The Urgent Need to Address Neonatal Sepsis in Low- and Middle-Income Countries
Healthcare-associated infections (HAIs) and antimicrobial-resistant (AMR) infections are leading causes of neonatal morbidity and mortality, contributing to extended hospital stays and increased healthcare costs. Although the burden and impact of HAI/AMR in resource-limited neonatal units are substantial, there are few HAI/AMR prevention studies in these settings.
The neonatal period, defined as the first 28 days from birth, is the most vulnerable time in a child’s life, accounting for 47% of deaths in children under 5 years old. For neonates in low- and middle-income countries (LMICs), the risk of death is up to 11 times greater than in high-income countries. Reducing neonatal mortality to below 12 per 1,000 live births globally by 2030 is a key target of the Sustainable Development Goals.
Despite progress in reducing global neonatal deaths from 5 to 2.5 million between 1990 and 2019, there has been no reduction in neonatal mortality in sub-Saharan Africa. Over 95% of the 2.5 million neonatal deaths each year now occur in LMICs, with sub-Saharan Africa and South-East Asia contributing approximately 1 million deaths each, with 27 and 23 deaths per 1,000 live births, respectively.
Approximately one-third of neonatal deaths annually (680,000) are caused by infections, notably severe bacterial infections such as bloodstream infection, pneumonia, and meningitis. In LMICs, the proportion of neonatal infections that are healthcare-associated is uncertain, as few neonatal units in resource-limited settings conduct systematic surveillance.
The burden and impact of neonatal HAI are substantial and likely to increase due to growth in population, in-hospital births, and preterm delivery rates in sub-Saharan Africa and South-East Asia. In resource-limited settings, early and heavy neonatal bacterial pathogen colonization occurs through exposure to suboptimal water, sanitation, hygiene, and infection prevention and control (IPC) practices, as well as high rates of maternal colonization with multidrug-resistant organisms (MDROs).
Implementing Evidence-Based Interventions to Prevent Neonatal Sepsis
To address the high morbidity and mortality of neonatal HAI in LMICs, IPC programs and evidence-based specific HAI prevention interventions should be identified and prioritized by institutions and national ministries of health. For the greatest impact, these interventions should be implemented simultaneously in care bundles or multimodal programs and target multiple mechanisms of sepsis prevention.
We reviewed the literature to identify, categorize, and prioritize HAI prevention interventions for hospitalized neonates in LMICs, including care bundles and multimodal infection prevention programs. Our findings are categorized into four main domains of interventions:
- Promotion of colonization with normal flora
- Prevention of colonization with pathogens
- Maintenance of skin integrity
- HAI surveillance, education, and advocacy
1. Promotion of Colonization with Normal Flora
Neonates are extremely vulnerable to HAIs due to their immature immune systems and poorly developed skin and gastrointestinal barriers. Both kangaroo mother care (KMC) and breastfeeding are evidence-based interventions that significantly reduce HAI risk, length of hospital stay, promote growth, and enhance neonatal survival.
Several meta-analyses concluded that KMC reduces in-hospital neonatal mortality by up to 40% in babies with a birth weight of 1.5 kg or more. Overall, the KMC bundle significantly reduced neonatal mortality risk by 21% (RR 0.79; 95% CI 0.76–0.83), as well as culture-proven and clinically suspected bloodstream infections in all but the smallest babies (<1 kg).
Promoting the use of probiotics has also shown promise in reducing the risk of necrotizing enterocolitis and late-onset sepsis in preterm infants. However, more research is needed on the effectiveness of probiotics in resource-limited settings.
2. Prevention of Colonization with Pathogens
Strategies to prevent neonatal colonization with healthcare-associated pathogens, including multidrug-resistant organisms (MDROs), are crucial. These include:
- Hand hygiene: Improving hand hygiene compliance among healthcare workers and caregivers is a core component of any HAI prevention program. The WHO’s “My Five Moments for Hand Hygiene” is a widely recognized framework for promoting and monitoring hand hygiene.
- Environmental cleaning: Ensuring thorough and consistent environmental cleaning, including disinfection of equipment and surfaces, is essential to reducing the environmental burden of pathogens.
- Antimicrobial stewardship: Implementing antimicrobial stewardship programs to optimize antibiotic use can help curb the spread of AMR and prevent HAIs.
- Surveillance and outbreak investigation: Strengthening HAI surveillance, including prompt recognition and investigation of outbreaks, is key to informing prevention strategies.
3. Maintenance of Skin Integrity
Maintaining the skin barrier is crucial to preventing neonatal sepsis. Strategies include:
- Chlorhexidine skin and cord care: The use of 2% chlorhexidine gluconate for umbilical cord and skin cleansing has been shown to reduce neonatal mortality and HA-BSI rates in resource-limited settings.
- Topical emollient therapy: Applying topical emollients, such as sunflower seed oil or coconut oil, can enhance the skin barrier and prevent invasive infections in preterm infants.
4. HAI Surveillance, Education, and Advocacy
Effective HAI prevention requires a multifaceted approach that includes:
- Standardized HAI surveillance: Establishing standardized definitions and methods for HAI surveillance is essential to monitor progress and guide prevention efforts.
- Education and training: Providing ongoing education and training for healthcare workers on IPC best practices is crucial for sustained behavior change.
- Advocacy and policy support: Engaging with national and local policymakers to prioritize neonatal HAI prevention and secure necessary resources is vital for long-term impact.
Implementing a Successful Prevention Bundle in a Malaysian Neonatal Unit
The Preventing Infections in Neonates (PIN) collaborative, a partnership between Johns Hopkins Hospital and the University of Malaya Medical Center in Malaysia, implemented a multidisciplinary, cross-cultural initiative to reduce neonatal hospital-associated bloodstream infections (HA-BSI) in a 27-bed Level IV neonatal intensive care unit (NICU).
Using quality improvement methodologies, the collaborative implemented phased and bundled interventions from July 2017 to September 2019, with the goal of achieving a 50% decrease in neonatal HA-BSI rates within 12 months.
The key elements of the prevention bundle included:
- Hand hygiene: Promoting consistent hand hygiene among healthcare workers and caregivers.
- Environmental cleaning: Ensuring thorough and regular disinfection of surfaces and equipment.
- Central line insertion and maintenance: Implementing checklists and standardized protocols for central line insertion and care.
- Skin antisepsis: Using 2% chlorhexidine gluconate for skin and umbilical cord cleansing.
- Surveillance and feedback: Establishing standardized HAI definitions, data collection, and feedback to staff.
Through the collaborative efforts, the monthly median HA-BSI rate decreased from 3.95 per 1,000 patient-days during the preintervention period to 1.73 per 1,000 patient-days during the intervention period, a 56% reduction. Quarterly HA-BSI rates also decreased from a preintervention median of 4.5 per 1,000 patient-days to 3.3 per 1,000 patient-days during the intervention period.
Importantly, the PIN collaborative achieved high compliance with the bundle elements, with hand hygiene and environmental cleaning audits exceeding 90% for consecutive months. Central line insertion and maintenance checklists also showed significant improvements, increasing from 25% and 13% at baseline to 94% and 53%, respectively, during the intervention period.
The success of the PIN collaborative demonstrates that a well-defined, locally contextualized bundle of interventions can effectively reduce neonatal HA-BSI in resource-limited settings. Key factors for this success included:
- Multidisciplinary approach: Engaging a diverse team of healthcare professionals, including neonatologists, nurses, infection preventionists, and quality improvement experts.
- Tailored interventions: Adapting the prevention bundle to the local context and addressing specific challenges faced by the NICU.
- Ongoing support and mentorship: Providing remote and on-site technical assistance from the Johns Hopkins team to build local capacity and ensure sustainability.
Conclusion: Scaling Up Neonatal Sepsis Prevention in LMICs
To address the urgent need to reduce neonatal sepsis in resource-limited settings, healthcare institutions and national ministries of health must prioritize the implementation of evidence-based IPC programs and targeted HAI prevention interventions.
By implementing multimodal prevention bundles that address key domains, such as promoting normal flora colonization, preventing pathogen colonization, maintaining skin integrity, and strengthening HAI surveillance and advocacy, neonatal units in LMICs can significantly reduce the burden of healthcare-associated infections and antimicrobial resistance.
The success of the PIN collaborative in Malaysia serves as a model for how a cross-cultural, multidisciplinary approach can drive sustainable improvements in neonatal sepsis prevention, even in settings with limited resources. Scaling up these proven strategies across neonatal units in LMICs is crucial to achieving the Sustainable Development Goal of reducing neonatal mortality.
