DISCUSSION

In this simulation, we identified characteristics of care in the NICU that allowed horizontal infant–infant transmission of MRSA, and we modeled prevalence of colonization during a typical length of stay. Our primary finding was the absence of a plateauing effect as hand-hygiene effectiveness increased. To answer our initial question, there is no “good enough” level of hygiene to suggest that MRSA transmission can effectively be blocked under our initial model assumptions. Even with perfect hand-hygiene compliance in the NICU, the number of secondary colonizations, inferred as the effective reproductive number (R), declined only when hand-hygiene effectiveness exceeded our hypothesized maximum benefit of 88% (or the per-contact probability decreased).

In other studies that have modeled MRSA spread in the adult ICU, lower levels of hand-hygiene compliance brought R to the epidemic threshold value of 1.0. McBryde et alReference McBryde, Pettitt and McElwain ⁸ observed an R of 1.0 with a compliance of 48%, implying that exceeding this level can reduce an outbreak of MRSA colonization in the unit, while Grundman et alReference Grundmann, Hori, Winter, Tami and Austin ⁹ detected this effect at 66% compliance. Sebille et alReference Sébille, Chevret and Valleron ⁷ noted that at 90% hand-hygiene compliance could yield a ~33% decrease in colonized patients, with little additional benefit when compliance exceeded ~66%. These studies have an important limitation: compliance with hand hygiene was assumed to confer 100% clearance of MRSA from the hands. In practice, hand-hygiene effectiveness is likely <90%.Reference Ho, Poh, Choudhury, Krishnan, Ang and Chow ¹⁴ Moreover, these study results are specific to the adult ICU and did not take the acuteness of the patient into account. Using the network modeling approach, as opposed to deterministic compartmental models or stochastic individual contact models (individual- or agent-based) we could more accurately capture the nuanced care that occurs in the NICU with respect to several markers of care delivery (patient acuteness and location).

These markers of care delivery have important implications for clinical practice. As noted, infants who were born preterm and/or required mechanical ventilation had a higher prevalence of MRSA post simulation, likely due to the increased care required of these acute patients. These infants are therefore at greater risk of MRSA colonization with possible subsequent invasive infection leading to sepsis. Additionally, we observed that patient location mattered in this risk profile in that largely clustered care practices may inhibit infant–infant transmission of MRSA into other locations.Reference Geva, Wright, Baldini, Smallcomb, Safran and Gray ¹⁶ While the design of our NICU led us to model location as a function of 1 of 3 possible hallways, the actual cocooning effect of the interactions may be driven by assignments or nurses, who deliver most of the hour-to-hour infant care and therefore have the most patient contacts. Assuming an average of 2 infants per nurse,Reference Rogowski, Staiger, Patrick, Horbar, Kenny and Lake ¹⁷ and even with ideal hand-hygiene compliance, infant–infant transmission of MRSA could still occur, particularly if both infants required continual care.

To our knowledge this is the first study to employ a network model for studying MRSA transmission in the NICU specifically addressing the question of adequate hand hygiene, although others have used network models in a similar setting. Geva et alReference Geva, Wright, Baldini, Smallcomb, Safran and Gray ¹⁶ employed a network modeling approach to MRSA spread in a NICU, and while they found, similar to our analysis, that the care network is the primary driver of transmission, their model did not incorporate acuteness markers of the infant or consider nonnursing care.

Although our modeling interest was specific to hand hygiene, other interventions, including contact precautions (ie, mask, gown, gloves),Reference Giuffrè, Cipolla and Bonura ^{18 ,} Reference Gregory, Eichenwald and Puopolo ¹⁹ patient cohorting, and isolation,Reference Giuffrè, Cipolla and Bonura ^{18 –} Reference Huang, Lien, Su, Chou and Lin ²⁰ and surveillance and decolonization,Reference Gregory, Eichenwald and Puopolo ^{19 ,} Reference Huang, Lien, Su, Chou and Lin ²⁰ have proven effective to control MRSA in the NICU. Often employed in combination, each of these interventions operates on a different aspect of pathogen transmission. Contact precautions alter the per-contact probability of either the HCW becoming the vector, or, if contaminated or previously colonized, lowers the chances of the HCW transmitting a pathogen to a patient. Cohorting of patients according to the presence of MRSA colonization, with dedicated staff and/or isolation rooms, will modify the NICU care network by altering the number of infant–infant MRSA transmissible opportunities. Lastly, surveillance and decolonization lowers the prevalence of MRSA in the NICU,Reference Popoola, Colantuoni and Suwantarat ²¹ reducing colonization pressure and subsequently mitigating the possibility of the HCW becoming a vector.

The initial prevalence of MRSA in our study ranged from 1.9% to 7.7%, and these levels may slightly overestimate the true prevalence of MRSA in NICUs. In a 2014 meta-analysis of MRSA colonization in various NICUs over a 12-year period, the mean prevalence was 1.5% (95% CI, 0.9%–2.2%).Reference Zervou, Zacharioudakis, Ziakas and Mylonakis ²² However, we chose this range in our sensitivity analysis for several reasons. First, we based these extremes on empiric surveillance cultures, and our NICU has experienced high rates in the past; even this surveillance program may not fully capture all true colonizations. Second, the infected-colonized compartmental model required us to start with a nonzero number of initially colonized infants in the unit. Third, we wished to represent a worst-case scenario in the time of an outbreak of MRSA colonization. This approach also allowed us to examine colonization pressure (the proportion of infants colonized with MRSA); as the proportion increases, the risk of infant–infant horizontal transmission also increases. As such, our modeling approach presents worst-case postsimulation prevalence estimates.

Several other limitations should be considered. Our models did not incorporate visitor–infant contact, which as a general trend in the NICU has substantially increased; thus, we may have underreported the total patient contacts if they were not documented in the EMR. The average number of infant contacts per hour in our study was similar to another NICU that reported an average of 1.8 contacts per hour, and only 6% of touches were by visitors (94% were nurses, doctors, and allied health staff).Reference Lam, Lee and Lau ¹ While visitors generally would not have had contact with other infants, this could lead to an infant becoming colonized independent of the HCW. We also did not consider fomite–person interactions, such as cell phones, which can harbor organisms.Reference Achermann, Seidl and Kuster ²³ This would alter the per-contact probability by including another source for HCW contamination between infant–infant contacts. Finally, the probabilities modeled for per-contact infant–infant transmission and hand-hygiene effectiveness are products of 2 independent probabilities. While their independent effects cannot be established in our work, the sensitivity analyses undertaken reflected the expected impact on results.

This work has notable strengths. We used empiric data on HCW and patient interactions to construct our NICU care network. Now that the environment has been accurately modeled, the model can readily adapt to other outcomes, such as investigating respiratory tract colonization in the NICU, or the model can be generalized to other non-NICU healthcare environments by modifying the assumptions. This work may contribute to the development of prospective surveillance programs based on horizontal transmission networks. For example, if a provider has had contact with a known MRSA colonized patient, all subsequent patient contacts by that provider for their shift can be monitored, tested, and potentially decolonized or isolated using this model.

In summary, we observed the care network in the NICU is a major contributor to the horizontal spread of MRSA. The care requirements in intensive care settings offer many opportunities for the healthcare provider to become the intermediary for transmission. Even under optimal hand-hygiene conditions, horizontal transmission of MRSA is possible, suggesting an important role for other complimentary interventions including contact precautions and decolonization. Additional prevention paradigms should focus on the most acute patients because they are at the greatest risk.