Neonatal Hospital-Acquired Infection

ByAnnabelle de St. Maurice, MD, MPH, UCLA, David Geffen School of Medicine
Reviewed/Revised Apr 2025
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Neonates may acquire infections after admission to the hospital nursery or neonatal intensive care unit rather than via maternal-fetal transmission in utero or intrapartum. For some infections (eg, group B streptococci, herpes simplex virus [HSV]) it may not be clear whether the source is maternal or the hospital environment.

Hospital-acquired (nosocomial) infection is primarily a problem for preterm infants and for term infants with medical disorders requiring prolonged hospitalization. Healthy, term neonates have infection rates < 1% (1). For neonates in special care nurseries, the incidence increases as birth weight decreases (2).

The most common nosocomial infections are central line-associated bloodstream infections (CLABSI) and hospital-acquired pneumonia.

(See also Overview of Neonatal Infections.)

General references

  1. 1. Testoni D, Hayashi M, Cohen-Wolkowiez M, et al. Late-onset bloodstream infections in hospitalized term infants. Pediatr Infect Dis J. 2014;33(9):920-923. doi:10.1097/INF.0000000000000322

  2. 2. Wang L, Du KN, Zhao YL, Yu YJ, Sun L, Jiang HB. Risk Factors of Nosocomial Infection for Infants in Neonatal Intensive Care Units: A Systematic Review and Meta-Analysis. Med Sci Monit. 2019;25:8213-8220. Published 2019 Nov 1. doi:10.12659/MSM.917185

Etiology of Neonatal Hospital-Acquired Infection

In term neonates, the most frequent hospital-acquired infection is:

Although hospital nursery personnel who are S. aureus nasal carriers are potential sources of infection, colonized neonates and mothers also may be reservoirs. The umbilical stump, nose, and groin can be colonized during the first few days of life. Often, infections do not manifest until the neonate is at home.

In very-low-birth-weight (VLBW; < 1500 g) infants, gram-positive organisms cause approximately 70% of late-onset infections, particularly coagulase-negative staphylococci (1). Gram-negative organisms, including Escherichia coli, Klebsiella, Pseudomonas, Enterobacter, and Serratia, are also important pathogens and may be more common causes of early-onset infection. Fungal infections (Candida albicans and C. parapsilosis) are more common among neonates receiving intravenous lipids for nutrition. Patterns of infection (and antibiotic resistance) vary among institutions and units and change with time. Intermittent outbreaks sometimes occur as a particularly virulent organism colonizes a unit.

The longer the stay in special care nurseries and the more procedures performed in VLBW infants (eg, long-term arterial and venous catheterization, endotracheal intubation, continuous positive airway pressure, nasogastric tubes or nasojejunal feeding tubes), the higher is the likelihood of infection.

Etiology reference

  1. 1. Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2 Pt 1):285-291. doi:10.1542/peds.110.2.285

Prevention of Neonatal Hospital-Acquired Infection

  • Reduction of S. aureus colonization in all hospitalized infants

  • Prevention of colonization and infection in special care nurseries and neonatal intensive care units (NICUs)

  • Hand hygiene

  • Surveillance for infection

  • Sometimes antibiotics

  • Vaccination

Colonization reduction

Using a topical antiseptic agent during routine bathing and/or skin preparation for sterile procedures can help reduce bacterial skin colonization in neonates. Chlorhexidine-based products are increasingly used for this purpose, but the U.S. Food and Drug Administration warns of risk of skin irritation and chemical burns in infants < 2 months of age. Some experts recommend routine Using a topical antiseptic agent during routine bathing and/or skin preparation for sterile procedures can help reduce bacterial skin colonization in neonates. Chlorhexidine-based products are increasingly used for this purpose, but the U.S. Food and Drug Administration warns of risk of skin irritation and chemical burns in infants < 2 months of age. Some experts recommend routinechlorhexidine bathing in neonates in the NICU who are at increased risk of CLABSI (1).

The American Academy of Pediatrics recommends dry umbilical cord care, but this practice may result in high rates of colonization with S. aureus, and outbreaks have occurred in some hospitals (2).

Routine cultures of personnel or of the environment are not recommended (3).

Prevention of colonization and infection in special care nurseries requires provision of sufficient space and personnel.

Proper techniques are required, particularly for placement and care of invasive devices and for meticulous cleaning and disinfection or sterilization of equipment. Active monitoring of adherence to techniques is essential. Formal evidence-based protocols for inserting and maintaining central catheters have significantly decreased the rate of CLABSI.

Similarly, a group of procedures and protocols that reduce hospital-acquired pneumonia in the NICU have been identified; these include staff education and training, active surveillance for hospital-acquired pneumonia, raising the head of an intubated neonate's bed 30 to 45°, and providing comprehensive oral hygiene. Placing the neonate in a lateral position with the endotracheal tube horizontal with the ventilator circuit also may be helpful (4, 5).

(See also current Centers for Disease Control and Prevention [CDC] guidelines for prevention and control [2024] and CLABSI prevention and control [2024] in the NICU.)

Hand hygiene

Other preventive measures include meticulous attention to hand hygiene. Cleansing with alcohol preparations is as effective as soap and water in decreasing bacterial colony counts on hands, but if hands are visibly soiled, they should first be washed with soap and water.

Incubators provide limited protective isolation; the exteriors and interiors of the units rapidly become heavily contaminated, and personnel are likely to contaminate their hands and forearms. Universal blood and body fluid precautions add further protection.

Infection surveillance

Active surveillance for infection should be performed. In an outbreak, establishing a cohort of infants who are diseased or colonized and assigning them a separate nursing staff are useful. Continuing surveillance for 1 month after discharge is necessary to assess the adequacy of controls instituted to end an outbreak.

Antibiotics

Prophylactic antimicrobial therapy is generally not effective, hastens development of resistant bacteria, and alters the balance of normal flora in the neonate. However, during a confirmed nursery outbreak, prophylactic antibiotics against specific pathogens may be considered (eg, penicillin G for prophylaxis against group A streptococcal infection).Prophylactic antimicrobial therapy is generally not effective, hastens development of resistant bacteria, and alters the balance of normal flora in the neonate. However, during a confirmed nursery outbreak, prophylactic antibiotics against specific pathogens may be considered (eg, penicillin G for prophylaxis against group A streptococcal infection).

Vaccination

Inactivated vaccines should be given according to the routine schedule to any infant who is in the hospital.

Live viral vaccines (eg, rotavirus vaccine) may lead to some asymptomatic viral shedding and can be given at hospital discharge or during hospitalization based on institutional preference. Live viral vaccines (eg, rotavirus vaccine) may lead to some asymptomatic viral shedding and can be given at hospital discharge or during hospitalization based on institutional preference.

Prevention references

  1. 1. Nelson MU, Shaw J, Gross SJ. Randomized Placebo-Controlled Trial of Topical Mupirocin to Reduce Staphylococcus aureus Colonization in Infants in the Neonatal Intensive Care Unit. J Pediatr. 2021;236:70-77. doi:10.1016/j.jpeds.2021.05.042

  2. 2. Stewart D, Benitz W; COMMITTEE ON FETUS AND NEWBORN. Umbilical Cord Care in the Newborn Infant. Pediatrics. 2016;138(3):e20162149. doi:10.1542/peds.2016-2149

  3. 3. Bryant K, Brady MT, Myers Cox K, et al. Recommendations for Prevention and Control of Infections in Neonatal Intensive Care Unit Patients: Central Line-associated Blood Stream Infections. Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion. 2022;1-37.

  4. 4. Manzoni P, De Luca D, Stronati M, et al. Prevention of nosocomial infections in neonatal intensive care units. Am J Perinatol. 2013;30(2):81-88. doi:10.1055/s-0032-1333131

  5. 5. Cipolla D, Giuffrè M, Mammina C, Corsello G. Prevention of nosocomial infections and surveillance of emerging resistances in NICU. J Matern Fetal Neonatal Med. 2011;24 Suppl 1:23-26. doi:10.3109/14767058.2011.607567

Key Points

  • Nosocomial infection is primarily a problem for preterm infants and for term infants with disorders requiring prolonged hospitalization.

  • Lower birth weight is a risk factor for infection, particularly in neonates with central catheters, endotracheal tubes, or both.

  • Meticulous technique for inserting and maintaining catheters, tubes, and devices is essential for prevention; formal protocols improve adherence.

  • Prophylactic antibiotics are not recommended except possibly during a confirmed nursery outbreak involving a specific pathogen.

  • Inactivated vaccines should be given according to the routine schedule.

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