MAJOR ARTICLE

Mupirocin-Based Decolonization of Staphylococcus

aureus Carriers in Residents of 2 Long-Term Care

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Facilities: A Randomized, Double-Blind, Placebo-
Controlled Trial
Lona Mody,1,3 Carol A. Kauffman,2,3 Shelly A. McNeil,2,3,a Andrzej T. Galecki,4 and Suzanne F. Bradley1,2,3
Divisions of 1Geriatric Medicine and 2Infectious Diseases, Department of Internal Medicine, Veterans Affairs Ann Arbor Healthcare System,
and 3University of Michigan Medical School and 4Institute of Gerontology, University of Michigan Ann Arbor, Michigan

Mupirocin has been used in nursing homes to prevent the spread of methicillin-resistant Staphylococcus aureus
(MRSA), despite the lack of controlled trials. In this double-blind, randomized study, the efficacy of intranasal
mupirocin ointment versus that of placebo in reducing colonization and preventing infection was assessed
among persistent carriers of S. aureus. Twice-daily treatment was given for 2 weeks, with a follow-up period
of 6 months. Staphylococcal colonization rates were similar between residents at the Ann Arbor Veterans
Affairs (VA) Extended Care Center, Michigan (33%), and residents at a community-based long-term care
facility in Ann Arbor (36%), although those at the VA Center carried MRSA more often (58% vs. 35%; P p
.017). After treatment, mupirocin had eradicated colonization in 93% of residents, whereas 85% of residents
who received placebo remained colonized (P ! .001 ). At day 90 after study entry, 61% of the residents in the
mupirocin group remained decolonized. Four patients did not respond to mupirocin therapy; 3 of the 4 had
mupirocin-resistant S. aureus strains. Thirteen (86%) of 14 residents who became recolonized had the same
pretherapy strain; no strain recovered during relapse was resistant to mupirocin. A trend toward reduction
in infections was seen with mupirocin treatment.

Colonization and infection with Staphylococcus aureus,
which are common in older persons, are perhaps as-
sociated with chronic disease and debility [1]. Mortality
due to staphylococcal bacteremia is greater among older
persons and is 160% among residents of long-term care
facilities (LTCFs) and hospitalized older adults [2–4].
For staphylococcal carriers, the risk of infection with
Received 13 May 2003; accepted 1 August 2003; electronically published 6
November 2003.
Financial support: National Institutes on Aging and Claude D. Pepper Older
Americans Independence Centers (AG08808).
a
Present affiliation: Division of Infectious Diseases, Dalhousie University School
of Medicine, Halifax, Nova Scotia, Canada.
Reprints or correspondence: Dr. Lona Mody, GRECC 11G, Veterans Affairs
Medical Center, 2215 Fuller Rd., Ann Arbor, MI 48105 (lonamody@umich.edu).
Clinical Infectious Diseases 2003; 37:1467–74
 2003 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2003/3711-0007$15.00
S. aureus is significantly higher than it is for noncarriers,
and infection is usually caused by the colonizing strain
[5, 6]. Carriage of methicillin-resistant S. aureus
(MRSA) has been shown to be a marker for increased
risk of infection and mortality among LTCF residents
[7–9].
Treatment of persistent staphylococcal carriage with
the topical antibiotic mupirocin has been shown to
decrease staphylococcal infections among patients un-
dergoing hemodialysis and those who have undergone
elective surgery [10–14]. Several noncontrolled studies
have shown that mupirocin alone or in combination
with other measures decreases S. aureus colonization
among residents of LTCFs [15–18]. However, there are
no controlled trials involving such individuals that have
definitively shown that mupirocin decreases S. aureus
colonization and infection.
This study, which was performed in both community

Mupirocin Treatment in Nursing Homes • CID 2003:37 (1 December) • 1467

and Veterans Affairs (VA) LTCFs in Ann Arbor, Michigan, as-
sessed whether a 2-week course of mupirocin therapy led to
prolonged reduction in colonization and prevented S. aureus
infection. Recolonization with S. aureus and acquisition of mu-
pirocin resistance were evaluated.
STUDY PARTICIPANTS AND METHODS
Study population. The Ann Arbor VA Extended Care Center
is a 50-bed facility attached to an acute care hospital. Residents
are admitted for long-term care (10 beds), rehabilitation (10
beds), and geriatric evaluation (30 beds). Glacier Hills Nursing
Center is a 163-bed community LTCF located within a few
miles of the VA Medical Center. It has a 127-bed skilled nursing
unit and a 36-bed dementia unit.
Eligibility. All residents of the VA and community LTCFs
were eligible. Appropriate informed consent was obtained, and
guidelines for human experimentation and the conduct of clin-
ical research were followed, as required by the University of
Michigan and Veterans Affairs Ann Arbor Healthcare System
institutional review boards. After obtaining written informed
consent, specimens were obtained from the nares and, when
present, wounds of all patients. Residents for whom culture
results were positive for S. aureus on 2 consecutive cultures
performed <2 weeks apart were considered persistent carriers
and were enrolled into the treatment trial.
Exclusion criteria. Residents were not enrolled if they were
receiving systemic antibiotic therapy or topical antibiotic ther-
apy for wounds, had active S. aureus infection, or were judged
unable to cooperate with the study. Known hypersensitivity to
mupirocin and the presence of large wounds (i.e., a surface
area of 110 3 10 cm and a depth of 13 cm) were also exclusion
factors. Residents who were initially found not to be carriers
were screened again if they required admission to the hospital
and then returned to the LTCF.
Group assignment. Enrolled residents were randomly as-
signed to study groups by stratification according to LTCF type
and presence of wounds. Randomization was performed sep-
arately on the basis of residence type and presence of wounds
in blocks of 2 to assure that the number of patients assigned
to study groups using these strata was equal. Investigators, nurs-
ing staff, and study participants were blinded to the treatment
group.
Treatment. Mupirocin therapy or placebo was adminis-
tered twice daily for 14 days by study personnel who wore
gloves after appropriate hand disinfection and who were
blinded to results of microbiological tests. The study drugs were
placed in identical containers labeled “A” or “B” by the study
pharmacist. Mupirocin 2% ointment in polyethylene glycol
(PEG) base or plain PEG ointment (placebo) was applied to
1468 • CID 2003:37 (1 December) • Mody et al.
each anterior naris, and the nose was massaged gently. Oint-
ment was applied over wound surfaces in a thin layer.
Samples were obtained from nares and wounds every other
day during the treatment period. On day 15 of the study—the
day after treatment ended—a sample was obtained. Successive
samples were obtained every week during the next 4 weeks,
every 2 weeks for 2 months, and monthly for an additional 2.5
months, as long as the patient remained in the facility. Enrolled
residents were observed for the development of staphylococcal
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infection during the same 6-month period, as long as they were
residents of the facility.
Permitted local wound care included whirlpool therapy, de-
bridement, and application of hydrogen peroxide, Dakin’s so-
lution (sodium hypochlorite 5.25%), and dressings. Wound
therapy was provided before the study drug or placebo was
administered. No topical or systemic antibiotic therapy with
activity against S. aureus was allowed.
Assessment. Demographic characteristics and risk factors
for S. aureus colonization were assessed at study entry. Di-
mensions of decubitus or vascular ulcers, other wounds, skin
conditions, and devices were recorded. Functional status was
measured using a modified Katz scale [19].
Enrolled residents were monitored daily for S. aureus infec-
tion, on the basis of the Centers for Disease Control and Pre-
vention definitions [20]. All cases were reviewed by a panel of
3 consultants who specialized in infectious diseases and geri-
atrics, all of whom were blinded to colonization data and treat-
ment regimens.
Outcomes. Outcomes were categorized as cure (i.e., no S.
aureus was recovered from any site) or failure (i.e., persistence
of S. aureus at the end of treatment or recolonization after
negative culture results on day 15). Recolonization was further
defined as relapse (i.e., recolonization by the previously colo-
nizing S. aureus strain) or reinfection (i.e., acquisition of a new
S. aureus strain).
To test the hypothesis that mupirocin therapy led to eradi-
cation of S. aureus colonization, short-term (15 days after study
entry) and long-term (90 days after study entry) responses were
assessed, with S. aureus colonization being the primary outcome
variable. Recolonization, emergence of mupirocin-resistant
strains, and reduction in S. aureus infections in residents treated
with mupirocin were secondary outcomes.
Microbiological methods. Nares and wounds were
swabbed with sterile rayon-tipped applicator sticks that were
then placed into Stuart’s transport medium. Samples were ob-
tained before daily local wound care and application of mu-
pirocin. Swabs were streaked onto colistin–nalidixic acid agar
with 5% sheep blood (BBL; Becton Dickinson) and incubated
at 35C for 24 h. S. aureus identification and methicillin-
susceptibility testing were performed using standard methods
[15, 16]. If a patient was found to have both MRSA and meth-
 Table 1. Demographic and clinical characteristics of residents of 2 long-term care facilities
(LTCFs) in Ann Arbor, Michigan, who were enrolled into the study.

LTCF type
Veterans Affairs Community-based
Variable hospital nursing center P
No. of residents screened 254 173 …
Persistent staphylococcal carriers 83 (33) 62 (36) .5
No. of residents enrolled 73 54 .6
Age, mean years  SD 69  9.9 86  7.1 !.001

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M ale sex 70 (96) 13 (24) !.001
Diabetes mellitus 26 (37) 14 (26) .25
a
Acute care 63 (86) 22 (41) !.001
a
Antibiotic use 43 (59) 13 (24) !.001
ADL
Class 1 39 (53) 7 (13) !.001
Class 2 30 (41) 34 (63) …
Class 3 4 (6) 13 (24) …
Device use 35 (48) 12 (22) .003
Renal insufficiency 11 (15) 5 (9) .33
Peripheral vascular disease 23 (32) 4 (6) .001
Injectable medication use 18 (25) 6 (11) .05
Skin disease 9 (12) 1 (2) .03
Wounds 7 (10) 1 (2) .08

NOTE. Data are no. or no. (% ) of individuals, unless otherw ise indicated. ADL, activities of daily living.
a
During the 30-day period before enrollment.

icillin-susceptible S. aureus (MSSA), methicillin resistance was
verified by a latex agglutination test for penicillin-binding pro-
tein 2a (Oxoid). Isolates were stored at 270C for later analysis.
Each isolate was screened for mupirocin resistance by in-
oculation onto Mueller-Hinton agar plates containing 2 mg/mL
mupirocin. The MICs of mupirocin for isolates that grew on
the screening plates were determined by Etest (AB Biodisk)
[21]. Mupirocin resistance was defined as an MIC of >4 mg/
mL, and high-level resistance was defined as an MIC of >500
mg/mL [22].
S. aureus strains recovered from residents who were reco-
lonized after therapy and from those who did not respond to
therapy were typed by PGFE to determine whether recoloni-
zation or therapy failure was due to the previous colonizing
strain or a new strain. Genomic DNA fragments obtained after
digestion with SmaI (New England BioLabs) were separated by
PFGE using a CHEF III system (BioRad) [23, 24]. Gels were
stained and photographed, and the banding patterns of differ-
ent isolates were compared visually. Strain relatedness was de-
termined as described elsewhere [25].
Statistical methods. Data were entered into EpiInfo 6.0
(Centers for Disease Control and Prevention) and analyzed
using SAS software. Demographic and clinical characteristics
at enrollment that predisposed residents to S. aureus coloni-
zation were compared between VA and community LTCFs and
between treatment groups. Depending on the scale by which
variables were measured, the following standard 2-group
comparison methods were used: 2-sample Student’s t test, for
normally distributed variables; Mann-Whitney U test, for con-
tinuous nonnormally distributed variables; or x2 test, for cat-
egorical variables. A P value of !.05 was considered to be sta-
tistically significant.
The proportion of residents in each treatment arm who were
colonized with S. aureus was compared after treatment was
stopped (i.e., 15 days after study entry) and on day 90 using
the standard Cochran-Mantel-Haenszel (CMH) test on day 15
and a modified CMH test on day 90 (because of residents lost
to follow-up) [26, 27]. The Andersen-Gill model was used to
analyze data on time to decolonization. The model, an exten-
sion of the classical Cox regression model, accounts for poten-
tial spontaneous clearance and recolonization.
RESULTS
Demographic and clinical characteristics of the study popu-
lation at enrollment. Of the 427 residents screened for col-
onization with S. aureus, 254 (59%) were from the VA LTCF
and 173 (41%) were from the community LTCF (table 1).
Overall, 83 (33%) of VA and 62 (36%) of community LTCF
residents were persistently colonized with S. aureus and eligible

Mupirocin Treatment in Nursing Homes • CID 2003:37 (1 December) • 1469

Table 2. Demographic and clinical characteristics of long- or to have received antibiotics, to have a device, peripheral
term care facility residents randomized to received mupirocin vascular disease, or skin disease, and to be functionally more
therapy or placebo.
independent than were community LTCF study participants
M upirocin Placebo
(table 1).
group group Response to treatment with study drug. Sixty-four and
Variable (n p 64) (n p 63) P 63 LTCF residents were randomized to the mupirocin and pla-
Age, mean years  SD 76.3  12.8 76.0  12.0 .9 cebo groups, respectively (table 2). No significant differences
M ale sex 43 (67) 40 (63) .7 were noted between the groups, with the exception of func-
Diabetes mellitus 17 (27) 23 (37) .2 tional status, which was slightly better in the mupirocin group

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Acute care
a
42 (66) 43 (68) .8 (P p .05) (table 2). Among study participants who received
a
Antibiotic use 28 (44) 28 (44) .9 mupirocin, 36 (56%) were at the VA LTCF, and 28 (44%) were
ADL at the community-based LTCF. Colonization with MRSA was
Class 1 27 (40) 19 (30) .05 noted in 27 (44%) of those in the mupirocin group and in 36
Class 2 33 (52) 31 (49) … (57%) of those in the placebo group (P p .07).
Class 3 4 (8) 13 (21) … Of the group of 127 residents who were treated, 102 (80%)
Device use 22 (35) 25 (40) .5
Renal insufficiency 7 (11) 9 (14) .6
Peripheral vascular disease 13 (20) 14 (22) .8
Injectable medication use 10 (16) 14 (22) .3
Skin disease 7 (11) 3 (5) .2
Wounds 5 (8) 3 (5) .5

NOTE. Data are no. (% ) of study participants, unless otherw ise indi-
cated. ADL, activities of daily living.
a
During the 30-day period before enrollment.

for enrollment. Of the patients eligible to participate, 127 (85%)

were enrolled into the treatment trial; 73 (57%) were from the
VA LTCF, and 54 (43%) were from the community LTCF.
A total of 83 enrolled residents (65%) were men, and 44
(35%) were women. The majority of men (84%) were VA LTCF
residents, and almost all women (93%) were community LTCF
residents. The mean age (SD) of study participants was
76.2  12.3 years (range, 45–102 years). The VA LTCF study
population was significantly younger than community LTCF
study population (69  9.9 vs. 86  7.1 years; P ! .001).
Among the 73 VA LTCF residents, colonization with MRSA
alone occurred in 42 (58%); an additional 2 (3%) were colo-
nized with both MRSA and MSSA at enrollment. Among the
54 community LTCF residents, 19 (35%) were colonized with
MRSA only, and 1 (2%) was colonized with both MRSA and
MSSA at enrollment; for 2 residents, methicillin susceptibility
was not determined because isolates recovered at enrollment
were lost. The difference in the prevalence of MRSA carriage
was significantly different between the 2 facilities (P p .017).
Risk factors for colonization with S. aureus. The most
common risk factors for persistent S. aureus carriage included
recent hospitalization (67% of study participants), antibiotic
use in the 30 days before study entry (44%), presence of devices
(37%), and diabetes mellitus (32%). Only 8 (6%) of enrolled
residents had wounds at enrollment. VA LTCF study partici- Figure 1. Number of study participants evaluated for Staphylococcus
pants were significantly more likely to have been hospitalized aureus decolonization, by time point.

1470 • CID 2003:37 (1 December) • Mody et al.

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Figure 2. Proportion of long-term care residents free of colonization with Staphylococcus aureus after receiving mupirocin therapy (unshaded
regions) or placebo (shaded regions) for 14 days. The number of patients remaining in the study at each time point is indicated above each bar.

completed 14 days of therapy and were evaluated for treatment of colonization was 4.12 times higher for the placebo group
efficacy (figure 1). Twenty-two study participants were dis- (95% CI, 2.68–6.31; P ! .0001).
charged before completing therapy, and 3 refused to complete Four residents in the mupirocin group—all of whom were
therapy. Figure 1 shows data on the number of participants colonized with MRSA—did not respond to decolonization
who were evaluated at each of the subsequent time points after therapy (table 3). However, decolonization rates did not differ
study entry. statistically between those with MRSA and those with MSSA
On day 15 of the study (the day after treatment ended), 51 (P p .08). All 4 remained colonized with the strain recovered
(93%) of 55 study participants who were randomized to receive at enrollment. One resident each had a low-level and a high-
mupirocin were no longer colonized with S. aureus, compared level mupirocin-resistant strain at enrollment that persisted,
with 7 (15%) of 47 in the placebo group (P ! .001) (figure 2). despite receipt of therapy. Another was colonized with a strain
Among 8 study participants with wounds, 3 did not complete that developed high-level mupirocin resistance during the
14 days of therapy and could not be evaluated; all 4 who had course of treatment, and the fourth remained colonized with
received mupirocin were no longer colonized with S. aureus, a mupirocin-susceptible strain throughout treatment.
and 1 who had received placebo remained colonized. Of the 14 study participants who became recolonized with
At 30 days after study entry (2 weeks after treatment was
stopped), 35 (88%) of the 40 residents who received mupirocin Table 3. MICs of mupirocin for Staphylococcus aureus isolates
recovered from long-term care residents who did not respond to
were free of S. aureus, compared with 5 (13%) of 38 of those
treatment with mupirocin.
who had received placebo (P ! .001 ). Three residents in the
mupirocin group and 1 in the placebo group had become re- M upirocin M IC, mg/mL (no. of isolates)
colonized with S. aureus. At day 60, 22 (79%) of 28 of the Before During After
a b
study participants remained decolonized, and, at day 90, 14 Patient no. therapy therapy therapy
(61%) of 23 who had received mupirocin remained free of S. 1 !0.98 (2) !0.98 (2) 1500 (2)
aureus. Among residents in the placebo group, decolonization 2 16–32 (4) 16–64 (8) 16–32 (9)
was uncommon, occurring in 7%–18% at the time points at 3 !0.98 (1) 1500 (2) 1500 (2)
which samples were obtained. S. aureus colonization did not 1500 (1)
differ between the 2 groups at 180 days, but too few residents 4 !0.98 (1) !0.98 (4) !0.98 (2)
remained in the study to draw conclusions about this time a
Isolates recovered on days 1–13.
period. Over the entire duration of the study, the hazard rate b
Isolates recovered on day 15 and thereafter.

Mupirocin Treatment in Nursing Homes • CID 2003:37 (1 December) • 1471


Figure 3. Study participants (n p 14 ) who were recolonized with
Staphylococcus aureus at various time points after initial decolonization.
Patients either relapsed with the same pretherapy strain (shadedregions)
or acquired a new strain (unshaded regions), as defined by PFGE.
S. aureus after initial decolonization, 12 (86%) relapsed with
the same strain and 2 acquired a new strain (figure 3). All
recolonizing strains remained mupirocin susceptible. The PEG
formulation was well tolerated; failure to complete therapy be-
cause of side effects occurred in only 1 placebo recipient, who
complained of nasal stuffiness.
Infections. Ten (10%) of 102 residents who finished the
14-day treatment course developed laboratory-confirmed or
probable infection with S. aureus. Three (5%) of 55 residents
treated with mupirocin and 7 (15%) of 47 who received placebo
developed infection (P p .10). In the placebo group, 3 and 4
residents, respectively, developed infection during treatment
and after the regimen was stopped. Cellulitis occurred in 3
study participants, conjunctivitis in 2, a perirectal abscess in 1,
and a urinary tract infection in 1. Of the 3 residents in the
mupirocin group who developed infection, all had cellulitis that
developed 5–38 days after treatment had stopped; all 3 had
cleared staphylococcal nasal carriage and remained free of S.
aureus in the nares at the time infection occurred. Culture
results for 2 patients were positive for MRSA, and culture was
not performed for the third, although the infection in this
patient responded to cephalexin.
DISCUSSION
In this study of LTCF residents, mupirocin was highly effective
in decolonizing persistent S. aureus colonization in the nares,
compared with placebo. At the end of therapy, 93% of residents
in the mupirocin group had cleared S. aureus from the nares.
Previous studies of mupirocin in LTCFs—although they were not
1472 • CID 2003:37 (1 December) • Mody et al.
placebo controlled—showed similar clearance rates [15, 16].
Clearance rates of 90% are similar to those noted for other patient
populations [12, 13, 28, 29] and health care workers [30].
Studies to assess decolonization strategies in older persons
have been infrequent [15, 16, 18, 31], and some regimens have
been less effective in such patients [31–33]. In an older pop-
ulation of hospitalized patients, mupirocin was no more effec-
tive than was placebo for clearing MRSA carriage [33]. In an
uncontrolled study in which oral antibiotics were administered
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with or without rifampin, persistent or recurrent colonization
within 30 days after treatment completion was demonstrated
in 56% of LTCF residents [31], and another study in which
oral antibiotics and rifampin were administered noted age as
a risk factor for failure to clear MRSA [32].
We found that decolonization due to mupirocin persisted
for 45 days after treatment had ended (day 60 after study entry)
and that, although the duration of decolonization was still sig-
nificantly different from that associated with placebo, decolo-
nization efficacy had begun to decrease by day 90 after study
entry. Few studies have assessed the effect of decolonization
regimens on the persistence of clearance for 130 days after
treatment was stopped. An earlier uncontrolled study in our
facility noted that 56% of residents remained decolonized for
60 days after mupirocin therapy was stopped [15], and a pla-
cebo-controlled study of intranasal bacitracin and oral rifampin
demonstrated that 44% of patients who were undergoing he-
modialysis remained decolonized for 90 days [34].
In this study, recolonization in 12 (86%) of 14 residents
involved the original strain. In contrast, health care workers
who were treated with mupirocin were as likely to relapse with
a new strain as with their pretherapy strain [35]. Relapse of S.
aureus carriage in residents of LTCFs is likely due to persistent
risk factors that contribute to initial colonization [9, 36, 37].
Relapse of S. aureus carriage in our study was not associated
with the development of mupirocin resistance.
One approach to decrease recolonization is intermittent mu-
pirocin treatment. Thrice-weekly, weekly, and twice-monthly
regimens have been used to maintain nasal decolonization in
patients undergoing dialysis [38, 39], without development of
mupirocin resistance. However, use of a weekly maintenance
regimen of mupirocin in MRSA-colonized residents of LTCFs
was less efficacious and was associated with mupirocin resis-
tance [16]. On the basis of the results of this study, an alter-
native approach might be pulse therapy with 14 days of mu-
pirocin every 2–3 months to prevent relapse and decrease the
likelihood of resistance. A similar approach has been successful
in patients with furunculosis (mupirocin was administered for
5 days each month) [40] and has been suggested for use in
patients undergoing hemodialysis [41].
Three of 4 residents who did not respond to therapy were
found to carry mupirocin-resistant S. aureus at the end of the
treatment period, only 1 of whom had a strain that developed
resistance. All 4 mupirocin failures in this study occurred in
MRSA-colonized residents, but the rate of failure was not sta-
tistically different from that for MSSA-colonized residents.
MRSA strains are no more likely to harbor or acquire mupi-
rocin resistance elements than are MSSA strains [22]. It is likely
that patient factors that select for MRSA—and not only for
mupirocin resistance—play a role in failure of decolonization.
Mupirocin PEG ointment has been used extensively for de-
colonization of staphylococcal carriage [15–17, 42–45]. Differ-
ent formulations were developed because of concern for nasal
side effects and absorption of PEG in neonates and in large
burns wounds [14]. In our study, the PEG formulation was
well tolerated.
It has been questioned whether data on S. aureus colonization
obtained from VA LTCFs are applicable to community LTCFs.
As a group, the VA LTCF population is younger, predominantly
male, and more functionally independent [8, 36]. We found
no differences in colonization rates for S. aureus between the
2 facilities, but the proportion of S. aureus isolates that were
methicillin resistant was higher in VA LTCF study participants,
confirming previous reports [8]. The colonization rates in the
community facility were higher than we anticipated. This could
reflect increasing MRSA rates in the community [46, 47] or
increasing trends toward transferring sicker patients from the
hospital to the LTCF [48].
Approximately 20% of the study participants did not com-
plete the 14-day therapy course; this hampered our ability to
detect differences in infection rates. The number of residents
in each treatment arm was too small to show a significant
difference in infection rates, although a trend toward decreased
infection rates was seen in the mupirocin group. Some S. aureus
carriers may be at greater risk of infection than others [1, 9,
36]. Mupirocin decolonization might prove more efficacious if
residents who were most dependent or who had devices in
place, diabetes mellitus, or peripheral vascular occlusive disease
were treated.
In conclusion, mupirocin was effective in decolonizing S.
aureus in persistent carriers enrolled from 2 LTCF populations.
Although recolonization occurred, development of resistance
was uncommon. There was a trend towards reduction in in-
fections with mupirocin use. Multicenter trials that focus on
persistent S. aureus carriers—who are at greatest risk—are
needed to assess the effectiveness of mupirocin in reducing
infections in LTCFs.
Acknowledgment
We thank SmithKline Beecham for providing Etest strips and
mupirocin powder.
Mupirocin Treatment in Nursing Homes • CID 2003:37 (1 December) • 1473
References
1. Bradley SF. Staphylococcus aureus infections and antibiotic resistance
in older adults. Clin Infect Dis 2002; 34:211–6.
2. McClelland RS, Fowler VG, Sanders LL, et al. Staphylococcus aureus
bacteremia among elderly vs. younger adult patients: comparison of
clinical features and mortality. Arch Intern Med 1999; 159:1244–7.
3. Muder RR, Brennen C, Wagener MM, et al. Bacteremia in a long-term
care facility: a five-year prospective study of 163 consecutive episodes.
Clin Infect Dis 1992; 14:647–54.
4. Whitelaw DA, Rayner BL, Willcox PA. Community-acquired bacter-
emia in the elderly: a prospective study of 121 cases. J Am Geriatr Soc
Downloaded from https://academic.oup.com/cid/article-abstract/37/11/1467/372049 by University of Florida user on 13 July 2019
1992; 40:996–1000.
5. Kluytmans J, van Belkam A, Verbrugh H. Nasal carriage of Staphylo-
coccus aureus: epidemiology, underlying mechanisms, and associated
risks. Clin Microbiol Rev 1997; 10:505–20.
6. Von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of
Staphylococcus aureus bacteremia. N Engl J Med 2001; 344:11–6.
7. Niclaes L, Buntinx F, Banuro F, Lesaffre E, Heyrman J. Consequences
of MRSA carriage in nursing home residents. Epidemiol Infect 1999;
122:235–9.
8. Mulhausen PL, Harrell LJ, Weinberger M, Kochersberger GG, Feussner
JR. Contrasting methicillin-resistant Staphylococcus aureus colonization
in Veterans Affairs and community nursing homes. Am J Med 1996;
100:24–31.
9. Muder RR, Brennen C, Wagener MM, et al. Methicillin-resistant staph-
ylococcal colonization and infection in a long-term care facility. Ann
Intern Med 1991; 114:107–12.
10. Perl TM, Cullen JJ, Wenzel RP, et al. Intranasal mupirocin to prevent
postoperative Staphylococcus aureus infections. N Engl J Med 2002;
346:1871–7.
11. Peacock SJ, Mandal S, Bowler IC. Preventing Staphylococcus aureus
infection in the renal unit. QJM 2002; 95:405–10.
12. Kluytmans JA, Manders MJ, van Bommel E, Verbrugh H. Elimination
of nasal carriage of Staphylococcus aureus in hemodialysis patients.
Infect Control Hosp Epidemiol 1996; 17:793–7.
13. Kluytmans JA, Mouton JW, VandenBergh MF, et al. Reduction of sur-
gical-site infections in cardiothoracic surgery by elimination of nasal
carriage of Staphylococcus aureus. Infect Control Hosp Epidemiol
1996; 17:780–5.
14. Bradley SF. Effectiveness of mupirocin in the control of methicillin-
resistant Staphylococcus aureus. Infections in Medicine 1993; 10:23–31.
15. Cederna JE, Terpenning MS, Ensberg M, Bradley SF, Kauffman CA.
Staphylococcus aureus nasal colonization in a nursing home: eradication
with mupirocin. Infect Control Hosp Epidemiol 1990; 11:13–6.
16. Kauffman CA, Terpenning MS, He X, et al. Attempts to eradicate
methicillin-resistant Staphylococcus aureus from a long-term care fa-
cility with the use of mupirocin ointment. Am J Med 1993; 94:371–8.
17. Simor AE, Augustin A, Ng J, Betschel S, McArthur M. Control of
MRSA in a long-term care facility. Infect Control Hosp Epidemiol
1994; 15:69–70.
18. Kotilainen P, Routamaa M, Peltonen R, et al. Eradication of methicillin-
resistant Staphylococcus aureus from a health center ward and associated
nursing home. Arch Intern Med 2001; 161:859–63.
19. Katz S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged.
The index of ADL: a standardized measure of biological and psycho-
logical function. JAMA 1963; 185:914–9.
20. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC defi-
nitions for nosocomial infections. Am J Infect Control 1988; 16:128–40.
21. Finlay JE, Miller LA, Poupard JA. Interpretive criteria for testing sus-
ceptibility of staphylococci to mupirocin. Antimicrob Agents Che-
mother 1997; 41:1137–9.
22. Bradley SF, Ramsey MA, Morton TM, Kauffman CA. Mupirocin re-
sistance: clinical and molecular epidemiology. Infect Control Hosp Ep-
idemiol 1995; 16:354–8.
23. Ramsey MA, Bradley SF, Kauffman CA, Morton TM. Identification of
a chromosomal location of the mupA gene encoding low level mu-
 pirocin resistance in staphylococcal isolates. Antimicrob Agents Che-
mother 1996; 40:2820–3.
24. Struelens MJ, Deplanno A, Godard C, Maes N, Surruys E. Epidemi-
ologic typing and delineation of genetic relatedness of methicillin-
resistant Staphylococcus aureus by macrorestriction analysis of genomic
DNA by using pulsed-field electrophoresis. J Clin Microbiol 1992; 30:
2599–605.
25. Tenover FC, Arbeit RD, Goering RV, et al. Interpreting chromosomal
DNA restriction patterns produced by pulsed-field gel electrophoresis:
criteria for bacterial strain typing. J Clin Microbiol 1995; 33:2233–9.
26. Andersen PK, Gill RD. Cox’s regression model for counting processes:
a large sample study. Ann Statistics 1982; 10:1100–20.
27. Therneau TM, Grambsch PM. Modeling survival data: extending the
Cox model. New York: Springer, 2000.
28. Parras F, Guerrero DC, Bouza E, et al. Comparative study of mupirocin
and oral co-trimoxazole plus topical fusidic acid in eradication of nasal
carriage of methicillin-resistant Staphylococcus aureus. Antimicrob
Agents Chemother 1995; 39:175–9.
29. Martin JN, Perdreau-Remington F, Kartalija M, et al. A randomized
clinical trial of mupirocin in the eradication of Staphylococcus aureus
nasal carriage in human immunodeficiency virus disease. J Infect Dis
1999; 180:896–9.
30. Reagan DR, Doebbling BN, Pfaller MA, et al. Elimination of coincident
Staphylococcus aureus nasal and hand carriage with intranasal appli-
cation of mupirocin calcium ointment. Ann Intern Med 1991; 114:
101–6.
31. Strausbaugh LJ, Jacobson C, Sewell DL, Potter S, Ward TT. Antimi-
crobial therapy for methicillin-resistant Staphylococcus aureus coloni-
zation in residents and staff of a Veterans Affairs nursing home care
unit. Infect Control Hosp Epidemiol 1992; 13:151–9.
32. Walsh TJ, Standiford HC, Reboli AC, et al. Randomized double-blinded
trial of rifampin with either novobiocin or trimethoprim-sulfameth-
oxazole against methicillin-resistant Staphylococcus aureus colonization:
prevention of antimicrobial resistance and effect of host factors on
outcome. Antimicrob Agents Chemother 1993; 37:1334–42.
33. Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler R, Pittet
D. Randomized, placebo-controlled, double-blind trial to evaluate the
efficacy of mupirocin for eradicating carriage of methicillin-resistant
Staphylococcus aureus. Antimicrob Agents Chemother 1999; 43:1412–6.
34. Yu VL, Goetz A, Wagener M, et al. Staphylococcus aureus nasal carriage
and infection in patients on hemodialysis: efficacy of antibiotic pro-
phylaxis. N Engl J Med 1986; 315:91–6.
35. Doebbling BN, Reagen DR, Pfaller MA, Houston AK, Hollis RJ, Wenzel
RP. Long-term efficacy of intranasal mupirocin ointment: a prospective
1474 • CID 2003:37 (1 December) • Mody et al.
cohort study of Staphylococcus aureus carriage. Arch Intern Med
1994; 154:1505–8.
36. Terpenning MS, Bradley SF, Wan JY, Chenoweth CE, Jorgensen KA,
Kauffman CA. Colonization and infection with antibiotic-resistant bac-
teria in a long-term care facility. J Am Geriatr Soc 1994; 42:1062–9.
37. Bradley SF, Terpenning MS, Ramsey M, et al. Methicillin-resistant
Staphylococcus aureus: colonization and infection in a long-term care
facility. Ann Intern Med 1991; 115:417–22.
38. Boelaert JR, Van Landuyt HW, Godard CA, et al. Nasal mupirocin
ointment decreases the incidence of Staphylococcus aureus bacteraemias
in haemodialysis patients. Nephrol Dial Transplant 1993; 8:235–9.
39. Mylotte JM, Kahler L, Jackson E. Pulse nasal mupirocin maintenance
Downloaded from https://academic.oup.com/cid/article-abstract/37/11/1467/372049 by University of Florida user on 13 July 2019
regimen in patients undergoing continuous ambulatory peritoneal di-
alysis. Infect Control Hosp Epidemiol 1999; 20:741–5.
40. Raz R, Miron D, Colodner R, et al. A 1-year trial of nasal mupirocin
in the prevention of recurrent staphylococcal nasal colonization and
skin infection. Arch Intern Med 1996; 156:1109–12.
41. Chow JW, Yu VL. Staphylococcus aureus nasal carriage in hemodialysis:
its role in infection and approaches to prophylaxis. Arch Intern Med
1989; 149:1258–62.
42. Watanakunakorn C, Brandt J, Durkin P, Santore S, Bota B, Stahl CJ.
The efficacy of mupirocin ointment and chlorhexidine body scrubs in
the eradication of nasal carriage of Staphylococcus aureus among pa-
tients undergoing long-term hemodialysis. Am J Infect Control
1992; 20:138–41.
43. Dacre J, Emmerson AM, Jenner EA. Gentamicin-methicillin–resistant
Staphylococcus aureus: epidemiology and containment of an outbreak.
J Hosp Infect 1986; 7:130–6.
44. Perez-Fontan M, Garcia-Falcon T, Rosales M, et al. Treatment of Staph-
ylococcus aureus nasal carriers in continuous ambulatory peritoneal
dialysis with mupirocin: long-term results. Am J Kidney Dis 1993; 22:
708–12.
45. Tuffnell DJ, Croton RS, Hemingway DM, Hartley MN, Wake PN,
Garvey RJ. Methicillin resistant Staphylococcus aureus; the role of an-
tisepsis in the control of an outbreak. J Hosp Infect 1987; 10:255–9.
46. Naimi TS, LeDell KH, Boxrud DJ, et al. Epidemiology and clonality
of community-acquired methicillin-resistant Staphylococcus aureus in
Minnesota, 1996–1998. Clin Infect Dis 2001; 33:990–6.
47. Cookson BD. Methicillin-resistant Staphylococcus aureus in the com-
munity: new battlefronts, or are the battles lost? Infect Control Hosp
Epidemiol 2000; 21:398–403.
48. Report of the Council on Scientific Affairs. American Medical Asso-
ciation white paper on elderly health. Arch Intern Med 1990; 150:
2459–72.