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
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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withdrawn because of adverse effects, such as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)