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Healthcare-Acquired Infections


Premature and very-low-birthweight (VLBW) infants often have prolonged hospitalizations and are particularly prone to healthcare-acquired infection ( HAI ) because of their inefficient innate immunity, deficient skin barriers, presence of indwelling catheters and other devices, and prolonged endotracheal intubation ( Table 130.1 ). HAIs are associated with increased length of hospitalization, increased cost of care, and significant morbidity and mortality.

Table 130.1
Definitions of Healthcare-Acquired Infections for Patients <12 Mo Old *
Adapted from Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care–associated infection and criteria for specific types of infections in the acute care setting, Am J Infect Control 36:309–332, 2008.
NOSOCOMIAL BLOODSTREAM INFECTIONS
Laboratory-Confirmed Bloodstream Infection (LCBI)
Must meet 1 of the following definitions:

  • Recognized pathogen in 1 or more blood specimens (culture-based or non–culture-based microbiologic methods), performed for clinical diagnostic or therapeutic purposes and not related to infection at another site.

  • Commensal organism (e.g., coagulase-negative staphylococci, diphtheroids, bacillus, viridans streptococci, aerococcus, micrococcus, propionibacterium), identified from 2 or more blood specimens obtained on separate instances (culture- or non–culture-based microbiologic methods), performed for clinical diagnostic or therapeutic purposes and not related to infection at another site and at least 1 of the following signs: (1) fever (temperature >38.0°C), (2) hypothermia (temperature <36.0°C), or (3) apnea or bradycardia.

Central Line–Associated Bloodstream Infection (CLABSI)

  • LCBI (as defined above) and

  • Central line or umbilical catheter in place for >2 days and

  • Central line in place on day of or day before CLABSI diagnosis.

Pneumonia

  • 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 1 chest radiograph with the aforementioned abnormalities for patients without underlying pulmonary or cardiac disease and

  • Worsening gas exchange and

  • At least 3 of the following; (1) temperature instability; (2) white blood cell count <4,000/µL or >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, wheezing, rales, or rhonchi; (5) cough; (6) bradycardia (<100 beats/min), and (7) tachycardia (>170 beats/min).

Ventilator-Associated Pneumonia (VAP)

  • Pneumonia (as defined above) and

  • Patient on ventilator for >2 days and

  • Ventilator in place on day of or day before VAP diagnosis

URINARY TRACT INFECTION
Symptomatic Urinary Tract Infection (SUTI)

  • At least 1 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 2 species identified, at least 1 of which is present at >10 5 CFU/mL.

Asymptomatic Bacteremic Urinary Tract Infection (ABUTI)

  • Urine culture with no more than 2 species identified, at least 1 of which is present at >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 >2 days and

  • Urinary catheter in place on day of or day before urinary tract infection diagnosis.

CFU, Colony-forming units.

* Centers for Disease Control and Prevention/National Healthcare Safety Network.

Incidence

The most common HAIs in the neonatal intensive care unit (NICU) are bloodstream infections, predominantly central line–associated bloodstream infections. Ventilator-associated pneumonia (VAP) is the next most common, followed by surgical site infection and catheter-associated urinary tract infection.

Approximately 11% of NICU patients develop nosocomial infection during their hospitalization; up to 25% of VLBW infants will have blood culture–proven sepsis during their hospitalization. Infection rates are highest among the most premature infants. Ventilator-associated pneumonia accounts for approximately 25% of HAIs.

Epidemiology

HAIs in the NICU are predominantly caused by gram-positive organisms. The largest fraction of bloodstream infections (BSIs) in the NICU are caused by coagulase-negative staphylococci ( Table 130.2 ). Other agents that often cause HAIs in the newborn include Staphylococcus aureus, enterococci, gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa ), and Candida. Viruses contributing to HAIs in the neonate include rotavirus, enteroviruses, hepatitis A virus (HAV), adenoviruses, influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza, and herpes simplex virus (HSV).

Table 130.2
Distribution of Organisms Responsible for Late-Onset Sepsis
Adapted from Ramasethu J. Prevention and treatment of neonatal nosocomial infections, Matern Health Neonatol Perinatol 3(5), 2017.
ORGANISM VLBW INFANTS: NICHD NRN (%)
1991–1993 1998–2000 2002–2008
Incidence of late-onset sepsis 25 21 25
GRAM POSITIVE
Staphylococcus, coagulase-negative 55 48 53
Staphylococcus aureus 9 8 11
Enterococcus /group D streptococcus 5 3 4
Group B streptococcus 2 2 2
Other 2 9 7
GRAM NEGATIVE
Enterobacter 4 3 3
Escherichia coli 4 5 5
Klebsiella 4 4 4
Pseudomonas 2 3 2
Other 4 1 2
Fungi
Candida albicans 5 6 5
Candida parapsilosis
Other 2 2 1
VLBW, Very-low-birthweight (≤1,500 g); NICHD NRN, National Institutes of Child Health and Human Development Neonatal Research Network.
Data from (1) 1991–1993: Stoll BJ, Gordon T, Korones SB, et al: Late-onset sepsis in very low birth weight neonates: a report from the NICHD NRN, J Pediatr 129:63–71, 1996; (2) 1998–2000: Stoll BJ, Hansen N, Fanaroff AA, et al: Late-onset sepsis in very low birth weight neonates: the experience of the NICHD NRN, Pediatrics 110:285–291, 2002; (3) 2002–2008: Boghossian NS, Page GP, Bell EF, et al: Late-onset sepsis in very low birth weight infants from singleton and multiple gestation births, J Pediatr 162:1120–1120, 2015.

Bacteria responsible for most cases of nosocomial pneumonia typically include staphylococcal species, gram-negative enteric aerobes, and occasionally, P. aeruginosa. Fungi are responsible for an increasing number of systemic infections, usually acquired during prolonged hospitalization of preterm neonates. Respiratory viruses cause isolated cases and outbreaks of nosocomial pneumonia. These viruses, usually endemic during the winter months and acquired from infected hospital staff or visitors to the nursery, include RSV, parainfluenza virus, influenza viruses, and adenovirus.

Pathogenesis

Colonization of the skin, oropharynx, or gastrointestinal (GI) tract is an important precursor to infection in hospitalized infants. Premature infants may first be exposed to pathogenic organisms from a parent or more frequently from the hospital environment. Hospitalized infants are more likely to be colonized with Staphylococcus aureus , pathogenic gram-negative bacteria, and Candida than are infants in the community setting. Antibiotic exposure, indwelling devices, and frequent contact with contaminated medical equipment or healthcare providers all likely contribute to high rates of pathogen colonization. Following colonization, organisms may gain access to the bloodstream directly through damaged skin or central venous catheters. Recent evidence suggests the intestine is an important reservoir for invasive organisms, which may transit directly from the gut to the bloodstream. Oropharyngeal colonization with subsequent aspiration into the lower respiratory tract is thought to be the major route of infection in infants with ventilator-associated pneumonia.

Gestational age and birthweight are the most important risk factors for HAI. Prolonged use of central venous or umbilical catheters, exposure to broad-spectrum antibiotics, parenteral nutrition, and high nurse-to-patient ratios are other documented risk factors. These factors may alter the patient's endogenous microbial community, placing the infant at risk for colonization with pathogenic organisms.

Types of Infection

Central Line–Associated Bloodstream Infection

Central venous catheters have become an essential component of the care of critically ill newborns. Presence of a percutaneous or umbilical catheter introduces risk for infection and thrombosis. Central line–associated bloodstream infection ( CLABSI ) is the most common HAI in NICUs, imposing significant burden on the affected infant and on healthcare systems. Each episode has an attributable mortality of 4–20%. Infants with CLABSI subsequently have increased requirement for NICU stay, mechanical ventilation, and increased rates of bronchopulmonary dysplasia and necrotizing enterocolitis. The median estimated additional cost per CLABSI episode is $42,609, and hospitalization is prolonged for a median of 24 days.

Coagulase-negative staphylococci (CoNS) are the most common cause of CLABSI, accounting for approximately half of cases. CoNS are much more likely to cause clinically evident sepsis in VLBW infants than in term infants of comparable postnatal age, despite the organism's low pathogenic potential. Isolation of the organism from blood culture may represent contamination from the infant's or healthcare worker's skin, and blood cultures should be obtained from both peripheral and central venous sites. If both yield CoNS, the likelihood of true infection is high, whereas a single positive is considered questionable. In practice, often a single culture is obtained, and antibiotics are initiated before availability of a 2nd culture. In this circumstance, clinical judgment is often used to assess the need for targeted therapy. S. aureus , Enterococcus spp., and gram-negative rods account for most of the remaining CLABSIs during the 1st mo of hospitalization. Thereafter, Candida spp. become more prevalent, caused at least in part by their enrichment after broad-spectrum antibiotic exposure.

CLABSIs are generally thought to result from contamination of the central venous catheter, predominantly at the connecting hub or the skin entry site. An association has been shown between density of hub colonization and risk for CLABSI. Prevention of CLABSI is aimed at reducing contamination of these sites. BSI may also result from direct transit from the GI tract or other cutaneous or mucosal surfaces, analogous to recently defined mucosal barrier injury–associated BSIs. The contribution of mucosal sites to direct invasive infection remains to be clarified but has implications for infection prevention.

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