Cost-Effectiveness Analysis of Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis is a Difficult Issue

Clinical Infectious Diseases, Sep 2009

Katarina Westling

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Cost-Effectiveness Analysis of Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis is a Difficult Issue

EDITORIAL COMMENTARY • CID Cost-Effectiveness Analysis of Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis Is a Difficult Issue Katarina Westling () 0 0 Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden - Methicillin-resistant Staphylococcus aureus (MRSA) was first detected in 1961. Today, MRSA is widely spread around the world. In the United States [1] and in many European countries, 25%–50% of S. aureus isolates are MRSA [2], even if some countries (eg, the Netherlands and the Scandinavian countries) have a low level of cases of invasive MRSA infection. Invasive MRSA infections, such as bacteremia and endocarditis, are difficult to treat because the treatment options are limited. MRSA bacteremia also has a higher mortality rate than does bacteremia due to methicillin-susceptible S. aureus (MSSA) [3]. Infective endocarditis due to MRSA has a trend toward a higher mortality rate compared with that due to MSSA [4]. Many of the patients are immunocompromised with underlying diseases and may have intracardiac devices or intravenous catheters in place, and such infections are difficult to treat without replacement of these devices. Vancomycin, a glycopeptide, is the firstline drug for treatment of invasive MRSA infection. However the failure rate is high, the bactericidal activity is poorer than that of the b-lactams, and nephrotoxicity is a problem. Failure of vancomycin can be attributed to low tissue penetration [5] and increasing minimum inhibitory concentrations (MICs) [6] associated with increased cell wall thickness [7], which is the barrier for penetration of the antibiotic. Cases of bacteremia due to MRSA with a high MIC of vancomycin have been shown to have a higher mortality rate than the rate for MRSA with a low MIC of vancomycin [8]. In such cases, higher doses of vancomycin have been suggested, but higher doses may also cause more nephrotoxic adverse effects [9]. Daptomycin, a bactericidal cyclic lipopeptide produced by Streptomyces roseospurus, has activity against several grampositive bacteria, including MRSA. It was discovered in the 1980s but was withdrawn because of adverse effects, such as myositis when high doses were used; development of the drug was aborted. Daptomycin was reintroduced in the 1990s, and lower doses were used. It was approved for use in the United States and the European Union for complicated softtissue and skin infections in 2003. A randomized study that compared conventional treatment with daptomycin treatment for bacteremia and native valve infective endocarditis due to S. aureus (MSSA and MRSA) was performed and published in 2006 and demonstrated noninferiority for daptomycin for bacteremia and right-side endocarditis [10]. That study was also the main reason why daptomycin was registered for these indications in the United States and the European Union. In this issue of Clinical Infectious Diseases, Bhavnani et al [11] compare the cost-effectiveness of daptomycin with that of vancomycin-gentamicin in patients with MRSA bacteremia and endocarditis. Cost-effectiveness studies of daptomycin and vancomycin have been presented for complicated skin and soft-tissue MRSA infections [12]. However, until now, no cost-effectiveness studies have been published on the treatment of MRSA bacteremia and endocarditis. Bhavnani et al [11] used data from 89 patients with MRSA bacteremia and endocarditis described in a study by Fowler et al [10] and performed a subset analysis. The study included patients with left-side native valve endocarditis, right-side complicated endocarditis, complicated bacteremia, and uncomplicated bacteremia due to MRSA. The daily doses were 6 mg/kg intravenously for daptomycin and 1 g intravenously twice per day for vancomycin, with dose adjustment for vancomycin based on renal function. Cost-effectiveness ratio was defined as the costs divided by the proportion of successes. Three cost-strata were used. In stratum 1, the costs of drug acquisition was compared between the arms; the findings were more favorable for vancomycin-gentamicin than for daptomycin. Stratum 2 included the costs from stratum 1 plus the costs of therapy for treatment failures and adverse events and the costs of therapeutic drug monitoring; the findings were more favorable for vancomycin-gentamicin. Finally, stratum 3 included all of the information from stratum 2 plus bed costs. In stratum 3, the cost-effectiveness for the treatments was similar. Rehm et al [13] evaluated 88 cases of MRSA infection reported in the same study by Fowler et al [10], providing additional information. The patients in the vancomycin-gentamicin arm, for example, more often had foreign intravascular materials present, compared with patients in the daptomycin arm. Treatment success rates were similar in both arms for cases of infective endocarditis, 0% of cases of left-side endocarditis, (...truncated)


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Katarina Westling. Cost-Effectiveness Analysis of Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis is a Difficult Issue, Clinical Infectious Diseases, 2009, pp. 699-701, 49/5, DOI: 10.1086/604711