Infectious Diseases in Clinical Practice:
Snapshot for September 2007
RANDOMIZED CONTROLLED TRIAL OF CHLORHEXIDINE GLUCONATE FOR WASHING, INTRANASAL MUPIROCIN, RIFAMPIN, AND DOXYCYCLINE VERSUS NO TREATMENT FOR THE ERADICATION OF STAPHYLOCOCCUS AUREUS COLONIZATION
Simor et al1 reported the results of open-label randomized study with 3:1 allocation. The study population was that of patients hospitalized in any of 8 hospitals (6 acute care hospitals, 1 rehabilitation hospital, and 1 chronic care hospital) in Toronto or Hamilton, Ontario, between July 1, 2000, and June 30, 2003. No patients were older than 18 years, and none were expected to survive for more than 3 months. The patients were considered colonized with methicillin-resistant Staphylococcus aureus (MRSA) that was obtained from cultured samples from more than 1 body site obtained at 2 separate times within 2 weeks, and there was no evidence of infection at the time of screening. All were patients who signed an informed consent to participate in this study and who had pretreatment samples done from the anterior nares, perianal area, any skin lesions, and catheter or medical exit sites. The patients were excluded if on concurrent treatment with antimicrobials for an infection, and MRSA decolonization was attempted in the previous 6 months (prior treatment of MRSA infection was not an exclusion criteria); if they have an allergy to the study medications; and if they have a known microbial resistant to any of the study medications before randomization. Patients were also excluded if they have a known hepatic dysfunction or planned surgery within 3 months. The patients were randomly assigned to receive a 7-day course of daily 2% chlorhexidine gluconate washes, 2% mupirocin intranasally with a cotton tip applicator daily; rifampin 300 mg twice a day, and doxycycline 100 mg twice a day or no treatment. Treatment was started within 4 days of the second culture. Follow-up cultures were obtained from initial sites and any other site that had previously yielded MRSA weekly for 4 weeks after randomization and then monthly for 7 months. Clinical data were obtained for identified development of MRSA infection for up to 8 months posttreatment. Cultures were processed within 8 hours of procurement, and the swabs were incubated overnight in a tryptone-based broth containing 7.5% of sodium chloride and 1% mannitol (Difco m-Staphylococcus broth; Becton Dickinson). Samples were subcultured onto mannitol salt agar supplemented with oxacillin (2 μg/mL; Quelab) and incubated at 37°C for up to 48 hours. Standard methods for identification of MRSA were performed including latex and agglutination tests for detection of penicillin-binding protein 2a. Laboratory staff was blinded to the study purposes and treatment allocations. In vitro susceptibility to mupirocin, rifampin, and tetracycline were determined by broth microdilution. High-level resistance to mupirocin was defined as a minimum inhibitory concentration of 512 μg/mL or greater. Low-level mupirocin resistance was defined as a minimum inhibitory concentration of 8 to 256 μg/mL. Isolates were typed by pulsed field gel electrophoresis (PFGE) using Smal digest of genomic DNA to determine whether a second strain from a patient represented relapse with the same strain or acquisition of a new strain. One hundred forty-six eligible consenting patients were recruited; 111 were randomized to receive decolonization, and 35 were randomized to receive no treatment. Thirty-four patients (23%) were not of any value at 3 months, leaving 112 patients for analysis, 87 in the treatment group, and 25 in the nontreatment group. At 3 months, 64 patients (74%) in the treatment group and 8 patients (32%) in the nontreatment group were negative for MRSA. One hundred ten of the initial MRSA isolates obtained at baseline (86 from treated patients and 24 from untreated patients) were available for antimicrobial susceptibility and genotyping by PFGE. Twenty-one of the MRSA isolates (19%) were subsequently found to have a high level of resistance to mupirocin compared with 5 isolates that had low-level mupirocin resistance. The most commonly identified MRSA strains were CMRSA-2 (46% identical or closely resembling USA 100 ST5) and CMRSA-1 (24% USA 600 ST45). Genotype distribution was similar to that seen in hospitalized patients in southern Ontario. There was 1 isolate identified at CMRSA-7 (USA 400 ST1) and none of the USA 300 profile. The genotypic distribution between the treatment and nontreatment group was similar. Eighty percent of the MRSA recovered from 72 patients in follow-up cultures; 82% of the isolates found in 72 patients in follow-up were identical to their baseline isolates as determined by PFGE typing. Thirteen patients had initial and follow-up isolates representing different strains by PFGE typing (9 patients in the treatment group and 4 patients in the nontreatment group). Three of the 61 treated patients developed high-level mupirocin resistance in follow-up cultures. Isolates were distinct, suggesting acquisition of a new strain of MRSA. Compliance with decolonization therapy was good in 102 patients (92% completing at least 6 days of treatment and the remaining 9 patients completing 2 to 5 days of treatment). Adverse reactions also related to medications were reported in 22 of the treated patients (25%). These reactions were considered mild and included nausea, vomiting, diarrhea, and dyspepsia. Therapy had to be discontinued in only 4 patients. Thirty-one study patients died during this study. Twenty-five of the patients (23%) in the treatment group were randomized to receive decolonization therapy, 6 (17%) in the nontreatment group. None of the patient developed an MRSA infection during the study.
In summary, the study indicated that hospitalized patients colonized for MRSA may be successfully decolonized with the 7-day course of multiple agents used. It also demonstrated that sustained decolonization for at least 3 months occurred in three fourths of the patients, and more than 50% were still culture negative at 8 months. The study demonstrated the importance of doing susceptibility testing to mupirocin to identify high-level resistant strains of MRSA.
For the past 20 years, MRSA has been an increasing problem in US hospitals. In the past 10 years, it has become an increasing problem in Canada. The editorial commentary by Bradley2 on the above article is an important reading for anyone involved in dealing with MRSA issues. Multiple approaches have been taken in an attempt to bring this significant problem under control. It is now of even greater importance because of the increasing incidents of community-acquired MRSA (CA-MRSA) in individuals with no apparent risk factors. Emergence of CA-MRSA has complicated the approach to any individual presenting to a physician's office or to an outpatient setting with a skin or soft tissue infection. Clinicians in the United States and, now, our Canadian colleagues can no longer rely on cephalosporins to treat skin and soft tissue infections. It is imperative that, whenever possible, the site of the infection be cultured and the patient be screened for MRSA colonization. Fortunately today, sulfamethoxazole trimethoprim and doxycycline are still effective oral agents to deal with CA-MRSA infections. There is still much debate about when and from whom surveillance cultures should be obtained. Review of the literature reveals a wide spectrum of approaches from total surveillance to focused surveillance on patients and procedures with a high incidence of morbidity-mortality MRSA infections.
1. Simor AE, Phillips E, McGeer A, et al. Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus
colonization. Clin Infect Dis
2. Bradley SF. Eradication or decolonization of methicillin-resistant Staphylococcus aureus
carriage: what are we doing and why are we doing it? Clin Infect Dis