“Overview of Global Challenges in Dealing with Neonatal Sepsis and Responsibility of Healthcare Workers”: A Narrative Review

Abstract

Neonatal sepsis, a global health concern, contributes significantly to neonatal mortality, particularly in low- and middle-income countries (LMICs). It manifests as early-onset sepsis (EOS), late-onset sepsis (LOS), and very late-onset sepsis (VLOS), with varied etiologies and risk factors, such as preterm birth, low birth weight, and maternal infections. High-income countries (HICs) have successfully reduced neonatal sepsis mortality through advanced diagnostic tools, antibiotic stewardship, and infection control practices. However, LMICs face persistent challenges, including inadequate healthcare infrastructure, poor access to quality care, and rising antimicrobial resistance. This narrative review aimed to address the global disparities in the incidence, mortality, etiology, diagnosis, and treatment of neonatal sepsis, emphasizing the critical role of healthcare workers. The review highlights the pivotal responsibilities of healthcare workers in early diagnosis, infection control, and education. Strengthened healthcare systems, capacity-building initiatives, and stringent infection control measures are imperative to mitigate neonatal sepsis and its associated mortality globally. This review emphasizes the urgent need for collaborative global efforts to address these challenges.

INTRODUCTION

Neonatal sepsis affects approximately 1.3 million infants globally, predominantly impacting preterm and low-weight newborns. It is a critical global health issue, causing systemic infections (septicemia, pneumonia, and meningitis) within the first 28 days of life. Neonatal sepsis is the third leading cause of neonatal mortality, resulting in about 203,000 deaths annually, and is categorized into early-onset and late-onset types based on time of occurrence.[1] Early-onset sepsis (EOS), occurring within 72 hours of birth, late-onset sepsis (LOS), occurring after 72 hours of birth, and very late-onset neonatal sepsis (VLOS) occur in neonatal intensive care unit (NICU)-hospitalized infants, typically beyond 28 days of age until discharge. Neonatal sepsis presents serious risks for neonates, often leading to severe complications and death if not promptly and effectively treated.[2]

In high-income countries, neonatal sepsis mortality rates have significantly decreased due to improved healthcare infrastructure, advanced medical technologies, and stringent infection control measures. According to the World Health Organization (WHO), neonatal sepsis accounts for 15% of neonatal deaths globally, with the majority occurring in low and middle-income countries (LMICs).[3] In these settings, factors such as poor maternal health, lack of access to quality healthcare, inadequate infection control practices, and antibiotic resistance contribute to higher mortality rates. For instance, in Sub-Saharan Africa and South Asia, neonatal sepsis mortality rates remain alarmingly high, stressing the urgent need for effective interventions.[4] India, home to one of the highest neonatal populations in the world, faces a significant burden of neonatal sepsis.[5]

According to the National Family Health Survey-5 (NFHS-5), neonatal sepsis contributes to approximately 20–30% of neonatal deaths in India.[6] Factors such as unhygienic birthing practices, inadequate neonatal care facilities, limited access to skilled healthcare professionals, and delayed diagnosis and treatment contribute to these high-mortality rates.[7] The healthcare workers play a pivotal role in combating neonatal sepsis and reducing mortality rates. The critical role of healthcare workers, whose vigilance, skill, and adherence to infection control practices determine the difference between survival and loss. Nurses, physicians, and other frontline providers responsibilities encompass a wide range of activities, including early diagnosis and prompt treatment, infection control practices, maternal and neonatal education, improving healthcare access, antibiotic stewardship, and data collection and research.[6]

While several studies have addressed individual aspects such as epidemiology, risk factors, or therapeutic protocols, there is no single comprehensive review that brings together global data on the incidence, mortality, etiology, diagnostic challenges, and treatment modalities of neonatal sepsis while simultaneously emphasizing the responsibility of healthcare workers in prevention and management. This article fills that gap and aims to provide a comparative overview of global and Indian perspectives on neonatal sepsis, highlighting the multifactorial nature of the condition and the indispensable role of healthcare professionals in reducing its burden.

INCIDENCE AND MORTALITY OF NEONATAL SEPSIS

Global status

Globally, approximately 1.3–3.9 million neonates are affected by sepsis each year reported by the global burden of disease (GBD), with an incidence rate of 22 per 1,000 live births. Among these affected neonates, 11% to 19% succumb to the condition.[8] A systematic review and meta-analysis on global incidence and mortality found in 26 studies a pooled neonatal sepsis incidence of 2824 sepsis cases per 100 000 live births and a mortality of 17.6%. Preterm and very low birthweight neonates were particularly affected, and there were considerable regional differences in incidence.[9] Neonates who survive sepsis are at a higher risk for altered neurodevelopmental outcomes. In countries with higher neonatal mortality rates (NMR > 45 per 1,000 live births), infections account for 20%–50% of neonatal deaths.[10]

High-income countries

The incidence of EOS with positive blood cultures in the United States is estimated to be 0.77 to 1 per 1,000 live births. The 2019 global disease burden study on neonatal sepsis and other neonatal infections (NSNIs) revealed significant trends over the past 30 years. The number of incident cases of NSNIs increased by 12.79% annually, while deaths decreased by 12.93% annually. The age-standardized incidence rate (ASIR) grew by an average of 46% annually, whereas the age-standardized death rate (ASDR) decreased by 53% annually. In high-Sociodemographic Index (SDI) regions, the ASIR grew by 14% annually from 1990 to 2019, and other SDI regions also saw rising ASIRs, with notable improvements in the past decade. All five SDI regions showed a general downward trend in ASDRs. Andean Latin America had the highest ASIR of NSNIs, while Western Sub-Saharan Africa experienced the highest mortality.[11]

Low middle-income counties

The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited 29,483 mothers and 30,557 neonates from 12 clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. The study aimed to investigate sepsis-associated factors and outcomes in neonates during the first 60 days of life. Key findings include: The incidence of clinically suspected sepsis was 166 per 1000 live births. The incidence of laboratory-confirmed sepsis was 46.9 per 1000 live births. The all-cause mortality rate was 0.83 per 1000 neonate-days. Significant factors associated with increased risk of sepsis and mortality included maternal hypertension, previous maternal hospitalization within 12 months, higher household income, larger ward size, neonatal ward type, living in a rural environment, preterm birth, perinatal asphyxia, and multiple births. Most laboratory-confirmed sepsis cases (72.5%) occurred within the first 3 days of life.[3]

India-specific context

India significantly contributes to the global burden of neonatal sepsis, accounting for almost one-fifth of total live births and 27% of global neonatal mortality.[12] A recent systematic review and meta-analysis indicated that the approximate EOS incidence is 2,496 per 100,000 live births, which was 2.6 times more common than LOS, 946 per 100,000 live births in India. According to the National Neonatal Perinatal Database (2002–2003), sepsis was noted in 30 per 1,000 live births, contributing to 19% of neonatal deaths in India.[13] A study in Gadchiroli, India, showed an 82.9% decline in neonatal sepsis incidence, from 111 per 1,000 live births (1998–2001) to 19 per 1,000 (2016–2019)[14] but this rate is still when high compared with HICs, which stresses the need for adoption of strict preventive strategies.

RISK FACTORS FOR NEONATAL SEPSIS

Global perspective

Preterm birth, occurring in approximately 11% of deliveries worldwide, is a major risk factor for neonatal sepsis due to immature immune function and the need for prolonged hospitalization. Similarly, low birth weight (<2500 grams) infants, accounting for 17.6% of global births, are highly vulnerable to infection because of underdeveloped immune and organ systems.[9,15] Maternal infections also significantly contribute to neonatal sepsis. Group B streptococcus (GBS) colonization, present in up to 30% of pregnant women, and chorioamnionitis, with an incidence of 2–4%, are key maternal factors associated with EOS.[16] Prolonged rupture of membranes (PROM) occurs in about 1% of all births, increasing to nearly 8% at term, and greatly facilitates ascending bacterial transmission from the maternal genital tract to the fetus. Preterm PROM, which is nearly twice as common among African Americans, complicates around 1% of deliveries, further heightening the risk of neonatal sepsis.[17] In addition, invasive neonatal procedures such as central line insertion, mechanical ventilation, and other intensive care interventions significantly elevate the risk of infection. The extent of risk varies depending on NICU infection control practices and adherence to standard aseptic protocols.[18,19]

Indian perspective

In India, approximately 5–6% of births occur at home, especially in rural areas with limited access to sterile conditions.[20] High prevalence of maternal infections like tuberculosis, coupled with maternal malnutrition and suboptimal breastfeeding practices, contributes to increased rates of low birth weight and susceptibility to infections. Antibiotic resistance further complicates treatment, exacerbated by delayed access to healthcare in rural and underserved areas.[2,21]

ETIOLOGY OF NEONATAL SEPSIS

Western data

In HICs, the primary causative organisms for EOS are Streptococcus agalactiae (GBS) and Escherichia coli.

While Coagulase-negative staphylococci comprise the majority of cases in late-onset.[22] Other organisms that cause neonatal sepsis are Haemophilus influenzae and Listeria monocytogenes.

Viruses, fungi, and parasites can also lead to the condition. For instance, the herpes simplex virus (HSV) can cause severe infections in newborns.

International data

The NeoOBS study, a prospective multi-center observational cohort conducted across 19 hospitals in Asia, Africa, Europe, and South America, enrolled 3,204 infants with a median birth weight of 2,500 g to investigate the epidemiology of neonatal sepsis. Data collected included demographic details, clinical features, microbiological cultures, and outcomes such as mortality. The study identified Klebsiella pneumoniae (132 cases), Acinetobacter (72 cases), Staphylococcus aureus (54 cases), and coagulase-negative staphylococci as the major pathogens, reporting an overall mortality rate of 11.3% (350 deaths). This study provides a global perspective on the burden of neonatal sepsis, particularly in LMICs, emphasizing the need for targeted infection prevention, early diagnosis, and effective treatment strategies. In contrast, Italian surveillance data from 2016 to 2020, which included 159,898 live births, reported 64 culture-proven EOS cases, comprising 39 caused by E. coli and 25 by GBS, with annual incidence rates of 0.24 and 0.16 per 1,000 live births, respectively. These findings reflect the impact of intrapartum antibiotic prophylaxis (IAP) for GBS in altering EOS epidemiology, with E. coli emerging as the leading cause in settings with widespread IAP use.[23]

Indian data

Indian data from studies like the Delhi Neonatal Infection Study (DeNIS) and research in Tamil Nadu highlight the bacterial profile and resistance patterns in neonatal sepsis. In DeNIS, total sepsis incidence is 14.3%, with 6.2% being culture-positive. EOS constitutes 83% of cases, predominantly caused by Acinetobacter (22%), Klebsiella (17%), and Escherichia coli (14%).[24] Similar organisms are responsible for LOS, with notable multidrug resistance among isolates. In Tamil Nadu, among 107 infants with probable sepsis, 26.2% had positive cultures, primarily EOS cases. Staphylococcus aureus and Klebsiella species were the predominant pathogens. Ampicillin resistance was observed in 52.9% of Gram-negative bacteria and 90% of Staphylococcus aureus isolates. Gentamicin resistance was noted in 31.2% of Gram-negative bacteria and 20% of Staphylococcus aureus isolates. Resistance to third-generation cephalosporins was reported in 31.2% of Gram-negative bacteria and 20% of Staphylococcus aureus isolates.[25]

CHALLENGES IN DIAGNOSIS OF NEONATAL SEPSIS

Global challenges in diagnosis

In LMICs, diagnosing neonatal sepsis is particularly challenging due to limited healthcare infrastructure. Many facilities lack essential diagnostic capabilities, including well-equipped laboratories for blood cultures and molecular testing. Unreliable electricity, inadequate refrigeration for reagents, and poor internet connectivity further restrict the use of advanced diagnostics. Shortages of trained laboratory personnel and insufficient education for healthcare providers contribute to delays in the timely recognition and management of sepsis. Additionally, disruptions in supply chains, high costs of diagnostic equipment and reagents, and poor maintenance of laboratory instruments prolong testing times. Antimicrobial resistance complicates initial antibiotic therapy, increases healthcare costs, and makes accurate pathogen identification through blood cultures and molecular diagnostics essential for effective treatment. Limited availability of newer antibiotics in LMICs often necessitates reliance on older, less effective drugs, while suboptimal infection control practices in healthcare settings facilitate the spread of resistant pathogens.[26,27]

Challenges in India

Rural-urban disparities amplify challenges in accessing advanced diagnostic facilities like molecular tests, worsened by infrastructure gaps such as unreliable electricity and inadequate refrigeration. A severe lack of trained healthcare personnel, particularly in remote areas, undermines prompt diagnosis and management. Antimicrobial resistance compounds these issues, necessitating accurate pathogen identification despite limited access to newer antibiotics. Dependency on older, potentially less effective drugs contributes to ongoing resistance development, highlighting the urgent need for enhanced diagnostic capacity and healthcare infrastructure across the country.[28,29]

Addressing these multifaceted challenges requires concerted efforts to bolster healthcare infrastructure, enhance diagnostic capabilities, expand training opportunities for healthcare providers, and implement rigorous antimicrobial stewardship programs nationwide. Improving access to advanced diagnostic technologies, ensuring consistent electricity and refrigeration facilities, and expanding educational initiatives are essential steps toward improving neonatal sepsis diagnosis and treatment outcomes globally and in India.

TREATMENT TRENDS FOR NEONATAL SEPSIS ACROSS THE WORLD

The treatment of neonatal sepsis varies significantly between high-income countries (HICs), LMICs, and specifically in India, reflecting differences in healthcare infrastructure, resources, and epidemiological factors.

High-income countries (HICs)

In HICs, the approach to treating neonatal sepsis is characterized by robust healthcare systems and access to advanced medical technologies. Prompt diagnosis is facilitated by extensive use of diagnostic tests such as blood cultures, complete blood count (CBC), C-reactive protein (CRP), and procalcitonin (PCT) levels. Early recognition is key, with healthcare providers vigilant for clinical signs like fever, respiratory distress, and poor feeding. Empiric antibiotic therapy is initiated immediately upon suspicion of sepsis, typically with broad-spectrum antibiotics like ampicillin or penicillin combined with aminoglycosides or third-generation cephalosporins to cover both Gram-positive and Gram-negative pathogens. Therapy is adjusted based on culture results to optimize efficacy and minimize resistance.[30,31] Supportive care includes respiratory support, fluid management, and nutritional support tailored to each patient’s needs. Vigilant monitoring encompasses clinical parameters and biomarkers, supported by advanced imaging when necessary. The duration of antibiotic therapy is usually shorter in uncomplicated cases, guided by clinical response and pathogen clearance. Long-term follow-up ensures comprehensive assessment of developmental outcomes and potential complications, reflecting a holistic approach to neonatal care in HICs.[32]

Low- and middle-income countries (LMICs)

In contrast, LMICs face significant challenges in managing neonatal sepsis due to limited healthcare infrastructure, diagnostic resources, and higher prevalence of antimicrobial resistance. Diagnosis often relies on clinical signs and symptoms due to constraints in performing blood cultures and other advanced tests. Empiric antibiotic therapy is initiated promptly using similar regimens to HICs, aiming to cover common pathogens such as GBS and Escherichia coli. However, due to resource limitations and higher rates of resistance, initial broad-spectrum coverage may be prolonged until culture results become available. Supportive care focuses on essential interventions like fluid resuscitation, temperature regulation through kangaroo mother care, and basic nutritional support. Monitoring relies on clinical assessment and limited laboratory tests such as point-of-care biomarkers, such as CRP or PCT, where available. Challenges include managing antimicrobial resistance with limited antibiotic options, ensuring infection control practices in healthcare settings, and addressing disparities in healthcare access between urban and rural areas.[32,33,34]

India-specific context

In India, treating neonatal sepsis requires a nuanced approach due to diverse microbial causes and varying healthcare resources across regions. EOS demands swift empiric antibiotic therapy, typically with ampicillin and gentamicin to cover common pathogens like Klebsiella, Escherichia coli, and Staphylococcus aureus.[35] Adjustments, based on local resistance patterns, may include cephalosporins or vancomycin for specific infections. LOS involves pathogens such as coagulase-negative Staphylococcus, Gram-negative bacteria, Candida, and viruses, often treated with combinations like ampicillin with gentamicin or cephalosporins, tailored to local epidemiology. Vancomycin may be added for suspected Staphylococcus aureus. Special cases like necrotizing enterocolitis may require anaerobic coverage with clindamycin or metronidazole. Management includes adjunctive therapies like IVIG and G-CSF, and antifungal treatment with amphotericin B or fluconazole based on culture results.[2,28,36] Duration of therapy varies, typically lasting 10–14 days for uncomplicated cases. Infection control strategies emphasize care bundles to reduce catheter-related infections, improve hand hygiene, and ensure judicious antibiotic use. Monitoring vital signs and biomarkers guides therapy adjustments, supported by fluid management, nutrition, and temperature regulation.[37]

Challenges in India include disparities in healthcare access and awareness, contributing to delays in referral and higher mortality rates from neonatal sepsis.

RESPONSIBILITY OF HEALTH CARE WORKERS IN MANAGEMENT AND PREVENTION OF NEONATAL SEPSIS

Healthcare workers play a pivotal role in preventing neonatal sepsis and reducing mortality rates through a range of critical responsibilities and interventions. These responsibilities are crucial across various stages of care, from prenatal to postnatal periods.

Prenatal care and education

Healthcare workers provide crucial prenatal care and education by screening for maternal infections like GBS, administering antibiotics during labor, and educating on hygiene, nutrition, and prenatal visits to prevent neonatal sepsis and ensure maternal and newborn health.[38]

Infection control practices

Implementing stringent infection control measures in healthcare settings is essential to prevent neonatal sepsis, particularly hospital-acquired cases. Key practices include rigorous hand hygiene, thorough cleaning with soap and water or alcohol-based sanitizers, and proper glove removal to reduce pathogen transmission. Sterilization of reusable medical equipment is critical, along with adherence to aseptic techniques during procedures using sterile gloves, masks, gowns, and drapes. Regular disinfection of surfaces, patient care equipment, and high-touch objects is vital to eliminate persistent pathogens. Isolation precautions for at-risk neonates and continuous education and training of healthcare personnel ensure effective protocol implementation, maintaining a safe healthcare environment.[39]

Early diagnosis and prompt treatment

Healthcare workers must monitor neonates for signs like temperature changes, heart rate, respiratory rate, and feeding difficulties. Physical exams should focus on lethargy, irritability, and abnormal skin coloration. Upon suspecting sepsis, swift initiation of diagnostic tests and blood cultures is essential to identify pathogens and determine appropriate antibiotic therapy. Early detection and timely antibiotic administration are crucial. Effective communication and collaboration among healthcare professionals ensure rapid assessment and treatment, enhancing recovery chances and reducing long-term complications.[2]

Antibiotic stewardship

Judicious antibiotic use is crucial to combat antimicrobial resistance. Healthcare workers must adhere to local guidelines, prescribing antibiotics only when clinically necessary, based on accurate diagnostics like bacterial cultures. This prevents unnecessary use, a key driver of resistance. Overuse leads to resistant bacteria, complicating treatment and posing public health risks. Educating healthcare professionals and raising patient awareness about antibiotic stewardship are vital.[40,41]

Neonatal care practices

Optimal neonatal care requires a clean environment, regular infection monitoring, and early recognition of signs like fever and respiratory distress. Prompt intervention with diagnostic tests and antibiotics prevents severe sepsis. Adherence to infection control practices, such as hand hygiene and cleanliness, minimizes hospital-acquired infections and improves newborn outcomes.[2,38,39,40,41,42]

Healthcare infrastructure and training

Enhancing neonatal care in underserved areas requires improving healthcare infrastructure with access to diagnostic facilities, a stable supply chain for medical supplies, and continuous electricity and refrigeration. Continuous training and education for healthcare workers in sepsis management, infection control, and diagnostic tools are essential for effective care, improving outcomes for newborns in resource-limited settings.[43]

Maternal and community education

Educating mothers and caregivers to recognize signs of neonatal sepsis, such as fever, poor feeding, and unusual behavior, is crucial for prompt medical attention. Healthcare workers lead community outreach programs focusing on maternal health, breastfeeding, and newborn care, emphasizing hygiene and timely consultations. This enhances awareness, reduces neonatal infections, and improves health outcomes.[21] Diligent healthcare workers improve patient outcomes and reduce neonatal sepsis mortality through prevention, early detection, and effective management, especially in high-mortality regions like India.

CONCLUSION

Neonatal sepsis is a major global health challenge, severely affecting preterm and low birth weight infants, especially in LMICs. While HICs have advanced healthcare systems and stringent infection control, LMICs face resource limitations, higher antimicrobial resistance, and poor healthcare access, exacerbating neonatal sepsis rates. In India, despite progress in healthcare access and maternal-child health programs, neonatal sepsis remains a leading cause of neonatal mortality due to diverse microbial causes and resource disparities. Healthcare workers are crucial in addressing neonatal sepsis through early detection, prompt treatment, infection control, and maternal education. Their role involves essential interventions to reduce mortality and improve neonatal outcomes. Comprehensive efforts are needed to strengthen healthcare infrastructure, improve diagnostics, promote antibiotic stewardship, and enhance healthcare provider training. Effective fulfillment of these responsibilities by healthcare workers can significantly improve neonatal health outcomes and contribute to global efforts to reduce neonatal sepsis and mortality.

Conflict of interest

The author(s) declare(s) that there is no conflict of interest.

Funding Statement

Nil.