Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.

BACKGROUND: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. METHODS: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. RESULTS: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. CONCLUSIONS: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).

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.

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.

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.

Magnitude of neonatal sepsis and its associated factors among neonates admitted to the neonatal intensive care unit in Hawassa Comprehensive Specialized Hospital, Sidama Regional State, Ethiopia, 2020.

BACKGROUND: Neonatal sepsis is one of the most common causes of disease and death among neonates globally. And it made a great contribution to neonatal admission to intensive care units. To mitigate the ongoing neonatal crisis and accomplish the goal of sustainable development through a decrease in neonatal mortality, information from various regions is needed. Despite the considerable burden of neonatal sepsis in our setting, no prior studies were conducted in the study area. So, this study aimed to assess the magnitude and associated factors of neonatal sepsis among neonates admitted to the neonatal intensive care unit at Hawassa University Comprehensive Specialized Hospital, Sidama Regional State, Ethiopia. METHODS: A hospital-based cross-sectional study was carried out among 287 neonates from March 1, 2020, to April 25, 2020. An interviewer-administered structured questionnaire was used to collect the data. The data were cleaned, coded, and entered into Epi Data 3.1 software and exported to Statistical Package for Social Science (SPSS) software version 23.0 for analysis. Binary logistic regression analyses were performed to identify variables having a significant association with neonatal sepsis. A p-value of ≤ 0.05 was considered statistically significant during multivariable logistic regression. RESULTS: The study found that the magnitude of neonatal sepsis was 56%. The mean age of neonates was 3.2(SD±2.2) days. Around two-fifths (39%) of neonates were in the gestational age of <37 completed weeks. A quarter of mothers(25.8%) were delivered through cesarean section. During labor, 251 (87.5%) mothers had ≤4 digital vaginal examinations. Moreover, the finding revealed that mothers who delivered by cesarean section [AOR = 2.13, 95% CI (1.090-4.163)]. neonates who had been resuscitated at birth [AOR = 4.5, 95% CI (2.083-9.707)], and neonates who had NG tube inserted [AOR = 4.29, 95% CI (2.302-8.004)] were found to be significantly associated with neonatal sepsis. CONCLUSIONS: The current study shows that neonatal sepsis was prevalent among more than half of the neonates admitted to the NICU. Therefore, designing strategies to enhance the aseptic techniques of professionals in the provision of care and actively and collaboratively working with cluster health facilities is highly recommended.

Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study.

BACKGROUND: Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition. METHODS: The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as "Confirmed LOS": positive blood culture - microorganism isolated and LOS symptoms, "Unconfirmed LOS": negative blood culture and LOS symptoms, and "Controls" group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression. RESULTS: A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as "Confirmed LOS", and "unconfirmed LOS" cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01-1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07-1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13-10.25). CONCLUSIONS: The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.

Risk factors of multidrug-resistant organisms neonatal sepsis in Surabaya tertiary referral hospital: a single-center study.

BACKGROUND: Bacterial organisms causing neonatal sepsis have developed increased resistance to commonly used antibiotics. Antimicrobial resistance is a major global health problem. The spread of Multidrug-Resistant Organisms (MDROs) is associated with higher morbidity and mortality rates. This study aimed to determine the risk factors for developing MDRO neonatal sepsis in the Neonatal Intensive Care Unit (NICU), dr. Ramelan Navy Central Hospital, in 2020-2022. METHODS: A cross-sectional study was performed on 113 eligible neonates. Patients whose blood cultures were positive for bacterial growth and diagnosed with sepsis were selected as the study sample. Univariate and multivariate analysis with multiple logistic regression were performed to find the associated risk factors for developing multidrug-resistant organism neonatal sepsis. A p-value of < 0.05 was considered significant. RESULTS: Multidrug-resistant organisms were the predominant aetiology of neonatal sepsis (91/113, 80.5%). The significant risk factors for developing MDRO neonatal sepsis were lower birth weight (OR: 1.607, 95% CI: 1.003 - 2.576, p-value: 0.049), history of premature rupture of the membrane (ProM) ≥ 18 (OR: 3.333, 95% CI: 2.047 - 5.428, p-value < 0.001), meconium-stained amniotic fluid (OR: 2.37, 95% CI: 1.512 - 3.717, p-value < 0.001), longer hospital stays (OR: 5.067, 95% CI: 2.912 - 8.815, p-value < 0.001), lower Apgar scores (OR: 2.25, 95% CI: 1.442 - 3.512, p-value < 0.001), and the use of respiratory support devices, such as invasive ventilation (OR: 2.687, 95% CI: 1.514 - 4.771, p-value < 0.001), and non-invasive ventilation (OR: 2, 95% CI: 1.097 - 3.645, p-value: 0.024). CONCLUSIONS: Our study determined various risk factors for multidrug-resistance organism neonatal sepsis and underscored the need to improve infection control practices to reduce the existing burden of drug-resistant sepsis. Low-birth-weight, a maternal history of premature rupture of the membrane lasting more than 18 hours, meconium-stained amniotic fluid, longer hospital stays, a low Apgar score, and the use of ventilators were the risk factors for developing drug-resistant neonatal sepsis.

Late-onset neonatal sepsis was not associated with impaired neurodevelopmental outcome: Results from the EPICE/SHIPS-PT cohort.

AIM: To assess the impact of late-onset neonatal sepsis (LONS) on the cognitive and motor development of five-year-old children who were born very preterm (VPT). METHODS: This study included 327 VPT children from the Portuguese EPICE/SHIPS cohort who attended the neurodevelopment assessment. Neuropsychological tests such as WPPSI-R, MABC-2 and NEPSY-II (language domain) were used to assess the children's cognitive and motor development. Statistical analysis was performed to compare the socio-demographic, clinical and neurodevelopment outcomes of VPT children with and without LONS. Regression analysis adjusted for confounding variables was performed when applicable. RESULTS: Underperformance in intelligence quotient and language development was similar regardless of a neonatal diagnosis of LONS. In contrast, VPT children with LONS had a higher risk of movement difficulties than those without LONS (p = 0.02). However, the association was lost after adjusting for confounders (ß = -0.25; p > 0.05). CONCLUSION: LONS per se was not associated with the risk for poor long-term cognitive or motor outcomes in VPT children. Social-demographic and clinical characteristics assessed during the neonatal period and at the time of neurodevelopment assessment were similar between groups suggesting that social-related factors such as parents' educational level could have mitigated the LONS impact.

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.

Cefotaxime/sulbactam plus gentamicin as a potential carbapenem- and amikacin-sparing first-line combination for neonatal sepsis in high ESBL prevalence settings.

BACKGROUND: Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent concern. Delineation of bacterial and viral sepsis can be challenging, often leading to patients receiving empirical antibiotics without or whilst waiting for a definitive causal diagnosis. Empirical therapy is often dependent on broad-spectrum 'Watch' antibiotics, contributing to further resistance. METHODS: ESBL-producing Enterobacteriaceae clinical isolates found to have caused neonatal sepsis and meningitis underwent a detailed in vitro screening including susceptibility testing, chequerboard combination analysis and hollow-fibre infection model dynamic analyses using combinations of cefotaxime, ampicillin and gentamicin in combination with ß-lactamase inhibitors. RESULTS: Additivity or synergy was found for all antibiotic combinations against seven Escherichia coli and three Klebsiella pneumoniae clinical isolates. Cefotaxime or ampicillin plus sulbactam combined with gentamicin was able to consistently inhibit the growth of ESBL-producing isolates at typical neonatal doses, and the combination cleared the hollow-fibre infection model system of organisms resistant to each agent alone. The combination of cefotaxime/sulbactam and gentamicin was consistently bactericidal at clinically achievable concentrations (Cmax of 180, 60 and 20 mg/L for cefotaxime, sulbactam and gentamicin, respectively). CONCLUSIONS: The addition of sulbactam to cefotaxime or ampicillin to the typical first-line empirical therapy could obviate the need for carbapenems and amikacin in settings with high ESBL-infection prevalence.

Neonatal sepsis in alloimmune hemolytic disease of the fetus and newborn: A retrospective cohort study of 260 neonates.

BACKGROUND: Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. STUDY DESIGN AND METHODS: All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. RESULTS: Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having ≥1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. CONCLUSIONS: Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high.

Prevalence of gram-negative bacteria and their antibiotic resistance in neonatal sepsis in Iran: a systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis, particularly gram-negative (GN) bacteria-induced, is a significant cause of morbidity and mortality in newborns. Healthcare professionals find this issue challenging because of antibiotic resistance. This study aims to combine findings to identify the prevalence of GN bacteria and their antibiotic resistance in Iranian neonates with sepsis. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed through international databases, including (PubMed/MEDLINE, EMBASE, Scopus, and Web of Science), Iranian local databases (Magiran, Iranmedex, Irandoc, Scimed, and SID), and the first 100 records of Google Scholar. Analytical cross-sectional study checklist from the Joanna Briggs Institute (JBI) was used for the quality assessment of included studies. Comprehensive Meta-Analysis Software Version 2 was used to conduct the meta-analysis. The between-study heterogeneity was investigated by I2 statistics. RESULTS: The prevalence of GN bacteria was estimated to be 53.6% [95% CI: 45.9- 61.1: P = 0.362] in Iranian neonates with sepsis, based on 31 studies with a sample size of 104,566. klebsiella pneumoniae (K.pneumonia) (23.2% [95% CI: 17.5-30.0, P < 0.001]) followed by Escherichia coli (E.coli) (13.5% [95% CI: 9.4-18.9, P < 0.001]) were more prevalent among GN bacteria. The highest resistance in K.pneumoniae was observed in Cefixime (80.6%, [95% CI: 56.3-93.1, P = 0.018]). E.coli showed greater resistance to Ampicillin (61.8%, [95% CI: 44.2-76.5, P = 0.188]. The prevalence of GN bacteria in Iranian neonates with sepsis has a decreasing trend based on the year, as shown by a meta-regression model (P < 0.0004). CONCLUSION: GN pathogens, particularly K.pneumoniae, and E.coli, are the leading cause of neonatal sepsis in Iran. GN bacteria showed the highest resistance to Third-generation cephalosporin and Aminoglycosides.

Epidemiology of neonatal sepsis in two neonatal intensive care units in Krakow, Poland in 2016-2017 years.

BACKGROUND: Sepsis in low-birth-weight neonates remains one of the most significant causes of neonatal morbidity and mortality. Approximately 3 million newborns suffer from sepsis globally every year. The aim of this study was to compare demographic and clinical features, as well as etiology and antibiotic susceptibility, of the main pathogens related to neonatal sepsis in two neonatal intensive units during a two-year period. METHODS: We observed early-onset (EO-BSI) and late-onset bloodstream infections (LO-BSI) cases in two high-reference neonatal intensive care units (NICU) over a 24-month period (2016-2017). Samples of patients' blood were tested for the presence of the microorganisms. All bacterial isolates were tested for susceptibility to antibiotics. RESULTS: The majority of sepsis cases weighed above 1000 g and were born by cesarean section. About 10% of the EO-BSI group died. There were differences in the EO-BSI /LO-BSI ratio in the compared wards due to differences among the admitted children. The most common pathogens isolated from blood were coagulase-negative staphylococci (CoNS) were represented by two dominating species: S. epidermidis and S. haemolyticus, followed by Klebsiella spp. strains and E.coli, which were mostly found in EO-BSI cases. No single S. agalactiae (GBS) strain was isolated. The majority of CoNS strains were resistant to methicillin, half were resistant to aminoglycosides, and one-third were resistant to macrolides and lincosamides. Half of the Gram-negative rods were resistant to beta-lactams. CONCLUSIONS: The epidemiology of sepsis in two observed NICUs is comparable to data obtained from other studies with a predominance of methicillin-resistant CoNS in LO-BSI and beta-lactam resistant E. coli in EO-BSI. It is of importance that the campaign for controlling GBS carriage in pregnant women in Poland resulted in the disappearance of GBS as a cause of sepsis. Unfortunately, there are no such measures to control E.coli related sepsis.

Incidence of neonatal sepsis after universal antenatal culture-based screening of group B streptococcus and intrapartum antibiotics: A multicentre retrospective cohort study.

OBJECTIVE: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP). DESIGN: Retrospective cohort study. SETTING: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong. POPULATION: 460 552 women attending routine antenatal service from 2009 to 2020. METHODS: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database. MAIN OUTCOME MEASURES: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli). RESULTS: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS. CONCLUSIONS: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred.

Global, regional, and national burden of neonatal sepsis and other neonatal infections, 1990-2019: findings from the Global Burden of Disease Study 2019.

To provide an overview of the global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections (NS) and their change trends from 1990 to 2019, based on the data from the 2019 Global Burden of Disease study. This was a retrospective demographic analysis based on aggregated data. Annual incident cases, deaths, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and their percentage changes of NS during 1990-2019 were collected from the 2019 Global Burden of Disease study. Globally, the incident cases of NS increased by 12.79% (from 5.59 million in 1990 to 6.31 million in 2019), and the deaths decreased by 12.93% (from 0.26 million in 1990 to 0.23 million in 2019). In the globe, the ASIR of NS per 100,000 population increased by 14.35% (from 85.21 in 1990 to 97.43 in 2019), and the ASMR decreased by 11.91% (from 3.97 in 1990 to 3.5 in 2019). CONCLUSION: Increasing trends in incidence and decreasing trends in mortality of NS were observed worldwide from 1990 to 2019. More robust epidemiological research and effective health strategies are urgently needed to reduce the disease burden of neonatal sepsis worldwide. WHAT IS KNOWN: • Neonatal sepsis has significant impacts on neonatal health, but estimates on the global burden and trends of neonatal sepsis are scarce and existing findings vary considerably. WHAT IS NEW: • Globally, there were 6.31 million incident cases of neonatal sepsis and 0.23 million deaths due to neonatal sepsis. • Increasing trends in incidence and decreasing trends in mortality of neonatal sepsis were observed worldwide from 1990 to 2019, with the highest absolute burden in sub-Saharan Africa and Asia.

Trends and spatial distribution of neonatal sepsis, Uganda, 2016-2020.

BACKGROUND: In Uganda, sepsis is the third-leading cause of neonatal deaths. Neonatal sepsis can be early-onset sepsis (EOS), which occurs ≤ 7 days postpartum and is usually vertically transmitted from the mother to newborn during the intrapartum period, or late-onset sepsis (LOS), occurring 8-28 days postpartum and largely acquired from the hospital environment or community. We described trends and spatial distribution of neonatal sepsis in Uganda, 2016-2020. METHODS: We conducted a descriptive incidence study using routinely-reported surveillance data on in-patient neonatal sepsis from the District Health Information System version 2 (DHIS2) during 2016-2020. We calculated incidence of EOS, LOS, and total sepsis as cases per 1,000 live births (LB) at district (n = 136), regional (n = 4), and national levels, as well as total sepsis incidence by health facility level. We used logistic regression to evaluate national and regional trends and illustrated spatial distribution using choropleth maps. RESULTS: During 2016-2020, 95,983 neonatal sepsis cases were reported, of which 71,262 (74%) were EOS. Overall neonatal sepsis incidence was 17.4/1,000 LB. EOS increased from 11.7 to 13.4 cases/1,000 LB with an average yearly increase of 3% (p < 0.001); LOS declined from 5.7 to 4.3 cases/1,000 LB with an average yearly decrease of 7% (p < 0.001). Incidence was highest at referral hospitals (68/1,000 LB) and lowest at Health Center IIs (1.3/1,000 LB). Regionally, total sepsis increased in Central (15.5 to 23.0/1,000 LB, p < 0.001) and Northern regions (15.3 to 22.2/1,000 LB, p < 0.001) but decreased in Western (23.7 to 17.0/ 1,000 LB, p < 0.001) and Eastern (15.0 to 8.9/1,000, p < 0.001) regions. CONCLUSION: The high and increasing incidence of EOS in Uganda suggests a major gap in sepsis prevention and quality of care for pregnant women. The heterogenous distribution of neonatal sepsis incidence requires root cause analysis by health authorities in regions with consistently high incidence. Strengthening prevention and treatment interventions in Central and Northern regions, and in the most affected districts, could reduce neonatal sepsis. Employment of strategies which increase uptake of safe newborn care practices and prevent neonatal sepsis, such as community health worker (CHW) home visits for mothers and newborns, could reduce incidence.

Prevalence and determinants of early onset neonatal sepsis at two selected public referral hospitals in the Northwest Ethiopia: a cross-sectional study.

INTRODUCTION: Globally, neonatal mortality is decreasing, and road maps such as the Early Newborn Action Plan set ambitious targets for 2030. Despite this, deaths in the first weeks of life continue to rise as a percentage of total child mortality. Neonatal sepsis with early onset continues to be a significant cause of death and illness. The majority of sepsis-related deaths occur in developing nations, where the prevalence and causes of newborn sepsis are yet unknown. As a result, the goal of this study was to determine the prevalence of early-onset sepsis and identify determinant factors. METHODS: A cross-sectional study was conducted on 368 study participants in referral hospitals of East and West Gojjam Zones from March 1st to April 30th, 2019. Study participants were selected at random using lottery method. Face-to-face interviews with index mothers for maternal variables and neonatal record review for neonatal variables were used to collect data using a structured pretested questionnaire. Data were entered into Epidata 3.1 and then exported to STATA/SE software version 14. Finally, the logistic regression model was used for analysis. Statistical significance was declared at P < 0.05 after multivariable logistic regression. RESULTS: A total of 368 newborns and their index mothers took part in this study. The mean age of the newborns was 4.69 days (± 1.93SD). Early-onset neonatal sepsis was seen in 34% of the babies. Nulliparity (AOR: 3.3, 95% CI: 1.1-9.5), duration of labor > 18 h after rupture of membranes (AOR: 11.3, 95% CI: 3.0-41.8), gestational age of 32-37 weeks (AOR: 3.2, 95% CI: 1.2-8.5), and neonates who require resuscitation at birth (AOR: 4, 95% CI: 1.4 -11.8) were all found to be significantly associated with early-onset neonatal sepsis. CONCLUSION AND RECOMMENDATION: Early-onset neonatal sepsis was found to be high in this study. Early-onset neonatal sepsis was found to be associated with maternal, obstetric, and neonatal variables. Comprehensive prevention strategies that target the identified risk factors should be implemented right away.

Prevalence and antibiotic resistance pattern of bacteria from sepsis suspected neonates at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

BACKGROUND: Neonatal sepsis is the major cause of neonatal mortality and morbidity, especially in low and middle-income countries. Continuous monitoring of pathogens and their antibiotic resistance pattern is crucial for managing neonatal sepsis. This study aimed to determine neonatal sepsis due to bacteria, antibiotic resistance patterns, associated risk factors and patient outcomes at St. Paul's Hospital Millennium Medical College. METHOD: An institutional-based cross-sectional study was conducted on 400 neonates suspected of sepsis at St. Paul's Hospital Millennium Medical College from March 2020 to July 2020. A questionnaire was used to collect socio-demographic information, clinical parameters and potential risk factors from study participants. About 2ml of blood was drawn aseptically and inoculated into Tryptone Soya Broth at the patient's bedside. Bacterial identification was performed by using standard microbiological techniques. The disk diffusion method was used to determine the antibiotic susceptibility patterns of each isolated bacteria. Data entry and analysis were done using Statistical Package for Social Sciences (SPSS) version 20 software. Bivariate and multivariable logistic regressions were used to assess associated risk factors of neonatal sepsis. A p-value less than 0.05 was considered statically significant with a 95% confidence interval. RESULTS: The overall prevalence of neonatal septicemia was 21% (84/400). Of these, 67 (79.8%) and 17 (20.2%) were gram-negative and gram-positive bacteria, respectively. Klebsiella spp, 37 (44%), E. coli 19 (21.6%) and Coagulase negative Staphylococci 13 (15.47%) were the leading cause of neonatal sepsis. Ciprofloxacin and amikacin were the most effective antibiotics for gram-negative and gram-positive bacteria. Multidrug resistance was observed in 84% of the bacterial isolates. Low birth weight and preterm were associated with neonatal septicemia (AOR = 49.90, 95% CI = 15.14-123.081, P = 0.002) and (AOR = 18.20, 95% CI = 6.835-27.541, P = 0.004) respectively. CONCLUSION: Klebsiella spp and E. coli were frequently isolated bacteria in our study. The proportion of multidrug-resistance was significantly high. Most isolated bacteria were resistant to ampicillin, ceftazidime, cefotaxime and gentamycin, which indicates the necessity of continuous evaluation of antibiotic resistance rate.

The Effect of Neonatal Sepsis on Risk of Autism Diagnosis.

OBJECTIVE: The study aimed to examine the association between neonatal sepsis and autism risk among children and whether the risk varied with the timing of exposure, child's sex, and race/ethnicity. STUDY DESIGN: We conducted a retrospective cohort study using electronic health records (EHR) extracted from Kaiser Permanente Southern California Health Care System. Mother-child dyads were constructed by linking records of children born to member mothers and continuing to receive care through the system during the follow-up period with those of their biological mothers (n = 469,789). Clinical health records were used to define neonatal sepsis. Diagnosis of autism was made by medical specialists. Potential confounders included maternal sociodemographic factors, obstetrical history, child's age, sex, race/ethnicity, and maternal and child medical history. Incident rates and adjusted hazard ratios (aHR) were used to estimate the associations. RESULTS: Compared with children without the diagnosis of autism, children with the condition were more likely to be from Asian/Pacific Islander descent and male sex. Exposed children showed higher rates of autism as compared with unexposed children (3.43 vs. 1.73 per 1,000 person-years, aHR: 1.67-95% confidence interval [CI]: 1.39-2.00). Both preterm (aHR: 1.47; 95% CI: 1.09-1.98) and term (aHR: 1.63; 95% CI: 1.29-2.06) births were associated with increased risk for autism. Although the magnitude of the HRs and incidence ratios for neonatal sepsis to increase autism risk varied between race ethnicities, neonatal sepsis was associated with significantly increased likelihood of autism diagnosis for all race-ethic groups except for Asian/Pacific Islanders. Although neonatal sepsis was associated with significantly increased autism risk for both boys and girls, incident rates and HR point estimates suggested that the effect may be stronger in girls. CONCLUSION: Neonatal sepsis is associated with increased risk of autism diagnosis in preterm- and term-born children. The association was significant for both girls and boys and all race ethnicities except for Asian-Pacific Islanders. KEY POINTS: · Neonatal sepsis is associated with increased risk of autism diagnosis.. · The association was significant in preterm- and term-born children.. · The association was significant for all race/ethnicities except for Asian-Pacific Islanders..