The parents of babies in neonatal intensive care units (NICUs)can serve as a gateway for Staphylococcus aureus to colonize and potentially infect their newborns, researchers report in a recently published clinical trial.1
Although there are considerable caveats and questions about the implications, the research also showed that treating colonized parents with mupirocin and chlorhexidine can reduce the risk of transmission to the baby by half.
“Parents may be an important reservoir that we really need to think about,” says lead author Aaron Milstone, MD, MHS, associate epidemiologist and professor of pediatrics at Johns Hopkins Hospital in Baltimore.
Approximately 25-30% of people frequently carry S. aureus asymptomatically as part of their normal microbiome, often in the nose. Thus, some parents may expose their newborns to staph by visiting them in NICUs, where they often are placed if born prematurely or have complications. It is well known that colonization with drug-susceptible staph or methicillin-resistant S. aureus (MRSA) can be a prelude to clinical infection in neonates.
While the study confirms the possibility of parent-to-child transmission, Milstone stresses that the results should not be used to undermine the critical bond between newborns and parents.
“What we in no way want to do is to discourage parents from coming [to the NICU] or being in touch with their kids,” says Milstone. “We want to raise awareness — to say as healthcare workers, ‘What can we do to mitigate risk? Is there a way we can safely have [colonized] parents participate in their child’s care and be with them as much as possible?’”
Treatment and Placebo
The researchers tested parents, who had given informed consent, for nasal carriage of MRSA and drug-susceptible staph. The culture-positive parents were randomized into two arms of the study. In one, parents were treated with intranasal mupirocin and topical chlorhexidine for five days. In the placebo arm, parents were treated with petrolatum intranasal ointment and nonmedicated soap cloths for the same time period.
The double-blinded, randomized clinical trial was conducted in two Johns Hopkins NICUs. Overall, S. aureus-colonized parents of 236 neonates were enrolled in the study from Nov. 7, 2014, through Dec. 13, 2018.
“The intervention was for the parents,” Milstone says. “We screened the parents and identified the parents that had Staph aureus. The outcome was measured in the neonates — which of them acquired the same staph strain as their parent had?”
The primary endpoint was concordant S. aureus colonization by 90 days, defined as neonatal acquisition of the same strain as the parents at the time of screening.
“Among 190 neonates included in the analysis, 74 (38.9%) acquired S. aureus colonization by 90 days, of which 42 (56.8%) had a strain concordant with a parental baseline strain,” Milstone and colleagues reported.
In the intervention group, 13 of 89 neonates (14.6%) acquired the same staph strain as their parents. In the placebo group, 29 of 101 neonates (28.7%) were colonized with the parental strain. The intervention “reduced the likelihood of a child acquiring the same strain as the parent by more than 50%,” he says. “In our primary analysis, there were six kids who acquired MRSA [colonization]. Four of the six got the same strain that their parent had. [In other words], two-thirds of the babies who acquired MRSA in this study in the NICU got the same strain that the parent had. For me that is a very important observation, because it does challenge our current thinking about MRSA prevention in NICUs.”
The standard practice in the two NICUs is active surveillance and decolonization if staph is identified, so the focus was less on actual clinical infections. However, preventing colonization and decolonizing infants is known to stave off subsequent infection, he says.
“Because of that [practice], we have a very low rate of infection in our NICUs,” Millstone says. “In NICUs that are not identifying staph and decolonizing, the infection rates may be higher, so [the intervention] may have more impact on reducing infections.”
The study was approved by an institutional review board that provided ethical oversight. Still, there are questions raised about studies that divide groups into one that receives an intervention and another that is given a placebo. That was not an issue for this intervention for a very simple reason, Milstone notes.
“The reason it wasn’t [an issue] was that we had no idea if this was going to do anything,” he says. “No one has done this before. The current standard of care is to do nothing. Nobody gives anything to parents, so I think what we were really doing was testing a treatment. There wasn’t concern, because we were not taking anything away. The standard of care was to do nothing.”
In that sense, the placebo essentially mimicked the standard of care, while the use of mupirocin and chlorhexidine tested a treatment. The original concept was to just do the intervention arm without a placebo, but the researchers thought that might change parents’ behavior if they were told they were colonized with staph but offered nothing.
“If parents saw that we were treating someone and we are not treating them, it might change their behavior,” Milstone explains. “By using the placebo, we were able to eliminate the likelihood that someone would feel like they were causing risk to their child. We told the parents that you have bacteria that you could give to your child. So just that itself may change people’s behavior, but that [disclosure] was consistent across both [arms of] the study.”
The parents who agreed to participate were told they had S. aureus, but not whether it was MRSA or drug-susceptible. Otherwise, the parents followed standard protocol in the NICUs. They were advised to wash their hands before interacting with their child, but infection control did not extend to the level of wearing gloves or gowns. Regarding hand hygiene in general, Milstone said parents typically are compliant at the onset but may not repeat handwashing after various actions throughout a visit.
The trial is the first to definitively link parent staph colonization to colonization of their babies in the NICU, raising the question of how many NICU staph infections could ultimately be traced to the patients’ parents.
“We don’t know,” Milstone said. “We have always speculated that parents were a reservoir. In the hospital, for example, we are very careful about tracking MRSA. Often, you would have twins or triplets who were separated in the different areas of the NICU and they would all get the same strain of MRSA. How did that happen? We always speculated that maybe a parent [or a healthcare worker] was the reservoir.”
Prior to this study, there was little data on this issue beyond anecdotal information and case reports. A clinical trial provides significant evidence, but there are open questions about the difficulty in enacting such practices routinely across NICUs.
“Obviously, the greatest concern we have is fostering family-centered care at the same time that we protect the child from infection,” Milstone says. “It is very similar to trying to think about sibling visitations, pet therapy — all of these things we do to make kids in the hospitals have a better stay.”
On the other hand, there are obvious challenges in asking parents of children in NICUs to comply with testing and treatment protocols. In addition, more broad use of mupirocin and chlorhexidine raise concerns about triggering resistant organisms.
An editorial accompanying the study raised that issue and other questions, including, “If an infant did become colonized or infected, could parents feel responsible or guilty?”2
Parents of a preterm baby are already stressed and face uncertain outcomes and concerns about developmental delays and long-term problems, says coauthor of the commentary Lisa Saiman, MD, a professor of pediatric infectious diseases at Columbia University in New York City. The unintended consequences would have to be weighed if the intervention is deemed clinically significant in further research to merit wider implementation, she explains.
“First, [parents] are being asked to understand the difference between colonization and infection, which may be a difficult thing for some people,” Saiman says. “You are doing the therapy [intervention] as best as you can, but if the baby gets an infection — what does that feel like to that parent? How would you really be able to explain that to them in a meaningful way?”
Typically, NICUs ask parents to practice hand hygiene and basic infection control, including avoiding visits if sick.
“This is really different — this is a completely different paradigm,” she says. “I think it is a very important proof-of-concept study. It shows something that no one has ever shown before, but it is certainly not ready for widespread implementation yet.”
It is important, for example, to avoid stigmatizing parents by emphasizing that a lot of people are colonized with staph as part of their normal flora and microbiota, she says.
“We encourage parents to bond with their babies, and one of the ways we do that is through frequent touching and skin contact,” Saiman adds. “But none of the current interventions that we have to fight staph infections are perfect.”
That said, to implement parental testing and treatment more broadly would require a much larger study over multiple sites that showed prevention of staph infections — not just colonization, she says.
“This is not such an easy intervention for families to do,” she says. “It took a long time to recruit for this study. As you can imagine, parents are under so much stress when they have a baby in the NICU. Their activities of daily living are totally disrupted. They are back and forth to the hospital all the time and they are probably not sleeping well.”
In addition, as Milstone acknowledged, both study units had active surveillance and decolonization protocols in place, limiting generalizability to other settings, she says.
“Scalability is another important factor,” the commentary noted. “Despite a presumably experienced research recruitment team, accrual of participants in this study appeared to be slow. The study took four years to complete. … This rate of accrual may reflect the complexity of the study question, strict inclusion criteria that limited participation, or parental concerns about randomization.”
- 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; Dec. 30. doi:10.1001/jama.2019.20785. [Online ahead of print].
- Zachariah P, Saiman L. Decreasing Staphylococcus aureus in the neonatal intensive care unit by decolonizing parents. JAMA 2019; Dec. 30; doi:10.1001/jama.2019.20784. [Online ahead of print].