Patient Safety Tip of the Week

May 19, 2015    Dueling Chlorhexidine Studies



Chlorhexidine in the past decade became the most widely used antiseptic agent in a variety of settings. Its use is part of the CDC Guidelines for the Prevention of

Intravascular Catheter-Related Infections (O'Grady 2011). It is the most widely used antiseptic agent used for skin preparation prior to surgical procedures. Many patients also use chlorhexidine bathing on the day prior to elective surgical procedures. And many ICU’s have adopted daily chlorhexidine bathing in an effort to reduce healthcare-associated infections (HAI’s).


But chlorhexidine has come under fire recently. We’ve previously noted that chlorhexidine preparations with alcohol are typically flammable and have been implicated in some surgical fires (see our Patient Safety Tips of the Week for December 13, 2011 “Surgical Fires Again”, August 12, 2014 “Surgical Fires Back in the News”, and December 16, 2014 “More on Each Element of the Surgical Fire Triad”). After a case described in the latter column a hospital implemented a policy prohibiting alcohol-based skin preps in any emergency surgery that does not allow sufficient drying time (usually 3 minutes or longer). Instead they have gone back to non-alcohol-based preps like Betadine for such emergency cases. We’ve also noted problems with “the fine print” on package inserts and labels in some cases. In several of our prior articles we noted another surgical fire in which a hospital had switched from the 10.5 ml Chloraprep applicator, which did not have the warning to avoid use in head and neck surgery, to the 26 ml applicator which did have the warning. It was actually quite predictable that staff would assume the new supplies were the same as the old and not “read the fine print”.


Then came patient safety’s infamous “first scandal” (Wachter 2014) in which several NQF Safe Practices included the recommendation to “use chlorhexidine gluconate 2% and isopropyl alcohol solution as skin antiseptic preparation…” after lobbying by Dr. Charles Denham. It was later revealed that Denham had an undisclosed financial relationship with CareFusion, the manufacturer of ChloraPrep which was the only one on the market containing that formulation. Both CareFusion and Denham faced heavy fines for their involvement and Denham was removed from NQF committees and his post as editor of the Journal of Patient Safety. The latter journal also uncovered several articles in which Denham failed to disclose conflicts of interest.


Wachter also notes that a key New England Journal of Medicine article (Climo 2013), that concluded daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections, has also been questioned because of conflict of interest issues.


Now a new study has challenged the reported efficacy of daily chlorhexidine bathing in ICU’s (Noto 2015). The study by Noto and colleagues was a cluster randomized, crossover study of 9340 patients admitted to 5 adult intensive care units of a tertiary medical center. It compared once-daily bathing of all patients with disposable cloths impregnated with 2% chlorhexidine or nonantimicrobial cloths as a control. Those researchers found that daily bathing with chlorhexidine did not reduce the incidence of health care–associated infections including CLABSIs, CAUTIs, VAP, or C difficile. They conclude their findings do not support daily bathing of critically ill patients with chlorhexidine.


Several commentaries have noted some limitations of the Noto study. Pittet and Angus (Pittet 2015) noted that the study was a single-center study and was not blinded (both staff and patients could have known which type of cloth was being used). They also questioned the validity of the composite endpoint since the strongest data supporting use of chlorhexidine is in preventing CLABSI’s, not the other component HAI’s. Soto-Hernandez (Soto-Hernandez 2015) points out considerable differences in the patient populations reported in the Climo and Noto studies. The Noto population had low rates of HAI’s in both arms and patients had very short ICU lengths of stay, whereas the Climo population had considerably longer ICU lengths of stay and included a unit with bone marrow transplantation patients.


But whether or not the findings by Noto et al. can be generalized to other ICU’s they certainly send the message that ICU’s should question the practice of daily chlorhexidine bathing and perhaps look at their own experience.


To make things even more complicated, another new study reported in the American Journal of Infection Control (Cassir 2015) found that daily chlorhexidine cleansing did reduce the incidence rate of HAI caused by gram-negative bacteria, highlighting the role of the transient gram-negative bacteria skin colonization in the pathogenesis of HAI. The study, which was relatively small, enrolled patients who had at least one previous episode of sepsis. Similarly, another recent small randomized controlled trial in a SICU demonstrated a 44% reduction in CLABSI, CAUTI, VAP, and incisional SSI’s (surgical site infections) with every other day chlorhexidine bathing compared to soap and water bathing (Swan 2014). That study was presented in abstract only.


Hence, our column title “dueling chlorhexidine studies”.


Good old betadine


The antiseptic that chlorhexidine largely replaced in many settings was povidone-iodine. As above, in several of our columns on surgical fires we have noted hospitals changing back to povidone-iodine for cases at high risk for surgical fire (see our December 16, 2014 Patient Safety Tip of the Week “More on Each Element of the Surgical Fire Triad”). Now another new study has demonstrated that application of povidone-iodine to the nostrils at least an hour prior to spinal surgery significantly reduced surgical infections (Flynn 2015).


Can resistance develop to antiseptics?


In addition to the conflicting studies on efficacy of chlorhexidine, there has been some additional research suggesting that bacteria might develop resistance to chlorhexidine (Suwantarat 2014). Those authors found that in units that bathe patients daily with chlorhexidine, organisms causing central line-associated bloodstream infections (CLABSIs) were more likely to have reduced chlorhexidine susceptibility than organisms causing CLABSIs in units that do not bathe patients daily with chlorhexidine (86% vs 64%). The investigators suggest that surveillance is needed to detect reduced chlorhexidine susceptibility with widespread chlorhexidine use.


The Bottom Line


You can bet that hospitals will begin to take a close look at their practice of daily chlorhexidine bathing in ICU’s. The Noto study suggests that the considerable expense of this practice is not likely paying off in terms of fewer HAI’s. You can expect also attempts to replicate the Noto study in other hospitals. And, while povidone-iodine is not practical for daily bathing, expect to see some more head-to-head trials of to povidone-iodine vs. chlorhexidine for some of the other indications.






O'Grady NP, Alexander M, Burns LA, et al. Guidelines for the Prevention of

Intravascular Catheter-Related Infections, 2011. CDC (Centers for Disease Control and Prevention) 2011

CDC (Centers for Disease Control and Prevention). Checklist for Prevention of Central Line Associated Blood Stream Infections. CDC 2011



Wachter R. Patient Safety’s First Scandal: The Sad Case of Chuck Denham, CareFusion, and the NQF. Wachter’s World blog.  January 30, 2014



Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med 2013; 368: 533-542



Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine Bathing and Health Care–Associated Infections. A Randomized Clinical Trial. JAMA 2015; Published online January 20, 2015



Pittet D, Angus DC. Daily Chlorhexidine Bathing for Critically Ill Patients: A Note of Caution. JAMA 2015; Published online January 20, 2015



Soto-Hernandez JL. Comment and Response. Chlorhexidine Bathing and Infections in Critically Ill Patients. N Engl J Med 2015; 313(18): 1863



Cassir N, Thomas G, Hraiech S, et al. Chlorhexidine daily bathing: Impact on health care–associated infections caused by gram-negative bacteria. American Journal of Infection Control 2015; Available online 19 March 2015



Swan J, Bui L, Pham V et al. RCT of Chlorhexidine vs. Soap & Water Bathing for Prevention of Hospital-Acquired Infections in SICU. Critical Care Medicine 2014; 42(12): A1369-A1370, December 2014



Suwantarat N, Carroll KC, Tekle TMT, et al. High Prevalence of Reduced Chlorhexidine Susceptibility in Organisms Causing Central Line-Associated Bloodstream Infections. Infection Control & Hospital Epidemiology 2014; 35(9): 1183-1186, September 2014



Flynn NA, Carr M. Society for Healthcare Epidemiology of America (SHEA) Spring 2015 Conference: Abstract 1809. Presented May 14, 2015.





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