Effect of Mupirocin Treatment on Nasal, Pharyngeal, and Perineal Carriage of Staphylococcus aureus in Healthy Adults

Nasal carriage of Staphylococcus aureus is an important riskfactor for S. aureus infections. Mupirocin nasal ointment ispresently the treatment of choice for decolonizing the anteriornares. However, recent clinical trials show limited benefitfrom mupirocin prophylaxis in preventing nosocomial S. aureusinfections, probably due to (re)colonization from extranasalcarriage sites. Therefore, we studied the effectiveness of mupirocinnasal ointment treatment on the dynamics of S. aureus nasaland extranasal carriage. Twenty noncarriers, 26 intermittentcarriers, and 16 persistent carriers had nasal, throat, andperineum samples taken 1 day before and 5 weeks after mupirocintreatment (twice daily for 5 days) and assessed for growth ofS. aureus. The identities of cultured strains were assessedby restriction fragment length polymorphisms of the coagulaseand protein A genes. The overall carriage rate (either nasal,pharyngeal, or perineal carrier or a combination) was significantlyreduced after mupirocin treatment from 30 to 17 carriers (P= 0.003). Of the 17 carriers, 10 (60%) were still colonizedwith their old strain, 6 (35%) were colonized with an exogenousstrain, and 1 (5%) was colonized with both. Two noncarriersbecame carriers after treatment. The acquisition of exogenousstrains after mupirocin treatment is a common phenomenon. Thefinding warrants the use of mupirocin only in proven carriersfor decolonization purposes. Mupirocin is effective overallin decolonizing nasal carriers but less effective in decolonizingextranasal sites.

INTRODUCTION

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Introduction

In humans, the nose is the primary reservoir of S. aureus (6,7). Approximately 30% of the healthy population carry S. aureusin the nose, which is an important risk factor for S. aureusinfections (6). S. aureus nasal carriers have a threefold-increasedrisk for nosocomial S. aureus bacteremia compared to noncarriers(16). Approximately 80% of invasive nosocomial S. aureus infectionsare of endogenous origin in nasal carriers (14, 16).

Mupirocin nasal ointment is effective in temporarily eradicatingS. aureus from the nose. When mupirocin is applied to the nosetwice daily for 5 consecutive days, it has been reported toresult in elimination rates of 91% directly after therapy, 87%after 4 weeks, and 48% after 6 months (2). However, despitethese high elimination rates, three recent clinical studiesfound little or no efficacy of mupirocin in preventing nosocomialS. aureus infections (5, 9, 18).

In order to determine the effect of mupirocin treatment on S.aureus carriage at extranasal sites, we studied the effectsof mupirocin treatment on different carrier types: persistent,intermittent, and nonnasal carriers of S. aureus. Pharyngealcarriage of S. aureus was assessed as well, since nasal applicationof mupirocin results in low concentrations of the drug in thepharynx (13, 15). Furthermore, perineal carriage was assessed,since perineal carriers are known to disperse more S. aureusorganisms into the environment (10). Noncarriers were also included,in order to be able to identify whether mupirocin applicationin noncarriers may lead to carriage due to loss of colonizationresistance (12). To assess the role of extranasal carriage sitesin recolonization of the nose after mupirocin treatment, allstrains were genotyped.

MATERIALS AND METHODS

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Materials and Methods

Study population and general study design. Healthy adult volunteers (n = 165) were screened for nasal carriageof S. aureus on at least five separate occasions, 1 week apart.A participant was labeled a persistent carrier if at least 80%of the cultures were S. aureus positive, as a noncarrier ifall nasal cultures were S. aureus negative, and as an intermittentcarrier in all other cases. Only participants who attended allculture occasions were included in the study.

Treatment and follow-up. Participants, who gave informed consent, self administered mupirocin2% nasal ointment (SmithKline Beecham, Rijswijk, The Netherlands)twice daily for 5 days, according to the manufacturer's guidelines.Nasal, pharyngeal, and perineal samples were taken just beforemupirocin treatment and once 5 weeks after treatment. Therapyfailure was defined as having a positive nasal culture withS. aureus 5 weeks after the end of treatment. A nasal culturewas taken by rotating a sterile swab four times in the anteriornares (Transwab; Medical Wire and Equipment Co. Ltd., Corsham,England). All swabs were processed on the same day. The swabwas plated on Columbia blood agar plate medium (Becton-Dickinson,Etten-Leur, The Netherlands) and submerged in phenol red mannitolbroth. The plates were read after 1 and 2 days of incubation,and the broths were read after 3 days of incubation at 35°C.Broths with a color change from red to orange-yellow were subculturedon blood agar plates. Identification of S. aureus was basedon colony morphology, gram stain, a catalase test, and a latexagglutination test (Staphaurex Plus; Murex, Dartford, UnitedKingdom).

Genotyping. Genotyping was performed on the last S. aureus strain culturedbefore mupirocin treatment and on those strains cultured aftermupirocin treatment. S. aureus DNA was obtained according tothe method of Boom et al. (1). Restriction fragment length polymorphisms(RFLP) of the coagulase and protein A genes were determinedfor typing of all cultured S. aureus strains, as described previously(3, 4). Pulsed-field gel electrophoresis was performed to confirmthe results obtained by RFLP, when appropriate, according topreviously described methods (8). Strains were considered tobe unrelated if the RFLP pattern of either the coagulase geneor the protein A gene differed from that of the other strain.Pulsed-field gel electrophoresis patterns were compared usingthe criteria of Tenover et al. (11).

Statistical analysis. Volunteers were classified, as described above, as persistent,intermittent, and nonnasal carriers using the results of atleast five screening cultures. For each carriage type, the efficacyof mupirocin was assessed by comparing the culture results ofthe samples taken just before mupirocin treatment with the cultureresults of the samples taken 5 weeks after mupirocin treatment.Mupirocin therapy was considered to have failed if an individualcarried S. aureus in the nose 5 weeks after treatment, irrespectiveof extranasal carriage. Nonparametric paired tests were usedwhere appropriate. P values, two-sided, of <0.05 were consideredsignificant.

RESULTS

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Results

At least five serial cultures each were obtained from 62 individualsfrom the initial cohort of 165 volunteers. Twenty volunteerswere noncarriers (32%), 26 were intermittent carriers (42%),and 16 were persistent carriers (26%) (Table 1), and all participatedin the mupirocin intervention. No serious side effects wereobserved, and all volunteers completed the treatment. The overallcarriage rate (either nasal, pharyngeal, or perineal carrieror a combination) was significantly reduced after treatment,from 30 to 16 carriers (P = 0.003) (Table 1).

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TABLE 1. Change in carriage sites just before and 5 weeks after mupirocin treatment

Mupirocin significantly reduces nasal carriage in persistent carriers. Of the 16 persistent carriers, 1 carrier had a negative nasalculture just before mupirocin treatment. Five carriers (31%)had therapy failure 5 weeks after mupirocin treatment (Table1). Four remained colonized with the same strain, all of whomhad at least one extranasal carriage site (three throat; oneperineum). One volunteer acquired a new strain and never carriedS. aureus in extranasal sites. In persistent carriers, mupirocinwas effective in decolonizing S. aureus from the nose 5 weeksafter treatment (P = 0.002) but was not effective in decolonizingthroat and perineal carriage (P = 0.69 and P = 0.5, respectively).

No significant reduction of nasal carriage in intermittent nasal carriers after mupirocin treatment. Of the 26 intermittent carriers, 11 (42%) carried S. aureusjust before treatment. Three of these (27%) had therapy failure.Two remained colonized with the same strain, one of whom wasa perineal carrier before treatment. Of those who did not carryS. aureus just before treatment, two became colonized aftertreatment, one of whom was a combined pharyngeal and perinealcarrier just before treatment. Overall, mupirocin treatmentdid not significantly reduce nasal (P = 0.11), throat (P = 0.29),and perineal (P = 1.0) carriage in this subgroup of intermittentcarriers.

Rare acquisition of exogenous S. aureus after mupirocin treatment in nonnasal carriers. Within the noncarrier group (n = 20), there was one apparentthroat carrier before mupirocin treatment. After treatment,two noncarriers became colonized with S. aureus (10%), one ofwhom carried S. aureus in extranasal sites before treatment.The pharyngeal carrier remained a pharyngeal carrier with thesame strain.

Special emphasis on pharyngeal carriage (n = 16) and perineal carriage (n = 5). In general, there were 16 pharyngeal carriers before treatment,irrespective of carriage at other sites (12 were also nasalcarriers). In 5 of the 12 nasal carriers (42%), the throat strainwas different from the nasal strain. After treatment, six (38%)remained throat carriers, one of whom acquired a new strain,a significant reduction in throat carriage after mupirocin treatment(P = 0.002). Interestingly, of those who were nonthroat carriersbefore treatment (n = 46), five (11%) became colonized in thethroat with S. aureus. Four of these new throat carriers werenasal carriers before treatment, and one was a noncarrier.

There were five perineal carriers (four were also nasal carriers)before treatment and three after treatment (a nonsignificantreduction). Only one perineal carrier remained a carrier aftermupirocin treatment, with an identical strain. Two nonperinealcarriers became perineal carriers after treatment, one of themwith an endogenous strain.

DISCUSSION

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Discussion

Our results showed mupirocin efficacy on nasal decolonization5 weeks posttreatment similar to that reported in previous studies(2). We found S. aureus nasal carriage elimination rates of69% in persistent carriers and 58% in intermittent carriers.Therapy failure is not likely to be due to mupirocin resistance,since the prevalence of mupirocin-resistant strains is verylow in The Netherlands: none was found in >1,000 strains(18). Only one strain was found to be mupirocin resistant aftertherapy in our study (data not shown). Though the prevalenceof methicillin-resistant S. aureus is very low in The Netherlands,the findings of this study may be extrapolated to an endemicmethicillin-resistant S. aureus setting, as long as the strainsare mupirocin sensitive (17).

Mupirocin nasal ointment also had a significant effect on pharyngealS. aureus carriage decolonization, but not on perineal carriage.The effectiveness of mupirocin in reducing the occurrence ofperineal carriage in this cohort was low, due to new acquisitionof S. aureus at this site. Unlike in nasal carriage, where theeffectiveness is much higher, mupirocin does not seem to havea preventive effect on S. aureus perineal carriage. Though thenose is the primary reservoir for S. aureus, the perineum itselfis not directly affected by local application of mupirocin tothe nose, as we saw in our study. Application of a local antibioticor disinfectant on the perineum could be an option for optimaldecolonization.

Interestingly, 10 volunteers became colonized at new sites 5weeks after mupirocin treatment, 5 of them with exogenous strains(2 were noncarriers). Furthermore, two carriers became colonizedwith exogenous strains at their old sites after treatment. Overall,we can state that of the 17 carriers at any site after treatment,10 (60%) were colonized with their old strains, 6 (35%) werecolonized with an exogenous strain, and 1 (5%) was colonizedwith both old and exogenous strains. Therefore, the acquisitionof exogenous strains after mupirocin treatment is a common phenomenon.The finding that two noncarriers became carriers after treatment(17% of all therapy failures) warrants the use of mupirocinonly in proven carriers for decolonization purposes. Mupirocinalso eradicates coagulase-negative staphylococci and corynebacteria,which may be present in noncarriers, and this change in thenasal flora may facilitate colonization with S. aureus by eliminatingbacterial interference (12).

We conclude that mupirocin is effective overall in decolonizingnasal carriers but less effective in decolonizing extranasalsites. These extranasal sites may be sources for S. aureus infections.The majority of the S. aureus strains in those who remain colonized5 weeks after treatment were endogenous, but acquisition ofexogenous S. aureus strains occurs and warrants the performanceof decolonization only in proven carriers. Furthermore, patientstreated with mupirocin should receive follow-up cultures todetermine treatment failure, which has already been introducedfor dialysis patients.

FOOTNOTES

* Corresponding author. Mailing address: Erasmus MC, Department of Clinical Microbiology and Infectious Diseases, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Phone: 31.10.4633510. Fax: 31.10.4633875. E-mail: h.wertheim{at}erasmusmc.nl.

REFERENCES

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