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.
References:
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
http://www.cdc.gov/hicpac/pdf/guidelines/bsi-guidelines-2011.pdf
CDC (Centers for
Disease Control and Prevention). Checklist for Prevention of Central Line Associated
Blood Stream Infections. CDC 2011
http://www.cdc.gov/HAI/pdfs/bsi/checklist-for-CLABSI.pdf
Wachter R. Patient Safety’s First Scandal: The Sad
Case of Chuck Denham, CareFusion, and the NQF. Wachter’s
World blog. The-Hospitalist.org 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
http://www.nejm.org/doi/full/10.1056/NEJMoa1113849
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
http://jama.jamanetwork.com/article.aspx?articleid=2091544
Pittet D, Angus DC. Daily
Chlorhexidine Bathing for Critically Ill Patients: A Note of Caution. JAMA 2015; Published online January
20, 2015
http://jama.jamanetwork.com/article.aspx?articleid=2091541
Soto-Hernandez JL. Comment and Response. Chlorhexidine
Bathing and Infections in Critically Ill Patients. N Engl
J Med 2015; 313(18): 1863
http://jama.jamanetwork.com/article.aspx?articleid=2290629
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
http://www.sciencedirect.com/science/article/pii/S0196655315000905
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.
http://shea2015.org/wp-content/uploads/OralAbstractPresentations.docx
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