Discussion

The benefit of CHG in reducing healthcare-associated infections, including bloodstream infections and MDROs, has been attributed to its antiseptic cleansing properties and residual germicidal effects lasting up to 24 hours. ^{Reference Edmiston, Krepel and Spencer5} It is long believed that residual CHG skin concentrations are important to clear MDRO carriage and reduce infection in presurgical and hospitalized patients. ^{Reference Edmiston, Krepel and Spencer5–Reference Lin, Lolans and Blom7} In this secondary analysis of the CLEAR trial, we did not find a significant association between residual CHG skin concentrations and either MRSA carriage or infection. Nevertheless, the CLEAR trial demonstrated that decolonization with CHG resulted in a 30% reduction in MRSA infection and a 17% reduction in all-cause infection compared to controls (standard bathing). ^{Reference Miller, McKinnell and Singh3} Thus, next-day residual skin concentration may not be important in this postdischarge population.

The lack of association between CHG skin concentration and clinical outcomes is notable because many participants had residual concentrations well below and well above the 5 mcg/ml MIC₉₀ of the target pathogen (MRSA). ^{Reference Edmiston, Krepel and Spencer5–Reference Rhee, Hayden and Schoeny6} Our findings challenge current assumptions that CHG concentrations must be persistently above the MIC to reduce infection risk from human pathogens. Clinical benefit may be predominantly due to direct application of CHG during a shower or bed bath. Participants in the CLEAR trial applied 4% CHG as shower soap, the equivalent of 40,000 mcg/mL to the skin. Because CHG is rapidly bactericidal and this concentration far exceeds the MICs of MDRO and non-MDRO healthcare-associated pathogens, reductions in MDRO carriage and infection may lie in the quality and comprehensiveness of direct application when bathing or showering. Moreover, the reduction in MDRO carriage at 24 hours postbath may be due to both direct germicidal activity and the time it takes for re-exposure and re-colonization to occur rather than a 24-hour persistent germicidal effect. Another possibility is that detectable CHG on the skin underestimates its microbial benefit. Finally, CHG levels that minimize infection may differ in postdischarge patients versus hospitalized patients due to different behaviors, activities, and physical contacts.

Regardless of whether residual CHG concentration is of consequence, feedback of postbathing skin concentrations improves bathing quality, which varies across healthcare providers. ^{Reference Popovich, Lyles and Hayes4–Reference Supple, Kumaraswami and Kundrapu8} Even CHG bathing by ICU nurses fails to achieve the known reduction in bloodstream infections without proper bathing training. ^{Reference Noto, Domenico and Byrne9} Thus, it is notable that CHG bathing education provided to CLEAR participants achieved a 30% reduction in infection despite showering on their own at home. Participants were told to comprehensively soap the body twice using firm massage for 2 minutes outside the water stream before rinsing.

Nevertheless, high residual CHG skin concentrations may further enhance clinical benefit in a way not detectable with the population and outcomes of the CLEAR trial, or the sample size of this study. For example, the CHG MICs for Gram-negative bacteria and especially Candidozyma auris are higher than S. aureus. ^{Reference Lin, Lolans and Blom7,Reference Gussin, Singh and Shimabukuro10} Additional limitations include the fact that CHG concentration was based on a convenience sample of those performing CHG bathing in the 24 hours prior to a follow-up visit. This may have favored those who showered more often on top of clinical trial volunteerism that would enhance adherence. Still, these bathing enhancements should have only improved our ability to detect a difference associated with residual CHG skin concentration. Another limitation is that concentrations were only assessed once, which may not have captured typical bathing behavior and quality. Finally, we did not link the CHG concentration to the MIC of the MRSA strain harbored by each participant. Nevertheless, representative sampling in the CLEAR trial found that nearly all MRSA strains (99.9%) had MICs under 8 mcg/mL. ^{Reference Huang, Singh and McKinnell2}

In summary, we did not find an association between postshower residual CHG skin concentrations and reductions in MRSA carriage or infection in the CLEAR trial. This suggests that CHG benefit may be predominantly imparted at the time of the bath or shower, with residual germicidal effects persisting despite what is detected on the skin, or attributed to the time it takes re-colonization to occur. Using residual CHG skin concentrations for training and ensuring bathing quality may be more important than the exact detected value for achieving the known clinical benefits of CHG.