Infection Prevention in the Neonatal Intensive Care Unit

Synopsis/abstract:

While many aspects of infection prevention and control (IPC) mirror institutional efforts, optimization of IPC practices in the neonatal intensive care unit (NICU) requires careful consideration of its unique population and environment, addressed here for key IPC domains. Additionally, innovative mitigation efforts to address challenges specific to limited resource settings are discussed.

Introduction

Hospitalized neonates are uniquely vulnerable to healthcare-associated infections (HAIs), which are associated with increased mortality, increased length of stay and healthcare costs, and risk of neurodevelopmental disability among survivors.^1-3 In the United States (US), incidence of neonatal central line-associated bloodstream infections (CLABSIs) declined significantly from 2007 to 2012, though rates have plateaued recently.^4,5 Global estimates suggest a significantly higher burden of HAI among hospitalized neonates in low- and middle-income countries (LMICs).^6,7 Infection prevention and control (IPC) strategies that address both patients and their environment are therefore of utmost importance in neonatal care settings, especially in the neonatal intensive care unit (NICU).⁸

Healthcare-associated infections in the neonate

Central line-associated bloodstream infections

CLABSIs are associated with substantial morbidity and mortality, as well as increased healthcare costs and prolonged length of stay.^4,5,9 In the US, Gram-positive pathogens account for the majority of neonatal CLABSIs. Staphylococcus aureus and coagulase negative staphylococci (CONS) account for nearly half of NICU CLABSI events.¹⁰ Among Gram-negative pathogens, Escherichia coli and Klebsiella spp. are responsible for the greatest number of infections. Candida albicans remains an important fungal etiology, especially among extremely preterm neonates. Patient factors that contribute to CLABSI risk include prematurity, low birth weight, mucosal barrier injury, and critical illness.¹¹

Catheter-associated urinary tract infection, surgical site infection, and ventilator-associated event

Due to limited use of indwelling urinary catheters in the NICU, reported catheter-associated urinary tract infection (CAUTI) rates have remained low. Despite this, standardized catheter insertion and maintenance bundles should be prioritized as part of effective infection prevention practices. Surgical site infections (SSIs) are associated with considerable morbidity, and hospital-wide prevention efforts often include the NICU. SSI surveillance may be performed locally or as part of a nework for high risk procedures common in neonates, such as ventriculoperitoneal shunt insertion or congenital heart defect repair¹² Lack of a standardized neonatal ventilator-associated event (VAE) definition hampers surveillance and prevention efforts. With the availability of revised 2015 pediatric VAE guidelines, some units have opted to identify VAE using standard guidelines.¹³ Incorporating changes in the fraction of inspired oxygen and mean airway pressure into surveillance definitions used by NICUs could standardize VAE reporting.

Infection prevention and control infrastructure and healthcare-associated infection surveillance in the NICU

Overview of infection prevention and control infrastructure and linkage to the NICU

In the US, federal regulations require an infection control officer who is qualified to oversee a facility’s plan for surveillance, prevention, and control of HAIs. IPC programs typically have a staff of infection preventionists (IPs) and may be governed by an Infection Control Committee comprised of representatives from clinical units, hospital administration, infectious diseases, and other specialties. IPs support target areas through data dissemination, staff education, and implementation of policies and prevention activities. IPC programs will often assign a lead IP to be a liaison to the NICU and its specialized population. Annual risk assessments in the NICU inform identification of opportunities for improvement in key domains (Table 1). By collaborating within and between hospital networks, infections can be prevented, harm reduced, and healthcare costs saved.^2,14

Table 1.

Key infection prevention and control domains and special considerations in the neonatal population

IPC domain	Special considerations in neonates
HAI surveillance	NHSN reporting required for CLABSI, stratified by birth weight15 NHSN CLABSI definition provides exclusion for neonatal infections (e.g., GBS, NEC)
MDRO colonization	Innovative strategies to reduce transmission (e.g., parental decolonization)19
HH	Potential role for wearing gloves after HH in high-risk populations97
Central line insertion and maintenance	Use of umbilical catheters
Topical antisepsis	Povidone-iodine systemic absorption rarely linked to hypothyroidism98 Chlorhexidine use may be restricted by age and weight to reduce potential adverse effects in very preterm neonates33
Medication and IV fluid preparation and administration	Small doses used in neonates may make consistent use of SDV impractical
Cleaning and disinfection of reused medical equipment	Specialized equipment used in neonates may be difficult to clean
Structure, water, and air	Multi-bed pods pose additional HAI risk due to less physical distancing between patients
Environmental cleaning	Avoidance of phenol in the NICU due to risk of hyperbilirubinemia99
Families and visitor policies	Family-centered care and promotion of breastfeeding and human milk feeding Sibling visitation Vaccination policies for family
Employee health	No restrictions are necessary for healthcare workers in the NICU who receive routine immunizations
Exposures	High risk given critically ill patient population without or incomplete immunization against high-risk pathogens
IPC bundles and multimodal improvement strategies	IPC bundles linked to CLABSI risk reduction in the NICU CUSP successfully adapted to the NICU

Abbreviations: CLABSI – central line-associated bloodstream infection; CUSP – Comprehensive Unit-based Safety Program; GBS – group B Streptococcus; HAI – healthcare-associated infection; HH – hand hygiene; IPC – infection prevention and control; IV – intravenous; MDRO – multi-drug resistant organism; MRSA – methicillin resistant Staphylococcus aureus; NEC – necrotizing enterocolitis; NHSN – National Healthcare Safety Network (NHSN); NICU – neonatal intensive care unit; SDV – single dose vial

Surveillance and reporting requirements

HAIs surveillance in the NICU is a key aspect of performance improvement. The Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) is a surveillance system that provides data collection and reporting capabilities to identify IPC issues, benchmark progress, and comply with public reporting mandates.¹⁵ Use of standardized definitions for HAIs creates a mechanism for comparison across healthcare facilities nationally. NHSN requirements for NICUs include reporting of CLABSI events, device days, and patient days. Definitions attempt to account for neonatal infections that may not be catheter-associated (Table 1). NHSN reporting for SSIs, CAUTIs, and VAEs is not required, but these are often tracked locally. When an HAI event or near-miss is identified, root cause analysis – a systematic evaluation of the factors contributing to the event – is beneficial in identifying opportunities for improvement.¹⁶

Colonization with resistant organisms

Prospective surveillance for multi-drug resistant organism (MDRO) colonization is limited in the NICU setting and rates of resistant infections are typically lower than in other pediatric units.¹⁷ Available MDRO data within US NICUs largely focus on methicillin-resistant S. aureus (MRSA). The recent decline in the prevalence of MRSA colonization and infection in the NICU is likely due to effective IPC measures such as decolonization, cohorting, and use of personal protective equipment (PPE), as well as enhanced antimicrobial stewardship.^18,19 However, reports of infections with other resistant pathogens such as Candida auris and carbapenem-resistant Enterobacteriaceae are increasing among neonates, especially in LMICs.^20,21

Outbreaks

Recognition of an outbreak requires vigilance by frontline staff and the IPC team; a cluster of infections with a known neonatal pathogen, increasing incidence above baseline, or the emergence of an unusual pathogen may signify an outbreak.²² Recognition that a point source may not be identified should inform broad strategies to improve general IPC practices to contain the outbreak. In some instances, partial or complete unit closure is necessary to contain an outbreak.²³

General IPC concepts and considerations in the neonate

Hand hygiene (HH)

HH is the foundation of IPC in any healthcare setting, including the NICU. The World Health Organization (WHO) recognizes five moments of HH (Box 1).²⁴ Although WHO guidelines recommend use of alcohol-based hand rub (ABHR) for 20-30 seconds or use of soap and water for 40-60 seconds, CDC guidelines for HH in healthcare settings recommend a shorter duration of 20 seconds and 15 seconds, respectively.^25,26 Use of ABHR rather than antimicrobial soap has been associated with increased compliance.²⁷ Factors that may impede effective HH include limited access to clean water or ABHR and the wearing of artificial nails.²⁸ Direct observation or electronic devices are typically used to monitor HH compliance. Only direct observation can properly capture HH compliance by moment and by HCW role; monitoring may be strengthened through routine observations over time or using ‘secret shoppers’ to reduce bias.²⁹

Box 1. Moments of hand hygiene.

Before patient contact

Before aseptic task

After body fluid exposure

After patient contact

After contact with patient surroundings

Central line insertion and maintenance

Preterm and critically ill neonates commonly require placement of central venous catheters (CVCs) and arterial catheters for provision of parenteral nutrition, medication administration, and hemodynamic monitoring. Umbilical venous and arterial catheters require attention due to their associated increased risk of infection. Recommendations for CLABSI prevention include standardized processes for insertion and maintenance (Box 2).³⁰ Topical antimicrobial ointments at the insertion site, systemic antibiotic prophylaxis, and antibiotic lock prophylaxis are not recommended. Prompt removal of central lines when no longer required is essential. Prolonged CVC presence and increased duration of parenteral nutrition has been associated with increased CLABSI risk in neonates.^3,31 Potential facilitators of early line removal include daily discussion of line necessity during rounds, documentation of line necessity in the medical record, and early introduction of enteral feeds.

Box 2. Central line insertion and maintenance.

Central line insertion

Use of insertion checklist

Dedicated procedure cart

Hand hygiene

Skin antisepsis

Use of maximal barrier precautions

Sterile occlusive dressing over PICC and tunneled catheter sites

Dedicated staff for insertion of PICCs¹⁰⁰

Central line maintenance

Daily assessment of dressing integrity

Dressing changes weekly and as needed

Prevention of insertion site bleeding

Scrubbing the hub with an appropriate antiseptic prior to access

Regular tubing changes

Reduced access frequency

Daily assessment of need and early catheter removal

• Replacement of emergently placed catheters as soon as possible in a controlled setting

• Replacement of UVCs with PICCs within the first week of life

Dedicated line maintenance team¹⁰¹

Topical antisepsis in the neonate

Selection of the appropriate topical antiseptic agent in the NICU must carefully consider patient factors (e.g., gestational age, birth weight, skin integrity) as well as intended use. Agents used for topical antisepsis in the NICU include isopropyl alcohol, povidone-iodine, and chlorhexidine. Povidone-iodine is routinely used for skin preparation prior to obtaining blood cultures and to performing surgical procedures. Associated harms include rare reports of systemic absorption with associated hypothyroidism in neonates.³² Chlorhexidine is increasingly used in the NICU, for skin preparation prior to procedures, S. aureus decolonization, and bathing for CLABSI prevention.^33-35 Burns and contact dermatitis have been reported, primarily with use of alcohol-based preparations and in young preterm neonates or those with non-intact skin.³⁶ Trace systemic absorption may occur although clinical significance is uncertain.³⁷ Age- and weight-based guidelines are commonly applied to avoid potential side effects.³³

Medication and intravenous fluid preparation and administration

Antibiotics, anti-epileptic drugs, and analgesics or sedatives may be stored in the NICU to facilitate timely administration. Injections should be prepared using aseptic technique and following recommended procedures (Box 3). Multi-dose vials (MDV) should be avoided when possible. When used, MDV should be stored appropriately, dated when first opened, and discarded within 28 days unless otherwise specified by the manufacturer. If MDV enter the immediate patient care area, their content should be reserved for a single patient. Single dose vials (SDV) should never be reused. IV fluid solution bags should only be used for a single patient. IV tubing should be changed regularly, between every 96 hours to every 7 days, except for tubing used to administer blood products or fat emulsions, which should be changed within 24 hours of the infusion or according to hospital policy.³⁰

Box 3. Injection safety.

Preparation in area separate from immediate patient care

Aseptic technique/proper cleansing of vials prior to drawing up medication

No reuse of needles and syringes

No needles left in the septum for access

Vials discarded if visible holes in septum

Appropriate sharp disposal in puncture-resistant container accessible to healthcare workers

Scheduled emptying of sharps disposals containers

Cleaning and disinfection of reused medical equipment

Levels of disinfection required for reused devices are based on intended use, and are summarized in Table 2.³⁸ A risk assessment should be conducted to ensure proper levels of disinfection for all devices used in the NICU. Noncritical devices and surfaces (e.g., bed rails, computer keyboards, thermometers) are a potential nidus for transmission and must be cleaned regularly.³⁹ Similarly, hand-held equipment used by ophthalmologists on multiple patients (such as during retinopathy of prematurity exams) must be properly disinfected between use to prevent potential pathogen transmission.⁴⁰ Due to its greater complexity and risk, facilities may centralize high-level disinfection (HLD) to ensure patient safety and regulatory compliance.^41,42 Outbreaks have been associated with airway and gastrointestinal devices due to defective design, improper reprocessing, and automated process failure.^43,44 Single use devices should never be reprocessed or reused. During an emergency, federal regulatory guidance should be consulted before single-use items are reprocessed.³⁸ In LMICs, devices are more difficult to procure; reuse may be common, and proper HLD can be challenging.⁴⁵ WHO guidelines recommend against single-use item reuse but also provide a recommended framework to ensure proper decontamination, cleaning, drying, and storage when reuse is necessary.⁴²

Table 2.

Agents appropriate for low level disinfection and concerns within neonatal intensive care units

Disinfecting agents Hospital-grade approved agents should be used with proper contact time	Device examples	NICU-specific issues
Alcohol (ethyl or isopropyl) 70-90%	Stethoscope	Not appropriate for protein-rich materials (remove residue with soap and water)
Hydrogen peroxide 3-5% (non-activated)	Ultrasound probe (only on intact skin)	Can be damaging to surfaces and metals
Hydrogen peroxide 0.5% (activated)	Blood pressure cuff Scale	Can be damaging to surfaces and metals
Household bleach (5.25%) diluted 1:500 (100 ppm)	Temperature probe (intact skin)	Can be damaging to surfaces and metals Can be damaging to sensitive electronics If diluting onsite need to mix daily Odor may be bothersome or irritating
	Horizontal surfaces in care area (e.g., bed rails, bedside tables, keyboards, ventilators, pumps, etc.)
Quaternary ammonium compounds	Monitor leads (multi-use)	Less damaging to surfaces (e.g., electronics, ultrasound probes, etc.) When mixed with bleach can release chlorine gas, a respiratory irritant
Phenols/phenolics	Surfaces/floors	Not recommended for NICU (including floors) May cause hyperbilirubinemia when used on devices and bassinets99 Irritating to skin – use on surfaces only
Hypochlorite bleach or saline solution	Ophthalmoscope, calipers, pincers for eye exams	Can leave residue on lenses and limit use Rinsing with sterile water after cleansing can remove residue40

Environment

Structure, water, and air

The structure and design of a NICU may influence HAI risk. For example, transmission risk for S. aureus was noted to be higher among infants in multi-bed pods compared to those in single bed rooms.⁴⁶ However, single occupancy room design is often not feasible, particularly in LMICs. NICUs with multi-bed pods could address the increased risk of HAI transmission by screening and cohorting, limiting shared equipment, or placing physical barriers between patients to prevent the potential for cross-contamination.

Colonization of plumbing fixtures has been linked to NICU outbreaks, both through direct and indirect water exposure.⁴⁷ Risk mitigation such as avoiding areas of decreased flow and ensuring proper disinfection should be included in water protection programs.⁴⁸ Sinks should be designated for waste disposal only or HH only.⁴⁹ Sterile water for infant bathing or dry warmers for human milk should be used to avoid infections associated with tap water, if possible.⁵⁰ Facilities with untreated source water should install filtration or chemical disinfection at the intake point. Environmental sampling, in the absence of an ongoing outbreak, is of unclear significance, but may be part of an environmental risk assessment.^48,51,52 Understanding plumbing and building structure is important to prevent inadvertent introduction of pathogens, if a breach occurs due to a leak or renovation.⁵³

Airflow and ventilation maintenance are guided by federal regulatory standards in the US.⁵⁴ If windows open or ventilation is decentralized, ensuring adequate exchange and accounting for humidity and potential vector encroachment may be necessary.⁵⁵ Because a NICU room has fewer air changes per hour than an operating room, emergent bedside surgical procedures for clinically unstable infants may pose an HAI risk. Implementing environmental control protocols during these procedures may be beneficial. A NICU should have at least one airborne isolation room (AIIR) for managing infants and their essential caregivers while preventing exposure to airborne pathogens by other infants and staff.⁵⁶

Environmental cleaning

Protocols for cleaning and disinfection at regular intervals and at patient discharge should be established to prevent HAI.^57,58 Bedside and environmental services (EVS) staff can share routine responsibilities, with clear delineation, to ensure regular cleaning. Routine closure of clinical areas can facilitate deep cleaning while not disrupting infant development, such as with bright lights and loud machinery.⁵⁹ Adherence monitoring with regular feedback and using dedicated EVS teams are strategies to support effective cleaning.^60,61

HAIs and outbreaks due to contaminated equipment requiring humidification (e.g., isolettes, ventilator drains) could result from water, environment, or clinician contamination.^62,63 Small size, need for user-specific training, and frequency of use may limit appropriate cleaning of NICU-specific equipment. Increasing device and disinfectant supply may ensure clean devices are available when needed.

Mitigating risk of potential exposures in the NICU

Families and Visitors

To promote family-centered care, NICUs must balance visitation policies with limiting opportunities for infection transmission. There are reports of outbreaks introduced by visitors or caregivers, leading NICUs to opt for intermittent visitor restrictions, such as during respiratory viral season.^64,65 However, restrictions might cause parent/caregiver dissatisfaction and adversely affect infant care.⁶⁶ Restrictions might be avoided with strict HH adherence, shown to reduce respiratory virus transmission.^66,67 Regardless of season, screening should be conducted to exclude ill individuals.

Recent guidance prioritizes HH for visitors to limit MRSA transmission within the NICU.^68,69 More restrictive visitation policies may apply to young children, who may not be fully vaccinated and have difficulty complying with HH.^67,70 Compliance with standard vaccination recommendations among parents and visitors may provide additional protection. Offering influenza vaccine to parents can improve vaccination rates while preventing influenza transmission.⁷¹ Ideally, visitors, in particular siblings, should show proof of proper vaccination. However, this may not be practical to implement.

Vaccines that contain inactivated organism components pose no risk of infection to NICU patients. Risk of transmission of live attenuated vaccine virus strains is very low.⁷² In infants the rotavirus and live attenuated influenza (LAIV) vaccines pose a theoretical risk of transmission of attenuated vaccine virus strains. Units may consider placing patients in precautions (e.g., contact for rotavirus) following receipt of vaccine for up to 2 weeks.

Employees

The CDC provides regularly updated guidance for healthcare worker vaccinations, often overseen by a system’s Employee Health/Occupational Health program.⁷³ Special consideration should be made for seasonal influenza vaccination, as studies show that facilities that mandate seasonal influenza immunization of employees have the highest levels of coverage.⁷⁴ This is especially important in settings such as the NICU where the majority of patients are age ineligible to receive a seasonal influenza immunization. Receipt of approved live-attenuated vaccines is not contraindicated in HCWs caring for severely immunocompromised patients.^72,75 Care must be taken for of recipients of varicella or zoster vaccine, as virus from vesicular lesions formed at the vaccination site or elsewhere may have the potential for transmission.⁷² Units may consider standard screening for receipt of these vaccines during the previous 1-2 weeks, and to ask specifically about rash following receipt of VZV.^72,76 Additionally, some recommend that LAIV recipients wait 1-2 weeks following immunization before caring for vulnerable patients.⁷⁶ Presenteeism, the practice of coming to work despite symptoms of infectious illness, is a potential source of pathogen transmission to employees and patients alike.⁷⁷ Employee Health (EH) and IPC can collaboratively promote minimal employee penalties for absences due to illness.⁷⁸ Any condition preventing adequate HH should result in exclusion from care until HH may be performed. Employees with herpes zoster lesions in a single dermatome should be excluded from the care of varicella non-immune patients in the NICU until their lesions have crusted.^79,80

Exposures

Despite prevention efforts, breaches in IPC or exposures to infectious agents will occur requiring a coordinated response. NICUs should collaborate with IPC and EH to develop and enforce policies to manage exposures. Pathogens of concern include severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), measles, VZV, and pertussis. Pre-emptive contact and droplet isolation of exposed infants may be necessary in multi-bed settings, where they can be assessed for the development of symptoms during the incubation period.

VZV transmission from contact with a clinician or visitor with uncovered herpes zoster lesions and the subsequent development of acute infection in a non-immune infant is rare in the post-vaccine era. Exposed non-immune infants should be moved to an AIIR during the incubation period and consideration should be given for administration of immune globulin.⁵⁶ Pertussis infections pose a significant risk to non-immune neonates, and post-exposure prophylaxis may be indicated, with consideration of the limited safety data available for recommended agents.^81,82 Assessing exposure events and notifying families of potential transmission risk is part of a comprehensive exposure plan recommended for NICUs.⁸³

IPC bundles and multi-modal improvement strategies

The use of bundles to reduce HAI risk via implementation of a package of evidence-based practices is a mainstay of IPC. A 2018 systematic review and meta-analysis of 24 NICU-based studies demonstrated a 60% reduction in CLABSI rate with care bundle implementation.⁸⁴ Care bundle composition varied significantly; the most common element included use of a specific protocol for skin preparation, maximal barrier precautions, and daily assessment of catheter need. IPC bundles have also been used to target other HAIs in the NICU, including VAE, and in response to outbreaks.^22,85 Antimicrobial stewardship interventions should be embedded in HAI prevention bundles to link the core concepts of infection prevention and stewardship to optimize neonatal outcomes.⁸⁶

Multimodal IPC improvement strategies are included in WHO core components for IPC programs and consist of five elements: (1) system change, (2) training and education, (3) monitoring and feedback, (4) reminders and communication, and (5) culture change (Figure 1).⁸⁷ Multimodal strategies to reduce HAI risk include the Comprehensive Unit-based Safety Program (CUSP), first implemented to reduce CLABSI risk in adult ICUs.⁸⁸ CUSP has been successfully adapted to the NICU setting, as part of a national quality collaborative.⁸⁹

Figure 1. The World Health Organization multimodal infection prevention and control improvement strategy.

The WHO multimodal IPC improvement strategy consists of five elements and is a core component of IPC programs.⁸⁷ Abbreviations: ABHR — alcohol-based hand rub; CUSP — Comprehensive Unit-based Safety Program; HH — hand hygiene; IPC — infection prevention and control; NICU — neonatal intensive care unit; WHO — World Health Organization.

Limited Resource Settings

Burden of healthcare-associated infections in low- and middle-income country NICUs

LMIC healthcare facilities increasingly care for preterm and ill neonates who are at risk for HAIs, especially due to multi-drug resistant Gram-negative pathogens.⁷ Given limited treatment options and increased morbidity and mortality associated with these infections, optimizing IPC practices to reduce HAI risk is a key strategy. Delivery of IPC best practices in LMIC healthcare facilities may be compromised by water supply, high patient-to-nurse ratios, facility overcrowding, PPE and HH supply shortages, reuse of single-use items, and high burden of AMR colonization and infection, among other factors.⁹⁰

Innovative approaches to preventing healthcare-associated infections in limited-resource settings

Kangaroo mother care, or provision of prolonged skin-to-skin contact and exclusive breastfeeding, was developed to support thermoregulation in low birth weight neonates in LMICs and is associated with decreased risk of sepsis and mortality.⁹¹ In settings where omphalitis and associated sepsis is more common, use of topical antiseptics for cord care may be indicated to reduce risk. Chlorhexidine application to the cord has been shown to be effective in reduction of cord bacterial burden and resultant neonatal infections; data to support routine use in hospitalized neonates are scarce.^92,93 Topical emollient massage, a common practice in South Asia and other LMIC settings, has been demonstrated to improve skin integrity and reduce late onset sepsis risk and mortality among hospitalized preterm neonates in LMICs.^94,95 Use of sunflower seed oil or coconut oil for topical emollient massage in hospitalized neonates with an HAI risk is a promising intervention, given its acceptance by caregivers and cost-effectiveness.⁹⁶

Summary

Numerous unique challenges exist within the NICU requiring innovative IPC strategies to deliver safe care to vulnerable neonates. Collaborative efforts to promote HH, standardize cleaning of specialized equipment, maintain environmental cleaning, perform HAI surveillance, and implement bundled interventions to prevent HAIs are integral to a NICU IPC program. Challenges of HAI prevention exist in both resource advantaged and limited settings can be addressed through innovation and utilization of local expertise and resources.

Key Points:

• Neonatal healthcare-associated infections (HAIs) are associated with significant morbidity and mortality.

• The NICU poses unique infection prevention and control (IPC) challenges due to its specialized population, equipment, and environment.

• IPC in the NICU requires a collaborative relationship between unit-based staff and the hospital’s IPC program as well as local, state, and federal resources.

• Innovative strategies are needed to reduce HAI risk in limited resource settings.

Clinical Care Points.

• Successful IPC programs in the NICU rely on a collaborative relationship between unit-based staff and the facility’s IPC infrastructure.

• HAI surveillance and root cause analyses should inform performance improvement in the NICU.

• Disinfection and environmental cleaning in the NICU must consider the population, structure, and environment unique to the NICU.

• IPC bundles and multimodal improvement strategies are effective in reducing HAI risks in the NICU.