Staphylococcus aureus
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The FDA has approved the antibiotic
daptomycin to treat systemic infections caused by Staphylococcus
aureus (S aureus) — including MRSA — based
on the results of a study published in the New England
Journal of Medicine on August 17. The drug is the
first new treatment for these life-threatening infections
in two decades. It's still awaiting approval in Canada.
Daptomycin was put on the US market
for the treatment of S aureus skin and soft tissue
infections in 2003. Now, after this promising Duke University
trial of 236 patients, the FDA has decided to approve
its use on more dangerous infections where the bacteria
invade the bloodstream (bacteremia), or the heart (right-sided
endocarditis).
This could be great news for some
very ill patients. "The 12-week all cause mortality
from these infections is about 25%," said lead author
Dr Vance G Fowler. "Even among those that survive, associated
longterm morbidity is devastating."
An increasing number of these heart
and blood infections are caused by methicillin-resistant
strains of S aureus (MRSA), making them even
harder to treat. A study published in the same issue
of the NEJM showed that MRSA is now the most
common cause of skin and soft-tissue infections in the
US, and it may well end up becoming the main cause of
systemic infections as well.
NOT
GOOD ENOUGH
Right now, vancomycin is a physician's best weapon against
MRSA. Thankfully, reports of resistance to this drug
have been relatively infrequent, but it's still a bit
of a letdown. "As clinicians, we use it because we have
to, not because we want to," explained Dr Fowler. "It's
been associated with suboptimal clinical outcomes, higher
relapse rates and longer durations."
We definitely need new antibiotics
to counter the threat, said Dr John Conly, director
of the Centre for Antimicrobial Resistance at the University
of Calgary. "Ones that are not only bactericidal, but
effective and inexpensive as well." He said that while
vancomycin-resistance isn't a big issue now — it
will be soon. "That's why an alternative is so important,"
Dr Fowler agreed.
A
SLIGHT EDGE
Patients in the randomized trial were assigned to one
of two groups. The first received daptomycin, while
the second got the standard combo of gentamicin and
either penicillin (for methicillin-susceptible strains)
or vancomycin.
Patients infected with MRSA infections
were evenly distributed between the two groups —
37.5% in the daptomycin arm, 38.3% in the other. Forty-two
days after the end of therapy, daptomycin had performed
as well as standard therapy, regardless of drug susceptibility.
In fact, daptomycin slightly outperformed vancomycin
in clearing MRSA, though the difference was not statistically
significant.
MAN
vs MICROBE
Daptomycin is not yet approved in Canada, neither for
skin and soft tissue infections nor for the more complicated
systemic infections studied here. But applications for
both indications have been submitted, and approval is
expected in the first half of 2007.
Concern about daptomycin's safety
— particularly an elevated risk of muscle toxicity
— caused the drug to be dropped in the early 90s.
But it has since made a comeback, and Dr Fowler said
his and previous studies have shown the drug to be mostly
safe. "CPK levels [a marker of muscle damage] were noticeably
higher in the daptomycin group, but manageable," he
explained. "It can be monitored, and if it gets too
high, you simply stop the drug."
A greater concern to him was the
development of resistance to daptomycin in a handful
of subjects. "Six cases developed in the study, and
it's not normal for resistance to happen so quickly.
I don't think we understand what's going on there, and
practitioners do need to be concerned about it," said
Dr Fowler. "They need to check susceptibility regularly
and remember that ultimately, the bugs are smarter than
we are."
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