Healthcare-Associated Infections

Key Points

Healthcare-associated infections (HAIs) are important preventable causes of morbidity and death in neonates.
Central line–associated bloodstream infections cause the bulk of HAIs in the neonatal intensive care unit; other HAIs include ventilator-associated pneumonias, urinary tract infections, surgical site infections, and nosocomial viral infections.
Several modifiable risk factors have been identified for these conditions. Preventive strategies must focus on basic hand hygiene and infection control measures, along with specific measures for the infection.
Quality improvement collaboratives have achieved great strides in infection reduction by developing improved surveillance and benchmarking strategies and implementation of bundles of preventive measures.
However, some high-risk infants continue to experience infections; additional customized strategies may be needed to enhance infection prevention in these high-risk patients.

Healthcare-associated infections (HAIs) are infections acquired by patients during hospitalization. For decades, HAIs were considered an unavoidable problem in the neonatal intensive care unit (NICU). Several factors converge to create a high risk of infection in the NICU patient: immature innate and adaptive immune defenses, the need for life-sustaining invasive interventions, broad-spectrum antibiotic exposure, colonization with potentially pathogenic microorganisms, and prolonged hospital stays. The improved survival of very low birthweight (VLBW) infants and their attendant need for invasive technologies during the NICU course magnify the impact of this problem. HAIs have been shown to impact neonatal outcomes, including short-term and long-term morbidities, hospital length of stay, healthcare costs, and death significantly and independently.

Continuous surveillance and monitoring of HAI rates and pathogens are necessary to establish reference points in each nursery and facilitate early identification of epidemics. Clinicians can prevent HAIs by consistently and reliably following best practices for infection prevention and minimizing invasive procedures to the extent possible. Quality improvement strategies, education of staff on bundles of preventive care, standardization of practice, and hospital programs such as antimicrobial stewardship are essential to preventing harm. Many centers have used these strategies to reduce the burden of HAIs with great success. In this chapter we will review the definitions, epidemiology, and adverse outcomes related to HAIs, as well as current concepts and evidence surrounding strategies for prevention of HAIs in NICUs.

Defining Neonatal Healthcare-Associated Infection

The Centers for Disease Control and Prevention (CDC) surveillance definition states that an HAI is an illness associated with a pathogen or its toxins that is not present or incubating at the time of admission. Although this definition appears straightforward, additional special considerations exist for neonates. Infections that manifest themselves early in the first week of life are typically related to perinatal risk factors and vertical transmission from the mother. HAIs occur later and are more often related to patient colonization and environmental risk factors. Although most sources define HAIs in neonates as infections occurring after 3 days of postnatal life, there is no specific age that clearly distinguishes maternally transmitted infections from HAIs. There may be substantial temporal overlap between HAIs. The CDC National Healthcare Safety Network (NHSN) currently defines HAIs in neonates as those infections initially identified on day 3 or later (or 7 days and later for group B streptococcus infections) and thus may include some infections that may have been acquired perinatally but manifest clinically beyond 3 days of life. Neonatal HAI rates may be slightly overestimated during the first few weeks of life. Definitions of central line–associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), pediatric ventilator-associated event (pedVAE), and catheter-associated urinary tract infection (UTI) are given in Box 37.1 .

Box 37.1

Definitions of Healthcare-Acquired Infections for Patients Younger Than 12 Months *

* Centers for Disease Control and Prevention National Healthcare Safety Network; modified from CDC NHSN modules for LCBI, CLABSI, VAP, pedVAE SSI.

Nosocomial Bloodstream Infections

Laboratory-confirmed bloodstream infection (LCBI). Must meet one of the following definitions:
Patient has a recognized bacterial or fungal pathogen (not included on the NHSN common commensal list), identified from one or more blood specimens obtained by a culture AND organism(s) identified in blood is not related to an infection at another site
Patient has at least one sign or symptom (fever >38.0°C, hypothermia <36.0°C, apnea, or bradycardia) AND organism(s) identified in blood is not related to an infection at another site AND the same NHSN common commensal is identified by a culture from two or more blood specimens collected on separate occasions. Common commensal organisms include, but are not limited to, diphtheroids ( Corynebacterium spp. not C. diphtheria ), Bacillus spp. (not B. anthracis ), Propionibacterium spp., coagulase-negative staphylococci (including S. epidermidis ), viridans group streptococci, Aerococcus spp., Micrococcus spp., and Rhodococcus spp.

Central Line–Associated Bloodstream Infection

LCBI (as defined above) AND
Central line or umbilical catheter in place for more than 2 days AND
Central line in place on day of or day before CLABSI diagnosis

Pneumonia

Imaging evidence: Two or more serial chest radiographs with new/progressive and persistent infiltrate, cavitation, consolidation, or pneumatoceles for patients with underlying pulmonary or cardiac disease (respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary edema) or one chest radiograph with the aforementioned abnormalities for patients without underlying pulmonary or cardiac disease AND
Worsening gas exchange AND
At least three of the following: (1) temperature instability, (2) white blood cell count less than 4000/μL or greater than 15,000/μL with 10% or more bands, (3) new-onset purulent sputum, change in character of sputum, increased respiratory secretions, or increased suctioning requirements, (4) physical examination findings consistent with increased work of breathing or apnea, (5) wheezing, rales, or rhonchi, (6) cough, (7) bradycardia (<100 bpm), or tachycardia (>170 bpm)

Ventilator-Associated Pneumonia

Pneumonia (as defined above) AND
Patient on ventilator for more than 2 days AND
Ventilator in place on day of or day before VAP diagnosis

Pediatric Ventilator-Associated Events

Patient has a baseline period of stability or improvement on the ventilator, defined by ≥2 calendar days of stable or decreasing daily minimum FiO ₂ or MAP values
After a period of stability or improvement on the ventilator, the patient has at least one of the following indicators of worsening oxygenation: (1) Increase in daily minimum FiO ₂ of ≥0.25 (25 points) over the daily minimum FiO ₂ of the first day in the baseline period, sustained for ≥2 calendar days. (2) Increase in daily minimum MAP values of ≥4 cmH ₂ O over the daily minimum MAP of the first day in the baseline period, sustained for ≥2 calendar days

Urinary Tract Infection

Symptomatic Urinary Tract Infection (SUTI)

At least one of the following symptoms: (1) fever (temperature >38.0°C), (2) hypothermia (temperature <36.0°C), (3) apnea, (4) bradycardia, (5) lethargy, (6) vomiting, or (7) suprapubic tenderness AND
Urine culture with no more than two species identified, at least one of which is present at more than 10 ⁵ CFU/mL

Asymptomatic Bacteremic Urinary Tract Infection (ABUTI)

Urine culture with no more than two species identified, at least one of which is present at more than 10 ⁵ CFU/mL AND
Bacteria identified in blood (culture-based or nonculture-based microbiologic method) that matches at least one of the bacteria present at more than 10 ⁵ CFU/mL in urine
Catheter–Associated Urinary Tract Infection:
Urinary tract infection (as defined above, either SUTI or ABUTI) AND
Indwelling urinary catheter for more than 2 days AND
Urinary catheter in place on day of or day before urinary tract infection diagnosis

Surgical Site Infection

Superficial Incisional SSI

Occurs within 30 days after the NHSN operative procedure AND
Involves only skin and subcutaneous tissue of the incision AND
At least one of: (1) purulent drainage from the superficial incision. (2) organism(s) identified from an aseptically obtained specimen from the superficial incision or subcutaneous tissue. (3) superficial incision deliberately opened and microbiologic testing of the superficial incision or subcutaneous tissue is not performed and at least one of: localized pain or tenderness; localized swelling; erythema; or heat. (4) diagnosis of a superficial incisional SSI by a physician or physician designee

Deep Incisional SSI

Occurs within 30 or 90 days after the NHSN operative procedure AND
Involves deep soft tissues of the incision (e.g., fascial and muscle layers) AND
At least one of: (1) purulent drainage from the deep incision; (2) a deep incision that spontaneously dehisces, or is deliberately opened or aspirated and at least one of the following: fever (>38°C); localized pain or tenderness; (3) abscess or other evidence of infection involving the deep incision detected on gross anatomical or histopathologic exam, or imaging test.

Organ/Space SSI

Occurs within 30 or 90 days after the NHSN operative procedure AND
Involves any part of the body deeper than the fascial/muscle layers that is opened or manipulated during the operative procedure AND
At least one of: (1) purulent drainage from a drain that is placed into the organ/space; (2) organism(s) identified from fluid or tissue in the organ/space by microbiologic testing; (3) abscess or other evidence of infection involving the organ/space that is detected on gross anatomic or histopathologic exam, or imaging test evidence suggestive of infection; AND
Meets at least one criterion for a specific organ/space infection (e.g., osteomyelitis, myocarditis, intraabdominal infection etc. as defined by NHSN module)

bpm , Beats per minute; CFU , colony-forming unit; SSI , surgical site infection.

Diagnosing Neonatal Healthcare-Associated Infection

Diagnosis of Central Line–Associated Bloodstream Infection

Although coagulase-negative staphylococci (CoNS) are common skin commensals, they are also the most common cause of CLABSIs in the NICU. Differentiating contamination from true infections with CoNS is one of the greatest challenges surrounding neonatal CLABSI definitions. The CDC introduced a change to its definition in 2008, namely, the requirement for two blood cultures positive for skin commensals to fulfill the definition of a CLABSI. However, the Vermont Oxford Network (VON), the National Institute for Child Health and Human Development (NICHD), and Children’s Hospital Neonatal Consortium (CHNC) include infants with only one culture positive for CoNS in the presence of clinical signs of infection. Furthermore, there is considerable clinical practice variation regarding whether single or multiple cultures (from phlebotomy and/or central line) are drawn, which could impact rates of CoNS diagnosis. Refinements of CLABSI definitions (relating to the timing of infection following hospital admission, line placement, etc.) may impact the number of CLABSIs reported.

Another area of uncertainty surrounds source attribution. For example, some CLABSIs in infants with underlying gastrointestinal (GI) conditions may result from translocation caused by mucosal barrier injury. However, studies to date have not fully borne out this hypothesis. Studies have demonstrated that International Classification of Diseases, Ninth Revision (ICD-9) coding of hospital administrative data has low concordance with NHSN definitions of CLABSI. Although these studies were not limited to neonatal data, the findings reflect limitations of the NHSN definitions in certain situations where clinicians may diagnose secondary etiologies for the infection, but infections remain attributed to the central line per NHSN criteria.

Diagnosis of Ventilator-Associated Pneumonia

Prior to 2013, VAP definitions were used by NHSN for surveillance of ventilator-associated events (VAEs). These definitions, including the NHSN definitions, are problematic to apply in neonates because overlap of signs and symptoms and radiographic findings with underlying respiratory conditions posed significant challenges to the diagnosis of VAP. Identifying a suitable source of pathogens is an additional cause of variability. Because of these challenges with defining VAP accurately in the neonatal population, in 2014 the NHSN discontinued surveillance of VAP in the NICU. However, many NICUs and collaboratives continue surveillance and internal benchmarking of this condition.

The CDC organized a working group in 2012 to consider whether the VAE surveillance approach used in adults could also be applied to neonatal and pediatric inpatient populations. Following the publication of a study on pediatric VAE, the CDC created a pedVAE definition. PedVAEs are identified by objective criteria defining deterioration in respiratory status after a period of stability or improvement on the ventilator. However, this approach has limitations because many pedVAE are not due to infectious etiologies but rather due to progression of underlying respiratory or cardiac disease.

Diagnosis of Urinary Tract Infection

Clinicians often use less stringent microbiologic criteria (ranging from 100 to 10,000 colony-forming units [CFUs] of bacteria per milliliter in urine) for neonatal UTI diagnosis compared with CDC definitions. CoNS may be isolated in urine samples, raising the question similar to bloodstream infections of whether they represent contamination or true infection.

Healthcare-Associated Infection Surveillance and Data Sources

Sources of data on neonatal HAIs in the United States include the CDC, NHSN, VON, NICHD, NRN, and the CHNC. Reporting overall incidence rates may be misleading because of wide variations in case mix and device utilization rates. In 2005, the CDC NHSN system developed monitors device-associated HAI rates by using an approach that accounts for variability in device use and length of hospital stay. These data are also stratified by birthweight categories and expressed as incidence density per 100 or 1000 patient or device days, which facilitates risk adjustment based on birthweight and the duration of exposure to the risk factor. Another approach to surveillance is the use of the standardized infection ratio (SIR), which is a summary measure used to track HAIs at a national, state, or local level over time. The SIR is calculated by measuring observed HAIs over predicted HAIs (derived using data from a baseline period) and adjusts for facility and/or patient-level factors that contribute to HAI risk within each facility.

NHSN tracks HAIs in more than 17,000 medical facilities and shares the data with the facilities, the CDC, other partners, and quality improvement organizations to help guide efforts at infection prevention. Outside of the United States, the International Nosocomial Infection Control Consortium runs a surveillance network for HAIs, using CDC NHSN definitions, in more than 1000 hospitals around the world, and provides aggregate data on HAI from several countries.

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