(See article by Popoola et al, on pages 381–387).
An interdisciplinary team of Investigators at Johns Hopkins Hospital performed a unique single-center study to reduce methicillin-susceptible S. aureus (MSSA) infections in the neonatal intensive care unit (NICU) using active surveillance and a decolonization intervention.Reference Popoola, Colantuoni and Suwantarat
1
To do so, they performed surveillance cultures of the anterior nares of all NICU patients and treated colonized infants with mupirocin (twice daily for 5 days) and chlorhexidine gluconate (CHG) bathing (twice using CHG-impregnated cloths). Their outcome measures were healthcare-associated infections (HAIs) as defined by the National Health Safety Network (NHSN) caused by MSSA and other MSSA clinical cultures obtained during the course of care. Using incidence rate ratios derived from an interrupted time series conducted from April 2011 to September 2014, the investigators found a significant reduction in MSSA-associated NHSN-defined HAIs and clinical cultures. Notably, this reduction occurred despite failure to screen ~25% of eligible infants for MSSA and failure to decolonize ~21% of colonized infants. Furthermore, interventions were only provided to infants >36 weeks gestational age or >4 weeks chronological age, thereby rendering the infants at highest risk ineligible to participate, as HAIs are inversely associated with birth weight in the NICU population.
No reductions in MRSA HAIs or clinical cultures occurred, but the numbers of such outcomes were small, and a similar intervention for MRSA was already in place during the pre-intervention period. The authors did not comment on infections caused by other pathogens.
Similar active surveillance and decolonization interventions have been used to combat MRSA in the NICU population, particularly during outbreaks,Reference Gerber, Jones and Scott
2
–
Reference Milstone, Budd and Shepard
4
and they have been reported to combat outbreaks of MSSA.Reference Graham, Morel and Zhou
5
,
Reference Delaney, Wang and Melish
6
Although these strategies have not been previously implemented to combat endemic MSSA, there is strong rationale to develop strategies to reduce MSSA burden in the NICU population: MSSA rates are higher than those of MRSA in the NICU population,Reference Gerber, Jones and Scott
7
,
Reference Shane, Hansen and Stoll
8
and the morbidity and mortality from HAIs in the NICU population can be devastating.Reference Stoll, Hansen and Adams-Chapman
9
Thus, safe interventions to reduce such infections would be welcome.
This study does address safety, but unanswered questions remain. The investigators did not note the emergence of mupirocin resistance, but only 65 of the first 85 MSSA isolates were tested, and the intervention period was relatively short, 18 months. Thus, this observation is not fully reassuring, and it is crucial to continue to monitor mupirocin resistance over time. The investigators did not address the long-term safety or short-term tolerability of CHG bathing. Concerns about the safety of CHG in preterm infants continue, including adverse neurologic effects and skin reactions.Reference Nelson, Bizzarro and Debmry
10
The Food and Drug Administration recently modified the labeling for 2% chlorhexidine gluconate cloths and added “use with care in premature infants or infants under 2 months of age. These products may cause irritation or chemical burns.”
11
As a result of these concerns, the CHG decolonization intervention in this study was only provided to infants >36 weeks gestational age or >4 weeks chronological age. The investigators did not assess CHG susceptibility, but recent studies have suggested reduced CHG susceptibility associated with daily CHG bathing.Reference Suwantarat, Carroll and Tekle
12
Finally, in the modern era, we must consider the potential unintended consequences of decolonization strategies that adversely impact the microbiome. For example, potentially more virulent organisms could become colonizing flora, or colonization with S. aureus could be critical for normal developmental processes.
In summary, this study has provided much-needed data to justify performing a large, multicenter study to establish the safety, tolerability, and efficacy of targeted surveillance cultures and decolonization strategies in the NICU population. Such a study design is likely to be embraced by the neonatology community.Reference Nelson, Bizzarro and Debmry
10
In addition, a larger future study could more fully assess the durability of decolonization, assess whether infected infants acquire new S. aureus strains or become infected with their colonizing strains, determine optimal timing and frequency of surveillance cultures, and measure the cost-effectiveness of the interventions.
(See article by Popoola et al, on pages 381–387).
An interdisciplinary team of Investigators at Johns Hopkins Hospital performed a unique single-center study to reduce methicillin-susceptible S. aureus (MSSA) infections in the neonatal intensive care unit (NICU) using active surveillance and a decolonization intervention.Reference Popoola, Colantuoni and Suwantarat 1 To do so, they performed surveillance cultures of the anterior nares of all NICU patients and treated colonized infants with mupirocin (twice daily for 5 days) and chlorhexidine gluconate (CHG) bathing (twice using CHG-impregnated cloths). Their outcome measures were healthcare-associated infections (HAIs) as defined by the National Health Safety Network (NHSN) caused by MSSA and other MSSA clinical cultures obtained during the course of care. Using incidence rate ratios derived from an interrupted time series conducted from April 2011 to September 2014, the investigators found a significant reduction in MSSA-associated NHSN-defined HAIs and clinical cultures. Notably, this reduction occurred despite failure to screen ~25% of eligible infants for MSSA and failure to decolonize ~21% of colonized infants. Furthermore, interventions were only provided to infants >36 weeks gestational age or >4 weeks chronological age, thereby rendering the infants at highest risk ineligible to participate, as HAIs are inversely associated with birth weight in the NICU population.
No reductions in MRSA HAIs or clinical cultures occurred, but the numbers of such outcomes were small, and a similar intervention for MRSA was already in place during the pre-intervention period. The authors did not comment on infections caused by other pathogens.
Similar active surveillance and decolonization interventions have been used to combat MRSA in the NICU population, particularly during outbreaks,Reference Gerber, Jones and Scott 2 – Reference Milstone, Budd and Shepard 4 and they have been reported to combat outbreaks of MSSA.Reference Graham, Morel and Zhou 5 , Reference Delaney, Wang and Melish 6 Although these strategies have not been previously implemented to combat endemic MSSA, there is strong rationale to develop strategies to reduce MSSA burden in the NICU population: MSSA rates are higher than those of MRSA in the NICU population,Reference Gerber, Jones and Scott 7 , Reference Shane, Hansen and Stoll 8 and the morbidity and mortality from HAIs in the NICU population can be devastating.Reference Stoll, Hansen and Adams-Chapman 9 Thus, safe interventions to reduce such infections would be welcome.
This study does address safety, but unanswered questions remain. The investigators did not note the emergence of mupirocin resistance, but only 65 of the first 85 MSSA isolates were tested, and the intervention period was relatively short, 18 months. Thus, this observation is not fully reassuring, and it is crucial to continue to monitor mupirocin resistance over time. The investigators did not address the long-term safety or short-term tolerability of CHG bathing. Concerns about the safety of CHG in preterm infants continue, including adverse neurologic effects and skin reactions.Reference Nelson, Bizzarro and Debmry 10 The Food and Drug Administration recently modified the labeling for 2% chlorhexidine gluconate cloths and added “use with care in premature infants or infants under 2 months of age. These products may cause irritation or chemical burns.” 11
As a result of these concerns, the CHG decolonization intervention in this study was only provided to infants >36 weeks gestational age or >4 weeks chronological age. The investigators did not assess CHG susceptibility, but recent studies have suggested reduced CHG susceptibility associated with daily CHG bathing.Reference Suwantarat, Carroll and Tekle 12 Finally, in the modern era, we must consider the potential unintended consequences of decolonization strategies that adversely impact the microbiome. For example, potentially more virulent organisms could become colonizing flora, or colonization with S. aureus could be critical for normal developmental processes.
In summary, this study has provided much-needed data to justify performing a large, multicenter study to establish the safety, tolerability, and efficacy of targeted surveillance cultures and decolonization strategies in the NICU population. Such a study design is likely to be embraced by the neonatology community.Reference Nelson, Bizzarro and Debmry 10 In addition, a larger future study could more fully assess the durability of decolonization, assess whether infected infants acquire new S. aureus strains or become infected with their colonizing strains, determine optimal timing and frequency of surveillance cultures, and measure the cost-effectiveness of the interventions.
ACKNOWLEDGMENTS
Financial support. No financial support was provided relevant to this article.
Potential conflicts of interest. The author reports no conflicts of interest relevant to this article.