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Effect of daily chlorhexidine bathing on hospital-acquired Effect of daily chlorhexidine bathing on hospital-acquired
infection infection
Michael W. Climo
Hunter Holmes McGuire Veterans Affairs Medical Center
Deborah S. Yokoe
Harvard Medical School
David K. Warren
Washington University School of Medicine in St. Louis
Trish M. Perl
John Hopkins University
Maureen Bolon
Northerwestern University
See next page for additional authors
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Recommended Citation Recommended Citation
Climo, Michael W.; Yokoe, Deborah S.; Warren, David K.; Perl, Trish M.; Bolon, Maureen; Herwaldt, Loreen
A.; Weinstein, Robert A.; Sepkowitz, Kent A.; Jernigan, John A.; Sanogo, Kakotan; and Wong, Edward S.,
,"Effect of daily chlorhexidine bathing on hospital-acquired infection." The New England Journal of
Medicine. 368,6. 533-542. (2013).
https://digitalcommons.wustl.edu/open_access_pubs/2575
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Authors Authors
Michael W. Climo, Deborah S. Yokoe, David K. Warren, Trish M. Perl, Maureen Bolon, Loreen A. Herwaldt,
Robert A. Weinstein, Kent A. Sepkowitz, John A. Jernigan, Kakotan Sanogo, and Edward S. Wong
This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/
open_access_pubs/2575
The
new engl a nd jour nal
o f
medicine
n engl j med 368;6 nejm.org february 7, 2013
533
original article
Effect of Daily Chlorhexidine Bathing
on Hospital-Acquired Infection
Michael W. Climo, M.D., Deborah S. Yokoe, M.D., M.P.H., David K. Warren, M.D.,
Trish M. Perl, M.D., Maureen Bolon, M.D., Loreen A. Herwaldt, M.D.,
Robert A. Weinstein, M.D., Kent A. Sepkowitz, M.D., John A. Jernigan, M.D.,
Kakotan Sanogo, M.S., and Edward S. Wong, M.D.
From the Hunter Holmes McGuire Veter-
ans Affairs Medical Center (M.W.C.,
E.S.W.) and the Virginia Commonwealth
University Medical Center (M.W.C., K.S.,
E.S.W.), Richmond; Brigham and Wom-
en’s Hospital and Harvard Medical
School, Boston (D.S.Y.); Washington
University School of Medicine, St. Louis
(D.K.W.); Johns Hopkins University, Bal-
timore (T.M.P.); Northwestern University
(M.B.) and Cook County Health and Hos-
pitals System (R.A.W.), Chicago; Iowa
University Hospital, Iowa City (L.A.H.);
Memorial Sloan-Kettering Cancer Cen-
ter, New York (K.A.S.); and the Preven-
tion Epicenters Program, Centers for Dis-
ease Control and Prevention, Atlanta
(J.A.J.). Address reprint requests to Dr.
Climo at the McGuire Veterans Affairs
Medical Center, 1201 Broad Rock Blvd.,
Section 111-C, Richmond, VA 23249, or at
michael.climo@va.gov.
This article was updated on May 23, 2013,
at NEJM.org.
N Engl J Med 2013;368:533-42.
DOI: 10.1056/NEJMoa1113849
Copyright © 2013 Massachusetts Medical Society.
ABSTR ACT
BACKGROUND
Results of previous single-center, observational studies suggest that daily bathing of
patients with chlorhexidine may prevent hospital-acquired bloodstream infections
and the acquisition of multidrug-resistant organisms (MDROs).
METHODS
We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evalu-
ate the effect of daily bathing with chlorhexidine-impregnated washcloths on the
acquisition of MDROs and the incidence of hospital-acquired bloodstream infec-
tions. Nine intensive care and bone marrow transplantation units in six hospitals
were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine–
impregnated washcloths or with nonantimicrobial washcloths for a 6-month peri-
od, exchanged for the alternate product during the subsequent 6 months. The inci-
dence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream
infections were compared between the two periods by means of Poisson regression
analysis.
RESULTS
A total of 7727 patients were enrolled during the study. The overall rate of MDRO
acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus
6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P = 0.03), the
equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hos-
pital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with
chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicro-
bial washcloths (P = 0.007), a 28% lower rate with chlorhexidine-impregnated wash-
cloths. No serious skin reactions were noted during either study period.
CONCLUSIONS
Daily bathing with chlorhexidine-impregnated washcloths significantly reduced
the risks of acquisition of MDROs and development of hospital-acquired blood-
stream infections. (Funded by the Centers for Disease Control and Prevention and
Sage Products; ClinicalTrials.gov number, NCT00502476.)
The New England Journal of Medicine
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The
ne w engl and jour na l
o f
medicine
n engl j med 368;6 nejm.org february 7, 2013
534
M
ultidrug-resistant organisms
(MDROs), including methicillin-resis-
tant Staphylococcus aureus (MRSA) and
vancomycin-resistant enterococcus (VRE), have
become endemic in many acute care and long-
term care facilities.
1-5
Infections with these or-
ganisms are often difficult to treat, owing to a
dwindling armamentarium of active antimicro-
bial agents. The Centers for Disease Control and
Prevention (CDC) has promulgated a variety of
strategies, including hand hygiene and the use of
isolation precautions, to limit the spread of these
organisms among patients, but these strategies
require consistent adherence to practices by large
numbers of health care personnel during fre-
quent patient encounters and can be difficult to
sustain.
6
In addition, health care–associated in-
fections involving these and other microorgan-
isms
7,8
are associated with considerable morbidity
and mortality and with substantial excess costs
that, in some cases, are no longer reimbursed by
third-party payers, including the Centers for Medi-
care and Medicaid Services.
9,10
Targeted interventions, particularly in inten-
sive care units (ICUs), can substantially reduce the
risk of hospital-acquired bloodstream infections
associated with the use of central venous cathe-
ters. Several large studies have shown that im-
proving catheter-insertion processes, including
standardizing insertion-site antisepsis with the
use of chlorhexidine-containing products, can
decrease the risk of infection.
11-13
However, the
use of antiseptic agents for patient bathing is
currently considered controversial.
Chlorhexidine gluconate is an antiseptic agent
that has broad-spectrum activity against many
organisms, including S. aureus and enterococcus
species. Unlike many other antiseptics, chlor-
hexidine has residual antibacterial activity, which
may decrease the microbial burden on patients’
skin and prevent secondary environmental con-
tamination. Vernon et al. found that daily bath-
ing with chlorhexidine-impregnated cloths de-
creased the number of VRE colonies on skin by
2.5 log, as compared with bathing with soap
and water, as well as decreasing VRE contami-
nation of health care workers’ hands by 40%
and environmental surfaces by 30%.
14
By con-
trolling the source, these investigators reduced
the rate of acquisition of VRE among patients
by 66%.
Because hospital-acquired bloodstream infec-
tions often result from the ingress of skin organ-
isms into the bloodstream along vascular cath-
eters or other breaks in skin integrity, skin
decontamination could theoretically also decrease
the risk of infection. Bleasdale et al. found that
daily bathing with 2% chlorhexidine–impreg-
nated washcloths reduced the incidence of pri-
mary bloodstream infections by 60%.
15
Our
previous observational study evaluating bathing
with chlorhexidine in six ICUs showed a 66%
reduction in VRE bacteremia.
16
Previous studies
of bathing with chlorhexidine have been primar-
ily single-center, before-and-after, observational
studies, with limited general applicability of re-
sults. We therefore conducted a multicenter,
randomized trial to evaluate the usefulness of
bathing with chlorhexidine to reduce the risks of
MDRO acquisition and hospital-acquired blood-
stream infection among patients at high risk for
health care–associated infections.
METHODS
STUDY DESIGN
We performed a cluster-randomized, crossover
study involving patients hospitalized in six ICUs
or bone marrow transplantation units between
August 2007 and February 2009. Units were
randomly assigned to perform daily bathing of
patients with either nonantimicrobial wash-
cloths (Comfort Bath, Sage Products) (control) or
washcloths impregnated with 2% chlorhexidine
gluconate (2% Chlorhexidine Gluconate Cloth
Patient Preoperative Skin Preparation, Sage Prod-
ucts) (intervention) during the initial 6-month
study period, followed by daily bathing with the
alternate product during the second 6-month
period.
Bathing was completed according to the man-
ufacturer’s instructions. In brief, washcloths were
used in sequential order to rinse all body sur-
faces, with the exception of the face during bath-
ing with the 2% chlorhexidine–impregnated
cloths in order to avoid exposure of the mucous
membranes of the eyes and mouth. There was
no washout period in the transition to the new
product. Infections and MDRO acquisitions were
monitored for 2 days after the transition and
assigned to the previous bathing treatment if
they occurred within that time period.
The New England Journal of Medicine
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Chlorhexidine and Hospital-Acquired Infection
n engl j med 368;6 nejm.org february 7, 2013
535
The order in which units were assigned to the
control or intervention period was stratified ac-
cording to unit type and facility. The nine par-
ticipating units were divided into two groups.
Group 1 (five units) started with bathing with
the chlorhexidine-impregnated washcloths, fol-
lowed by bathing with nonantimicrobial wash-
cloths. Group 2 (four units) started with bathing
with nonantimicrobial washcloths, followed by
bathing with the chlorhexidine-impregnated wash-
cloths. The investigators and clinical staff were
aware of the use of the control or intervention
bathing product.
Before the study was initiated, nurses were
instructed on the proper techniques for bathing
patients with both washcloth products. Skin-care
products that were not compatible with chlorhex-
idine were eliminated before the study began.
Nursing personnel monitored patients for skin
reactions and reported them to the investigators,
who graded skin reactions on a scale of 1 to 4
(with higher numbers indicating greater severity)
and determined whether the reactions were at-
tributable to bathing (for details of the assess-
ments and scales, see the Supplementary Appen-
dix, available with the full text of this article at
NEJM.org).
All units performed active surveillance testing
for MRSA and VRE throughout the study period.
Unit staff obtained swabs from the nares (for
MRSA) and perirectal area (for VRE) from pa-
tients up to 48 hours after admission to the unit
and on discharge from the unit. The microbiology
laboratory at each institution processed surveil-
lance specimens using either standard culture-
based or molecular-based (polymerase chain re-
action) identification of MRSA and VRE. All
patients found to be colonized or infected with
MRSA or VRE were placed on contact precautions
once test results became available. Patients with
a history of MRSA or VRE colonization or infec-
tion were placed on contact precautions at the
time of admission.
Each participating unit submitted at least 10
separate MRSA and VRE isolates obtained from
patients to the coordinating center each month
for chlorhexidine susceptibility testing. Suscepti-
bility testing was completed by means of the
agar dilution method, with chlorhexidine con-
centrations ranging from 0.1 to 1024.0 μg per
milliliter.
17
STUDY OVERSIGHT
Sage Products supplied the chlorhexidine-impreg-
nated and nonantimicrobial washcloths to par-
ticipating units for the duration of the study, pro-
vided technical and educational support, and
participated in weekly teleconferences with the
study group during the conduct of the study but
was not involved in the study design, the data
analysis, or the preparation of the manuscript.
Approval of the study protocol was obtained from
institutional review boards at the study centers
and the CDC. Waiver of written informed consent
was obtained at each institution, owing to the
minimal-risk nature of the study. Patients who
declined to participate were not bathed with
chlorhexidine-impregnated washcloths. All au-
thors vouch for the completeness and accuracy
of the data presented and for the fidelity of
this report to the study protocol, which is
available at NEJM.org.
DEFINITIONS
Incident and prevalent cases of MRSA or VRE
colonization or infection were classified as previ-
ously described.
16
Bloodstream infections were
identified with the use of National Healthcare
Safety Network definitions.
18
Hospital-acquired
bloodstream infections were defined as blood-
stream infections detected more than 48 hours
after admission to the unit. Primary bloodstream
infections were defined as hospital-acquired blood-
stream infections detected more than 48 hours
after admission to the unit without an attributable
secondary source of infection. Central-catheter–
associated bloodstream infections were defined
as primary bloodstream infections in patients
with at least one central venous catheter in place
within 48 hours before detection of the infection.
TREATMENT INTERRUPTION
On June 28, 2008, Sage Products initiated a nation-
wide recall of the 2% chlorhexidine–impregnated
washcloths, because of Burkholderia cepacia con-
tamination of some product lots. Units using the
chlorhexidine product at the time of the recall were
switched to the nonantimicrobial washcloths, and
the institutional review boards were immediately
notified. After remediation and approval by the
institutional review boards, use of the chlorhexi-
dine product was resumed. Data from units that
had been assigned to use the chlorhexidine-based
The New England Journal of Medicine
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