Recommendations for Prevention and Control of Infections in NICU Patients: S. aureus (2020)

The first Staphylococcus aureus (S. aureus) outbreak in infants in hospital nurseries was reported in the literature in the late 1800s.[24] This organism is now the most commonly reported healthcare-associated infection (HAI) pathogen in United States neonatal intensive care units (NICUs).[25] Rates of invasive S. aureus infections are high in neonates, especially in preterm and low birthweight infants.[26] Methicillin-resistant S. aureus (MRSA) infections in the neonatal population have been described since the early 1980s,[27] and numerous outbreaks in NICUs have been reported.[6,2839] Although outbreaks of S. aureus among patients, especially MRSA, pose significant challenges for NICUs,[40] S. aureus is endemic in the NICU as well,[21] giving rise to the need for prevention strategies in both outbreak and endemic settings. While MRSA has long been the focus of prevention efforts due to the difficulty in treating and eradicating it, recent studies have demonstrated that methicillin-sensitive S. aureus (MSSA) has morbidity and mortality equal to MRSA and occurs more frequently in NICU patients.[26,40]

When work on this Guideline effort began in 2009, the draft recommendations focused only on MRSA. At that time, the literature base for MSSA in NICUs was sparse and deemed insufficient to support a full literature review on the topic. Since then, studies have been published demonstrating the burden of MSSA disease and prevention in the NICU. While MRSA remains epidemiologically significant and a priority pathogen, MSSA infections far exceed MRSA infections in the NICU, so prevention strategies for S. aureus as a whole are needed.

Neonates who acquire S. aureus colonization are at increased risk of S. aureus infection.[21] The ultimate goal driving efforts to prevent and control S. aureus transmission in NICUs is the prevention of disease in vulnerable neonates. Any neonatal infection can be associated with long-term sequelae, including negative long-term neurocognitive outcomes and poor prognosis. In practice, NICU patients with MRSA, and in some cases MSSA, are decolonized with the intent of preventing progression to invasive diseases and limiting further transmission. Limited evidence about optimal decolonization regimens exists in this population, and new drugs and alternative therapies for decolonization are rarely studied in neonates and are unlikely to achieve approval for widespread implementation. Strategies to mitigate risk when colonization occurs are urgently needed, but in the meantime, efforts to prevent transmission and subsequent colonization should therefore be prioritized.

This document is based on current understanding of the transmission dynamics of S. aureus in the NICU setting.[41,42] New laboratory methods, including whole genome sequencing (WGS), suggest that related strains account for the largest proportion of transmission events in NICUs, presumably from patient-to-patient spread via indirect contact transmission, but multiple unrelated strains may be transmitted concurrently in parallel and new, unrelated strains are introduced frequently.[4346] The reservoirs for new and existing strains are incompletely understood. Infection prevention measures targeting spread from healthcare personnel and the hospital environment — the focus of this document — may not be sufficient to prevent all transmission. Specifically, parents are a known reservoir from which neonates can acquire S. aureus colonization, and an intervention targeting parents may reduce transmission.[47] Further studies are needed to determine when strategies to interrupt transmission from parents, such as hand hygiene educational intervention or decolonization, can prevent neonatal S. aureus disease.

This document makes specific recommendations about interventions to be implemented when there is evidence of ongoing transmission of S. aureus, an increased incidence of S. aureus infection, or in an outbreak setting. However, no discrete benchmark or threshold for S. aureus or MRSA infection rates indicates when additional efforts are required. It is necessary for healthcare facilities to use their own data to determine when to add interventions and where to target prevention efforts when infections are occurring. As part of a comprehensive infection prevention and control strategy, facilities can employ a quality improvement framework to maximize efficiency in reducing infections. Tools such as CDC’s Targeted Assessment for Prevention (TAP) Strategy Toolkit[48] enable hospitals to target locations within facilities, assess gaps, and implement interventions to prevent and control S. aureus.

This Guideline was developed to provide evidence-based recommendations for the prevention of S. aureus in this vulnerable population. For important topics where evidence was insufficient to formulate evidence-based recommendations, companion guidance is available to inform the delivery of healthcare in NICUs:  SHEA neonatal intensive care unit (NICU) white paper series: Practical approaches to Staphylococcus aureus disease preventionexternal icon. Additionally, guidance is available elsewhere regarding the management of multidrug-resistant organisms (MDROs) in healthcare settings , including limiting MRSA outbreaks.[49]

References on this Page
  1. Jernigan JA, Titus MG, Groschel DH, Getchell-White S, Farr BM. Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus. American journal of epidemiology. 1996;143(5):496-504.
  2. Huang YC, Chou YH, Su LH, Lien RI, Lin TY. Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units. Pediatrics. 2006;118(2):469-474.
  3. Kilham EB. An epidemic of pemphigus neonatorum. In: Adams T, ed. American Journal of Obstetrics and Diseases of Women and Children. Vol 22.1889:1039-1041.
  4. Lake JG, Weiner LM, Milstone AM, Saiman L, Magill SS, See I. Pathogen Distribution and Antimicrobial Resistance Among Pediatric Healthcare-Associated Infections Reported to the National Healthcare Safety Network, 2011-2014. Infection control and hospital epidemiology. 2018;39(1):1-11.
  5. Ericson JE, Popoola VO, Smith PB, et al. Burden of Invasive Staphylococcus aureus Infections in Hospitalized Infants. JAMA pediatrics. 2015;169(12):1105-1111.
  6. Weeks JL, Garcia-Prats JA, Baker CJ. Methicillin-resistant Staphylococcus aureus osteomyelitis in a neonate. Jama. 1981;245(16):1662-1664.
  7. Andersen BM, Lindemann R, Bergh K, et al. Spread of methicillin-resistant Staphylococcus aureus in a neonatal intensive unit associated with understaffing, overcrowding and mixing of patients. The Journal of hospital infection. 2002;50(1):18-24.
  8. Zafar AB, Butler RC, Reese DJ, Gaydos LA, Mennonna PA. Use of 0.3% triclosan (Bacti-Stat) to eradicate an outbreak of methicillin-resistant Staphylococcus aureus in a neonatal nursery. American journal of infecion control. 1995;23(3):200-208.
  9. Gerber SI, Jones RC, Scott MV, et al. Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement. Infection control and hospital epidemiology. 2006;27(2):139-145.
  10. Azarian T, Maraqa NF, Cook RL, et al. Genomic Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit. PLoS One. 2016;11(10):e0164397.
  11. Koser CU, Holden MT, Ellington MJ, et al. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. The New England journal of medicine. 2012;366(24):2267-2275.
  12. Harris SR, Cartwright EJ, Torok ME, et al. Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study. The Lancet Infectious diseases. 2013;13(2):130-136.
  13. Madigan T, Cunningham SA, Patel R, et al. Whole-genome sequencing for methicillin-resistant Staphylococcus aureus (MRSA) outbreak investigation in a neonatal intensive care unit. Infection control and hospital epidemiology. 2018;39(12):1412-1418.
  14. Nubel U, Nachtnebel M, Falkenhorst G, et al. MRSA transmission on a neonatal intensive care unit: epidemiological and genome-based phylogenetic analyses. PLoS One. 2013;8(1):e54898.
  15. Ugolotti E, Larghero P, Vanni I, et al. Whole-genome sequencing as standard practice for the analysis of clonality in outbreaks of meticillin-resistant Staphylococcus aureus in a paediatric setting. The Journal of hospital infection. 2016;93(4):375-381.
  16. Milstone AM, Voskertchian A, Koontz DW, et al. Effect of Treating Parents Colonized With Staphylococcus aureus on Transmission to Neonates in the Intensive Care Unit: A Randomized Clinical Trial. Jama. 2019.
  17. Centers for Disease Control and Prevention. The Targeted Assessment for Prevention (TAP) Strategy. 2019. Accessed January 15, 2020.
  18. Siegel, JD, Rhinehart, E, Jackson, M and Chiarello, L, HICPAC. Management of Multidrug-Resistant Organisms in Healthcare Settings. 2006. Accessed January 15, 2020.