Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study.

BACKGROUND: Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. METHODS: Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. RESULTS: We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period. CONCLUSIONS: The use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Morbidity and Mortality Profile of Neonates Admitted in Neonatal Intensive Care Unit.

BACKGROUND: The neonatal period faces the greatest risk of death as they are vulnerable to sepsis, birth asphyxia, hypoxic injuries etc. A substantial disparity exists in NMR between Nepal and other developed countries and among different provinces of Nepal as well. This study was conducted to describe the pattern of neonatal admission, and immediate hospital outcomes from NICU located in a remote part of Nepal. METHODS: This prospective study was conducted in The Province Hospital, Karnali, Nepal over a period of six months (June 2021 to Dec 2021 AD). The variables used were neonatal age, sex, gestation, birth weight, maternal age, mode and place of delivery. Neonatal morbidities and final outcomes at discharge were recorded in a predesigned proforma. RESULTS: A total of 396 neonates included, the majority were inborn 283(71%), male 241(61%), term 301(76%) and had normal birth weight 279 (70.4%). Neonatal sepsis 188(37.2%), prematurity 95(24%), and birth asphyxia 55(15.2%) were main indications for hospitalization. The majority 337(85%) improved after treatment, while 33(8.3%) died, 12 (3%) left against medical advice and 14(3.5%) cases were referred. Preterm neonates had thrice the risk of mortality than term neonates (OR =3.27). Low birth weight (< 2500 grams) had higher odds of poor outcomes (OR =3.5). Low maternal age (<20 years), prematurity, LBW, mechanical ventilation and inotrope use were predictors of poor outcomes. CONCLUSIONS: Neonatal sepsis, prematurity and perinatal asphyxia were the most common causes of NICU admissions. Mechanical ventilation, inotropes use, extreme prematurity, low birth weight and younger age of the mother were predictors of poor outcome.

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.

Early-onset neonatal sepsis as a risk factor for peri-intraventricular hemorrhage in premature infants.

OBJECTIVE: To assess early-onset sepsis as a risk factor of peri-intraventricular hemorrhage in premature infants born at less than or equal to 34 weeks' gestation and admitted to a neonatal intensive care unit (NICU). METHODS: This retrospective cohort study included premature patients born at less than or equal to 34 weeks' gestation who were admitted to the NICU of a tertiary hospital in southern Brazil, and born from January 2017 to July 2021. Data were collected from patients' medical records. Early-onset sepsis was measured according to the presence or absence of diagnosis within the first 72 hours of life, whereas the outcome, peri-intraventricular hemorrhage, was described as the presence or absence of hemorrhage, regardless of its grade. RESULTS: Hazard ratios were calculated using Cox regression models. A total of 487 patients were included in the study, of which 169 (34.7%) had some degree of peri-intraventricular hemorrhage. Early-onset sepsis was present in 41.6% of the cases of peri-intraventricular hemorrhage, which revealed a significant association between these variables, with increased risk of the outcome in the presence of sepsis. In the final multivariate model, the hazard ratio for early-onset sepsis was 1.52 (95% confidence interval 1.01-2.27). CONCLUSION: Early-onset sepsis and the use of surfactants showed to increase the occurrence of the outcome in premature children born at less than or equal to 34 weeks' gestation. Meanwhile, factors such as antenatal corticosteroids and gestational age closer to 34 weeks' gestations were found to reduce the risk of peri-intraventricular hemorrhage.

Albumin and C-reactive protein as diagnostic markers for neonatal sepsis: a retrospective study.

OBJECTIVE: To assess the applicability of albumin (ALB) and C-reactive protein (CRP) concentrations in the diagnosis of sepsis in neonates on the day of admission, and to help with early identification and intervention in the development of sepsis. METHODS: This retrospective study included all neonates who were admitted to the neonatal intensive care unit from January 2020 to June 2023. We studied 160 full-term neonates, including 80 with sepsis and 80 healthy controls. A multivariate analysis was conducted to evaluate the associations between ALB, CRP, and sepsis. RESULTS: CRP concentrations were significantly higher in neonates with sepsis than in controls (26.5 ± 8.6 vs. 3.6 ± 1.2 ng/L). At a cut-off point of 10.8 ng/L, CRP showed a sensitivity of 74.3% and a specificity of 80%. Moreover, ALB concentrations were significantly lower in neonates with sepsis than in controls (25.4 ± 2.5 g/L vs. 29.2 ± 2.6 g/L). At a cut-off point of 26.8, ALB showed a sensitivity of 75.6% and a specificity of 84.2%. CONCLUSIONS: Our findings suggest that ALB and CRP concentrations on the first day of admission are different between neonates who do and those who do not develop sepsis. Higher CRP concentrations and lower ALB concentrations may indicate an increased risk of sepsis.

[Clinical practice guidelines for meropenem therapy in neonatal sepsis (2024)]. / 美罗培南治疗新生儿脓毒症的临床实践指南（2024年版）.

Meropenem is one of the most widely used special-grade antimicrobial agents in the treatment of neonatal sepsis. However, its irrational use has led to an increasingly severe problem of bacterial multidrug resistance. The guideline was developed following standardized methods and procedures, and provides 12 recommendations specifically addressing 9 clinical issues. The recommendations cover various aspects of meropenem use in neonates, including timing of administration, recommended dosage, extended infusion, monitoring and assessment, antimicrobial adjustment strategies, treatment duration, and treatment strategies for carbapenem-resistant Enterobacteriaceae infections. The aim of the guideline is to provide evidence-based recommendations and guidance for the rational use of meropenem in neonates with sepsis.

Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum ß-lactamase- and carbapenemase-producing bacteria.

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum ß-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.

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.

Stenotrophomonas maltophilia neonatal sepsis: a case report.

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacteria known for causing opportunistic and nosocomial infections in humans. S. maltophilia is an emerging pathogen of concern due to it's increasing prevalence, diverse disease spectrum, intrinsic multi-drug resistance and high mortality rates in immunocompromised individuals. S. maltophilia is a rare cause of neonatal sepsis associated with significant morbidity and mortality. The bacterium's multi-drug resistance poses a considerable challenge for treatment, with various mechanisms contributing to its resistance. CASE PRESENTATION: We report a case involving a 40-h-old male African neonate who exhibited symptoms of neonatal sepsis. The blood culture revealed Stenotrophomonas maltophilia, which was sensitive to ciprofloxacin and gentamicin but resistant to other antibiotics. Lumbar puncture for CSF could not be done because the father declined. We treated the newborn with the empirical first-line antibiotics as per the national guideline intravenous ampicillin and gentamicin for six days, and the child recovered fully with a repeated negative blood culture. CONCLUSIONS: This report describes a neonatal sepsis case caused by S. maltophilia, a multi-drug resistant bacteria and a rare cause of neonatal sepsis. We report that early detection of the bacterial and antimicrobial management based on local antibiogram data may be essential for successful patient's management.

The footprint of SARS-COV-2 infection in neonatal late sepsis.

BACKGROUND: Predicting and finding the viral agents responsible for neonatal late-sepsis has always been challenging. METHOD: In this cross-sectional study, which has been done from September 2020 to December 2022, 145 hospitalized neonates suspected to late-onset sepsis alongside routine sepsis workup, were also evaluated for severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) infection, by nasopharyngeal real-time polymerase chain reaction (RT-PCR) or serological tests. RESULT: 145 neonates including 81 girls and 64 boys with a mean age of 12.3 ± 5.9 days and an average hospitalization stay of 23.1 ± 15.4 days were enrolled in the study. While 76.6% of them had negative bacterial culture, 63 patients (43.4%) showed evidence of SARS-COV-2 infection in RT-PCR or serology tests. None of the underlying factors including gender, age, and laboratory investigation had a significant relationship with SARS-COV-2 infection. Similarly, the outcomes of death and length of hospitalization were not different between the two groups with positive and negative SARS-COV-2 RT-PCR (P < 0.05). There was only a significant relationship between radiological changes including reticulonodular pattern, consolidation, pleural effusion, and different types of infiltrations and SARS-COV2 infection. CONCLUSION: Considering the widespread of coronavirus disease 2019 (COVID-19) in newborns, it seems logical to investigate the SARS-COV-2 infection in late-sepsis.

Development of risk prediction nomogram for neonatal sepsis in Group B Streptococcus-colonized mothers: a retrospective study.

Neonatal clinical sepsis is recognized as a significant health problem, This study sought to identify a predictive model of risk factors for clinical neonatal sepsis. A retrospective study was conducted from 1 October 2018 to 31 March 2023 in a large tertiary hospital in China. Neonates were divided into patients and controls based on the occurrence of neonatal sepsis. A multivariable model was used to determine risk factors and construct models.The utilization and assessment of model presentation were conducted using Norman charts and web calculators, with a focus on model differentiation, calibration, and clinical applicability (DCA). Furthermore, the hospital's data from 1 April 2023 to 1 January 2024 was utilized for internal validation. In the modelling dataset, a total of 339 pairs of mothers and their newborns were included in the study and divided into two groups: patients (n = 84, 24.78%) and controls (n = 255, 75.22%). Logistic regression analysis was performed to examine the relationship between various factors and outcome. The results showed that maternal age < 26 years (odds ratio [OR] = 2.16, 95% confidence interval [CI] 1.06-4.42, p = 0.034), maternal gestational diabetes (OR = 2.17, 95% CI 1.11-4.27, p = 0.024), forceps assisted delivery (OR = 3.76, 95% CI 1.72-5.21, p = 0.032), umbilical cord winding (OR = 1.75, 95% CI 1.32-2.67, p = 0.041) and male neonatal sex (OR = 1.59, 95% CI 1.00-2.62, p = 0.050) were identified as independent factors influencing the outcome of neonatal clinical sepsis. A main effects model was developed incorporating these five significant factors, resulting in an area under the curve (AUC) value of 0.713 (95% CI 0.635-0.773) for predicting the occurrence of neonatal clinical sepsis. In the internal validation cohort, the AUC value of the model was 0.711, with a 95% CI of 0.592-0.808. A main effects model incorporating the five significant factors was constructed to help healthcare professionals make informed decisions and improve clinical outcomes.

Relevance and antimicrobial resistance profile of Klebsiella pneumoniae in neonatal sepsis.

BACKGROUND: Newborns are particularly susceptible to infection in hospitals, with neonatal sepsis being the most common infection symptom and the third leading cause of neonatal death. Klebsiella pneumoniae is a gram-negative bacterium of Enterobacteriaceae, which is a common pathogen of neonatal septicemia. In this study, we will analyze and evaluate the current status, clinical characteristics, and drug resistance of Klebsiella pneumoniaesepsis infection in Neonatal Intensive Care Unit (NICU), with the aim of providing effective basis for timely and accurate clinical diagnosis and treatment in clinical practice. METHODS: Statistical analysis was performed on 75 cases of Enterobacteriaceae septicemia in infants admitted to NICU in a special obstetrics and gynecology hospital in Shanghai from January 2020 to June 2022. Based on bacterial identification, isolates were divided into the Klebsiella pneumoniae (KP) group (n = 49) and the non-KP Enterobacteriaceae group (n = 26). The infection, clinical characteristics, and bacterial resistance of the two groups of infected patients were compared. RESULTS: Comparing the clinical characteristics of the two groups, the results showed that most of the subjects in the KP and non-KP groups were premature infants, accounting for 100% and 92.3% of subjects, respectively; late onset was the main disease in both groups, accounting for 93.9% and 80.8% of subjects, respectively. All patients received Peripherally Inserted Central Catheter(PICC). The levels of pro calcitonin and CRP (C-reactive protein) were significantly higher in the KP group compared with those in the non-KP group (p < .05). At the same time, the incidence of thrombocytopenia in the KP group was significantly higher than that in the non-KP group (p < .05). The proportion of antimicrobial drug exposure in the KP group is higher than that in the non-KP group. The drug resistance of the KP group to ceftazidime, ceftriaxone, cefepime, ampicillin/sulbactam, aztreonam, ciprofloxacin and compound sulfamethoxazole was significantly higher than that of the non-KP group, whereas the drug resistance rate to cefotetan, gentamycin and to bramycin was significantly lower than that of the non-KP group, Statistically significant differences (p < .05). 38 cases of Klebsiella pneumoniae producing ESBLs were tested for related resistance genes. The results showed that the main resistance types were SHV and TEM, with detection rates of 60.6% and 28.9%. CONCLUSIONS: This study shows that neonatal sepsis caused by Klebsiella pneumoniae infection has a high incidence and drug resistance in premature and low birth weight infants, and has become a serious public health problem; Clinicians should pay attention to differential diagnosis, Reasonable selection of antibiotics to reduce the generation of drug-resistant bacteria.

Late onset neonatal sepsis: Can plasma gelsolin be a promising diagnostic marker?

Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63 ±â€…20.64 vs 451.83 ±â€…209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.

Early procalcitonin assays may reduce antibiotic exposure in premature newborn infants.

AIM: The diagnosis of early-onset neonatal sepsis (EOS) remains difficult. The main aim was to study the effect of a new algorithm for EOS, which includes the level of procalcitonin in umbilical cord blood, on the exposure to antibiotic therapy of premature newborn infants. METHODS: This was a monocentric, observational and retrospective study with before-and-after design. The duration and dose of antibiotic therapy provided as well as the morbidity and mortality were compared in two groups, one included 01 May 2015-30 November 2015 when procalcitonin was not used, and one after the change 01 November 2016-30 May 2017 when procalcitonin was used in a hospital setting in Nice, France. RESULTS: Sixty newborn infants were included in the before group and 54 in the after group. Antibiotic therapy was stopped after 24 h for 18 newborn infants in the after group and four in the before group, and after 48 h for 26 newborn infants in the after group and 10 in the before group. CONCLUSION: The implementation of a new decision-making algorithm including early procalcitonin assay of premature newborn infants significantly reduced exposure to antibiotics without modifying mortality or morbidity.

Application of Advanced Molecular Methods to Study Early-Onset Neonatal Sepsis.

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S-23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings.

Efficacy and safety of short- vs. standard-course antibiotics for culture-negative neonatal sepsis: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis of evidence from randomized controlled trials (RCTs) comparing a short course of antibiotics (2-4 days), to a standard course (5-7 days), for the treatment of culture-negative neonatal sepsis. METHODS: Relevant databases were searched for RCTs comparing short- vs. standard-course of antibiotics for culture-negative sepsis. The primary outcomes were mortality and treatment failure, defined as the reappearance of clinical signs suggestive of sepsis within 7 days of stoppage of antibiotics. Secondary outcomes included neurological impairment, duration of hospital stay, need for oxygen, respiratory support and double-volume exchange transfusion (DVET). RESULTS: Seven RCTs were included in the review with 729 neonates >30 weeks gestational age at birth. No mortality occurred in either of the groups (2 studies; 276 neonates). Treatment failure rates were similar in the short- and standard-course antibiotic groups [7 studies; 729 neonates; risk ratio (RR) = 1.01; 95% confidence interval (CI), 0.55 to 1.86; very low certainty]. The short course of antibiotics resulted in a shorter hospital stay [3 studies; 293 neonates; mean difference (MD), -2.46 days; 95% CI, -3.16 to -1.75]. There was no difference in the need for oxygen supplementation (2 studies; 258 neonates; RR, 1.40; 95% CI, 0.40 to 4.91), any respiratory support (2 studies; 258 neonates; RR, 1.04; 95% CI, 0.92 to 1.17) or DVET (2 studies; 258 neonates; RR, 1.29; 95% CI, 0.56 to 2.95). CONCLUSION: Very-low certainty evidence suggests that a short antibiotic course, compared to a standard course, does not affect treatment failure rates in culture-negative neonatal sepsis. There is a need for well-designed RCTs powered enough to assess critical outcomes such as mortality and neurological sequelae to generate stronger evidence and inform guidelines. PROSPERO REGISTRATION NUMBER: CRD42023437199.

Prolonged antibiotic usage has been associated with increased mortality and morbidity in neonates. The standard practice in culture-negative neonatal sepsis has been to administer antibiotics for 5­7 days, based on expert consensus. In this systematic review, a short course of antibiotics (2­4 days), in comparison to a standard course (5­7 days), did not affect the treatment failure rates in culture-negative neonatal sepsis. However, the certainty of evidence was too low to make robust conclusions. There is a need for well-designed large trials to generate stronger evidence and inform guidelines.

Association between vitamin D receptor gene variants and neonatal sepsis: A systematic review and meta-analysis.

The objective of this systematic review and meta-analysis was elucidating the association of VDR SNPs (FokI, TaqI, BsmI, BgII, and ApaI) with neonatal sepsis. Literature search was performed to retrieve records published until August 2nd, 2023 (PROSPERO registration: CRD42023451355). Meta-analysis was carried out to determine the pooled estimates for Odds Ratio (OR). A total of four studies were included with 500 neonates (250 sepsis cases and 250 healthy controls). There was an association observed between TaqI SNP with neonatal sepsis for CT vs. CC+TT (OR=1.95) and TT vs CT+CC (OR=0.40). Moreover, the pooled estimates also suggested that CC vs. CT+TT (OR= 0.37) and C vs. T (OR=0.66) of FokI SNP were significantly associated with neonatal sepsis. SNP of BgII was found to be significantly associated with neonatal sepsis, but only reported in a single study.

Early detection of late-onset neonatal sepsis from noninvasive biosignals using deep learning: A multicenter prospective development and validation study.

BACKGROUND: Neonatal sepsis is responsible for significant morbidity and mortality worldwide. Its accurate and timely diagnosis is hindered by vague symptoms and the urgent necessity for early antibiotic intervention. The gold standard for diagnosing the condition is the identification of a pathogenic organism from normally sterile sites via laboratory testing. However, this method is resource-intensive and cannot be conducted continuously. OBJECTIVE: This study aimed to predict the onset of late-onset sepsis (LOS) with good diagnostic value as early as possible using non-invasive biosignal measurements from neonatal intensive care unit (NICU) monitors. METHODS: In this prospective multicenter study, we developed a multimodal machine learning algorithm based on a convolutional neural network (CNN) structure that uses the power spectral density (PSD) of recorded biosignals to predict the onset of LOS. This approach aimed to discern LOS-related pathogenic spectral signatures without labor-intensive manual artifact removal. RESULTS: The model achieved an area under the receiver operating characteristic score of 0.810 (95 % CI 0.698-0.922) on the validation dataset. With an optimal operating point, LOS detection had 83 % sensitivity and 73 % specificity. The median early detection was 44 h before clinical suspicion. The results highlighted the additive importance of electrocardiogram and respiratory impedance (RESP) signals in improving predictive accuracy. According to a more detailed analysis, the predictive power arose from the morphology of the electrocardiogram's R-wave and sudden changes in the RESP signal. CONCLUSION: Raw biosignals from NICU monitors, in conjunction with PSD transformation, as input to the CNN, can provide state-of-the-art prediction performance for LOS without the need for artifact removal. To the knowledge of the authors, this is the first study to highlight the independent and additive predictive potential of electrocardiogram R-wave morphology and concurrent, sudden changes in the RESP waveform in predicting the onset of LOS using non-invasive biosignals.

Prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa: a systematic review and meta-analysis.

Objectives: This study aimed to determine the prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa. Methods: This systematic review and meta-analysis used the PRISMA guideline on sepsis data in sub-Saharan Africa. The bibliographic search was carried out on the following databases: Medline/PubMed, Cochrane Library, African Index Medicus, and Google Scholar. Additionally, the reference lists of the included studies were screened for potentially relevant studies. The last search was conducted on 15 October 2022. The Joanna Briggs Institute quality assessment checklist was applied for critical appraisal. Estimates of the prevalence of maternal and neonatal sepsis were pooled using a random-effects meta-analysis model. Heterogeneity between studies was estimated using the Q statistic and the I2 statistic. The funnel plot and Egger's regression test were used to assess the publication bias. Results: A total of 39 studies were included in our review: 32 studies on neonatal sepsis and 7 studies on maternal sepsis. The overall pooled prevalence of maternal and neonatal sepsis in Sub-Saharan Africa was 19.21% (95% CI, 11.46-26.97) and 36.02% (CI: 26.68-45.36), respectively. The meta-analyses revealed that Apgar score < 7 (OR: 2.4, 95% CI: 1.6-3.5), meconium in the amniotic fluid (OR: 2.9, 95% CI: 1.8-4.5), prolonged rupture of membranes >12 h (OR: 2.8, 95% CI: 1.9-4.1), male sex (OR: 1.2, 95% CI: 1.1-1.4), intrapartum fever (OR: 2.4, 95% CI: 1.5-3.7), and history of urinary tract infection in the mother (OR: 2.7, 95% CI: 1.4-5.2) are factors associated with neonatal sepsis. Rural residence (OR: 2.3, 95% CI: 1.01-10.9), parity (OR: 0.5, 95% CI: 0.3-0.7), prolonged labor (OR: 3.4, 95% CI: 1.6-6.9), and multiple digital vaginal examinations (OR: 4.4, 95% CI: 1.3-14.3) were significantly associated with maternal sepsis. Conclusion: The prevalence of maternal and neonatal sepsis was high in sub-Saharan Africa. Multiple factors associated with neonatal and maternal sepsis were identified. These factors could help in the prevention and development of strategies to combat maternal and neonatal sepsis. Given the high risk of bias and high heterogeneity, further high-quality research is needed in the sub-Saharan African context, including a meta-analysis of individual data.Systematic review registration: PROSPERO (ID: CRD42022382050).

The Sensitivity and Specificity of Procalcitonin in Diagnosing Bacterial Sepsis in Neonates.

CONTEXT AND OBJECTIVES: Neonatal sepsis accounts for 15% of all neonatal deaths. Early detection enables prompt administration of antibiotic treatment, reducing morbidity and mortality. This study aims to review the sensitivity and specificity of procalcitonin in diagnosing microbiologically-proven sepsis in neonates to determine the optimal procalcitonin cut-off value for use in clinical practice. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Medline, EMBASE and PubMed were searched on 3 May 2023 for original studies in symptomatic neonates in whom both blood culture and procalcitonin levels were taken, and a procalcitonin cut-off with either sensitivity or specificity reported. Studies that included asymptomatic or culture-negative neonates in the proven sepsis group were excluded. Risk of bias was assessed using the Qualitative Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Nineteen original studies enrolling a total of 1920 symptomatic neonates (721 with proven sepsis) were included. Six studies used a procalcitonin cut-off of 0.5 ng/mL and found a sensitivity of 87% to 100% and specificity of 17% to 89%. Nine studies evaluated higher procalcitonin cut-off values between 0.99 ng/mL and 2 ng/mL, which were 67% to 98% sensitive and 41% to 89% specific. All other procalcitonin thresholds were neither sensitive nor specific. Meta-analysis was not performed because of high risk of bias within the identified studies. CONCLUSIONS: This review found that procalcitonin was highly sensitive (87% to 100%) at a cut-off value of 0.5 ng/mL, although specificity varied greatly across all cut-off values reviewed. The variation in diagnostic accuracy between studies suggests that procalcitonin may be useful to guide antibiotic cessation but should not be used alone as a diagnostic marker for neonatal sepsis.