JBUR-4289; No. of Pages 5

The evaluation of nasal mupirocin to preventStaphylococcus aureus burn wound colonization inroutine clinical practice

M.E.H. Jaspers a,*, R.S. Breederveld a,b, W.E. Tuinebreijer a,B.M.W. Diederen a,c

aBurn Center, Department of Surgery, Red Cross Hospital, Beverwijk, The NetherlandsbDepartment of Surgery, University Medical Center Leiden, Leiden, The NetherlandscRegional Laboratory of Public Health, Boerhaavelaan 26, 2035 RC Haarlem, The Netherlands

b u r n s x x x ( 2 0 1 4 ) x x x – x x x

a r t i c l e i n f o

Article history:

Accepted 26 January 2014

Keywords:

Staphylococcus aureus

Nasal carriage

Nasal mupirocin ointment

Burn wound colonization

a b s t r a c t

Background: Staphylococcus aureus wound colonization frequently occurs in patients with

burns and can cause impaired wound healing. Nasal mupirocin application may contribute

to the reduction of burn wound colonization of endogenous origin, whereas colonization by

the exogenous route can be reduced by blocking cross-infection from other sources. In this

study we evaluated whether the implementation of routine treatment of patients and burn

center personnel using nasal mupirocin ointment reduces S. aureus burn wound colonization.

Methods: We composed three study groups, consisting of a control period (Control), a

mupirocin period (MUP), in which patients with burns were all receiving nasal mupirocin

at admission, and a mupirocin + personnel period (MUP + P), in which we also screened the

burn center personnel and decolonized S. aureus carriers by nasal mupirocin.

Results: The patients who carried S. aureus in their nose and did not have S. aureus burn

wound colonization at admission were considered as patients susceptible for the use of

nasal mupirocin. In these patients, the S. aureus burn wound colonization rate was the same

in all study groups. S. aureus nasal carriage was a significant independent risk factor for burn

wound colonization (OR: 3.3; 95% CI: 1.4–7.6) when analyzed within the three study groups.

Conclusion: Although S. aureus carriage is a significant risk factor for developing burn wound

colonization, the routine use of nasal mupirocin did not contribute to a reduction of burn

wound colonization.

# 2014 Elsevier Ltd and ISBI. All rights reserved.

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.elsevier.com/locate/burns

1. Introduction

Burn wounds cause a disruption of the physical skin barrier

that normally prevents invasion of microorganisms [1].

Therefore, burn patients are highly vulnerable for burn wound

* Corresponding author at: Burn Center, Department of Surgery, Red CTel.: +31 251 265458; fax: +31 251 222570.

E-mail addresses: mjaspers@rkz.nl, mariellejaspers@gmail.com (M

Please cite this article in press as: Jaspers MEH, et al. The evaluation of nasain routine clinical practice. Burns (2014), http://dx.doi.org/10.1016/j.burns

http://dx.doi.org/10.1016/j.burns.2014.01.0240305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.

colonization and may subsequently develop burn wound

infection [2,3]. The most common burn wound pathogen is

Staphylococcus aureus, [1,4] which may originate from the

patient (endogenous origin), or may be transmitted by cross-

infection from other sources, which is defined as exogenous

transmission (Fig. 1). Several studies performed in burn

ross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands.

.E.H. Jaspers).

l mupirocin to prevent Staphylococcus aureus burn wound colonization.2014.01.024

Fig. 1 – Transmission dynamics of S. aureus colonization.

Source: Adapted from M. Kooistra-Smid, FEMS Immunol

Med Mircobiol, 57, 2009.

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JBUR-4289; No. of Pages 5

centers show a S. aureus burn wound colonization rate with a

wide range: 14–95% [5–8]. The negative effects of colonization are

delayed wound healing, increased need for surgical interven-

tions and prolonged length of stay at the burn center [5,9].

Therefore, eradication of S. aureus nasal carriage may serve

two purposes: prevention of infection and prevention of

transmission. Mupirocin displays a strong activity against

Gram-positive bacteria, including S. aureus [10]. Decoloniza-

tion therapy with nasal mupirocin ointment has been

explored during the last decades in a variety of clinical

settings and patients, and shown to be effective [10–14]. A

pooled analysis of eight studies showed a significant reduction

in the infection rate by use of intranasal mupirocin application

[15]. Also, a single center study in burn patients showed a

decrease of the relative risk of burn wound colonization after

mupirocin application at admission [16].

The routine treatment of patients with nasal mupirocin has

been implemented from January 2011 in the Burn Center of

Beverwijk, The Netherlands. The primary aim of this study

was to evaluate whether the use of nasal mupirocin reduces

the burn wound colonization rate in clinical practice (blocking

endogenous transmission). Secondly, in addition to treating

patients, we analyzed the effect of screening the burn center

personnel for S. aureus carriage and decolonizing carriers with

nasal mupirocin (blocking part of the exogenous transmission

route).

2. Methods

2.1. Setting

This study was performed at the Burn Center of the Red Cross

Hospital, Beverwijk, The Netherlands. The burn center is a

closed unit consisting of several quarters, including intensive

treatment rooms and an operating theater. By ‘closed’ we mean

that the Burn Center is a section in the hospital which one can

only enter by passing a lock. Compared to other wards, the Burn

Center is less easy accessible. A dedicated team of health care

personnel takes care of the patients and several precautions to

prevent transmission of microorganisms are daily routine,

i.e., cohort care, hand washing procedures, equipment and

environmental cleansing and regulation of positive air-flow in

the whole burn center. In terms of isolation, several restrictions

Please cite this article in press as: Jaspers MEH, et al. The evaluation of nasain routine clinical practice. Burns (2014), http://dx.doi.org/10.1016/j.burn

were already inserted before the start of this study. All patients

with a total burned surface area over 30% were isolated. In case

of a positive swab for Pseudomonas aeruginosa or for highly

resistant microorganisms, including MRSA, a patient was also

put in isolation. The presence of microorganisms on admission

was detected by samples of nose, throat, perineum and all burns

before receiving nasal mupirocin. Also, routine swabs of these

body surface areas were obtained twice weekly until burn

wounds were closed. All burns of one patient were cultured

separately and labeled by the location on the body.

2.2. Study design

In this before-and-after study, consecutive patients admitted

to the burn center were included during three different

periods. The first period, preceding the implementation of

mupirocin, served as a control group (Control: January to

December 2010). Only precautions, as described above, were

taken in this period. Following mupirocin ointment imple-

mentation, we studied two groups. Study group 1 (MUP:

February 2011 to October 2011) and study group 2 (MUP + P:

December 2011 to May 2012). In both study periods all patients

received nasal mupirocin on admission, three times daily for 5

days, according to the manufacturer’s guidelines (2% mupir-

ocin calcium cream; Bactroban Nasal, GlaxoSmithKline BV,

Zeist, The Netherlands). Additionally, in the second study

period (MUP + P), the burn center personnel was screened and

S. aureus carriers were decolonized by nasal mupirocin. Patient

data were obtained by reviewing medical records and swabs

that were taken during hospital stay. Burn wound colonization

with S. aureus during the two study periods (MUP and MUP + P)

was compared to the burn wound colonization rate in the

control period (Control).

2.3. Definitions

The patients ‘at risk for endogenous transmission’ were

defined as patients who carried S. aureus in their nose and did

not have S. aureus burn wound colonization on admission.

This subgroup was considered to be candidates for the use of

nasal mupirocin. Secondly, patients ‘at risk for exogenous

transmission’ were defined as patients who did not carry S.

aureus in their nose and did not have S. aureus burn wound

colonization on admission. Hereby, this subgroup was

considered to be susceptible for the transmission of S. aureus

by other patients or health care workers.

2.4. Exclusion criteria

The patients hospitalized for less than two days or patients

admitted with a different trauma than acute burn

(e.g., fasciitis necroticans) were excluded. Moreover, we

excluded patients from further analyses in case of insufficient

data (i.e., no swabs on admission or the absence of a burn

wound swab during admission).

2.5. Statistical analysis

All data were analyzed using SPSS 18.0 (SPSS Inc., Chicago,

USA). The crude comparisons were done with Chi-square or

l mupirocin to prevent Staphylococcus aureus burn wound colonizations.2014.01.024

Table 1 – General characteristics of patients included in the study.

Period Control MUP MUP + P Differencep-valueb (ns: non-significant)

Patients, n (%) 69 (42.6) 55 (34.2) 37 (22.8)

Age (years), mean (SD) 33.5 (25.2) 38.6 (24.7) 29.7 (27.8) ns

Hospitalization (days), mean (SD) 24.9 (22.6) 20.6 (15.6) 17.0 (15.4) ns

TBSAa (%), mean (SD) 14.2 (11.6) 14.4 (14.3) 12.5 (13.4) ns

S. aureus carriage on admission, n (%) 21 (30.4) 11 (19.6) 10 (27.0) ns

S. aureus burn wound colonization during admission, n (%) 32 (46.4) 21 (37.5) 24 (64.9) 0.012 (MUP + P vs. MUP)

0.069 (MUP + P vs. Control)

a Total burned surface area.b Calculated with Chi-square test and ANOVA.

b u r n s x x x ( 2 0 1 4 ) x x x – x x x 3

JBUR-4289; No. of Pages 5

Student’s t-test. A multivariable regression analysis was used

to evaluate the effect of age, hospitalization, TBSA and study

group on burn wound colonization risk, while adjusting for

these variables.

3. Results

The number of patients admitted to the Burn Center during

the three different periods was 214 (Control), 192 (MUP), and

138 (MUP + P). After application of the exclusion criteria

described above, 69 patients were included during the control

period (Control), 56 and 37 during the MUP and MUP + P period,

respectively. The general characteristics of analyzed patients

are shown in Table 1. There were no differences in mean age,

duration of hospital stay or total burned surface area (TBSA)

among the three study groups. Also, there was no statistical

difference in S. aureus nasal carriage rate on admission; 30.4%,

19.6% and 27.0%, for the three groups, respectively. The burn

wound colonization rate during admission, regardless for S.

aureus carriage, was significantly higher in the MUP + P group

compared to the MUP group ( p = 0.012).

The results of ‘patients at risk for endogenous transmis-

sion’, as defined previously, are shown in Table 2. In every

study group two-thirds of patients developed burn wound

colonization during admission, in spite of mupirocin treat-

ment in the MUP and MUP + P group and the high elimination

rate of 83% among S. aureus nasal carriers, so there was no

significant difference in burn wound colonization rate

between the Control and MUP group and/or MUP + P group.

Though, when analyzed within the three groups, S. aureus

nasal carriage was found to be a significant independent risk

factor for burn wound colonization adjusted for age and TBSA

(OR: 3.3; 95% CI: 1.4–7.6).

After screening the burn center personnel, 22% (14/63)

carried S. aureus in their nares. The patients ‘at risk for

exogenous transmission’, n = 111, were included to evaluate

the effect of screening and treating the burn center personnel,

Table 2 – Burn wound colonization rate for patients ‘atrisk for endogenous transmission’.

Period Control MUP MUP + P

Patients, n 16 8 9

Burn wound colonization, n (%) 11 (68.8) 5 (62.5) 6 (66.7)

Please cite this article in press as: Jaspers MEH, et al. The evaluation of nasain routine clinical practice. Burns (2014), http://dx.doi.org/10.1016/j.burns

additionally to the mupirocin treatment for all patients. The

burn wound colonization rate for the control, MUP and

MUP + P group was respectively, 34.0%, 29.3% and 56.5%

( p = 0.082).

4. Discussion

To the best of our knowledge, this is the first study evaluating

the effect of a short course of nasal mupirocin ointment at

admission to prevent burn wound colonization with S. aureus

in routine clinical practice. In this study we did not find a

reduction in burn wound colonization rate after implementa-

tion of nasal mupirocin. However, as described in previous

studies, we confirmed a significant increase in burn wound

colonization risk in nasal carriers of S. aureus.

A previous study showed that 78% of patients with burn

wound colonization were contaminated with their own

carried nasal S. aureus strain [8]. This supports the important

role of nasal carriage in burn wound colonization and thus the

presence of endogenous transmission. The elimination rate of

83% that we found for S. aureus nasal carriers by application of

nasal mupirocin, is similar to that reported in previous studies

[10,16]. Despite this high elimination rate, we did not find a

reduction in burn wound colonization rate during the

mupirocin period.

This may be explained by the complexity of the transmis-

sion dynamics of S. aureus. Nasal mupirocin only interferes

with the primary source of S. aureus, i.e., the anterior nares of

the nose, but burn wound colonization may also be derived

from other endogenous sources such as the groin, axilla or

other parts of the skin, and the respiratory- and gastrointest-

inal flora of the patient [17]. Therefore, it seems to be

necessary to eliminate S. aureus from all the possible reservoirs

to positively affect the burn wound colonization rate. This

assumption is strengthened by the results of a multi center

study on patients who underwent any surgical procedure [18].

They found a significantly reduced risk of hospital acquired S.

aureus infections by immediate decolonization of nasal and

extranasal sites with nasal mupirocin ointment and chlorhex-

idine gluconate soap.

Moreover, cross-contamination via exogenous sources,

e.g., inanimate objects, environmental surfaces, other

patients or the burn center personnel, also occurs frequently.

In a previous Dutch Burn Center study, 74% of the non-carriers

got their burn wounds colonized by one of the types carried by

l mupirocin to prevent Staphylococcus aureus burn wound colonization.2014.01.024

b u r n s x x x ( 2 0 1 4 ) x x x – x x x4

JBUR-4289; No. of Pages 5

patients or by the Burn Center personnel [8]. This is also

confirmed by another study performed in our own Burn Center

in 2011. In this study S. aureus isolates were identified by

molecular typing methods, and they found a 67% infection

rate of exogenous origin [19].

We also screened and decolonized carriers among the Burn

Center personnel in the second study period, but remarkably

this intervention yielded no reduction in burn wound

colonization rate. This supports the importance of also

eliminating S. aureus from the environment and from the

hands of the burn center personnel, as these sources form an

important link in the transmission routes (Fig. 1). A major

drawback of the latter measure, however, is that compliance

rates of contact precautions such as hand hygiene are known

to be around 50%, which is too low to effectively block this part

of the exogenous route of transmission completely [20].

The present study has some important limitations. We

performed a retrospective analysis, which was indispensable

to achieve the main goal of our study, but also caused several

gaps in our database. Therefore, we were provided with fewer

inclusions than expected and not able to report significant

results of the three study groups separately. The small sample

size could also have increased the risk of a type II error (false

negative result). Another limitation was formed by the

composition of the control period, consisting of a historical

population. Possibly the circumstances in the Burn Center

changed over time, thus the findings may not be generalized to

the other two study groups. Furthermore, burn wound

colonization could have been affected through other non-

measured confounders (e.g., cause of burn and burn wound

depth). Finally, the study could be subject of attention bias or

Hawthorne effect. After implementation of nasal mupirocin

for decolonizing S. aureus in the burn center personnel, the

personnel could have behaved differently by working less

appropriately in the use of precautions to prevent exogenous

transmission.

However, we experienced the difficulty of implementing a

novel protocol into clinical practice. The implementation

requires collaboration from every single person involved in

the patients’ treatment. As there never seems to be entire

compliance with a protocol, it can be very useful to also

evaluate the effectiveness of a protocol in routine clinical

practice, instead of evaluation during a high-awareness period

only as performed in the studies described previously. More-

over, the negative side effects of using nasal mupirocin, such

as the development of mupirocin resistance, have to be

considered. Between 2005 and 2012, 18 cases of mupirocin

resistant S. aureus colonization were identified in our Burn

center. The main issue in the cases of these patients is the

limited availability of topical anti-microbial agents for treat-

ment, because fucidic acid (FA) is the only effective treatment

option [21]. Moreover, even by using FA, resistance can be

provoked by inappropriate use of topical FA ointment, such as

using FA monotherapy instead of combining FA with other

agents to remain low resistance rates [22].

This study shows that although nasal carriage was found to

be a significant independent risk factor for burn wound

colonization, implementing nasal mupirocin ointment did not

result in a reduction of the burn wound colonization rate with

S. aureus. At present we conclude that there is insufficient

Please cite this article in press as: Jaspers MEH, et al. The evaluation of nasain routine clinical practice. Burns (2014), http://dx.doi.org/10.1016/j.burn

evidence to support the use of nasal mupirocin in routine

clinical practice in burn care patients. The possible efficacy of

S. aureus decolonization in patients with burns has not been

established firmly in which case prospective, randomized,

placebo-controlled efficacy trials are needed.

Conflict of interest statement

We certify that there is no conflict of interest with any

financial organization regarding the material discussed in this

manuscript.

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