Abstract & Commentary
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Source: Simor AE, 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.
Synopsis: A combination of topical and systemic therapies was associated with successful MRSA decolonization.
In an open label study, hospitalized adults with MRSA colonization at one or more sites were randomized (3:1) to attempted decolonization or no treatment. Treatment consisted of 7 days of bathing with 2% chlorhexidine gluconate, together with application of 2% mupirocin ointment to the anterior nares 3 times daily and administration of rifampin (300 mg twice daily) and doxycycline (100 mg twice daily). Follow-up cultures were obtained from the anterior nares, perianal area, skin lesions, catheter or other medical device exit sites, as well as any other site from which MRSA had previously been recovered. Among the reasons for exclusion from the study were prior attempts at decolonization within the previous 6 months, known resistance of the MRSA to any of the study drugs (including mupirocin), AST or ALT >5 times the upper limit of normal, and planned surgery in the following 3 months.
Of the 112 patients (from among the 146 randomized), who were followed for at least 3 months, 87 received decolonization treatment and 25 did not. At 3 months, successful decolonization was achieved in 64 (74%) of the treated and 8 (32%; P = 0.0001) of those not treated. At 8 months, 54% of those treated continued to have negative MRSA cultures. Initial and follow-up strains differed by PFGE typing in 18% of cases, however, indicating acquisition of a new strain, rather than failure of decolonization. Baseline resistance to mupirocin (approximately 20% of baseline isolates were resistant) was an independent risk factor for treatment failure. Although known mupirocin resistance was a reason for exclusion from the study, this information was often not available until after randomization. In addition to resistance at baseline, mupirocin resistance emerged in 5% of isolates obtained from follow-up cultures.
The high rate of persistent success of this decolonization procedure is encouraging. While MRSA colonization is associated with an increased risk of infection, evidence that decolonization is associated with a reduction in that risk remains to be demonstrated, except in a few circumstances, such as chronic peritoneal dialysis and some surgical patients. One benefit of decolonization that can be agreed upon, however, is that it allows the hospitalized or institutionalized patient to be removed from isolation.
Rifampin and doxycycline were reported to be well tolerated in this study. Concern must be maintained, however, about the possibility of adverse effects, such as the development of Clostridium difficile-associated disease. Furthermore, the polypharmacy to which most hospitalized patients are exposed makes the routine use of rifampin difficult because of its induction of cytochrome P450 enzymes and the resultant increased clearance of a large number of medications that are metabolized by those enzymes.
The high baseline rate of mupirocin resistance seen in this study (despite attempted exclusion of those with known mupirocin resistance prior to randomization) is not without precedent in hospital-acquired MRSA and all but one of the isolates (a USA 400 strain) were hospital strains as determined by multilocus sequence typing. Mupirocin resistance, however, appears to also be a problem in USA 300, the community-acquired MRSA prevalent in the United States. Thus, a gene encoding high-level resistance to mupirocin, ileS, carried on a conjugative plasmid, pUSA03 has been detected in 46% of multidrug-resistant strains of USA300, the most prevalent community acquired MRSA in the United States.1 Alternative anti-MRSA nasal applications that may be considered include triple antibiotic ointment2 and investigative agents, such as REP8839, an inhibitor of methionyl-tRNA synthetase .3
- Jones RN, et al. Contemporary Antimicrobial Activity of Triple Antibiotic Ointment: A Multiphased Study of Recent Clinical Isolates in the United States and Australia. Diagn Microbiol Infect Dis. 2006;54:63-71.
- Fung S, et al. The Utility of Polysporin Ointment in the Eradication of Methicillin-Resistant Staphylococcus aureus Colonization: A Pilot Study. Infect Control Hosp Epidemiol. 2000;21:653-655.
- Critchley IA, et al. Antibacterial Activity of REP8839, A New Antibiotic for Topical Use. Antimicrob Agents Chemother. 2005;49:4247-4252.