Mupirocin for Eradication of Methicillin-Resistant Staphylococcus aureus
Abstract & Commentary
Synopsis: The use of nasal mupirocin is reasonably effective in eradication of local, but not extranasal MRSA colonization.
Source: Harbarth S, et al. Randomized placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 1999;43:1412-1416.
The university hospital in geneva is a 1500-bed institution that recently witnessed a major increased prevalance of methicillin-resistant Staphylococcus aureus (MRSA). By 1994, the rate had increased to 0.57 cases per 100 admissions. This study took place at the same time Infection Control was trying to reduce this high MRSA rate using various control measures. Harbarth and associates defined colonization as isolation of MRSA from any body site at which time patients 16 years of age and older were eligible for the study. Patients with active staphylococcal infection or tracheal colonization were excluded. Both treatment and placebo groups used chlorhexidine soap for daily washing of their body. The details were not given of how washing was done.
Study patients were treated with 2% mupirocin (Bactroban nasal; SmithKline Beecham) or a placebo (of soft white paraffin base). Patients put in the ointment themselves twice daily for five days with a cotton swab and then they gently massaged the nostrils. At days 12, 19, and 26 (± 3 days) multiple sites were cultured: nose, groin, decubitus, urine if catheter present, lacerated skin sites, etc. Semiquantitative cultures were performed as well as qualitative cultures from staphylococcal enrichment broth with 7.5% NaCl.
During the trial lasting from October 1995 until September 1997, 275 patients were eligible for the study; 110 were excluded due to active MRSA infection but 98 were ultimately randomized to the study. The average age of subjects was 74 years and 59% of the patients were men. Of interest, 63 patients were new carriers and 35 were known MRSA carriers. Only 54% of the treatment group and 62% of the control group had nares colonization and the others had colonization of the groin, skin, or urine.
Mupirocin was no more likely to produce overall eradication of MRSA than placebo (25% vs 18%, respectively), whereas of the 87 patients screened for nasal MRSA carriage at the end of follow-up, 44% in the mupirocin group compared to 23% of the placebo group were free of nasal MRSA (P = 0.06). A major finding was in 40 patients who retained MRSA in the nose (12 in treatment group and 16 in placebo group); 28 also had groin colonization, 14 had skin colonization, and eight had urine colonization.
During follow-up, three of the treated patients and seven of the placebo patients developed MRSA infections, all of whom required systemic glycopeptide therapy.
Molecular typing disclosed that only two of the subjects had follow-up isolates that differed from their original isolates. All of the isolates tested were susceptible to chlorhexidine. Low-level mupirocin resistance (8-64 mcg/mL) was detected among 27 of 46 strains tested.
Comment by Joseph F. John, MD
The Infection Control team of Dr. Didier Pittet at the University Hospital in Geneva has been making a major effect on the field of infection control and hospital epidemiology. In this study—the first ever to include a double-blind, placebo-controlled format—the team sought to determine if mupirocin could eliminate MRSA from multiple sites after a single application to the nose.
There were some unforeseen problems with the study, mostly the fact that 42% of the patients studied did not have MRSA nasal colonization. So, the hidden hypothesis that eradication of MRSA from the nose would lead to eradication of extranasal sites had to be modified to state that mupirocin applied to the noncolonized nose would lead to eradication of extranasal sites, a somewhat unlikely thesis. In fact, the second hypothesis was not supported. The best that could be claimed with the application of mupirocin was that it led to eradication of or persistence of reduced colonization of the nares with MRSA. It did not produce a decrease in extranasal colonization.
Harbarth et al conclude that mupirocin is best used for patients without extranasal MRSA colonization. Confounding the study was the fact that a large percentage of patients enrolled had no nasal colonization at the outset. Furthermore, we do not know if these patients had chronic colonization of vagina or axillae. Harbarth et al raise a valid issue concerning the low-level mupirocin resistance (MIC £ 64 mcg/mL). Even though local concentrations of the agent approach 20,000 mcg/mL, in the study low-level resistance seemed to predict persistence of MRSA, even in the placebo group. We will eagerly await further studies from Geneva and elsewhere looking more closely at the effect of low-level mupirocin resistance.
Finally, the group of patients studied here had complex comorbidity. Studying a less severely ill group of patients who have a lower rate of extranasal colonization may improve the efficacy of mupuriocin. Harbarth et al note that most treatment regimens have generally been "unsatisfactory." One multicenter study in which I participated as an investigator used only oral therapy including a combination of an old gyrase inhibitor, novobiocin, with rifampicin, as compared to trimethoprim/sulfa plus rifampicin. Eradication of nasal carriage with MRSA approached 75% and was unlikely when extranasal colonization existed.
Mupirocin remains the only agent that can reliably eradicate nasal MRSA in individual patients. This study reinforces that its efficacy for altering extranasal carriage in specific patient cohorts may be disappointing. Hospital epidemiologists need to define their treatment cohorts carefully before embarking on a decolonization initiative using only mupirocin. v
What is the major problem of using nasal mupirocin (Bactroban) for decolonization of methicillin-resistant Staphylococcus aureus (MRSA)?
a. The nares of many patients will not tolerate the ointment.
b. The eradication of MRSA from the nose is only temporary, lasting only several days.
c. High-level resistance occurs in many persisting strains (MIC ³ 500 mcg/mL).
d. Extranasal colonization with MRSA was not altered.
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