Plasma D-dimer level in early and late-onset neonatal sepsis

BACKGROUND Neonatal sepsis is a life-threatening disease.Early diagnosis is essential,but no single marker of infection has been identified.Sepsis activates a coagulation cascade with simultaneous production of the D-dimers due to lysis of fibrin.Ddimer test reflects the activation of the coagulation system.AIM To assess the D-dimer plasma level,elaborating its clinicopathological value in neonates with early-onset and late-onset neonatal sepsis.METHODS The study was a prospective cross-sectional study that included ninety neonates;divided into three groups:Group I:Early-onset sepsis(EOS);Group II:Late-onset sepsis(LOS);and GroupⅢ:Control group.We diagnosed neonatal sepsis according to our protocol.C-reactive protein(CRP)and D-dimer assays were compared between EOS and LOS and correlated to the causative microbiological agents.RESULTS D-dimer was significantly higher in septic groups with a considerably higher number of cases with positive D-dimer.Neonates with LOS had substantially higher levels of D-dimer than EOS,with no significant differences in CRP.Neonates with LOS had a significantly longer hospitalization duration and higher gram-negative bacteriemia and mortality rates than EOS(P<0.01).Gramnegative bacteria have the highest D-dimer levels(Acinetobacter,Klebsiella,and Pseudomonas)and CRP(Serratia,Klebsiella,and Pseudomonas);while gram-positive sepsis was associated with relatively lower levels.D-dimer had a significant negative correlation with hemoglobin level and platelet count;and a significant positive correlation with CRP,hospitalization duration,and mortality rates.The best-suggested cut-off point for D-dimer in neonatal sepsis was 0.75 mg/L,giving a sensitivity of 72.7%and specificity of 86.7%.The D-dimer assay has specificity and sensitivity comparable to CRP in the current study.CONCLUSION The current study revealed a significant diagnostic value for D-dimer in neonatal sepsis.D-dimer can be used as an adjunct to other sepsis markers to increase the sensitivity and specificity of diagnosing neonatal sepsis.

Prevalence and Predictors of Neonatal Sepsis among Neonates Admitted at the Newborn Unit of Kenyatta National Hospital, Nairobi, Kenya

Background: Neonatal sepsis is one of the primary causes of neonatal morbidity and mortality especially in developing countries. Despite the availability of different preventive interventions, in Kenya, the burden of neonatal sepsis remains critically high. Aim: To determine the prevalence and predictors of neonatal sepsis among newborns admitted at the newborn unit of Kenyatta National Hospital, Kenya. Methods: This is a hospital-based, cross-sectional study design carried out among 196 neonates and their mothers at the new born unit of Kenyatta National Hospital. A systematic random sampling technique was employed to select the study subjects. Data on the possible contributing factors of neonatal sepsis was collected using a semi-structured questionnaire. Statistical analyses were performed using the statistical package for the Social Sciences (SPSS: version 22). Data were descriptively analyzed into frequencies and proportions. The chi-square test of independence and binary logistic regression were employed to determine associations between the dependent (neonatal sepsis) and various independents variables. A multiple logistic regression model was carried out to determine the variables independently contributed to the occurrence of neonatal sepsis. Results: Our study revealed that the prevalence of neonatal sepsis was 28.6%. Neonates born of single mothers (AOR = 5.454, p = 0.012), mothers with history of UTI (AOR = 2.969, p = 0.013), PROM (AOR = 6.124, p = 0.001) and anaemia (AOR = 3.379, p = 0.010) were at higher risk to develop neonatal sepsis. Prematurity (AOR = 6.402, p < 0.001), low Apgar score at 5th minutes (AOR = 8.212, p < 0.001) and history of invasive procedure (AOR = 2.464, p = 0.046) were the neonatal factors independently associated with neonatal sepsis. Conclusion and Recommendations: The prevalence of neonatal sepsis in Kenyatta National Hospital is high. This is another piece of evidence showing both maternal and neonatal-related factor had a significant effect on the risk of neonatal sepsis. Provision of community-based health education is highly recommended to increase awareness of women on the risk factors of neonatal sepsis and their preventive methods such as anaemia and UTI during pregnancy. Healthcare providers should exercise a high standard of care when handling premature and babies with low Apgar score to reduce the risks of neonatal sepsis.

Retrospective Epidemiological Investigation on Nosocomial Neonatal Sepsis in Shaanxi Province (2008-2010)

Objective: This study assessed the incidence, mortality, and pathogens associated with nosocomial neonatal sepsis (NNS) in Shaanxi Province to improve the prevention and control of NNS. Methods: Nine large neonatal departments in Shaanxi Province participated in this retrospective epidemiological investigation of NNS during the period of 2008-2010, using standardized protocol. The incidence, mortality, pathogens, antibiotic sensitivity, clinical characteristics, prognosis, and costs were analyzed. Results: Of 16,642 neonates admitted to neonatal departments in the 9 hospitals during 2008-2010, there were 139 cases of NNS, with incidence of 8.3% and mortality of 20.8%. The predominant pathogens were Gram-negative bacteria, accounting for 67.6% of positive cultures. Gram-positive bacteria accounted for 24.5% and fungal infection accounted for 7.9%. The most common Gram-negative species were Klebsiella pneumonia (22.3%), Escherichia coli (15.1%), and Enterobacter cloacae (8.6%). The dominant Gram-positive species identified were coagulase negative staphylococcal species (CONS) (8.6%), followed by Staphylococcus aureus (7.9%). The recovered bacterial pathogens demonstrated varying antibiotic resistance, but no meropenem-or-vancomycin-resistant strains were detected. Preterm and full-term infants showed significant difference in clinical manifestations, laboratory findings, mortality, and cost. Conclusion: NNS in the hospitals of Shaanxi Province showed a decreasing trend from 2008 to 2010, but the mortality did not reduce significantly. The predominant bacteria were Gram negative, and pathogens were found to have varying antibiotic resistance. The preterm group had higher mortality and costs than the full-term infants. Therefore, effective measures should be taken to control NNS, especially in preterm infants.

Role of intravenous immunoglobulin in suspected or proven neonatal sepsis

Neonatal sepsis remains the major cause of mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay in newborn infants. Despite of advances in technology and optimal antibiotic treatment,incidence of neonatal sepsis and its complications remains unacceptably high especially in developing countries. Premature neonates in particular are at higher risk due to developmentally immature host defence mechanisms. Though not approved by Food and Drug Administration(FDA) U. S. A,off label use of intravenous immunoglobulin as prophylactic or adjuvant agent in suspected or proven neonatal infections continues in many countries. In a recent large multicenter clinical trial by International Neonatal Immunotherapy Study(INIS) group, the use of polyvalent IgG immune globulin was not associated with significant differences in the risk of major complications or other adverse outcomes in neonates with suspected or proven sepsis. Hence,use of intravenous immunoglobulin in suspected or proven neonatal sepsis is not recommended. The expense of prophylactic use of intravenous immunoglobulin administration for both term and preterm newborn population,given the minimal benefit as demonstrated by many individual studies and by meta-analysis is not justified.

MBL2 Gene Polymorphism and the Association with Neonatal Sepsis in Egyptian Neonates, a Case Control Study

Mannose binding lectin (MBL) is an important component of innate immunity particularly in neonates whose adaptive immunity is not fully developed. Polymorphism in MBL2 gene promoter and exon1 determines MBL serum level and function. The aim of this study was to investigate the frequency of different MBL2 genotypes in neonatal sepsis among patients of neonatal intensive care unit (NICU). Two hundred and forty-five neonates were enrolled in this study (127 infected and 118 uninfected controls). Multiplex PCR and double amplification refractory mutation system (dARMS) were used for typing of MBL2 exon1 and promoter respectively. Klebsiella species were the most frequently isolated organisms (22.8%). There is no statistical significance difference in the distribution of different expression genotypes between infected group and controls (P = 0.11). However, prevalence of low MBL2 expression genotypes (XA/O and O/O) was higher in infected patients compared to control group (patients 25.2% and controls 15.3%). Low and medium MBL2 expression genotypes were mostly associated with Gram-negative bacterial infections (18.9% and 22.8%) respectively. A statistically significant association of Gram-negative bacterial infections with low MBL2 expression genotypes was found (P = 0.02). Higher frequency of AB and BB genotypes was observed (31.5% and 7.9%) in patients group compared to control, but without statistical significant difference.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

Neonatal sepsis: within and beyond China

Sepsis remains a significant cause of neonatal morbidity and mortality in China.A better understanding of neonatal sepsis in China as compared with other industrialized and non-industrialized countries may help optimize neonatal health care both regionally and globally.Literature cited in this review was retrieved from PubMed using the keywords"neonatal sepsis,""early-onset(EOS)"and"late-onset(LOS)"in English,with the focus set on population-based studies.This review provides an updated summary regarding the epidemiology,pathogen profile,infectious work-up,and empirical treatment of neonatal sepsis within and beyond China.The incidence of neonatal EOS and the proportion of Group B Streptococcus(GBS)within pathogens causing EOS in China seem to differ from those in developed countries,possibly due to different population characteristics and intrapartum/postnatal health care strategies.Whether to adopt GBS screening and intrapartum antibiotic prophylaxis in China remains highly debatable.The pathogen profile of LOS in China was shown to be similar to other countries.However,viruses as potential pathogens of neonatal LOS have been underappreciated.Growing antimicrobial resistance in China reflects limitations in adapting antibiotic regimen to local microbial profile and timely cessation of treatment in non-proven bacterial infections.This review stresses that the local epidemiology of neonatal sepsis should be closely monitored in each institution.A prompt and adequate infectious work-up is critically important in diagnosing neonatal sepsis.Adequate and appropriate antibiotic strategies must be overemphasized to prevent the emergence of multi-resistant bacteria in China.

Prediction modelling in the early detection of neonatal sepsis

Background Prediction modelling can greatly assist the health-care professionals in the management of diseases,thus sparking interest in neonatal sepsis diagnosis.The main objective of the study was to provide a complete picture of performance of prediction models for early detection of neonatal sepsis.Methods PubMed,Scopus,CINAHL databases were searched and articles which used various prediction modelling measures for the early detection of neonatal sepsis were comprehended.Data extraction was carried out based on Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist.Extricate data consisted of objective,study design,patient characteristics,type of statistical model,predictors,outcome,sample size and location.Prediction model Risk of Bias Assessment Tool was applied to gauge the risk of bias of the articles.Results An aggregate of ten studies were included in the review among which eight studies had applied logistic regression to build a prediction model,while the remaining two had applied artificial intelligence.Potential predictors like neonatal fever,birth weight,foetal morbidity and gender,cervicovaginitis and maternal age were identified for the early detection of neonatal sepsis.Moreover,birth weight,endotracheal intubation,thyroid hypofunction and umbilical venous catheter were promising factors for predicting late-onset sepsis;while gestational age,intrapartum temperature and antibiotics treatment were utilised as budding prognosticators for early-onset sepsis detection.Conclusion Prediction modelling approaches were able to recognise promising maternal,neonatal and laboratory predictors in the rapid detection of early and late neonatal sepsis and thus,can be considered as a novel way for clinician decisionmaking towards the disease diagnosis if not used alone,in the years to come.

Association between innate immunity gene polymorphisms and neonatal sepsis development:a systematic review and meta-analysis

Background The aim of this meta-analysis was to analyze all available data from studies investigating associations between polymorphisms in genes responsible for innate immunity and neonatal sepsis development.Methods A comprehensive literature search,reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-S guidelines,was performed with no language restriction.Studies derived using the PICO(population,intervention,comparison and outcomes)strategy,with data on the genotype distribution for innate immunity gene polymorphisms in newborns with and without sepsis.Data were analyzed using Review Manager.The Cochran–Mantel–Haenszel test was used to calculate odds ratios with 95%confidence intervals.Heterogeneity was tested using the I2 index.Results From a total of 9428 possibly relevant articles,33 qualified for inclusion in this systematic review.According to the STrengthening the REporting of Genetic Association Studies,23 studies were found to be of moderate quality,while 10 were of low quality.The results showed an association of the mannose-binding lectin(MBL)exon 1 genetic polymorphism with the risk of culture-proven sepsis.Toll-like receptor(TLR)4 rs4986791 genotype distribution suggests its association with the increased risk of culture-proven sepsis.The certainty of evidence per GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)varied from very low to low.Publication bias was not detected.Conclusions Out of the 11 investigated single-nucleotide polymorphisms,this meta-analysis found a possible association between the risk for culture-proven sepsis and MBL exon 1 and TLR4 rs4986791 polymorphisms.There is an evident need for larger well-designed,multicentric observational studies investigating inflammatory gene polymorphisms in neonatal sepsis.

Feasibility and efficacy of gentamicin for treating neonatal sepsis in community-based settings:a systematic review

Background:Neonatal sepsis is a leading cause of neonatal deaths in developing countries.The current recommended in-hospital treatment is parenteral ampicillin(or penicillin)and gentamicin in young infants for 10-14 days;however,very few could access and afford.The current review is to evaluate the feasibility of gentamicin in community based settings.Methods:Both observational and randomized controlled trials were included.Medline,Embase,Cochrane Central Register of Controlled Trials and Central Trial Register of India were searched until September 2013.We assessed the risk of bias by Cochrane Collaboration’s"risk of bias"tool.Results:Two observational studies indicated feasibility ensuring coverage of population,decrease in case fatality rate in the group treated by community health workers.In an RCT,no significant difference was observed in the treatment failure rates[odds ratio(OR)=0.88],and the mortality in the first and second week(OR=1.53;OR=2.24)between gentamicin and ceftriaxone groups.Within the gentamicin group,the combination of penicillin and gentamicin showed a lower rate of treatment failure(OR=0.44)and mortality at second week of life(OR=0.17)as compared to the combination of gentamicin and oral cotrimoxazole.Conclusion:Gentamicin for the treatment of neonatal sepsis is both feasible and effective in community-based settings and can be used as an alternative to the hospitalbased care in resource compromised settings.But there was less evidence in the management of neonatal sepsis in hospitals as was seen in this review in which we included only one RCT and three observational studies.

Screening for early-onset neonatal sepsis on the Kaiser Permanente sepsis risk calculator could reduce neonatal antibiotic usage by two-thirds

Importance:Effective screening strategies for early-onset neonatal sepsis(EONS)have the potential to reduce high volume parenteral antibiotics(PAb)usage in neonates.Objective:To compare management decisions for EONS,between CG149 National Institute for Health and Care Excellence(NICE)guidelines and those projected through the virtual application of the Kaiser Permanente sepsis risk calculator(SRC)in a level 2 neonatal unit at a district general hospital(DGH).Methods:Hospital records were reviewed for maternal and neonatal risk factors for EONS,neonatal clinical examination findings,and microbial culture results for all neonates born at≥34 weeks’gestation between February and July 2019,who were(1)managed according to CG149-NICE guidelines or(2)received PAb within 72 h following birth at a DGH in Winchester,UK.SRC projections were obtained using its virtual risk estimator.Results:Sixty infants received PAb within the first 72 h of birth during the study period.Of these,19(31.7%)met SRC criteria for antibiotics;20(33.3%)met the criteria for enhanced observations and none had culture-proven sepsis.Based on SRC projections,neonates with’’≥1 NICE clinical indicator and≥1 risk factor’were most likely to have a sepsis risk score(SRS)>3.Birth below 37 weeks’gestation(risk ratio[RR]=2.31,95%confidence interval[CI]:1.02–5.22)and prolonged rupture of membranes(RR=3.14,95%CI:1.16–8.48)increased the risk of an SRS>3.Interpretation:Screening for EONS on the SRC could potentially reduce PAb usage by 68%in term and near-term neonates in level 2 neonatal units.

Neonatal and Young Infant Sepsis in a Regional Hospital in Ghana

Background: Neonatal sepsis is a global health problem that mainly affects low- and middle-income countries. We have previously shown that early neonatal mortality is high at the Ho Teaching Hospital (HTH) of Ghana. We sought to determine the prevalence of neonatal sepsis, sepsis-related mortality, and bacterial species patterns in neonatal and young infant sepsis in this hospital. Methods: A hospital-based study was conducted in the hospital’s neonatal intensive care unit (NICU) from March to June 2018. Blood samples from 96 babies clinically diagnosed with or at risk of sepsis were cultured using the BACTEC 9050® machine. Clinical data including gravida, parity and antibiotic medication before delivery of mother and delivery type, gestation, birth weight and antibiotic medication status were collected for analysis. MALDI-TOF MS identified bacterial isolates, and their identities were confirmed via tuf gene sequence typing. The data were analyzed using GraphPad Prism 8.0.2. Results: Blood cultures were positive in 28 of the babies, with 14 and 12 representing early-onset and late-onset neonatal sepsis, respectively, and two cases of unknown sepsis type. Of the bacterial species that caused sepsis in the babies, coagulase-negative staphylococcus (CoNS) was the most prevalent isolate in 22 cases, followed by Klebsiella pneumoniae in two and Staphylococcus aureus, Streptococcus agalactiae, the Acinetobacter species, and Escherichia coli in the rest (one each). Of the CoNS, S. haemolyticus and S. epidermidis were the most prevalent species, found in eight and six cases, respectively. Thirteen neonates died, of whom seven had positive blood cultures, and two were referred. A case fatality rate of 7/26 was estimated. Neonatal mortality caused by Gram-negative bacterial infection was higher than that caused by Gram-positive bacteria. Conclusions: These data suggest a significant burden of sepsis among neonates and young infants and are associated with substantial morbidity and mortality at the HTH. There is a need to investigate risk factors associated with the increased sepsis rate in this hospital to inform measures to reduce the neonatal sepsis rate.

The association between mycotic pneumonia and neonatal septicemia

Background:Candida species are the fourth most common etiological agents of late-onset infection in the neonatal intensive care unit(NICU)and are responsible for considerable morbidity and mortality.Objectives:From November 2023 to February 2024,we investigated the association of mycotic pneumonia with septicemia in 60 neonates,and their roles of mycotic pneumonia in the morbidity and mortality of neonates in two NICUs in the Al-Ramadi Teaching Hospital for Maternity and Children.Methods:All infants in this study had been diagnosed with septicemia and treated with empirical antimicrobial therapy.An early morning nasogastric tube(NG-tube)was used to collect swallowed sputum by suction for culture and sensitivity testing.Results:The average white blood count for the neonates was 8547±5884.5 cells/mm^(2).The mean C-reactive protein was 39.3±26 mg/l,the mean serum albumin was 2.9±0.2 g/dl and the positive bacterial blood culture was 28(46.7%).9(15%)neonates died during the study period.The NG-tube culture identified fungal growth in all samples.Of these,49(81.6%)were identified as Candida albicans,6(10%)as Candida tropicalis,and 5(8.3%)as Cryptococcus laurentii.The bacterial culture results from the NG-tube samples identified 13(21.6%)patients with gram-positive bacteria and 47(78.3%)with gram-negative bacteria.Conclusion:We found a prevalence of Candida spp.among neonates in addition to microbial oxygen tube contamination,indicating a biosafety breach in the neonatal unit.Mycotic infection requires global attention as a probable cause of respiratory failure in neonatal septicemia.

Stenotrophomonas maltophilia,an emerging pathogen in newborns:Three case reports and a review of the literature

BACKGROUND Stenotrophomonas maltophilia(S.maltophilia)is a rare cause of neonatal sepsis with significant morbidity and mortality and has extensive resistance to several antibiotics leaving few options for antimicrobial therapy.Only a few cases have been reported in neonates from developing countries.We report three cases of critically ill,extramural babies with neonatal S.maltophilia sepsis.All three babies recovered and were discharged.CASE SUMMARY All three cases were term extramural babies,who were critically ill at the time of presentation at our neonatal intensive care unit.They had features of multiorgan dysfunction at admission.Blood culture was positive for S.maltophilia in two babies and one had a positive tracheal aspirate culture.The babies were treated according to the antibiogram available.They recovered and were subsequently discharged.CONCLUSION Although various authors have reported S.maltophilia in pediatric and adult populations,only a few cases have been reported in the newborn period and this infection is even rarer in developing countries.Although S.maltophilia infection has a grave outcome,our three babies were successfully treated and subsequently discharged.

Scrotoschisis in a Central African Newborn

Scrotoschisis, a rare congenital disease, is defined by an extracorporeal ectopic testis eviscerated as a result of a scrotal wall defect. We report a case in a Central African newborn, born via vaginal delivery, to non-consanguineous parents, admitted at three days of life from a level II health center. The pregnancy was poorly monitored without ultrasound. On admission, the temperature was 40&ordm;C, he was polypneic and tachycardic. There was a congenital defect of the scrotal wall with exteriorization of the left testis and the right testis was normal. The blood count showed pancytopenia and the blood culture isolated amiklin-sensitive Klebseilla pneumonia. The diagnosis of scrotoschisis associated with sepsis was made. A tri-antibiotic therapy associated with general resuscitation followed by testicular transposition and orchidopexy performed on the eleventh day of life did not prevent the fatal outcome three hours after the surgery. This observation confirms the rarity of the malformation and the benefit of an early management.

Application of Kaiser Sepsis Calculator in culture-positive infants with early onset sepsis

Background Kaiser Sepsis Calculator(KSC)reduces antibiotic use,testing and intravenous infiltrates but there are concerns about the missed early onset sepsis(EOS)cases.We sought to apply the KSC score for culture-positive infants retrospectively in infants born in the last 10 years in our hospital.Methods In a retrospective cohort study,the comparison groups were divided into Group A(no antibiotics recommended by KSC)and Group B(antibiotics recommended).Results Overall,17/24(71%)infants would have been started on antibiotics per KSC but 7/24(29%)would not.The initial EOS risk was not significantly different between the groups(Group A vs.Group B:0.44 vs.0.76,P=0.41),but the final risk score was(0.33 vs.9.41,P<0.001).In Group A(no antibiotics),3/7 infants became symptomatic between 9 and 42 hours.Conclusion There may be a potential delay in starting antibiotics in infants that are asymptomatic at birth while using KSC.