Neonatal sepsis in a tertiary health facility in Cape Coast, Ghana.

BACKGROUND: Neonatal Sepsis remains a significant burden globally, accounting for over 2.5 million neonatal deaths annually, with low-and middle-income countries (LMIC) including Ghana disproportionately affected. The current study sought to ascertain the prevalence of neonatal sepsis and associated factors based on analysis of institutional records from Cape Coast Teaching Hospital (CCTH) in Ghana. METHODS: The study involved a retrospective cross-sectional review of randomly sampled medical records of 360 neonates CCTH from January 2018 to December 2021. Descriptive proportions and binary logistic regression analysis were conducted to estimate the prevalence of neonates with sepsis and associated factors. RESULTS: The prevalence of neonates with sepsis over the period was estimated to be 59%, with early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) accounting for about 29% and 30%, respectively. Neonatal factors associated with sepsis were low Apgar score (AOR = 1.64; 95% CI:1.01-2.67, p = 0.047) and low birth weight (AOR = 2.54; 95% CI:1.06-6.09, p = 0.037), while maternal factors were maternal education (AOR = 2.65; 95% CI:1.04-6.7, p = 0.040), caesarean deliveries (AOR = 0.45; 95% CI:0.26-0.75, p = 0.003), maternal infection (AOR = 1.79; 95% CI:1.09-2.94, p = 0.020) and foul-smelling liquor (AOR = 1.84; 95% CI:1.09-3.07, p = 0.020). CONCLUSION: The study underscores the need for improved routine care and assessment of newborns to prevent the onset of neonatal sepsis, with particular emphasis on the neonatal and maternal risk factors highlighted in the current study.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes.

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here provide the mechanistic evidence in support of the relevance for these observations. Angiopoetin-1 (Ang-1), which promotes vascular integrity, was decreased in blood plasma of human and murine septic newborns. In preclinical models, administration of Ang-1 provided prophylactic protection from septic death. Arachidonic acid metabolism appears to be functionally connected to Ang-1 via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Strengthening this intersection via oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death while also increasing plasma Ang-1 levels among septic newborns. Our data highlight that targeting angiogenesis-associated pathways with interventions that increase Ang-1 activity directly or indirectly through ROS/eNOS provide promising avenues to prevent and/or treat severe neonatal sepsis.

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.

Herpes virus entry mediator signaling blockade produces mortality in neonatal sepsis through induced cardiac dysfunction.

Introduction: Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is a checkpoint regulator which can both stimulate or inhibit immune responses and demonstrates altered expression after sepsis. We hypothesized that signaling via HVEM would be essential for the neonatal response to sepsis, and that therefore blockade of this pathway would improve survival to septic challenge. Methods: To explore this, neonatal mice were treated with cecal slurry (CS), CS with Anti-HVEM antibody (CS-Ab) or CS with isotype (CS-IT) and followed for 7-day survival. Mice from all treatment groups had thymus, lung, kidney and peritoneal fluid harvested, weighed, and stained for histologic evaluation, and changes in cardiac function were assessed with echocardiography. Results: Mortality was significantly higher for CS-Ab mice (72.2%) than for CS-IT mice (22.2%). CS resulted in dysregulated alveolar remodeling, but CS-Ab lungs demonstrated significantly less dysfunctional alveolar remodeling than CS alone (MCL 121.0 CS vs. 87.6 CS-Ab), as well as increased renal tubular vacuolization. No morphologic differences in alveolar septation or thymic karyorrhexis were found between CS-Ab and CS-IT. CS-Ab pups exhibited a marked decrease in heart rate (390.3 Sh vs. 342.1 CS-Ab), stroke volume (13.08 CS-IT vs. 8.83 CS-Ab) and ultimately cardiac output (4.90 Sh vs. 3.02 CS-Ab) as well as a significant increase in ejection fraction (73.74 Sh vs. 83.75 CS-Ab) and cardiac strain (40.74 Sh vs. 51.16 CS-Ab) as compared to CS-IT or Sham animals. Discussion: While receptor ligation of aspects of HVEM signaling, via antibody blockade, appears to mitigate aspects of lung injury and thymic involution, stimulatory signaling via HVEM still seems to be necessary for vascular and hemodynamic resilience and overall neonatal mouse survival in response to this experimental polymicrobial septic insult. This dissonance in the activity of anti-HVEM neutralizing antibody in neonatal animals speaks to the differences in how septic cardiac dysfunction should be considered and approached in the neonatal population.

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.

Diagnostic capacity of miRNAs in neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis is the third leading cause of mortality during the neonatal period, with manifestations atypical and obscure. But the gold standard-blood culture test, requiring 3-5 days, makes it difficult to unveil the final pathogen and leads to the increasing ratio of false-negative results. The empirical method is consulting traditional biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count. However, they are not specific for neonate in diagnostic capacity, especially for infants within three days after delivery, so more novel biomarkers are urgently needed to assist diagnosing neonatal sepsis. microRNAs (miRNAs) have been widely studied in recent years for their diagnostic and prognostic values in different diseases and we conducted a meta-analysis of miRNAs on the topic that whether they are potentially novel biomarkers in early detection of neonatal sepsis. OBJECTIVES: The purpose of the study was to assess whether circulating miRNAs could be used as potential biomarkers for neonatal sepsis, including early and late-onset neonatal sepsis, then calculate their overall accuracy (OA) via meta-analysis. METHODS: PubMed, Cochrane Library, Embase, Web of Science, Scopus, and Ovid databases were retrieved; data cutoff for this analysis was 15 January 2023. Methodological quality assessment of included studies was performed through the Quality in Prognostic Studies tool. Corresponding 95% confidence interval (95%CI) was calculated to present miRNAs' diagnostic value including the pooled sensitivity (Sen), specificity (Spe), positive or negative likelihood ratios (PLR or NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). Differences in OA between the septic group and non-septic group were compared using Chi-square test. RESULTS: After identification, 16 records out of 11 selected articles were eligible for systematic review of miRNAs and four records for PCT; the case group for miRNAs included 945 neonatal sepsis cases; contrast group included 190 respiratory tract infections or pneumonia cases, 60 systemic inflammatory response syndrome (SIRS) cases and 559 healthy neonates. The pooled Sen, Spe, and DOR of miRNAs were 0.87 (95%CI 0.81-0.91), 0.79 (95%CI 0.71-0.85), and 24 (95%CI 12-50), respectively. The pooled Sen, Spe, and DOR of PCT were 0.92 (95%CI 0.83-0.96), 0.64 (95%CI 0.56-0.70), and 20 (95%CI, 7-56), respectively. The OA value of miRNAs was 80.38% and that of PCT was 77.36%, which were not statistically significant difference (p = .13) after the Chi-square test. In addition, no significant publication bias was indicated (p = .92). CONCLUSIONS: Circulating miRNA levels could be applied as diagnostic biomarkers in neonatal sepsis.

Time to Death and Its Predictors among Neonates Hospitalized with Sepsis in Eastern Ethiopia.

Background: Although neonatal sepsis is a major public health problem contributing to 30-50% of neonatal deaths in low- and middle-income countries, data on predictors of time to death are limited in Eastern Ethiopia. This study is aimed at determining predictors of time to death among neonates with sepsis admitted in public hospitals in Eastern Ethiopia. Methods: An institutional-based retrospective cohort study was conducted among 415 neonates admitted to referral hospitals in Eastern Ethiopia with sepsis from January 1, 2021, to December 31, 2021. Data were collected from medical records by using structured checklist and entered using EpiData 3.1 and analyzed using Stata 17. The Kaplan-Meier curves and log-rank tests were used to describe survival experience among different categories. The proportional hazard assumption and goodness of fit for the Cox regression model were checked. The Cox regression model was used to identify the significant predictors. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. Finally, statistical significance was set at a p value < 0.05 in the Cox regression analysis. Results: Of the 415 neonates with neonatal sepsis, 71 (17.1%) (95% CI: 13.60-21.08) died at discharge, with a median time to death of 14 days. The overall incidence rate of mortality was 36.5 per 1000 neonate days. Low birthweight (AHR = 2.50; 95% CI: 1.15-5.44), maternal age ≥ 35 years (AHR = 3.17; 95% CI: 1.11, 9.04), low fifth-minute Apgar score (AHR: 2.32; 95% CI: 1.30-4.14), and late initiation of breastfeeding (AHR = 4.82; 95% CI: 1.40-16.65) were independent predictors of mortality among neonates with sepsis. Conclusions: Almost one in five neonates with sepsis died at discharge. Low birthweight, maternal age ≥ 35 years, low fifth-minute Apgar score, and late initiation of breastfeeding were predictors of mortality.

Reducing intravenous antibiotics in neonates born ≥35 weeks' gestation: A quality improvement study.

AIM: To assess the impact of the Early Onset Sepsis (EOS) calculator, implemented as a quality improvement study, to reduce the rate of unnecessary antibiotics in neonates born ≥35 weeks' gestation. METHODS: An audit of routinely collected hospital data from January 2008 to March 2014 (retrospective) and from January 2018 to September 2019 (prospective) determined baseline incidence of EOS intravenous antibiotic use in neonates born ≥35 weeks' gestation in a tertiary level perinatal centre. Plan-do-study-act (PDSA) cycles were applied to implement the EOS calculator. Statistical process control methodology and time series analysis assessments were used to assess the potential impact of the PDSA cycles on the rate of intravenous antibiotics, blood culture collection, EOS, length of stay and health care costs (not adjusted for potential confounders). RESULTS: In the study population, from January 2008 to March 2014, the baseline incidence of intravenous antibiotic use was 10.49% (2970/28290), whilst only 0.067% (19/28290) neonates had culture proven EOS. From January 2018 to October 2019, prior to implementation of the EOS calculator, 13.3% (1119/8411) neonates were treated with intravenous antibiotic and the use decreased to 8.3% (61/734) post-implementation. The rate of blood culture collection decreased from 14.4% (1211/8411) to 11.9% (87/734). There were no cases of missed EOS. Length of stay decreased from 2.68 to 2.39 days, with an estimated cost saving of $366 per patient per admission. CONCLUSION: Implementing the EOS calculator in a tertiary hospital setting reduced invasive investigations for EOS and intravenous antibiotic use among neonates ≥35 weeks' gestation. This can result in reduced length of neonatal hospital stays, and associated health care cost savings and may reduce separation of mother and baby.

γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis.

Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.

Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study.

BACKGROUND: Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country. METHODS: This case-control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture. RESULTS: Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml). CONCLUSION: In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).

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.

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.

Short-term variation of the fetal heart rate as a marker of intraamniotic infection in pregnancies with preterm prelabor rupture of membranes: a historical cohort study.

INTRODUCTION: Intraamniotic infection (IAI) and subsequent early-onset neonatal sepsis (EONS) are among the main complications associated with preterm prelabor rupture of membranes (PPROM). Currently used diagnostic tools have been shown to have poor diagnostic performance for IAI. This study aimed to investigate whether the exposure to IAI before delivery is associated with short-term variation of the fetal heart rate in pregnancies with PPROM. METHODS: Observational cohort study of 678 pregnancies with PPROM, delivering between 24 + 0 and 33 + 6 gestational weeks from 2012 to 2019 in five labor units in Stockholm County, Sweden. Electronic medical records were examined to obtain background and exposure data. For the exposure IAI, we used the later diagnosis of EONS in the offspring as a proxy. EONS is strongly associated to IAI and was considered a better proxy for IAI than the histological diagnosis of acute chorioamnionitis, since acute chorioamnionitis can be observed in the absence of both positive microbiology and biochemical markers for inflammation. Cardiotocography traces were analyzed by a computerized algorithm for short-term variation of the fetal heart rate, which was the main outcome measure. RESULTS: Twenty-seven pregnancies were categorized as having an IAI, based on the proxy diagnosis of EONS after birth. Fetuses exposed to IAI had significantly lower short-term variation values in the last cardiotocography trace before birth than fetuses who were not exposed (5.25 vs 6.62 ms; unadjusted difference: -1.37, p = 0.009). After adjustment for smoking and diabetes, this difference remained significant. IAI with a later positive blood culture in the neonate (n = 12) showed an even larger absolute difference in STV (-1.65; p = 0.034), with a relative decrease of 23.5%. CONCLUSION: In pregnancies with PPROM, fetuses exposed to IAI with EONS as a proxy have lower short-term variation of the fetal heart rate than fetuses who are not exposed. Short-term variation might be useful as adjunct surveillance in pregnancies with PPROM.

Evaluation of systemic inflammatory indices in the diagnosis of early onset neonatal sepsis in very low birth weight infants.

BACKGROUND: Previously, not six systemic inflammatory indices were evaluated in the diagnosis of early onset sepsis (EOS) in very low birth weight (VLBW, <1500g) premature infants. OBJECTIVES: We evaluated the effectiveness of systemic inflammatory indices in the diagnosis of EOS in VLBW infants. METHODS: Premature infants with birth weight <1500 g were included in the study. Six systemic inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were compared in patients with EOS (treatment group) and without EOS (control group). RESULTS: Of 917 infants enrolled, 204 infants were in the EOS group and 713 infants comprised the control group. NLR, MLR and SIRI values were significantly higher in the EOS group than in the control group (p < 0.001). The AUC value of SIRI for the predictivity of EOS was 0.803. CONCLUSIONS: The SIRI can be used together with other parameters as both an easily accessible and the reliable systemic inflammatory indices in the diagnosis of EOS in VLBW preterm infants.

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.

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.

Heart rate and oxygen saturation patterns in very low birth weight infants with early onset sepsis and histologic chorioamnionitis.

BACKGROUND: Chorioamnionitis and early onset sepsis (EOS) in very low birth weight (VLBW,< 1500 g) infants may cause a systemic inflammatory response reflected in patterns of heart rate (HR) and oxygenation measured by pulse oximetry (SpO2). Identification of these patterns might inform decisions about duration of antibiotic therapy after birth. OBJECTIVE: Compare early HR and SpO2 patterns in VLBW infants with or without early onset sepsis (EOS) or histologic chorioamnionitis (HC). STUDY DESIGN: Retrospective study of placental pathology and HR and SpO2 in the first 72 h from birth in relation to EOS status for inborn VLBW NICU patients 2012-2019. RESULT: Among 362 VLBW infants with HR and SpO2 data available, clinical, or culture-positive EOS occurred in 91/362 (25%) and HC in 81/355 (22%). In univariate analysis, EOS was associated with higher mean HR, lower mean SpO2, and less negative skewness of HR in the first 3 days after birth. HC was associated with higher standard deviation and skewness of HR but no difference in SpO2. In multivariable modeling, significant risk factors for EOS were mean HR, gestational age, HC, mean SpO2, and skewness of SpO2. CONCLUSION: HR and SpO2 patterns differ shortly after birth in VLBW infants exposed to HC or with EOS, likely reflecting a systemic inflammatory response.

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.

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.