Factors associated with persistent bloodstream infection in the Neonatal Intensive Care Unit – Nature

Report on Factors Associated with Persistent Bloodstream Infections in Neonates and Alignment with Sustainable Development Goals

Executive Summary

This report details the findings of a single-center study investigating factors associated with persistent bloodstream infections (BSIs) in infants within a Neonatal Intensive Care Unit (NICU). The primary objective was to identify clinical and microbial characteristics that could inform diagnostic stewardship and optimize the use of follow-up blood cultures (FUBCs). This research directly supports several United Nations Sustainable Development Goals (SDGs), primarily SDG 3 (Good Health and Well-being) by aiming to reduce neonatal mortality and improve patient care. The study identified four significant factors associated with persistent BSI: the presence of Staphylococcus aureus, male sex, the use of a central venous catheter (CVC), and late-onset sepsis (LOS). Conversely, no persistent infections were observed in cases of early-onset sepsis (EOS) or infections caused by Streptococcal species. These findings have significant implications for creating more sustainable and equitable healthcare practices, aligning with SDG 5 (Gender Equality) by highlighting gender-specific health risks and SDG 10 (Reduced Inequalities) by improving outcomes for a highly vulnerable patient population.

Introduction: Enhancing Neonatal Health through Evidence-Based Practice

Contribution to SDG 3: Good Health and Well-being

Bloodstream infections represent a major cause of morbidity and mortality in premature infants, a critical challenge to achieving SDG Target 3.2, which aims to end preventable deaths of newborns and children under five years of age. The process of diagnosing these infections, particularly through repeated blood draws for FUBCs, is invasive, painful, and carries risks of contamination and excessive antibiotic use. This study addresses this challenge by seeking to establish an evidence-based framework for diagnostic stewardship. By identifying when FUBCs have the highest utility, healthcare providers can reduce unnecessary procedures, minimize infant distress, and limit iatrogenic harm, thereby promoting the overall health and well-being of this vulnerable population.

Study Design and Methodology

Patient Cohort and Data Collection

A single-center cohort study was conducted over a five-year period at a Level IV NICU. The study analyzed data from 121 infants who had a positive blood culture. Key data points collected included:

• Patient demographics (e.g., sex, gestational age)
• Clinical variables (e.g., presence of a CVC, timing of sepsis onset)
• Microbiological data (e.g., organism identified)

Analytical Approach

The study employed bivariate and multi-regression analyses to examine the association between various clinical and microbiological variables and the primary outcome: persistent BSI. A persistent BSI was defined as the growth of the same organism in a FUBC more than 48 hours after the initial positive culture. This rigorous approach ensures that the identified risk factors are statistically significant and can reliably inform clinical practice.

Key Findings and Implications for Sustainable Development

Factors Significantly Associated with Persistent BSI

The multivariate analysis identified four factors that were significantly associated with a higher likelihood of persistent BSI. These findings are crucial for developing targeted clinical protocols that enhance patient safety and resource management.

1. Recovery of Staphylococcus aureus: This organism was the strongest predictor of persistent infection (OR = 6.10).
2. Male Sex: Male infants were found to have a significantly higher risk of persistent BSI compared to female infants (OR = 3.31).
3. Presence of a Central Venous Catheter (CVC): The presence of a CVC at the time of infection was a major risk factor (OR = 3.73).
4. Late-Onset Sepsis (LOS): Infections occurring more than three days after birth were strongly associated with persistence.

Notably, the study found that no infants with either early-onset sepsis (EOS) or bacteremia caused by any Streptococcal species experienced a persistent BSI.

Implications for SDG 3 (Good Health and Well-being) and SDG 12 (Responsible Consumption)

These results provide a clear pathway to improve neonatal care and promote sustainable healthcare practices.

• Targeted Diagnostic Stewardship: By focusing FUBCs on infants with the identified high-risk factors, clinicians can avoid unnecessary and painful procedures for low-risk infants. This reduces the potential for harm and aligns with the core principle of promoting patient well-being under SDG 3.
• Resource Optimization: Reducing the number of unnecessary blood cultures contributes to SDG 12 (Responsible Consumption and Production) by minimizing the use of laboratory resources, reducing healthcare costs, and preventing waste.
• Antimicrobial Stewardship: A targeted approach to FUBCs can support more judicious use of antibiotics. Documenting clearance is often used to determine treatment duration; forgoing FUBCs in low-risk scenarios (e.g., Streptococcal bacteremia) encourages adherence to standard treatment guidelines, helping to combat the global threat of antimicrobial resistance.

Implications for SDG 5 (Gender Equality) and SDG 10 (Reduced Inequalities)

• Gender-Specific Health Risks: The finding that male infants are at higher risk highlights a biological disparity that requires clinical attention. Recognizing this vulnerability is a step toward ensuring equitable health outcomes, a key component of SDG 5, by tailoring monitoring and treatment strategies to the specific risks faced by different patient groups.
• Protecting Vulnerable Populations: Premature infants in the NICU represent one of the most vulnerable patient populations. Research that improves their survival and long-term health outcomes is fundamental to achieving SDG 10, which calls for reducing inequalities in all forms, including health disparities.

Conclusion and Recommendations for Sustainable Healthcare Practices

Summary of Conclusions

This study concludes that specific patient and microbial characteristics can effectively guide diagnostic stewardship in the NICU. The data strongly suggest that FUBCs provide the greatest clinical value in infants with S. aureus bacteremia, a CVC, late-onset sepsis, or who are male. Conversely, routine FUBCs may offer limited utility in cases of early-onset sepsis or Streptococcal bacteremia.

Recommendations for Clinical Practice and Policy

• Develop Evidence-Based Guidelines: Healthcare institutions should develop and implement clinical guidelines that recommend FUBCs for infants with identified high-risk factors while discouraging their routine use in low-risk scenarios.
• Promote Patient-Centered Care: Adopting these findings into practice reduces invasive procedures, directly improving the patient experience and supporting the goal of SDG 3 to ensure healthy lives and promote well-being for all at all ages.
• Encourage Further Research: Validation of these findings in larger, multi-center studies is recommended to strengthen the evidence base and promote the widespread adoption of these sustainable and effective diagnostic practices in neonatal care globally.

Analysis of Sustainable Development Goals (SDGs) in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

The primary SDG addressed in the article is SDG 3, which focuses on ensuring healthy lives and promoting well-being for all at all ages. The article’s entire scope is centered on improving health outcomes for a highly vulnerable population—premature infants in the Neonatal Intensive Care Unit (NICU).

• SDG 3: Good Health and Well-being: The study directly contributes to this goal by investigating bloodstream infections (BSIs), which the article identifies as “a significant cause of morbidity and mortality in this high-risk population.” By seeking to improve diagnostic practices and understand risk factors for persistent infections, the research aims to enhance the quality of care, reduce harm from unnecessary procedures, and ultimately improve the survival and health of newborns.

2. What specific targets under those SDGs can be identified based on the article’s content?

Based on the article’s focus on neonatal health, infection control, and quality of care, several specific targets under SDG 3 are relevant:

1. Target 3.2: By 2030, end preventable deaths of newborns and children under 5 years of age.
   • Explanation: The article’s core objective is to reduce the negative impacts of BSIs, which are a major contributor to neonatal mortality. The introduction explicitly states that these infections are a “significant cause of morbidity and mortality.” The study’s investigation into persistent BSI and its risk factors is a direct effort to improve treatment and management, thereby contributing to the prevention of deaths in this vulnerable group. The exclusion of infants who “died prior to 48 h after the initial positive culture” further underscores the direct link between the subject matter and neonatal mortality.
2. Target 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.
   • Explanation: While sepsis is not a named epidemic in this target, it falls under the category of “other communicable diseases,” especially in the context of hospital-acquired infections. The study analyzes the prevalence and persistence of various pathogens like Staphylococcus aureus and enteric GNRs, which cause communicable BSIs in the NICU. By identifying factors associated with persistent infections, the research contributes to better management and control of these diseases within a healthcare setting.
3. Target 3.8: Achieve universal health coverage, including financial risk protection, access to quality essential health-care services…
   • Explanation: The article promotes the concept of “diagnostic stewardship,” defined as “the practice of avoiding tests when the pre-test probability of a clinically actionable result is low.” This directly relates to improving the quality and efficiency of essential healthcare services. The finding that “99% of infants with an initial positive blood culture had a FUBC, including 95% of likely contaminants,” is presented as an “opportunity to safely reduce the number of FUBCs and associated needle sticks.” This approach enhances the quality of care by minimizing invasive, painful, and potentially unnecessary procedures for infants.
4. Target 3.d: Strengthen the capacity of all countries…for early warning, risk reduction and management of national and global health risks.
   • Explanation: The study strengthens the capacity for risk reduction and management by identifying clear risk factors for persistent BSI. The conclusion states that “S. aureus bacteremia, the presence of a CVC, male sex and LOS were associated with persistent BSI.” This knowledge allows clinicians to better manage health risks by targeting interventions and follow-up testing to the infants who need it most, which is a core component of strengthening risk management capacity in healthcare.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

The article contains several data points and outcomes that can serve as direct or implied indicators for measuring progress toward the identified SDG targets.

1. Indicator for Target 3.2 (Neonatal Mortality Rate):
   • Implied Indicator: The article implies the importance of the neonatal mortality rate by stating that BSIs are a “significant cause of…mortality” and by noting that 19 infants were excluded because they “died within 48 h of the index culture.” A reduction in deaths from BSI in the NICU would directly contribute to a lower neonatal mortality rate (Indicator 3.2.2).
2. Indicator for Target 3.3 (Incidence of Communicable Diseases):
   • Direct Indicator: The study provides data on the incidence and persistence of specific infections. For example, it reports that “Seventeen percent (24/138) of positive index cultures were persistently positive on FUBC.” It also details the rates for specific organisms, such as “41% (15/37) of S. aureus BSIs remained positive at 48 h.” These statistics serve as direct measures of the incidence and persistence of communicable diseases within the studied population.
3. Indicator for Target 3.8 (Quality of Essential Health Services):
   • Implied Indicator: The rate of unnecessary medical procedures can be used as a proxy for the quality of care. The article highlights that “95% of likely contaminants” received a follow-up blood culture, suggesting a high rate of potentially unnecessary tests. The study’s goal is to reduce this rate through “informed diagnostic stewardship.” Therefore, a decrease in the number of FUBCs for low-risk infants (e.g., those with Streptococcal bacteremia, for which “no persistent BSIs were identified”) would be an indicator of improved quality and efficiency of care.
4. Indicator for Target 3.d (Risk Reduction and Management):
   • Direct Indicator: The identification of specific risk factors serves as an indicator of improved capacity for risk management. The article’s multivariate model identifies four key factors: “LOS, recovery of S. aureus, presence of a CVC, and male sex.” The development and application of clinical guidelines based on these risk factors would be a tangible measure of strengthened risk management capacity.

4. Table of SDGs, Targets, and Indicators

Source: nature.com