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Neonatal nosocomial infection (NNI) remains a significant factor in both mortality and morbidity within our NICUs. The rapid and often unexpected decline of an infant from acute septicemia has a devastating effect on both parents and staff. Although NNI mortality is relatively low, it has become increasingly evident that nonfatal, late-onset septicemia contributes significantly to the incidence and severity of common adverse neonatal outcomes. A review of outcomes of >6000 extremely low birth weight (ELBW) infants with respect to NNI, published by the National Institute of Child Health and Human Development (NICHD) network, found NNI was statistically associated with adverse cognitive and motor development after correcting for the known confounders.1 Shah and coworkers (see Review 1) have recently taken this a step further by demonstrating an association between NNI, cerebral white matter damage, and later neurodevelopmental delay.
Their work builds on the concept of remote effects of inflammation on the brain associated with chorioamnionitis.2 Perhaps of greatest concern is that both studies demonstrated a clear propensity for coagulase-negative Staphylococcus (CoNS) infection to induce brain injury, and adverse neurologic development. Despite its relatively low mortality rates, CoNS infection must be considered a serious illness with long-term complications.
To address any issue, one must first accurately quantify the problem. In order to compare NNI rates from nursery to nursery, collected data must be comparable. When assessing NNI appropriately, it is vital to use robust definitions for the numerator, while the denominator must reflect exposure and account for the fact that an individual infant may have multiple NNIs. The adoption of infant “days” rather than a simple count of infants has been a major advance in quantifying data, and is now an accepted standard. The evolution of a robust epidemiologic methodology for describing NNI is discussed in Review 2. It is only through the continuous application of such methodologies that we can accurately delineate true rates of NNI and determine the effects of interventions in an individual unit or the variations in practices between units.
The high prevalence of NNI is not surprising when one considers the etiologic factors. The newborn is relatively immunodeficient, and poorly equipped to deal with the challenging and microbial-rich extrauterine environment. The neonatal immune system is an area of intense study, and we are slowly unveiling its secrets. Although neonatal vaccination and immune modulation are promising approaches to boost responses to nosocomial pathogens, much remains to be learned before they enter the clinical stage, as discussed in Review 3.
In addition to the immature neonatal immune system, we must also consider the environment into which the infant is delivered. The average NICU is a warm, moist, and cramped environment ideal for the propagation of microorganisms. The liberal use of disinfectants and antibiotics may ensure their rapid destruction but also allows for more virulent and resistant species to emerge. The natural barrier defenses of the respiratory tract, gut, and skin are continually breached during many routine neonatal care practices. The remainder of this issue explores the ways in which we can collectively shift the balance to favor the “blossoming of the babies and not the bugs.”
In tackling NNI, there is no magic bullet. Attention to detail in all facets of neonatal care and harnessing a collective will to change is necessary. Edwards was the first to describe the effects of unit “culture” on responses to NNI (see Review 4) and the author supports the need for a collective mind shift away from an “entitlement” to a “prevention” model of thinking. Rather than a fatalistic approach, the prevention model views NNIs in the neonate as preventable with appropriate and continuously evolving care practices. The introduction of a quality improvement team approach has repeatedly demonstrated both changes in culture and reduction in NNIs. An exemplary protocol for the introduction of a quality improvement initiative is discussed in Review 4, with similar work having been conducted within the Vermont Oxford Network3 and by many other neonatal units.
Practice changes in all facets of neonatal care have been associated with decreased NNI. Perhaps the most significant and fundamental is the need for appropriate hand hygiene. This concept was first introduced in 1847 by Dr. Ignaz Semmelweis, who documented that hand washing with chlorine could halt the spread of puerperal fever. A latter-day champion of adequate hand hygiene has been Dr. Didier Pittet, who has successfully introduced alcohol-based gels. One of Dr. Pittet’s original papers is addressed in Review 5. Dr. Pittet has continued to promote this work through the recognition of opportunities for hand hygiene (moments of care).4 The ergonomics of the work environment can also be designed to minimize the likelihood of lapses in practice. The current requirements for adequate separation of neonatal beds, and the trend toward clear and distinct boundaries between beds, are good examples of this approach.
Other notable discoveries have included the recognition of the strong association between NNI and central lines. Benchmark care now involves a more conservative use of long lines, meticulous asepsis in their insertion, and minimal breaches in lines during care. Many of these aspects are addressed in the paper by Schulman and colleagues, also discussed in Review 4.
Where are we going in the prevention of NNIs? Moving from documented evidence to informed speculation, it appears that much could be gained from the “deintensifying” of our neonatal intensive care units (NICUs). Such strategies appear not only to reduce NNIs, but to decrease the occurrence of other common morbidities as well. The move toward “gentilation” and the introduction of rapid extubation to nasal continuous positive airway pressure (nCPAP) is one example. Similarly, we will need to reduce our reliance on parenteral nutrition and improve our enteral feeding practices. The paper by Rønnestad and associates (Review 6) describes a potential reduction in NNIs through very early introduction of breast milk. In addition to decreasing the need for central lines and antibiotic use, this practice may facilitate colonization of the gut with physiologic rather than nosocomial organisms. Reduction in NNIs, and particularly necrotizing enterocolitis (NEC), has been demonstrated with supplementation of feeds with probiotics5 or lactoferrin.6 Although early introduction of breast milk would seem to be physiologic, combined approaches should be explored.
Considerations must also be given to the role of antibiotics, as they can predispose infants to NNIs. A recent NICHD publication by Cotton and collaborators addressed this issue, demonstrating a significantly increased risk for NEC in ELBW infants receiving prolonged initial courses of antibiotics despite having negative cultures. There were similar trends for an increase in NNIs.7 Interestingly, these effects were more pronounced in infants in whom enteral feeds were delayed (>day 5).7 It is tempting to speculate that a reduction in the antibiotic load prescribed for such infants may actually reduce NNIs. Future clinical studies should use our increasingly sophisticated immunologic knowledge and technology to allow for early and accurate identification of true infections to minimize unnecessary antibiotic exposure.
In addition, emerging understanding of the intricacies of early immune development may facilitate prediction of those infants at highest risk for NNI and allow for targeted preventive intervention.
The future of NNI prevention in NICUs is at a crossroads. We can continue to pursue a nihilistic “entitlement” model, whereby we continue to treat ever more resistant bugs with increasingly more powerful antibiotics. Alternatively, we might adopt a physiologic model and collaborate to identify and institute best practices for “deintensifying” nurseries, thereby reducing our reliance on antibiotics, and improving the outcomes for our infants.
Commentary References
| 1. |
Stoll BJ, Hansen NI, Adams-Chapman I, et al; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292(19):2357-2365.
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| 2. |
Dammann O, Leviton A.
Infection remote from the brain, neonatal white matter damage, and cerebral palsy in the preterm infant. Semin Pediatr Neurol.
1998;5(3):190-201. |
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| 3. |
Kilbride HW, Powers R, Wirtschafter DD, Sheehan MB, Charsha DS, LaCorte M.
Evaluation and development of potentially better practices to prevent neonatal nosocomial bacteremia. Pediatrics.
2005;111(4 pt 2):504-518. |
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| 4. |
Sax H, Allegranzi B, Uçkay I, Larson E, Boyce J, Pittet D.
My five moments for hand hygiene’: a user-centred design approach to understand, train, monitor and report hand hygiene. J Hosp Infect.
2007;67(1):9-21. |
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| 5. |
Deshpande G, Rao S, Patole S.
Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet.
2007;369(9573):1614-1620. |
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| 6. |
Manzoni P, Rinaldi M, Cattani S, et al; Italian Task Force for the Study and Prevention of Neonatal Fungal Infection, Italian Society of Neonatology.
Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA.
2009;302(13):1421-1428. |
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| 7. |
Cotton CM, Taylor S, Stoll B, et al; NICHD Neonatal Research Network.
Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics.
2009;123(1):58-66. |
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