphylococcus aureus and extensive drug resistance in 115/137 (83.9%) of Acinetobacter species (2009-2018). The crude mortality rate of neonatal HA-BSI episodes increased from Period 1 to Period 2 from 139/717 (19.4%) to 179/718 (24.9%) (p = 0.014), but HA-BSI attributable mortality remained unchanged (97/139 [69.8%] vs 118/179 [65.9%], p = 0.542). The in-vitro activity of piperacillin-tazobactam and amikacin declined during Period 2 (74.6% to 61.4%; p<0.001)., Conclusion: Although HA-BSI rates declined in the neonatal unit, antimicrobial resistance rates in BSI pathogens remained high. Continuous BSI surveillance is a valuable tool to detect changes in pathogen and AMR profiles and inform empiric antibiotic recommendations for neonatal units in resource-limited settings., Competing Interests: The authors have declared that no competing interests exist.

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

Background: Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018., Methods: GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny., Results: Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons., Conclusions: A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

Listeriosis is a rare and severe foodborne infection caused by Listeria monocytogenes . It manifests as septicemia, neurolisteriosis, and maternal-fetal infection. In pregnancy, it may cause maternal fever, premature delivery, fetal loss, neonatal systemic and central nervous system infections. Maternal listeriosis is mostly reported during the 2nd and 3rd trimester of pregnancy, as sporadic cases or in the context of outbreaks. Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the most associated to maternal-neonatal infections. Here we review the clinical, pathophysiological, and microbiological features of maternal-neonatal listeriosis.

Infants and young children are uniquely susceptible to primary viral and bacterial infections, predisposing them to responses of greater frequency and severity than in adults. Etiologies and manifestations of infections in pediatric patients are often different than those in adults. It can be challenging for clinical laboratories to implement appropriate microbiologic methods for rapid and accurate diagnoses in this population. Laboratorians should be cognizant of the distinctive features of children to provide comprehensive pediatric clinical microbiology services. This article discusses laboratory aspects of several clinically significant pediatric pathogens that cause severe harm to patients and impact public health responses., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Group B Streptococcus (GBS) infections caused by Streptococcus agalactiae is a leading cause of meningitis and sepsis in neonates, with early-onset GBS symptoms emerging during the first week of life and late-onset occurring thereafter. Perinatal transmission of GBS to the neonate through the birth canal is the main factor associated with early-onset neonate infections, while less is understood about the source of late-onset infections., Methods: In this report we describe a case of twin ex-premature infants who presented one month after birth with GBS septicemia. The mother had been appropriately screened at gestational age 35-37 weeks and laboratory methods failed to detect GBS colonization by culture or clinical molecular methods. In attempts to identify and isolate the source of GBS infection, additional surveillance swabs were collected from the mother at the time of neonate admission. Culture and a commercially available, FDA-cleared molecular PCR assay were performed., Results: No GBS was detected from swabs collected from the perianal, thigh/groin or axillary areas. However, expressed breast milk and swabs from the breastmilk pump were positive by both methods. Since simultaneous culture and molecular methods which used breastmilk as a source were performed, investigators ascertained the limit of detection for GBS in breastmilk. The limit of detection was determined to be tenfold lower than that of LIM-broth enriched cultures-the FDA-approved source. Subsequent whole genome sequencing (WGS) analysis of isolates recovered from breastmilk and blood cultures from the infants demonstrated all strains were related and characterized as ST-452. Both infants responded very well to treatment and continued to have no related events or concerns at the two-year follow up appointment., Conclusions: Strain type 452 (capsular type IV) has recently emerged as a hypervirulent strain and has previously been documented as causing GBS infections in elderly populations. Antibiotic therapy resolved both mother and infant infections. Subsequent testing for the presence of GBS in breastmilk samples also showed an absence of bacteria. This is the first report of infant twins late-onset GBS infections caused by the hypervirulent S. agalactiae ST-452 with breastmilk as the source.

Objective: To test the association between exposure to perinatal inflammation - i.e. clinical chorioamnionitis or early-onset neonatal infection - in preterm children without severe neonatal brain injury and neurodevelopmental outcome at 30 months of corrected age (CA)., Design: Cross-sectional study from a French regional cohort of clinical follow-up (SEVE Network)., Patients: One hundred sixty-four surviving neonates without severe brain injury - namely, grade III and IV cerebral hemorrhage and cystic periventricular leukomalacia - and without late-onset neonatal inflammation exposure - namely, late-onset neonatal infection and necrotizing enterocolitis -, born at less than 33 weeks of gestational age from November 2011 to June 2015 and enrolled in the SEVE Network., Main Outcome Measure: Global developmental quotient (DQ) score of the revised Brunet-Lézine scale and its four indices measured by the same neuropsychologist at 30 months of CA., Results: After multivariate analysis, exposure to perinatal inflammation was not found significantly associated with a modification of the global DQ score (coefficient -1.7, 95% CI -4.8 to 1.3; p = 0.26). Exposure to perinatal inflammation was associated with a decrease of the gross motor function DQ score (coefficient -6.0, 95% CI -9.9 to -2.1; p < 0.01) and a decrease of the sociability DQ score (coefficient -5.1, 95% CI -9.2 to -0.9; p = 0.02). Language and visuospatial coordination DQ scores were not affected by exposure to perinatal inflammation., Conclusion: Exposure to perinatal inflammation in preterm children without severe neonatal brain injury is independently associated with decreased motor and social abilities at 30 months of CA., Competing Interests: Declaration of competing interest The authors have stated that they had no interest which might be perceived as posing a conflict or bias., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The perinatal period is crucial to the establishment of lifelong gut microbiota. The abundance and composition of microbiota can be altered by several factors such as preterm delivery, formula feeding, infections, antibiotic treatment, and lifestyle during pregnancy. Gut dysbiosis affects the development of innate and adaptive immune responses and resistance to pathogens, promoting atopic diseases, food sensitization, and infections such as necrotizing enterocolitis (NEC). Recent studies have indicated that the gut microbiota imbalance can be restored after a single or multi-strain probiotic supplementation, especially mixtures of Lactobacillus and Bifidobacterium strains. Following the systematic search methodology, the current review addresses the importance of probiotics as a preventive or therapeutic tool for dysbiosis produced during the perinatal and infant period. We also discuss the safety of the use of probiotics in pregnant women, preterm neonates, or infants for the treatment of atopic diseases and infections.

The microbiome is composed of many organisms and is impacted by an intricate exchange between genetics and environmental factors. The perinatal microbiome influences both the developing fetus and the pregnant person. The purpose of this article is to describe the tests that are currently available for laboratory analysis of the perinatal microbiome in relationship to probiotic interventions. This article focuses on the bacterial component of the microbiome. Although adverse outcomes associated with the perinatal microbiome have been studied, a comprehensive understanding of the physiologic perinatal microbiome is still emerging. Early efforts to influence the perinatal microbiome through probiotics are currently under investigation. Unique terminology is defined, and the microbial composition of perinatal microbiota is summarized. The outcomes of studies of antenatal probiotics are summarized. Microbiome testing and analysis are defined and compared. Implications for perinatal care and probiotics research are presented.

Introduction: Invasive fungal infections are an important cause of morbidity and mortality in infants, particularly in extreme prematurity. Successful systemic treatment requires consideration of antifungal efficacy, safety, and pharmacokinetics, including optimization of dosing in this population., Areas Covered: This review summarizes published pharmacokinetic data on four classes of antifungal agents used in the neonatal population. Alterations in absorption, distribution, drug metabolism and clearance in infants compared to adult populations are highlighted. Additionally, pharmacodynamics, safety, and therapeutic drug monitoring are discussed. Recent advancements in neonatal antifungal pharmacotherapies are examined, with emphasis on clinical application., Expert Opinion: Over the last two decades, published studies have provided increased knowledge on pharmacokinetic considerations in the neonatal population. Future research should focus on filling in the knowledge gaps that remain regarding the benefits and risks of combination antifungal therapy, the rising use of micafungin for invasive candidiasis given its fungicidal activity against polyene and azole-resistant Candida species and its minimal adverse effect profile, and the need for pharmacokinetic and safety data of broad spectrum triazoles, like voriconazole and posaconazole, in infants. Furthermore, efforts should focus on well-designed trials, including population pharmacokinetic studies, to develop dosing recommendations with subsequent implementation into clinical practice.

We report an unusual case of an 11-day-old neonate presenting with haemolacria on a background of sticky conjunctival discharge. This was secondary to Chlamydia pseudomembranous conjunctivitis which responded well to systemic erythromycin. Early appropriate treatment is important to prevent progression of the ophthalmic infection, which could lead to blindness, and to prevent other manifestations of neonatal chlamydial infection, particularly pneumonia, which could be fatal. Management also includes treating the mother and educating about sexually transmitted infections., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: PCRctic is an innovative assay based on 16S rDNA PCR technology that has been designed to detect a single intact bacterium in a specimen of cerebro-spinal fluid (CSF). The assay's potential for accurate, fast and inexpensive discrimination of bacteria-free CSF makes it an ideal adjunct for confident exclusion of bacterial meningitis in newborn babies where the negative predictive value of bacterial culture is poor. This study aimed to stress-test and optimize PCRctic in the "field conditions" to attain a clinically useful level of specificity., Methods: The specificity of PCRctic was evaluated in CSF obtained from newborn babies investigated for meningitis on a tertiary neonatal unit. Following an interim analysis, the method of skin antisepsis was changed to increase bactericidal effect, and snap-top tubes (Eppendorf™) replaced standard universal containers for collection of CSF to reduce environmental contamination., Results: The assay's specificity was 90.5% in CSF collected into the snap-top tubes - up from 60% in CSF in the universal containers. The method of skin antisepsis had no effect on the specificity. All CSF cultures were negative and no clinical cases of neonatal bacterial meningitis occurred during the study., Conclusions: A simple and inexpensive optimization of CSF collection resulted in a high specificity output. The low prevalence of neonatal bacterial meningitis means that a large multi-centre study will be required to validate the assay's sensitivity and its negative predictive value.

Objective: To determine the incidence and the clinical, bacteriological and cerebrospinal fluid characteristics of neonatal meningitis in Lima hospitals., Materials and Methods: An observational, multicenter study was conducted in six hospitals in the city of Lima during 1 year of epidemiological surveillance., Results: The cumulative hospital incidence was 1.4 cases per 1000 live births. A total of 53 cases of neonatal meningitis were included, 34% (18/53) were early and 66% (35/53) late. The associated maternal factors were meconium-stained amniotic fluid and urinary tract infection. Insufficient prenatal check-ups were found in 58.8% (30/51). The most associated neonatal factor was sepsis. The main symptoms were fever, irritability, hypoactivity and respiratory distress. Pleocytosis in cerebrospinal fluid (CSF) was significant, without predominance of polymorphonuclear lymphocytes (PMN), hypoglycorrhagia and proteinorrhagia. The most frequent pathogens isolated were Escherichia coli and Listeria monocytogenes., Conclusions: The hospital incidence of neonatal meningitis was 1.4 per 1000 live births, being ten times higher in preterm infants. Breathing difficulty was the most frequent symptom in the early stage, while fever and irritability in the late stage. CSF showed pleocytosis without predominance of PMN. The most frequent germs were Escherichia coli and Listeria monocytogenes. Ventriculitis and hydrocephalus were the most common neurological complications.

Purpose of Review: Current management approaches for asymptomatic neonates at risk of early onset sepsis remain controversial. Strategies based entirely on clinical observation (SCO, serial clinical observation) have gained consensus., Recent Findings: We briefly compare different strategies for managing asymptomatic newborns suggested in four high-income countries. Then this review details the existing differences in carrying out the SCO in the United Kingdom, the USA, and Italy; the experiences from the studies performed using the SCO; and open questions regarding this strategy. Advantages and limitations of SCO are also discussed. There is a need to assess which symptoms at birth are more predictive of early onset sepsis and therefore require immediate interventions versus those symptoms that can be monitored and re-evaluated., Summary: SCO strategy may require changes in the processes of newborn care at birthing centers. Nonetheless, SCO is safe and is associated with fewer laboratory evaluations and unnecessary antibiotics. Thoughtful and thorough practices related to the care of all newborns will benefit any birthing centre. VIDEO ABSTRACT: http://links.lww.com/MOP/A40.

Fetal and neonatal development represents a critical window for setting a path toward health throughout life. In this review, we focus on intestinal immunity, how it develops, and its implications for subsequent neonatal diseases. We discuss maternal nutritional and environmental exposures that dictate outcomes for the developing fetus. Although still controversial, there is evidence in support of an in utero microbiome. Specific well-intentioned and routine applications of antibiotics, steroids, and surgical interventions implemented before, during, and after birth skew the neonate towards pro-inflammatory dysbiosis. Shortly after birth, a consortium of maternal and environmentally derived bacteria, through cross-talk with the developing host immune system, takes center stage in developing or disrupting immune homeostasis at the intestinal interface. We also examine subsequent immunological cross-talks, which involve neonatal myeloid and lymphoid responses, and their potential impacts on health and disease such as necrotizing enterocolitis and sepsis, especially critical disease entities for the infant born preterm.

Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants.

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide, and the human Ureaplasma species are most frequently isolated from the amniotic fluid and placenta in these cases. Ureaplasma colonisation is associated with infertility, stillbirth, histologic chorioamnionitis, and neonatal morbidities, including congenital pneumonia, bronchopulmonary dysplasia, meningitis and perinatal death. The human Ureaplasma spp. are separated into Ureaplasma urealyticum and Ureaplasma parvum with 14 known serotypes. The small genome has several genes, which code for surface proteins; most significantly the Multiple Banded Antigen (MBA) where an antigenic C-terminal domain elicits a host antibody response. Other genes code for various virulence factors such as IgA protease and urease. Ureaplasma spp. infection is diagnosed by culture and polymerase chain reaction (PCR) and commercial assays are available to improve turnaround time. Microbroth dilution assays are routinely used to test antimicrobial susceptibility of clinical Ureaplasma spp. especially against doxycycline, azithromycin, ofloxacin and josamycin. Resistance to macrolides, fluoroquinolones and tetracyclines has been reported. A concise review of Ureaplasma spp. and their role in pregnancy outcomes, especially preterm birth, offers insight into the early diagnosis and appropriate antibiotic therapy to prevent long-term complications of Ureaplasma spp. infections.

Cataract and uveitis are rare in newborns but potentially blinding. Three newborns with cataract and severe anterior uveitis underwent cataract surgery. Spiroplasma ixodetis was detected in lens aspirates using bacterial 16S-rRNA PCR and transmission electron microscopy. These findings, which suggest maternal-fetal infection, are consistent with previous experimental Spiroplasma-induced cataract and uveitis.

Background: Neonatal antibiotics disturb the developing gut microbiome and are therefore thought to influence the developing immune system, but exact mechanisms and health consequences in later life still need to be elucidated. Therefore, we investigated whether neonatal antibiotics influence inflammatory markers at 1 year of age. In addition, we determined whether health problems during the first year of life, e.g., allergic disorders (eczema and wheezing) or infantile colics, were associated with changes in the circulating immune marker profile at 1 year of age. Methods: In a subgroup ( N = 149) of the INCA-study, a prospective birth-cohort study, a blood sample was drawn from term born infants at 1 year of age and analyzed for 84 immune related markers using Luminex. Associations of antibiotic treatment, eczema, wheezing, and infantile colics with immune marker concentrations were investigated using a linear regression model. The trial is registered as NCT02536560. Results: The use of broad-spectrum antibiotics in the first week of life, was significantly associated with different levels of inflammatory markers including sVCAM-1, sCD14, sCD19, sCD27, IL-1RII, sVEGF-R1, and HSP70 at 1 year of age. Eczema was associated with decreased concentrations of IFNα, IFNγ, TSLP, CXCL9, and CXCL13, but increased concentrations of CCL18 and Galectin-3. Wheezing, independent of antibiotic treatment, was positively associated to TNF-R2 and resistin. Infantile colics were positively associated to IL-31, LIGHT, YKL-40, CXCL13, sPD1, IL1RI, sIL-7Ra, Gal-1, Gal-9, and S100A8 at 1 year of age, independent of early life antibiotic treatment. Conclusion: In this explorative study, we identified that neonatal antibiotics are associated with immunological alterations at 1 year of age and that, independent of the antibiotic treatment, infantile colics were associated with alterations within gut associated markers. These findings support the importance of the first host microbe interaction in early life immune development., (Copyright © 2020 Oosterloo, van't Land, de Jager, Rutten, Klöpping, Garssen, Vlieger and van Elburg.)

We report a case of neonatal meningitis with subdural empyema, caused by Ureaplasma parvum. In this case, diagnosis was made by genus-specific polymerase chain reaction, after regularly used diagnostic techniques failed. This unusual pathogen should be considered in cases that do not respond to therapy and/or where cultures for typical pathogens in neonatal sepsis and meningitis remain negative.

Hospitalized preterm infants receive frequent and often prolonged exposures to antibiotics because they are vulnerable to infection. It is not known whether the short-term effects of antibiotics on the preterm infant gut microbiota and resistome persist after discharge from neonatal intensive care units. Here, we use complementary metagenomic, culture-based and machine learning techniques to study the gut microbiota and resistome of antibiotic-exposed preterm infants during and after hospitalization, and we compare these readouts to antibiotic-naive healthy infants sampled synchronously. We find a persistently enriched gastrointestinal antibiotic resistome, prolonged carriage of multidrug-resistant Enterobacteriaceae and distinct antibiotic-driven patterns of microbiota and resistome assembly in extremely preterm infants that received early-life antibiotics. The collateral damage of early-life antibiotic treatment and hospitalization in preterm infants is long lasting. We urge the development of strategies to reduce these consequences in highly vulnerable neonatal populations.

Background: Worldwide many neonates suffer from bacterial infections. Adequate treatment is important but is associated with prolonged hospitalization for intravenous administration. In older children, oral switch therapy has been proven effective and safe for several indications and is now standard care., Objectives: To evaluate the currently available evidence on pharmacokinetics, safety and efficacy of oral antibiotics and oral switch therapy in neonates (0-28 days old)., Methods: We performed systematic searches in Medline, Embase.com, Cochrane, Google Scholar and Web of Science. Studies were eligible if they described the use of oral antibiotics in neonates (0-28 days old), including antibiotic switch studies and pharmacological studies., Results: Thirty-one studies met the inclusion criteria. Compared with parenteral administration, oral antibiotics generally reach their maximum concentration later and have a lower bioavailability, but in the majority of cases adequate serum levels for bacterial killing are reached. Furthermore, studies on efficacy of oral antibiotics showed equal relapse rates (OR 0.95; 95% CI 0.79-1.16; I2 0%) or mortality (OR 1.11; 95% CI 0.72-1.72; I2 0%). Moreover, a reduction in hospital stay was observed., Conclusions: Oral antibiotics administered to neonates are absorbed and result in adequate serum levels, judged by MICs of relevant pathogens, over time. Efficacy studies are promising but robust evidence is lacking, most importantly because in many cases clinical efficacy and safety are not properly addressed. Early oral antibiotic switch therapy in neonates could be beneficial for both families and healthcare systems. There is a need for additional well-designed trials in different settings., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Neonatal listeriosis is a rare but severe disease manifesting as septicemia and central nervous system (CNS) infections with a high fatality rate of around 20 to 30%. Whole genome sequencing (WGS) is a promising technique for pathogen identification and infection source tracing with its high resolution., Case Presentation: A case of neonatal sepsis with listeriosis was reported with positive blood culture for Listeria monocytogenes. The case was investigated to confirm the vertical transmission of the infection and identify the potential food source of the maternal L. monocytogenes infection using WGS. L. monocytogenes was isolated from the neonate's blood sample the day after caesarean delivery and from the mother's genital and pudenda swab samples 5 days and 13 days after caesarean delivery. WGS showed that the isolate from the neonate was identical to the genome type of the isolates from the mother, with only one of the 4 isolates from the mother differing by one single nucleotide polymorphism (SNP). By WGS, one L. monocytogenes isolate from a ready-to-eat (RTE) meat sample in the patients' community market shared the same sequence type but was ruled out as the cause of infection, with 57 SNP differences to the strain causing the maternal-neonatal infection. The food isolate also carried a novel plasmid pLM1686 that harbored heavy metal resistance genes. After caesarean section, the mother was treated with a third generation cephalosporin which L. monocytogenes is naturally resistant to, which may explain why genital and pudenda swabs were still culture-positive for L. monocytogenes 13 days after delivery., Conclusions: Genital swab culture for L. monocytogenes had been informative in the diagnosis of maternal listeriosis in this case. The high resolution of WGS confirmed the maternal-neonatal transmission of L. monocytogenes infection and ruled out the L. monocytogenes contaminated RTE meat from the local market as the direct source of the mother's infection.

Immediately after birth, newborn babies experience rapid colonization by microorganisms from their mothers and the surrounding environment 1 . Diseases in childhood and later in life are potentially mediated by the perturbation of the colonization of the infant gut microbiota 2 . However, the effects of delivery via caesarean section on the earliest stages of the acquisition and development of the gut microbiota, during the neonatal period (≤1 month), remain controversial 3,4 . Here we report the disrupted transmission of maternal Bacteroides strains, and high-level colonization by opportunistic pathogens associated with the hospital environment (including Enterococcus, Enterobacter and Klebsiella species), in babies delivered by caesarean section. These effects were also seen, to a lesser extent, in vaginally delivered babies whose mothers underwent antibiotic prophylaxis and in babies who were not breastfed during the neonatal period. We applied longitudinal sampling and whole-genome shotgun metagenomic analysis to 1,679 gut microbiota samples (taken at several time points during the neonatal period, and in infancy) from 596 full-term babies born in UK hospitals; for a subset of these babies, we collected additional matched samples from mothers (175 mothers paired with 178 babies). This analysis demonstrates that the mode of delivery is a significant factor that affects the composition of the gut microbiota throughout the neonatal period, and into infancy. Matched large-scale culturing and whole-genome sequencing of over 800 bacterial strains from these babies identified virulence factors and clinically relevant antimicrobial resistance in opportunistic pathogens that may predispose individuals to opportunistic infections. Our findings highlight the critical role of the local environment in establishing the gut microbiota in very early life, and identify colonization with antimicrobial-resistance-containing opportunistic pathogens as a previously underappreciated risk factor in hospital births.

Background: To explore the features and function of gut microbiota in necrotizing enterocolitis patients over 28 gestational age weeks through a case-control study., Methods: Fecal samples from patients with NEC over 28 gestational week age and matched control cases were collected. DNA of the fecal samples was extracted for 16 s rRNA sequencing to estimate the composition of the microbiota. Functional inference analyses were conducted through PICRUSt based on the sequencing raw data., Results: There was no significant difference in the total diversity of microbiota between the fecal samples from the patients with NEC and the controls (P = .40). Propionibacterium was more abundant in the NEC cases than in the controls. Conversely, Lactobacillus, Phascolarctobacterium, and Streptococcus&#95;salivarius were found to be more plentiful in the controls through LEfSe analysis. Functional inference analysis revealed that the xenobiotic biodegradation and metabolic activity was lower in the NEC cases than in the controls (P < .05)., Conclusion: The NEC cohort with a gestational age of over 28 weeks has a different pattern of microbiota compared with the controls. Functional inference analysis indicated that the potential function of the microbiota may also differ between these groups.

Group B Streptococcus (GBS) is one of the most important pathogens for neonates. This study included 69 invasive GBS diseases in neonates, including 7 early-onset disease (EOD), 55 late-onset disease, and 7 very-late-onset disease from 2013 to 2017. A significant reduction of EOD after the deployment of intrapartum antibiotic prophylaxis (IAP) in 2012 was observed. A previously-recognized hypervirulent clone GBS III ST17, accounting for 68% of the overall infections and 71% of the meningitis, was identified among the 69 cases. A novel GBS Ia ST890 emerged, becoming the fourth most common clone. Overall 96% of the invasive GBS infections were caused by serotypes Ia, Ib, and III. We collected 300 GBS isolates from vagina of the healthy pregnant women in 2014 and 2017. The serotype distribution of the maternal colonization isolates was VI (35%), III (21%), V (15%), Ib (13%) and Ia (11%) in 2014, and VI (32%), III (22%), V (16%), Ia (16%), and Ib (8%) in 2017. The most common sequence types were ST1 (32%), ST12 (22%), and ST23 (15%). Serotype diversity of maternal colonization strains did not change between 2014 and 2017. The study provides useful information in surveillance of GBS disease in the era of IAP.

Considerable evidence has shown that intra-amniotic infection with Ureaplasma spp. increases the risk of chorioamnionitis and preterm labor. Ureaplasma spp. are among the smallest organisms, and their isolation is uncommon in routine clinical practice because of their size and high auxotrophy. Although Ureaplasma spp. have been reported as causative agents of preterm birth, they also have a high incidence in vaginal swabs collected from healthy reproductive-age women; this has led to questions on the virulence of Ureaplasma spp. and to them being considered as harmless commensal bacteria. Therefore, many efforts have been made to clarify the pathogenicity of Ureaplasma spp. at the molecular level. Ureaplasma spp. are surrounded by lipoproteins, including multiple-banded antigen. Both multiple-banded antigen and its derivative, that is, the synthetic lipopeptide, UPM-1, induce an inflammatory response in a preterm mice model, which was adequate to cause preterm birth or stillbirth. In this review, we present an overview of the virulence mechanisms of Ureaplasma spp. and treatment of ureaplasma infection during pregnancy to prevent possible serious sequelae in infants. In addition, relevant mechanisms underlying antibiotic resistance in Ureaplasma spp. are discussed. Ureaplasma spp. are naturally resistant against β-lactam antibiotics because of the lack of a cell wall. Azithromycin is one of the effective agents that can control intrauterine ureaplasma infection. In fact, macrolide- and fluoroquinolone-resistant isolates of Ureaplasma spp. have already been observed in perinatal practice in Japan., (© 2019 Japan Society of Obstetrics and Gynecology.)

Objective: To investigate the epidemiology and healthcare factors associated with late-onset neonatal enterococcal infections., Design: Multicentre, multinational retrospective cohort study using prospectively collected infection data from a neonatal infection surveillance network between 2004 and 2016; this was supplemented with healthcare data from a questionnaire distributed to participating neonatal units., Setting: Sixty neonatal units across Europe (UK, Greece, Estonia) and Australia., Patients: Infants admitted to participating neonatal units who had a positive culture of blood, cerebrospinal fluid or urine after 48 hours of life., Results: In total, 414 episodes of invasive Enterococcus spp infection were reported in 388 infants (10.1% of a total 4083 episodes in 3602 infants). Enterococcus spp were the second most common cause of late-onset infection after coagulase-negative Staphylococcus spp and were strongly associated with necrotising enterocolitis (NEC) (adjusted OR 1.44, 95% CI 1.02 to 2.03, p=0.038), total parenteral nutrition (TPN) (adjusted OR 1.34, 95% CI 1.06 to 1.70, p=0.016), increasing postnatal age (per 1-week increase: adjusted OR 1.04, 95% CI 1.02 to 1.06, p<0.001) and decreasing birth weight (per 1 kg increase: adjusted OR 0.85, 95% CI 0.74 to 0.97, p=0.017). There was no evidence that inadequate nurse to patient staffing ratios in high-dependency units were associated with a higher risk of enterococcal infections., Conclusions: Enterococcus spp were the second most frequent cause of late-onset infections. The association between enterococcal infections, NEC and TPN may inform empiric antimicrobial regimens in these contexts and provide insights into reducing these infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Congenital tuberculosis is a rare disease, especially in non-endemic countries. We present a preterm infant who developed congenital tuberculosis in a neonatal intensive care unit (NICU). The male patient, weighing 1140 g was born by cesarean section at 26 weeks gestation. The baby's respiratory condition suddenly deteriorated at 18 days old, and he was diagnosed with congenital tuberculosis after Gram stain revealed "ghost bacilli" in his tracheal aspirate. The mother, who was born in an endemic country, had fever with unknown cause during labor and was diagnosed with miliary tuberculosis after the infant was diagnosed. Both were successfully treated for tuberculosis with a four-drug regimen. The genotyping profiles of Mycobacterium tuberculosis were identical in both mother and baby based on variable number of tandem repeat (VNTR) analysis. The lineage was considered to be East-African Indian. To prevent nosocomial infection in the NICU, 23 potentially exposed infants received isoniazid for 2 months. Two infants showed a transient liver enzyme elevation that seemed to be due to isoniazid. For 10 months after the incident, there were no infants and medical staff who developed tuberculosis. Although the incidence of tuberculosis has steadily decreased in Japan, the percentage of foreign-born individuals has increased yearly, especially those of reproductive age. The evaluation of active tuberculosis should be considered in pregnant women with unexplained fever, history of tuberculosis, or emigration from high-burden areas., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Asymptom of invasive candidiasis (IC) and low positive rate of blood culture lead to delay diagnose of neonatal infection. Serum (1,3)-β-D-glucan (BDG) performs well in adult IC, but its use in neonatal IC is unclear. We evaluated the use of BDG, procalcitonin (PCT), high-sensitive C-reactive protein (hsCRP) or platelet count (PC) in neonatal IC., Methods: We collected the data of neonates admitted to our institute. Eighty neonates were enrolled, and divided into IC group, bacterial infection (BI) group and control (CTRL) group. We analyzed the difference of these indicators between groups, and generated Receiver operator characteristic (ROC) curve. The value of BDG in antifungal therapy efficacy assessment was also investigated., Results: The BDG level was higher in IC group compared with BI and CTRL group. C. albicans lead to significant increase of BDG compared with C. parapsilosis. IC group had highest hsCRP level and lowest PC. PCT level was similar between groups. ROC showed that BDG or hsCRP performs well in neonatal IC, the optimal cut-off for BDG was 13.69 mg/ml. Combined BDG with hsCRP, PCT and PC increased diagnostic value. Serum BDG level was decreased during antifungal treatment., Conclusion: Serum BDG performs well in identification of neonatal IC and in monitoring the antifungal therapy efficacy.

Group B Streptococcus (GBS) is a one of the main causes of perinatal disease, yet the method for GBS detection, broth-enriched culture, is time-consuming and has low sensitivity and accuracy. We aimed to develop a GBS digital PCR (GBS-dPCR) assay for detecting GBS colonization. More rapid and accurate detection of GBS colonization could increase GBS diagnosis and treatment closer to delivery. A single-center, retrospective, case-controlled study was performed. A total of 182 rectovaginal swabs from pregnant women, who were undergoing prenatal screening by broth-enriched culture, were evaluated using GBS-dPCR targeting the cfb gene of GBS. Pregnant women with GBS colonization were followed up for correlation analysis between GBS DNA copy numbers and perinatal outcomes. The results of the GBS-dPCR assay were compared to those from the broth-enriched culture, which is the gold standard for GBS detection. The sensitivity and specificity of GBS-dPCR were 98% and 92.5%, respectively. By discrepant result analysis, the specificity of GBS-dPCR was raised to 97.4%. The incidence of premature rupture of membrane (PROM) and neonatal infection were statistically significantly positively correlated with GBS DNA copy numbers. GBS - dPCR has the advantage of directly detecting GBS colonization from swabs with high specificity and sensitivity, while reducing turnaround time (<4 h). Analysis of clinical samples with GBS-dPCR shows that GBS DNA copy numbers are positively correlated with the incidence of PROM and neonatal infection, suggesting that dPCR is a promising method for detection of GBS colonization during pregnancy.

Probiotics intervention has been proposed as a feasible preventative approach against adverse health-related complications in infants. Nevertheless, the umbrella concept of probiotics has led to a massive application of probiotics in a range of products for promoting infant health, for which the strain-specificity, safety and efficacy findings associated with a specific probiotics strain are not clearly defined. Bifidobacterium breve M-16V is a commonly used probiotic strain in infants. M-16V has been demonstrated to offer potential in protecting infants from developing the devastating necrotising enterocolitis (NEC) and allergic diseases. This review comprehends the potential beneficial effects of M-16V on infant health particularly in the prevention and treatment of premature birth complications and immune-mediated disorders in infants. Mechanistic studies supporting the use of M-16V implicated that M-16V is capable of promoting early gut microbial colonisation and may be involved in the regulation of immune balance and inflammatory response to protect high-risk infants from NEC and allergies. Summarised information on M-16V has provided conceptual proof of the use of M-16V as a potential probiotics candidate aimed at promoting infant health, particularly in the vulnerable preterm population., Competing Interests: The authors, C.B.W., N.I., and J.-Z.X. are employees of Morinaga Milk Industry Co., Ltd., which has several probiotic products marketed worldwide. This does not alter our adherence to Nutrients policies on sharing data and materials.