Analysis of Differences in Neonatal Sepsis Caused by Streptococcus Agalactiae and Escherichia Coli.

BACKGROUND: Streptococcus agalactiae (GBS) and Escherichia coli (E. coli) are the main pathogenic bacteria in neonatal sepsis. Therefore, the clinical characteristics, nonspecific indicators, and drug susceptibilities of these two bacteria were studied. METHODS: In total, 81 and 80 children with sepsis caused by GBS and E. coli infection, respectively, admitted to the neonatal department of our hospital between May 2012 and July 2023, were selected, and the clinical characteris-tics of the two groups were analyzed. Nonspecific indicators and drug sensitivity test results were analyzed retrospectively. RESULTS: Birth weight, tachypnea, groan, tachycardia or bradycardia, and the incidence of complications, such as pneumonia, respiratory failure, and purulent meningitis, were higher in the GBS group than in the E. coli group. The children were born prematurely, and the mother had a premature rupture of membranes. The incidence of jaundice, abdominal distension, atypical clinical manifestations, and complications of necrotizing enterocolitis was lower than of the E. coli group, and the differences were statistically significant (p < 0.05). The WBC, NE#, NE#/LY#, hs-CRP, and PCT of the GBS group were higher than those of the E. coli group, whereas the MPV, D-D, and FDP levels were lower than those in the E. coli group. The differences were all statistically significant (p < 0.05). The 81-bead GBS had high resistance rates against tetracycline (95%), erythromycin (48.8%), and clindamycin (40%), and no strains resistant to vancomycin, linezolid, penicillin, or ampicillin appeared, whereas 80 strains of E. coli were more resistant to penicillin and third-generation cephalosporins, with the higher resistance rates to ampicillin (68.30%), trimethoprim/sulfamethoxazole (53.6%), and ciprofloxacin (42.90%). Resistance rates to carbapenems and aminoglycosides were extremely low. CONCLUSIONS: Both GBS and E. coli neonatal sepsis have specific clinical characteristics, especially in terms of clinical manifestations, complications, non-specific indicators, and drug resistance. Early identification is important for clinical diagnosis and treatment.

Loop-mediated isothermal amplification (LAMP) assay for early on-site detection of Group B Streptococcus infection in neonatal sepsis blood sample.

BACKGROUND: Neonatal sepsis, often attributed to Group B Streptococcus (GBS) infection, poses a critical health risk to infants, demanding rapid and accurate diagnostic approaches. Existing diagnostic approaches are dependent on traditional culture methods, a process that requires substantial time and has the potential to delay crucial therapeutic assessments. METHODS: This study introduces an innovative Loop-Mediated Isothermal Amplification (LAMP) assay for the early on-site detection of GBS infection from neonatal sepsis blood samples. To develop a LAMP assay, the primers are designed for the selective targeting of a highly conserved segment within the cfb gene encoding the CAMP factor in Streptococcus agalactiae ensuring high specificity. RESULTS: Rigorous optimization of reaction conditions, including temperature and incubation time, enhances the efficiency of the LAMP assay, enabling rapid and reliable GBS detection within a short timeframe. The diagnostic efficacy of the LAMP assay was evaluated using spiked blood samples by eliminating the DNA extraction step. The simplified colorimetric LAMP assay has the capability to detect S. agalactiae in a neonatal blood sample containing 2 CFU/mL during sepsis. Additionally, the LAMP assay effectively detected S. agalactiae in both the standard and spiked blood samples, with no detectable interference with blood. CONCLUSION: This optimised LAMP assay emerges as a promising tool for early GBS detection, offering a rapid and accurate on-site solution that has the potential to inform timely interventions and improve outcomes in neonatal sepsis cases.

Factors associated with neonatal sepsis among neonates admitted in Kibungo Referral Hospital, Rwanda.

More than one million neonatal deaths occur every year worldwide, of which 99% take place in low-income countries. In Rwanda, nearly 71% of neonatal deaths are preventable and among these, 10% are due to neonatal sepsis. Nevertheless, limited information exists on neonatal sepsis and its associated factors in Rwanda. The objectives of the study were to find prevalence and factors associated with neonatal sepsis among neonates admitted in Kibungo Referral Hospital, Ngoma District, Rwanda. We used a retrospective cross-sectional study design reviewing a subset of neonatal, maternal and laboratory records from Kibungo Hospital in 2017. Data were reviewed and collected from March to May, 2018. Logistic regression and odds ratios were calculated to identify the factors associated with neonatal sepsis at 95% CI, p < 0.05. Of the 972 total neonates' medical records from 2017, we randomly selected 422 of which 12.8% (n = 54) had neonatal sepsis. When blood cultures were positive, 62% grew Klebsiella pneumoniae. Among neonates with sepsis, 38 (70%) recovered while 16 (30%) died. Neonatal sepsis was strongly associated with neonatal age less than or equal to three days (aOR: 2.769, 95% CI 1.312-5.843; p = 0.008); and gestational age less than 37 weeks (aOR: 4.149; CI 1.1878-9.167; p ≤ 0.001). Increased use of blood cultures including sensitivity testing, routine surface cultures of the neonatology and maternity wards facilities, and systematic ward cleaning are all important approaches to prevent and treat neonatal infections in additional to regular neonatal sepsis evaluations.

Impacts of COVID-19 pandemic on culture-proven sepsis in neonates.

Objective: To assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved. Methods: This retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children's hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016-2019) and during the COVID-19 pandemic Phase II (2020-2022). Results: A total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p < 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p < 0.05) and meningitis (p < 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis. Conclusion: COVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Neonatal sepsis with meningitis, ventriculitis and brain abscess caused by Edwardsiella tarda.

A case of neonatal sepsis caused by Edwardsiella tarda, an uncommon pathogen typically associated with aquatic lifeforms, is described. The infant presented in septic shock with seizures and respiratory failure and was found to have meningitis, ventriculitis and a brain abscess requiring drainage. Only a small number of case reports of neonatal E. tarda infection, several with sepsis with poor auditory or neurodevelopmental outcomes or meningitis, have been described in the literature. This case report suggests that E. tarda, while uncommon, can be a cause of serious central nervous system disease in the neonatal population and that an aggressive approach to pursuing and treating complications may lead to improved neurodevelopmental outcomes.

Neonatal sepsis due to NDM-1 and VIM-2 co-producing Pseudomonas aeruginosa in Morocco.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa are being increasingly described worldwide. Here, we investigated the molecular mechanisms underlying carbapenem resistance in an extremely drug-resistant P. aeruginosa isolate from a neonatal intensive care unit in Morocco. MATERIALS AND METHODS: P. aeruginosa strain O82J1 was identified using MALDI-TOF-MS. Carba NP, immunochromatographic assay NG Carba5 and antimicrobial susceptibility testing using disc diffusion and microbroth were performed. Whole-genome sequencing using the Illumina and MinION technologies and different software packages available at the Center of Genomic Epidemiology were used to predict the resistome, sequence type and plasmid types. RESULTS: P. aeruginosa O82J1 co-expressed two metallo-ß-lactamases, blaNDM-1 and blaVIM-2, and was susceptible to colistin and apramycin only. It belonged to ST773 that is frequently reported worldwide as a high-risk P. aeruginosa clone. The blaVIM-2 gene was integron-borne on a IncP-2 465-kb plasmid, whereas the blaNDM-1 gene was chromosomally encoded and embedded in an integrative conjugative element, probably at the origin of its acquisition. A total of 23 antimicrobial resistance genes were detected including a blaPER-1 ESBL gene, and an 16S-rRNA methyltransferase gene rmtB. CONCLUSIONS: The isolation of XDR P. aeruginosa isolates expressing several carbapenemases in a neonatal intensive care unit is of great concern due to the reduced treatment options, relying only on colistin, but not recommended in neonates, and apramycin, not yet approved for human therapy. Concerns were further elevated due to the resistance to cefiderocol and ATM/AVI, two novel and last-resort antibiotics recommended to treat infections caused by Gram-negative bacteria, particularly XDR P. aeruginosa in adults.

The neonatal gut microbiome and global health.

The role of gut microbiome in health, a century-old concept, has been on the center stage of medical research recently. While different body sites, disease conditions, and populations have been targeted, neonatal and early infancy appear to be the most suitable period for such interventions. It is intriguing to note that, unlike traditional use in diarrhea and maintenance of gastrointestinal health, microbiome-mediating therapies have now addressed the most serious medical conditions in young infants such as necrotizing enterocolitis and neonatal sepsis. Unfortunately, almost all new endeavors in this space have been carried out in the Western world leaving behind millions of neonates that can benefit from such manipulations while serving as a large resource for further learning. In this review, an attempt has been made to quantify the global burden of neonatal morbidity and mortality, examples presented on interventions that have failed as a result of drawing from studies conducted in the West, and a case made for manipulating the neonatal gut microbiome to address the biggest killers in early life. A brief comparative analysis has been made to demonstrate the differences in the gut microbiota of North and South and a large clinical trial of synbiotics conducted by our group in a South Asian setting has been presented. Although challenging, the value of conducting such global health research is introduced with an intent to invite medical scientists to engage in well-planned, scientifically robust research endeavors. This can bring about innovation while saving and serving the most vulnerable citizens now and protecting them from the negative health consequences in the later part of their lives, ultimately shaping a resilient and equitable world as pledged by 193 United Nations member countries in 2015.

High prevalence of multidrug-resistant Enterobacterales carrying extended-spectrum beta-lactamase and AmpC genes isolated from neonatal sepsis in Ahvaz, Iran.

OBJECTIVES: In the recent years, multidrug resistant (MDR) neonatal septicemia-causing Enterobacterales has been dramatically increased due to the extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes. This study aimed to assess the antibiotic resistance pattern, prevalence of ESBLs/AmpC beta-lactamase genes, and Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) fingerprints in Enterobacterales isolated from neonatal sepsis. RESULTS: In total, 59 Enterobacterales isolates including 41 (69.5%) Enterobacter species, 15 (25.4%) Klebsiella pneumoniae and 3 (5.1%) Escherichia coli were isolated respectively. Resistance to ceftazidime and cefotaxime was seen in all of isolates. Furthermore, all of them were multidrug-resistant (resistant to three different antibiotic categories). The phenotypic tests showed that 100% of isolates were ESBL-positive. Moreover, AmpC production was observed in 84.7% (n = 50/59) of isolates. Among 59 ESBL-positive isolates, the highest percentage belonged to blaCTX-M-15 gene (66.1%) followed by blaCTX-M (45.8%), blaCTX-M-14 (30.5%), blaSHV (28.8%), and blaTEM (13.6%). The frequency of blaDHA, blaEBC, blaMOX and blaCIT genes were 24%, 24%, 4%, and 2% respectively. ERIC-PCR analysis revealed that Enterobacterales isolates were genetically diverse. The remarkable prevalence of MDR Enterobacterales isolates carrying ESBL and AmpC beta-lactamase genes emphasizes that efficient surveillance measures are essential to avoid the more expansion of drug resistance amongst isolates.

Neonatal Sepsis Due to Multidrug-resistant Bacteria at a Tertiary Teaching Hospital in Ethiopia.

BACKGROUND: The burden of multidrug-resistant bacterial infections in low-income countries is alarming. This study aimed to identify the bacterial etiologies and antibiotic resistance patterns among neonates in Jimma, Ethiopia. METHODS: An observational longitudinal study was conducted among 238 presumptive neonatal sepsis cases tested with blood and/or cerebrospinal fluid culture. The bacterial etiologies were confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The antibiotic resistance patterns were determined using the automated disc diffusion method (Bio-Rad) and the results were interpreted based on the European Committee on Antimicrobial Susceptibility Testing 2021 breakpoints. Extended-spectrum ß-lactamases were detected using a double disc synergy test and confirmed by Mast discs (Mast Diagnostica GmbH). RESULTS: A total of 152 pathogens were identified. Of these, Staphylococcus aureus (18.4%) was the predominant isolate followed by Klebsiella pneumoniae (15.1%) and Escherichia coli (10.5%). All the isolates exhibited a high rate of resistance to first- and second-line antibiotics ranging from 73.3% for gentamicin to 93.3% for ampicillin. Furthermore, 74.4% of the Gram-negative isolates were extended-spectrum ß-lactamase producers and 57.1% of S. aureus strains were methicillin resistant. The case fatality rate was 10.1% and 66.7% of the deaths were attributable to infections by multidrug-resistant pathogens. CONCLUSIONS: The study revealed a high rate of infections with multidrug-resistant pathogens. This poses a significant challenge to the current global and national target to reduce neonatal mortality rates. To address these challenges, it is important to employ robust infection prevention practices and continuous antibiotic resistance testing to allow targeted therapy.

A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

PURPOSE: To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016. METHODS: A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency. RESULTS: We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates. CONCLUSION: GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

Late Neonatal Sepsis in Very-low-birth-weight Premature Newborns Is Associated With Alterations in Neurodevelopment at Twenty-five Months of Age.

AIM: To evaluate the impact of late-onset sepsis (LOS) on the neurodevelopment of very-low-birth-weight (VLBW) premature infants. METHODS: This is a retrospective cohort study of VLBW premature infants. The Mental Development Index (MDI) was determined for a population of 546 VLBW infants, at 14 and 25 months of age, and evaluated using the Bayley test. A history of meningitis or early neonatal sepsis was considered an exclusion criterion. The study parameters analyzed included perinatal variables, the development of neonatal comorbidities and a history of LOS. Multivariate linear regression and multinomial logistic regression analyses were performed. RESULTS: LOS was observed in 115 newborns, among whom microbiological testing showed that 65.0% presented Gram-positive bacteria, with Staphylococcus epidermidis being responsible for 55.4%. There was a significant association between the 25-month MDI and a history of LOS. This represents a decrease of 7.9 points in the MDI evaluation of newborns with a history of LOS. The latter history is also associated with the following neurodevelopmental alternations: mild motor disorders [odds ratio (OR): 2.75; 95% confidence intervals (CI): 1.07-7.05], moderate cognitive delay (OR: 3.07; 95% CI: 1.17-8.00) and cerebral palsy (OR: 2.41; 95% CI: 1.09-5.35). CONCLUSIONS: In our study cohort, LOS was associated with alterations in neurodevelopment, including reduced MDI, together with motor and cognitive disorders and cerebral palsy. To improve neurodevelopmental outcomes in this group of newborns, neonatal intensive care unit personnel should focus attention on preventing hospital-acquired infections.

Clinical characteristics and risk factors for neonatal bloodstream infection due to carbapenem-resistant Enterobacteriaceae: A single-centre Chinese retrospective study.

OBJECTIVES: To analyse the clinical characteristics and risk factors for bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) in neonates. METHODS: This single-centre, retrospective study included all patients with BSIs admitted to a neonatal intensive care unit between 1 January 2015 and 30 April 2022. The clinical and microbiological data of patients were collected; predictors of 30-day mortality in patients with CRE BSIs were also identified in this study. RESULTS: Among the 224 neonates with Enterobacteriaceae BSIs, 39.29% (88/224) of the patients developed CRE BSIs. The 30-day mortality rate reached up to 21.59% (19/88). The Quick Sequential Organ Failure Assessment score > 2 (odds ratio [OR] and 95% credibility interval [CI]: 3.852 [1.111-13.356], P < 0.05), prior to more than two kinds of antibiotics use (OR and 95% CI: 9.433 [1.562-56.973], P < 0.05), pneumonia (OR and 95% CI: 3.847 [1.133-13.061], P < 0.05), and caesarean section (OR and 95% CI: 2.678 [1.225-5.857], P < 0.05) were independent risk factors associated with CRE BSIs. Moreover, the risk factors for mortality in neonates with CRE BSIs were significantly associated with neonatal Sequential Organ Failure Assessment score > 6 (OR and 95% CI: 16.335 [1.446-184.517], P < 0.05). CONCLUSION: Prior to more than two kinds of antibiotics use, Quick Sequential Organ Failure Assessment score > 2, pneumonia and caesarean section were independent risk factors for CRE BSIs. The Neonatal Sequential Organ Failure Assessment score > 6 was a risk factor for mortality associated with CRE BSIs.

Differential Abundances of Bdellovibrio and Rheinheimera in the Oral Microbiota of Neonates With and Without Clinical Sepsis.

BACKGROUND: Neonatal sepsis is associated with high rates of morbidity and mortality, long hospital stays and high cost of care, thereby inflicting a burden on health care systems. Oral care with breast milk has been shown to modify the intestinal tract microbiota and immune system. Herein, we attempted to identify probiotics that may be beneficial to prevent or treat neonatal sepsis. METHODS: This was a secondary analysis comparing the microbiota during oropharyngeal care in very-low-birth-weight infants with and without clinical sepsis. Oral samples were collected before oral feeding was initiated. The primary outcome was oral microbiota composition including diversity, relative abundance and linear discriminant analysis effect size. RESULTS: Sixty-three neonates, including 39 and 24 with and without clinical sepsis, respectively, were enrolled. The medians gestational age and birth weight were 29 (27-30) weeks and 1010 (808-1263) g. Neonates with clinical sepsis had lower gestational age, birth weight (both P < 0.001) and lower rate of oral care with breast milk ( P = 0.03), but higher doses and days of antibiotic exposure (both P < 0.001) compared to neonates without clinical sepsis. No differences in alpha and beta diversities were found between groups and Streptococcus agalactiae was the most common bacteria in both groups. Linear discriminant analysis effect size analysis revealed that neonates without clinical sepsis had significantly higher abundances of order Bdellovibrionales, family Bdellovibrionaceae, genus Bdellovibrio and genus Rheinheimera . CONCLUSIONS: Neonates without clinical sepsis had a significantly greater abundance of the Bdellovibrio and Rheinheimera genera.

Ten- vs. 14-day antibiotic therapy for culture-positive neonatal sepsis.

BACKGROUND: Neonatal sepsis is a major determinant of neonatal mortality. There is a scarcity of evidence-based guidelines for the duration of antibiotics in culture-positive sepsis. OBJECTIVES: The aim of this study was to compare the efficacy of 10- and 14-day antibiotic therapies in the management of culture-positive neonatal sepsis. METHODS: This randomized controlled trial was conducted in the neonatal intensive care unit of a tertiary care center among the neonates suffering from culture-positive sepsis (with signs of clinical remission on day 9 of antibiotic) between January 2023 and May 2023. Newborns with major congenital anomaly, deep-seated infections, multi-organ dysfunction, associated fungal infections/infection by multiple organisms and severe birth asphyxia were excluded. Two hundred and thirty-four newborns were randomized into two groups-study (received 10 days of antibiotics) and control (received 14 days of antibiotics). Treatment failure, hospital stay and adverse effects were compared between the two groups. p < 0.05 was taken as the limit of statistical significance. RESULTS: Median [interquartile range (IQR)] birth weight and gestational age of the study population (53.8% boys) were 2.424 kg (IQR: 2.183-2.695) and 37.3 weeks (IQR: 35.5-38.1), respectively. Acinetobacter was the most commonly isolated species (56, 23.9%). The baseline characteristics of both groups were almost similar. Treatment failure was similar in the study and control groups (3.8% vs. 1.7%, p = 0.40), with a shorter hospital stay [median (IQR): 14 (13-16) vs. 18 (17-19) days, p < 0.001]. CONCLUSION: Ten-day antibiotic therapy was comparable with 14-day antibiotic therapy in efficacy, with a shorter duration of hospital stay and without any significant increase in adverse effects.

Neonatal sepsis is a major cause of neonatal mortality in developing countries like India. Textbooks recommend 14-day antibiotic treatment for culture-positive neonatal sepsis. However, these guidelines are not strictly evidence based. Prolonged antibiotic treatment might be associated with drug resistance, secondary infections and organ damage. A shorter course of antibiotic, if found effective, would be beneficial especially in the resource-constrained settings like India. Hence, this study was undertaken to compare a shorter duration antibiotic treatment (10 days) with the conventional 14-day antibiotic therapy. Two hundred and thirty-four newborns with culture-positive sepsis were randomized into the study group (received 10 days of antibiotics) and the control group (received 14 days of antibiotics). Socio-demographic characters, clinical and laboratory features and bacteriological profile of both the groups were recorded. Both the groups were comparable in baseline features. Two-thirds of them were suffering from Gram-negative sepsis, Acinetobacter being the most commonly isolated organism. Incidence of treatment failure was similar in the study and control groups. Duration of hospital stay was significantly lower in the study group than in the control group. This observation was true irrespective of gestational age and type of organisms. There were no significant differences in adverse effects between the groups. However, there are certain limitations in the study, and hence, multi-centric research should be undertaken before making generalized recommendations of practising short duration of antibiotics.

Vaginal carriage of Haemophilus influenzae in a non-pregnant reproductive-age population.

BACKGROUND: Haemophilus influenzae (Hi) is an emerging cause of early onset neonatal sepsis, but mechanisms of transmission are not well understood. We aimed to determine the prevalence of vaginal carriage of Hi in reproductive age women and to examine behavioral and demographic characteristics associated with its carriage. METHODS: We performed a secondary analysis of stored vaginal lavage specimens from a prospective cohort study of nonpregnant reproductive-age women. After extraction of bacterial genomic DNA, samples were tested for the presence of the gene encoding Haemophilus protein d (hpd) by quantitative real-time polymerase chain reaction (PCR) using validated primers and probe. PCR for the V3-V4 region of the 16 S rRNA gene (positive control) assessed sample quality. Samples with cycle threshold (CT) value < 35 were defined as positive. Sanger sequencing confirmed the presence of hpd. Behavioral and demographic characteristics associated with vaginal carriage of Hi were examined. RESULTS: 415 samples were available. 315 (75.9%) had sufficient bacterial DNA and were included. 14 (4.4%) were positive for hpd. There were no demographic or behavioral differences between the women with Hi vaginal carriage and those without. There was no difference in history of bacterial vaginosis, vaginal microbiome community state type, or presence of Group B Streptococcus in women with and without vaginal carriage of Hi. CONCLUSION: Hi was present in vaginal lavage specimens of 4.4% of this cohort. Hi presence was unrelated to clinical or demographic characteristics, though the relatively small number of positive samples may have limited power to detect such differences.

Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis.

BACKGROUND: Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. METHODS AND FINDINGS: We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. CONCLUSIONS: A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

Perinatal bacterial colonization and neonatal early-onset sepsis: A case-control study.

BACKGROUND: The utility of determining maternal-neonatal surface colonization as detected by standard microbiological cultures around the time of birth is unclear. The aim of this study is to evaluate the association between maternal and neonatal surface colonization at birth and neonatal early onset sepsis (EOS). OBJECTIVE: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. METHODS: We conducted a case-control study of newborns admitted to the neonatal department of a referral women's and children's hospital from 2009 to 2017. Cases were infants with blood-culture-confirmed EOS (<3 days of life), and controls were infants without EOS randomly chosen based on the cases' date of birth. Maternal genitourinary and neonatal ear swab cultures were used to determine bacterial surface colonization status. RESULTS: Fifty-one infants were diagnosed with EOS during the study period, where Escherichia coli (45%), and Group B Streptococcus (23%) accounted for 68% of infecting organisms. Compared to infants without EOS, those infected were more likely to have surface colonization of the mothers (60% vs 40%, p = 0.048) and infants (90% vs 11%, p < 0.001). In univariate analysis, chorioamnionitis [7.1 (95% CI 2.9, 16.8)], small-for-gestational-age [OR 0.08 (95% CI 0.02, 0.4)], exposure to antibiotics around time of birth [2.3 (95% CI 1.0, 5.1)], maternal surface colonization [2.2 (95% CI 1.0, 4.9)] and neonatal surface colonization [23.5 (95% CI 7.3, 76.1)] were significantly associated with EOS. Adjusting for potential confounders, neonatal colonization remained significantly associated with neonatal EOS [AOR 15.0 (95% CI 3.5, 64.2), p < 0.001]. CONCLUSION: In our setting with predominant Gram-negative EOS, neonatal colonization but not maternal colonization was significantly associated with EOS in the newborn.

Early warning for healthcare acquired infections in neonatal care units in a low-resource setting using routinely collected hospital data: The experience from Haiti, 2014-2018.

In low-resource settings, detection of healthcare-acquired outbreaks in neonatal units relies on astute clinical staff to observe unusual morbidity or mortality from sepsis as microbiological diagnostics are often absent. We aimed to generate reliable (and automated) early warnings for potential clusters of neonatal late onset sepsis using retrospective data that could signal the start of an outbreak in an NCU in Port au Prince, Haiti, using routinely collected data on neonatal admissions. We constructed smoothed time series for late onset sepsis cases, late onset sepsis rates, neonatal care unit (NCU) mortality, maternal admissions, neonatal admissions and neonatal antibiotic consumption. An outbreak was defined as a statistical increase in any of these time series indicators. We created three outbreak alarm classes: 1) thresholds: weeks in which the late onset sepsis cases exceeded four, the late onset sepsis rates exceeded 10% of total NCU admissions and the NCU mortality exceeded 15%; 2) differential: late onset sepsis rates and NCU mortality were double the previous week; and 3) aberration: using the improved Farrington model for late onset sepsis rates and NCU mortality. We validated pairs of alarms by calculating the sensitivity and specificity of the weeks in which each alarm was launched and comparing each alarm to the weeks in which a single GNB positive blood culture was reported from a neonate. The threshold and aberration alarms were the strongest predictors for current and future NCU mortality and current LOS rates (p<0.0002). The aberration alarms were also those with the highest sensitivity, specificity, negative predictive value, and positive predictive value. Without microbiological diagnostics in NCUs in low-resource settings, applying these simple algorithms to routinely collected data show great potential to facilitate early warning for possible healthcare-acquired outbreaks of LOS in neonates. The methods used in this study require validation across other low-resource settings.