COMMENTARY

Literature Commentary by Dr. John G. Bartlett: MRSA, August 2007

John G. Bartlett, MD

Disclosures

August 03, 2007

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. 2007;44:178-185. The study authors noted that eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage may reduce rates of infection by this organism and examined the method to accomplish decolonization.

Method: Hospitalized patients who were colonized with MRSA with culture on 2 separate occasions were randomized to treatment or no treatment in a 3:1 ratio. The treatment included a 7-day course of daily washes with 2% chlorhexidine, 2% mupirocin ointment applied to the anterior nares 3 times daily, rifampin given as 300 mg twice daily, and doxycycline given as 100 mg twice daily. Follow-up cultures were obtained from the anterior nares, perianal area, skin lesions, and catheter or other medical device sites at weekly intervals or 4 weeks after randomization and then monthly for 7 months.

Results: Baseline cultures were available from 110 MRSA isolates and 21 (19%) showed high-level resistance to mupirocin. The genotype distribution was primarily USA100-ST5 and USA600-ST45; there were no USA300 strains. The follow-up cultures showed that 13 patients (18%) had discordance between the MRSA genotype for the initial vs follow-up strains, including 9 patients from the treatment group and 4 from the control group. Three of 61 (5%) treated patients had baseline MRSA isolates that were susceptible to mupirocin that subsequently showed high-level resistance; 2 of these strains were new genotypes. Compliance with treatment was good, with 92% of subjects completing at least 6 days of treatment. Adverse reactions were reported in 25% of treated patients, but were generally due to gastrointestinal intolerance and were regarded by the investigators as "mild." The results at 3 and 8 months, the basis of cultures for MRSA, are shown in Table 1 , which indicates successful eradication at the 3-month evaluation in 74% and at the 8-month evaluation for 54%.

Conclusion: The study authors concluded that this method of eradication of MRSA is safe and effective with a follow-up of at least 3 months.

Comment: The report had an editorial review by Suzanne Bradley,[1] from Michigan, who made several important points:

  1. MRSA carriage may be transient, intermittent, or persistent when subjects are followed for years.

  2. The most frequent site of carriage is thought to be the anterior nares, but this is not universal and the rectum may be important in some with community-acquired MRSA.[2]

  3. Mupirocin is unrelated to existing antibiotics used systemically, thus giving some assurance that use would not be complicated by cross-resistance, and prior reports have shown success in eradication of nasal colonization of 95% to 100%.[3]

  4. Mupirocin use is associated with increased drug resistance and failure. Resistance is due to mupA, which is found in USA300 strains. These were not present in the current study, but are of substantial concern in community-acquired MRSA infections.[4]

  5. The duration of treatment is arbitrary, but mupirocin treatment of nares is usually 5-7 days. When used for methicillin-sensitive S aureus (MSSA), recolonization rates at 12 months are 50% to 75% in healthcare workers.[5]

  6. Decolonization of MRSA reduces the rates of infection by this organism in some patient populations,[6] but the results are somewhat inconsistent.

The results of this review indicated that multiple questions still persist about when eradication of MRSA carriage should be attempted and how best to do it in terms of agents or tactics to use and the patients who would be best served, including the question with regard to those with recurrent community-acquired MRSA infections. Of concern is the potential negative impact of antibiotic resistance, drug interactions, side effects, recolonization, and cost.

Centers for Disease Control and Prevention (CDC). Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza -- Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep. 2007;56:325-329. This is a report from the US Centers for Disease Control and Prevention (CDC) of 10 cases of community-acquired pneumonia (CAP) due to community-acquired MRSA during the first 2 months of the influenza season of 2006-2007 in Louisiana and Georgia.

The patients described were relatively young, with a median age of 18 years; none had significant comorbidities. The median duration of symptoms prior to admission was 3 days. Five of 6 patients who had a rapid test for influenza had positive results; chest x-rays generally showed multilobar infiltrates; 5 patients had positive blood cultures; and 4 had a history of MRSA skin infection in either themselves or a close contact.

With regard to management, 8 were initially given ceftriaxone and 3 were given vancomycin prior to culture results for S aureus. The outcome was generally poor: Six people died with this infection, including 4 who died within the first 4 days.

These results are summarized in Table 2 .

Conclusion: The review authors called attention to the fact that MRSA CAP is "uncommon," but has characteristics that distinguish this from other common causes of CAP. This infection tends to occur in young, otherwise healthy persons; is usually associated with influenza; and is often associated with cavitary infiltrates. The putative agents are the USA300 strains of S aureus, which are resistant to betalactams and macrolides, and contain genes for the Panton-Valentine leukocidin (PVL) toxin. The review authors urge physicians to abide by the recent recommendations of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines for CAP for adults, which recommend sputum cultures plus blood cultures in patients with severe CAP. In the present study, 3 of the 10 patients had positive cultures only from sputum. They also noted that severe cases of MRSA CAP should be reported to the CDC Division of Health Care Quality Promotion by telephone (800-893-0485) or by email ( search@cdc.gov ).

Comment: These 10 cases are similar to those reported previously: generally young, previously healthy adults with probable or established influenza complicated by fulminant pneumonia often characterized by shock and/or necrotizing pneumonia with cavitation on computed tomographic (CT) scan or x-ray. The antibiotics generally used for CAP would not be effective in most cases; the recommendation of the 2007 IDSA/ATS guidelines for adults with MRSA CAP is for vancomycin or linezolid. The strains responsible are the epidemic MRSA (USA300) strains that have the PVL gene. PVL characterizes these strains and generally distinguishes them from the MRSA that has historically accounted for most nosocomial infections. This toxin attracts leukocytes and then lyses them to release cytokines ("fatal attraction"); the role of this toxin in the pathophysiologic events has been controversial, but recent studies in a rodent model indicated that PVL alone may cause pulmonary necrosis and death.[7]

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