Management Of Neonatal Sepsis Research Articles

IJCM_120A: Factors associated with neonatal sepsis in tertiary care hospitals of Mangalore: A retrospective study

Background: Neonatal sepsis remains a significant cause of morbidity and mortality globally, particularly in developing countries like India. Early and late onset sepsis present unique challenges in diagnosis and management, with maternal and neonatal factors playing crucial roles in the manifestation of the condition. Methodology: Data were collected from tertiary care hospitals affiliated with Kasturba Medical College, Mangaluru. A structured proforma was used to gather information on maternal factors, birth history, neonatal conditions, and complications. Statistical analysis was performed using Chi- square test and student’s ‘t’ test. Results: Out of 132 cases, 50.75% were early onset sepsis (EOS) and 49.25% were late onset sepsis (LOS). Blood culture reports were positive in 46.1% cases. Maternal comorbidities included gestational diabetes mellitus (GDM), antepartum hemorrhage (APH), and pregnancy-induced hypertension (PIH). Neonatal comorbidities such as convulsions, congenital malformations, neonatal jaundice, preterm birth, and low birth weight were observed. Positive blood culture reports correlated with low birth weight and preterm births. Staphylococcus aureus was the most common organism, followed by Citrobacter Spp., Enterobacter Spp., and Pseudomonas aeruginosa. Sensitivity analysis revealed varying degrees of susceptibility to different antibiotics. Conclusion: Maternal factors like GDM, APH, and PIH showed no significant correlation with neonatal sepsis, whereas neonatal factors such as low birth weight and preterm birth were associated with an increased risk. Consanguinity also emerged as a potential risk factor. Staphylococcus aureus was the predominant causative organism, with varying antibiotic sensitivities. This study underscores the importance of understanding maternal and neonatal factors in the prevention and management of neonatal sepsis.

Neonatal sepsis and cardiovascular dysfunction I: mechanisms and pathophysiology.

The highest incidence of sepsis across all age groups occurs in neonates leading to substantial mortality and morbidity. Cardiovascular dysfunction frequently complicates neonatal sepsis including biventricular systolic and/or diastolic dysfunction, vasoregulatory failure, and pulmonary arterial hypertension. The haemodynamic response in neonatal sepsis can be hyperdynamic or hypodynamic and the underlying pathophysiological mechanisms are heterogeneous. The diagnosis and definition of both neonatal sepsis and cardiovascular dysfunction complicating neonatal sepsis are challenging and not consensus-based. Future developments in neonatal sepsis management will be facilitated by common definitions and datasets especially in neonatal cardiovascular optimisation. IMPACT: Cardiovascular dysfunction is common in neonatal sepsis but there is no consensus-based definition, making calculating the incidence and designing clinical trials challenging. Neonatal cardiovascular dysfunction is related to the inflammatory response, which can directly target myocyte function and systemic haemodynamics.

Clinical Utility of Procalcitonin and C-Reactive Protein in the Management of Neonatal Sepsis in a Resource-Limited Nigerian Hospital.

Neonatal sepsis is an invasive infection of the bloodstream in neonates and a leading cause of morbidity and mortality among them. To investigate the role of procalcitonin (PCT) and C-reactive protein (CRP) in the management of neonatal sepsis. This was a prospective case-control study over one-year period using convenience sampling. Blood samples for PCT and CRP were taken from all neonates, while blood culture and white blood cell count samples were additionally taken from babies with neonatal sepsis. PCT and CRP were repeated at 24 and 48 hours. The continuous variables were found to have a nonparametric distribution. They were presented as median and interquartile range, and compared using Wilcoxon signed rank and Friedman test as appropriate. The blood culture analysis yielded a prevalence of 12.7% with Staphylococcus aureus being the commonest organism. Baseline concentrations of PCT (1.28 ng/ml) and CRP (17.31 mg/L) in neonates with sepsis were higher than that of controls (PCT-0.63 ng/ml, CRP-5.40 mg/L). PCT concentrations decreased after two days of antibiotic treatment, while CRP concentrations decreased after a day. The concentration of both decreased to normal levels after two days of treatment. This study showed that CRP was more reliable in monitoring antibiotic therapy, unlike other studies which suggested PCT. In cases where the management of neonatal sepsis may be limited by a low blood culture yield, therapeutic monitoring may be aided by CRP and/or PCT.

Improving the Treatment of Neonatal Sepsis in Resource-Limited Settings: Gaps and Recommendations.

Neonatal sepsis causes significant global morbidity and mortality, with the highest burden in resource-limited settings where 99% of neonatal deaths occur. There are multiple challenges to achieving successful treatment of neonates in this setting. Firstly, reliable and low-cost strategies for risk identification are urgently needed to facilitate treatment as early as possible. Improved laboratory capacity to allow identification of causative organisms would support antimicrobial stewardship. Antibiotic treatment is still hampered by availability, but also increasingly by antimicrobial resistance - making surveillance of organisms and judicious antibiotic use a priority. Finally, supportive care is key in the management of the neonate with sepsis and has been underrecognized as a priority in resource-limited settings. This includes fluid balance and nutritional support in the acute phase, and follow-up care in order to mitigate complications and optimise long-term outcomes. There is much more work to be done in identifying the holistic needs of neonates and their families to provide effective family-integrated interventions and complete the package of neonatal sepsis management in resource-limited settings.

The changing profile of neonatal pathogens and susceptibility pattern: prospective observational study from a tertiary center in South India

Introduction: Changing the pattern of neonatal pathogens poses challenges to the management of neonatal sepsis. Profile and antimicrobial susceptibility of neonatal pathogens were evaluated in this prospective observational study in a tertiary center. Methods: Neonates with risk factors and clinical features of sepsis were screened. Blood culture performed in positive-screen babies. Antimicrobial susceptibility was also evaluated. Statistical significance was tested by the chi-square test and t test accordingly. Univariate analysis was performed to study possible correlations in this regard. Results: Out of 431 suspected cases, 89 neonates (20.65%) had sepsis. The rate of early and late-onset sepsis (LOS) was 48.3% and 51.7%, respectively. The clinical spectrum included septicemia 68 (76.5%), congenital pneumonia 13 (14.7%), meningitis 5 (5.7%), and septic arthritis 3 (3.4%), respectively. Gram-positive bacteria constituted 61 (68.5%), while gram-negative was 28 (31.5%) (P<0.05). Staphylococcus aureus (23.6%) and methicillin-resistant S. aureus (MRSA) (22.5%) were the most common isolates. Acinetobacter (15.8%), coagulase-negative staphylococcus areus (CoNS) (11%), Klebsiella (7.9%), enterococci (8%), E. coli (4.5%), and ß hemolytic streptococci (1 case) were other detected pathogens. MRSA, Acinetobacter, and coagulase-negative S. aureus as a single entity involved in sepsis pathogenesis (50.6%) showed a positive correlation with inborn babies, pre-term, low birth weight, and early-onset sepsis (OR; 95% CI: 2.20; 0.94–5.20, 1.82; 0.79–4.22, 1.25; 0.55–2.89 and 1.05; 0.46–2.50 respectively). Susceptibility pattern was penicillin (12.3%), ampicillin (6.7%), cloxacillin (42.9%), cefotaxime (8%), cefazolin (37.9%), cefoperazone sulbactam (81.5%), piperacillin-tazobactam (68.9%), gentamicin (63.5%), amikacin (47.9%), vancomycin (88.9%), linezolid (88.6%), co-trimoxazole (55.4%), and clindamycin (50%). Conclusion: Gram-positive pathogens and opportunistic pathogens like Acinetobacter predominate over the conventional gram-negative pathogens in neonates. Of note, penicillin, ampicillin, and cefotaxime are not suitable for the empiric treatment of neonatal sepsis.

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Isolated Bacterial Resistance to Antibiotics and Common Pathogens that Cause Neonatal Sepsis

Objective: to record the frequency of isolating organisms causing early-onset neonatal sepsis resistant to common antibiotics, Methodology: This research was a cross-sectional study that was conducted in 2017 and 2018 at the Neonatal Intensive Care Unit of the Benazir Bhutto Hospital in Rawalpindi on 180 children who satisfied the following criteria and were delivered between 34 and 40 weeks of gestation either Spontaneous Vertex Delivery or Cesarean Section. The study was conducted on infants who were born between 34 and 40 weeks of gestation. Those newborns who had congenital defects, had had surgical intervention, had hypoxic ischemic encephalopathy, or had been treated with antibiotics were not included in the research. Every infant had three millilitres of its blood collected and stored in a sterile environment. The blood was placed into the Bactec 9240 blood culture bottles in a direct inoculation. After being transported to the BBH children's hospital pathology lab, the injection bottles were placed in a Bactee 9240 continuous monitoring blood culture system. The temperature inside the incubator was 37 degrees Celsius. The use of catalase, coagulase, and Dnase in the examination of Gram-positive bacteria was carried out. Using the Kirby-Bauer method, the isolated organism was put through a battery of tests to determine whether or not it was resistant to ampicillin, amikacin, tobramycin, cefotaxime, ceftazidime, ceftriaxone, meropenem, sulbactam, and vancomycin. Meuller Hinton Agar was the medium that was employed. Results: In our study, out of 140 cases, 65.71%(n=92) were between 1-48 hours and 34.29%(n=48) were between 49-72 hours, mean+sd was calculated as 35.96+16.65 hours, 47.86%(n=67) were male and 52.14%(n=73) were females. Frequency of isolated organisms shows that 27.86%(n=39) had S.Aureus, 22.14%(n=31) had E.Coli, 15%(n=21) had Staphylococcus epidermidis, 12.86%(n=18) had Klebseila and 22.14%(n=31) had others. Practical Implication: determination of the isolated bacterial resistance to antibiotics and common pathogens that cause neonatal sepsis would help in the appropriate and effective management of neonatal sepsis in our population Conclusion: Our results reveal that S.Aureus and E.Coli were the common showing 27.86% S.Aureus, 22.14% E.Coli, 15%, Staphylococcus epidermidis, 12.86% Klebseila and 22.14% had others isolates. organisms in EOS cases followed by Staphylococcus epidermidis and Klebseila whereas Ampicillin, Cefotaxime, Ceftriaxon, and Ceftazidime are also resistant in these cases. Keywords: Early onset neonatal sepsis, common pathogens, antimicrobial resistance of isolated organism

Clinical and bacteriological profile of culture-negative and culture-proven neonatal sepsis in Palembang, Indonesia

Culture-negative and multidrug-resistant neonatal sepsis frequently occur in developing countries and complicate neonatal sepsis management. These conditions contribute to a high neonatal mortality rate and accelerate the misuse of antibiotics. However, the extent of culture-negative and multidrug-resistant neonatal sepsis in developing countries remains poorly characterized. This study aims to describe culture-negative and culture-proven neonatal sepsis epidemiology and the antimicrobial resistance patterns in Palembang, Indonesia. A retrospective review of the medical records of all neonatal admissions between January 2016 and December 2018 was conducted at a tertiary-level referral hospital in Indonesia. The maternal and neonatal characteristics and microbiological results of the identified sepsis cases were obtained and analyzed. Three hundred and fifty-six neonatal sepsis cases were admitted from 2016 to 2018, accounting for 14.1% of neonatal hospital admissions. The percentages of early-onset and late-onset sepsis were comparable (49.7% vs. 50.3%), with an 18.1% case fatality rate. The proportion of culture-negative sepsis was 44%. The mortality rates between culture-proven and culture-negative sepsis cases did not differ statistically (p = 0.11). Coagulase-negative staphylococci (30.9%), Klebsiella pneumoniae (18.1%), and Acinetobacter spp. (10.7%) were the most frequently isolated pathogens. Overall, 62.6% of all isolated organisms were multidrug-resistant bacteria, with a high prevalence of extended-spectrum cephalosporin-resistant and carbapenem-resistant strains. Culture-negative sepsis accounts for a significant proportion of neonatal sepsis cases. Early- and late-onset and culture-negative and culture-proven neonatal sepsis contribute to a comparable proportion of neonatal sepsis morbidity and mortality. There is an alarmingly high prevalence of resistance to extended-spectrum cephalosporin and carbapenem in neonatal sepsis cases.

Home-based management of neonatal sepsis: 23 years of sustained implementation and effectiveness in rural Gadchiroli, India, 1996–2019

IntroductionAlthough hospitalisation remains the preferred management for neonatal sepsis, it is often not possible in resource-limited settings. The Home-Based Newborn Care (HBNC) study in Gadchiroli, India (1995–1998) was the first...

Infections in the NICU: Neonatal sepsis

Neonatal infections remain an important cause of neonatal morbidity and mortality worldwide. Neonatal sepsis is a systemic infection that can be classified as early-onset or late-onset pending the timing of presentation. The pathophysiology and causative pathogens of neonatal sepsis vary, with early-onset sepsis being associated with a vertically transmitted infection from mother to neonate versus late onset sepsis being commonly associated with nosocomial infections. The signs and symptoms of neonatal sepsis mimic those associated with prematurity, making timely diagnosis difficult for treating clinicians. The management of neonatal sepsis is centered around obtaining adequate culture data and initiation of broad-spectrum parenteral antibiotics. Controversies surrounding the management of neonatal sepsis include the administration of empiric antibiotics, given recent clinical studies associating early antibiotic use with clinical sequelae such as late-onset sepsis, necrotizing enterocolitis, and death in the preterm, low-birthweight infant population.

Diagnostic utility of combined immature and total neutrophil counts along with C-reactive protein in early detection of neonatal sepsis: A cross-sectional study

IntroductionA timely diagnosis is critical for management of Neonatal sepsis. Blood Culture is considered to be the “Gold Standard” for its diagnosis, but it has some limitations. In recent times, highly sensitive and specific inflammatory markers like interleukins, ELISA, counter immune-electrophoresis etc. have been in use for its diagnosis. But these are impractical for developing countries, due to their high cost and requirement of sophisticated equipments. A combination of haematological parameters like total leucocyte count (TLC), immature to total neutrophil ratio (I/T ratio), absolute neutrophil count (ANC), platelet count and C-reactive protein (CRP) estimation provide an early diagnosis of bacteremia. This study was undertaken to evaluate the usefulness of the above mentioned parameters as indicators for early diagnosis of neonatal sepsis. Material and methodsIn the present cross-sectional study, we intent to analyse various hematologic parameters in 160 neonates admitted in the neonatal care unit of a tertiary care hospital in Delhi. We obtained data from the records of blood culture and complete blood counts of neonates from pathology and microbiology departments of the hospital. Out of 160 admitted neonates, 80 were taken as cases and remaining 80 were taken as controls. Medical records were studied to identify infants born at ≥ 34 weeks gestation. CBCs was analysed, blood cultures and CRP were done in department of Microbiology. CBC, CRP and Blood culture was done as per standard protocols and clinical assesment by paediatrician. The statistical analyses were performed using SPSS version 22 for windows. ResultsAmong 80 neonates, who were in early neonatal sepsis, 44 cases (55%) were females, and 36 (45%) were males. The Microbiological profile of 80 septic neonates was analysed. The I/T value, ANC and CRP values were significantly higher in the neonates suffering from sepsis as compared to the control group. Among 80 septic neonates (cases), 30 (37.5%) were having normal ANC while 50 (62.5%) were having increased ANC and 34 (42.5%) were having normal I:T ratio while 46 (57.5%) were having increased I:T ratio. Out of 80 septic neonates (cases), 18 (22.5%) were having normal CRP while 62 (77.5%) were having increased CRP. ConclusionANC, I/T Ratio and CRP are quick, simple and cost-effective routine laboratory tests which help in early diagnosis of neonatal sepsis. Although there are many serological markers available, ANC and I/T Ratio serves as a reliable predictor of neonatal sepsis. With a good sensitivity, high specificity and a good negative predictive value these parameters can therefore help in timely and early identification of neonatal sepsis.

Biomarkers of Neonatal Sepsis: From Being Mere Numbers to Becoming Guiding Diagnostics.

Neonatal sepsis is a common cause of neonatal morbidity and mortality. The diagnosis of newborn sepsis is still difficult. Different early objective diagnostic tests or specific signs and symptoms, particularly in preterm infants, make it difficult to diagnose neonatal sepsis. This review article describes biomarkers and their role in the early diagnosis, treatment, and prognosis of neonatal sepsis. It also explores the possible advances and future prospects of these biomarkers. An ideal sepsis biomarker will not only help in the guidance of the use of antibiotics when not needed but also the duration of the course of antibiotics if sepsis is proven. It should also have high sensitivity, specificity, positive predictive value, and negative predictive value. These biomarkers hold a promising position in the management of neonatal sepsis and translate into use in clinical settings. Metabolomics, a diagnostic method based on detecting metabolites found in biological fluids, may open new possibilities in the management of critically ill newborns.

Challenges in the Diagnosis & Management of Neonatal Sepsis

Neonatal sepsis is the main cause of neonatal mortality and a major public health problem, especially in underdeveloped countries. Although recent medical services have improved neonatal care, but still challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of non-infectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically start antibiotics to infants with risk factors with and without signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries.

Antimicrobial resistance in neonates with suspected sepsis.

SETTING:Nobel Medical College and Teaching Hospital, Biratnagar, Nepal.OBJECTIVE:To determine the pattern of antimicrobial resistance and hospital exit outcomes in neonates with suspected sepsis in a tertiary neonatal intensive care unit (NICU).DESIGN:This hospital-based cohort study was conducted to follow patients from January to December 2019. All identified cases of suspected sepsis were enlisted from hospital records.RESULTS:Sepsis was suspected in 177 (88%) of the 200 cases admitted in the NICU; 52 (29%) were culture-positive. Pseudomonas was the predominant organism isolated (n = 40; 78%), followed by coagulase negative staphylococcus (n = 12, 23%). Nine (17%) of the 52 isolates were resistant to the Access and Watch group of antibiotics, including some resistance to Reserve group drugs such as imipenem and linezolid. Most treated cases (n = 170, 96%) improved, although 7 (4%) left against medical advice.CONCLUSION:Most of the pathogens were resistant to WHO Access and Watch antibiotics and occasional resistance was observed to Reserve group drugs. Most sepsis was caused by Gram-negative bacilli. Improving turnaround times for antibiotic sensitivity testing using point-of-care testing, and a greater yield of culture-positive results are needed to enhance the management of neonatal sepsis.

Neonatal sepsis in Sana\u2019a city, Yemen: a predominance of Burkholderia cepacia

BackgroundNeonatal sepsis is a global concern with increasing morbidity and mortality. The burden of neonatal sepsis is highest in developing countries, especially in those lacking proper surveillance systems. The causative pathogens and their drug-resistance levels vary between countries with emergence of multidrug resistance organisms. Thus, accurate records on the recent trends of organisms causing neonatal sepsis will provide vital information for appropriate intervention. We aimed to investigate neonatal sepsis, identify its associated factors and causative pathogens and to assess the antibiotic susceptibility patterns in Sana’a city, Yemen.MethodsA cross-sectional study was conducted on neonates admitted to intensive care units of six hospitals in Sana’a city, Yemen, in the period from January 15, to March 30, 2020. Natal and prenatal medical data were collected using well-structured questionnaire. Neonates were subjected to sepsis work-up including blood culture, complete blood count and C-reactive protein. Organisms were identified by Gram staining and analyzed by the VITEK II system for bacterial bio-typing and antibiotic susceptibility testing.FindingsOf the 199-neonates with suspected neonatal sepsis, 154 (77.38%) had culture-proven sepsis. Early-onset neonatal sepsis (EOS) was higher (50.25%; 100/199) than late-onset neonatal sepsis (LOS) (27.13%; 54/199). Multivariable analysis identified vaginal delivery as an independent risk factor for neonatal sepsis p = 0.005. Majority of isolated bacteria (74.39%) were gram-negative with Burkholderia cepacia (39%) and Klebsiella oxytoca (13%) being the most common pathogens of EOS and LOS. The most common gram-positive pathogens were Staphylococcus haemolyticus (9.1%) and Staphylococcus epidermidis (7.1%). B. cepacia showed multidrug resistance except for cefepime. All Klebsiella species isolates (100%) and most Pantoea species (93%) were ESBL and carbapenemase positive. All Escherichia coli and Acinetobacter baumannii isolates were ESBL positive. A significant number of gram-positive bacteria showed resistance to vancomycin.ConclusionThe study findings show a high proportion of neonatal sepsis among neonates admitted to hospitals in Sana’a city with antibiotic-resistant B. cepacia being the single most common pathogen causing EOS and LOS. Findings also emphasize the emerging threat of multidrug-resistant bacteria in neonatal units and will help develop evidence-based management of neonatal sepsis in Yemen.

Severe bacterial neonatal infections in Madagascar, Senegal, and Cambodia: A multicentric community-based cohort study.

BackgroundSevere bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries (LMICs). However, most data came from hospitals, which do not include neonates who did not seek care or were treated outside the hospital. Studies from the community are scarce, and few among those available were conducted with high-quality microbiological techniques. The burden of SBI at the community level is therefore largely unknown. We aimed here to describe the incidence, etiology, risk factors, and antibiotic resistance profiles of community-acquired neonatal SBI in 3 LMICs.Methods and findingsThe BIRDY study is a prospective multicentric community-based mother and child cohort study and was conducted in both urban and rural areas in Madagascar (2012 to 2018), Cambodia (2014 to 2018), and Senegal (2014 to 2018). All pregnant women within a geographically defined population were identified and enrolled. Their neonates were actively followed from birth to 28 days to document all episodes of SBI. A total of 3,858 pregnant women (2,273 (58.9%) in Madagascar, 814 (21.1%) in Cambodia, and 771 (20.0%) in Senegal) were enrolled in the study, and, of these, 31.2% were primigravidae. Women enrolled in the urban sites represented 39.6% (900/2,273), 45.5% (370/814), and 61.9% (477/771), and those enrolled in the rural sites represented 60.4% (1,373/2,273), 54.5% (444/814), and 38.1% (294/771) of the total in Madagascar, Cambodia, and Senegal, respectively. Among the 3,688 recruited newborns, 49.6% were male and 8.7% were low birth weight (LBW). The incidence of possible severe bacterial infection (pSBI; clinical diagnosis based on WHO guidelines of the Integrated Management of Childhood Illness) was 196.3 [95% confidence interval (CI) 176.5 to 218.2], 110.1 [88.3 to 137.3], and 78.3 [59.5 to 103] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively. The incidence of pSBI differed between urban and rural sites in all study countries. In Madagascar, we estimated an incidence of 161.0 pSBI per 1,000 live births [133.5 to 194] in the urban site and 219.0 [192.6 to 249.1] pSBI per 1,000 live births in the rural site (p = 0.008). In Cambodia, estimated incidences were 141.1 [105.4 to 189.0] and 85.3 [61.0 to 119.4] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.025), while in Senegal, we estimated 103.6 [76.0 to 141.2] pSBI and 41.5 [23.0 to 75.0] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.006). The incidences of culture-confirmed SBI were 15.2 [10.6 to 21.8], 6.5 [2.7 to 15.6], and 10.2 [4.8 to 21.3] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively, with no difference between urban and rural sites in each country. The great majority of early-onset infections occurred during the first 3 days of life (72.7%). The 3 main pathogens isolated were Klebsiella spp. (11/45, 24.4%), Escherichia coli (10/45, 22.2%), and Staphylococcus spp. (11/45, 24.4%). Among the 13 gram-positive isolates, 5 were resistant to gentamicin, and, among the 29 gram-negative isolates, 13 were resistant to gentamicin, with only 1 E. coli out of 10 sensitive to ampicillin. Almost one-third of the isolates were resistant to both first-line drugs recommended for the management of neonatal sepsis (ampicillin and gentamicin). Overall, 38 deaths occurred among neonates with SBI (possible and culture-confirmed SBI together). LBW and foul-smelling amniotic fluid at delivery were common risk factors for early pSBI in all 3 countries. A main limitation of the study was the lack of samples from a significant proportion of infants with pBSI including 35 neonatal deaths. Without these samples, bacterial infection and resistance profiles could not be confirmed.ConclusionsIn this study, we observed a high incidence of neonatal SBI, particularly in the first 3 days of life, in the community of 3 LMICs. The current treatment for the management of neonatal infection is hindered by antimicrobial resistance. Our findings suggest that microbiological diagnosis of SBI remains a challenge in these settings and support more research on causes of neonatal death and the implementation of early interventions (e.g., follow-up of at-risk newborns during the first days of life) to decrease the burden of neonatal SBI and associated mortality and help achieve Sustainable Development Goal 3.

Variations in Antibiotic Use and Sepsis Management in Neonatal Intensive Care Units: A European Survey.

Management of neonatal sepsis and the use of antimicrobials have an important impact on morbidity and mortality. However, there is no recent background on which antibiotic regimens are used in different European neonatal intensive care units (NICUs). Our study aimed to describe the use of antibiotics and other aspects of early- and late-onset sepsis (EOS and LOS, respectively) management by European NICUs. We conducted an online survey among NICUs throughout Europe to collect information about antibiotic stewardship, antibiotic regimens, and general aspects of managing neonatal infections. NICUs from up to 38 European countries responded, with 271 valid responses. Most units had written clinical guidelines for EOS (92.2%) and LOS (81.1%) management. For EOS, ampicillin, penicillin, gentamicin, and amikacin were the most commonly used antibiotics. Analysis of the combinations of EOS regimens showed that the most frequently used was ampicillin plus gentamicin (54.6%). For LOS, the most frequently used antibiotics were vancomycin (52.4%), gentamicin (33.9%), cefotaxime (28%), and meropenem (15.5%). Other aspects of the general management of sepsis have also been analyzed. The management of neonatal sepsis in European NICUs is diverse. There was high self-reported adherence to the local clinical guidelines. There was homogeneity in the combination of antibiotics in EOS but less in LOS.

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

SummaryBackgroundSepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis.MethodsIn BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability.FindingsBetween Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis.InterpretationOur data raise questions about the empirical use of combined ampicillin–gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs.FundingThe Bill & Melinda Gates Foundation.

The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis.

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Role of Zinc in Neonatal Sepsis.

Sepsis emerges as a complex clinical syndrome with activation of an innate host response to infections. Despite advancement in therapeutic approaches, infants with sepsis remain hospitalized for longer durations and it remains to be a major health problem in today's world. Zinc as a trace element, has the potential to improve the host's defence mechanism against various pathogenic diseases. During sepsis, a redistribution of zinc from serum into the liver has been observed and earlier studies imply a correlation between serum zinc levels and the outcome of sepsis. Zinc also appears to have a potential to be used as a biomarker of sepsis outcome. There are only few reports available to show the efficacy of zinc supplements in the management of neonatal sepsis.