Shorter
antibiotic
treatment
worked
better
in
clinically
stabilized
patients
with
infective
endocarditis
on
the
left
side
of
the
heart,
even
though
the
risk
of
infection
relapse
may
be
greater,
according
to
the
open-label
randomized
POET
II
trial.
After
a
minimum
of
2-4
weeks
to
achieve
clinical
stability,
those
randomized
to
cease
antibiotic
treatment
(tailored
approach)
had
the
edge
over
those
receiving
the
typical
standard
of
care
regimen
(4-6
weeks
total
duration)
in
terms
of
days
alive
within
6
months
without
antibiotic
therapy
for
infective
endocarditis
or
bacteremia
(median
183
vs
169
days,
P<0.001).
Patients
in
the
tailored-approach
group
ended
up
taking
antibiotics
for
15
fewer
days
(median
26
vs
41
days,
respectively),
Henning
Bundgaard,
MD,
of
the
University
of
Copenhagen
in
Denmark,
reported
at
the
European
Society
of
Cardiology
(ESC)
Congress
in
Munich.
As
for
the
primary
safety
endpoint,
the
strategy
of
tailored
antibiotic
treatment
was
associated
with
no
excess
all-cause
death,
unplanned
cardiac
surgery,
or
symptomatic
embolic
events
within
6
months
(8.2%
vs
10.7%,
P<0.001
for
noninferiority),
findings
published
simultaneously
in
the
New
England
Journal
of
Medicine
showed.
“We
have
challenged
dogmas
showing
that
less-intensive
antibiotic
therapy
after
stabilization
is
superior
and
safe,
and
we
think
that
defining
the
stabilization
point
is
a
kind
of
personalized
endocarditis
treatment,”
Bundgaard
explained
during
a
press
briefing
at
ESC.
The
508
randomized
participants
had
one
of
three
pathogens
responsible
for
about
70%
of
all
infective
endocarditis
cases:
Staphylococcus
aureus,
Enterococcus
faecalis,
or
Streptococcus
species.
A
shorter
antibiotic
regimen
is
attractive
for
various
reasons,
including
the
potential
for
fewer
side
effects,
less
risk
of
antimicrobial
resistance,
better
patient
recovery,
and
lower
costs.
Nevertheless,
study
authors
noted
that
6
weeks
of
high-dose
antibiotics
is
standard
for
infective
endocarditis.
This
longer
approach
is
based
on
expert
opinion,
given
the
lack
of
a
biomarker
that
definitively
shows
when
patients
have
reached
bacterial
clearance.
In
the
POET
II
trial,
investigators
used
a
combination
of
clinical,
biochemical,
and
imaging
criteria
from
the
earlier
POET
trial
to
determine
when
patients
were
clinically
stabilized.
Their
hypothesis
was
that
this
response-tailored
treatment
would
result
in
2
to
3
fewer
weeks
of
IV
or
oral
step-down
antibiotic
treatment.
In
a
key
secondary
analysis,
standard
therapy
was
linked
with
a
significantly
lower
risk
of
relapse
than
tailored
therapy,
however.
A
return
of
bacteremia
or
infective
endocarditis
during
6-month
follow-up
happened
in
5.1%
of
the
tailored-therapy
group
and
1.6%
of
the
standard-therapy
group
(P=0.04).
“Considering
the
potential
benefits
of
a
reduction
in
antibiotic
exposure,
an
increase
in
the
risk
of
relapse
could
be
deemed
acceptable
if
it
is
not
associated
with
major
clinical
complications,”
Bundgaard’s
group
argued.
“The
results
of
the
sensitivity
analysis
in
which
relapse
was
included
in
the
primary
safety
endpoint
were
reassuring
for
patients
with
infective
endocarditis
caused
by
streptococcus
species
or
S.
aureus,
but
more
events
appeared
to
occur
among
patients
with
infective
endocarditis
caused
by
E.
faecalis
in
the
tailored-therapy
group.”
Even
without
accounting
for
relapses,
tailored
therapy
held
the
advantage
in
the
incidence
of
the
composite
safety
endpoint
when
streptococcal
and
S.
aureus
infections
were
the
causes:
3.6
percentage
points
lower
with
streptococcus
species
and
6.4
percentage
points
lower
with
S.
aureus.
E.
faecalis
infections
told
a
different
story.
Composite
safety
endpoint
incidence
rates
were
6.8
percentage
points
lower
among
standard-therapy
patients
than
tailored-therapy
patients
when
E.
faecalis
was
the
causative
pathogen.
Relapse
was
also
more
common
among
E.
faecalis
patients
(6.4%)
than
in
the
S.
aureus
(3.3%)
or
streptococcal
(2.4%)
patients.
The
investigators
cautioned
that
firm
conclusions
couldn’t
be
reached
about
E.
faecalis,
however,
given
that
the
study
didn’t
recruit
its
planned
number
of
E.
faecalis
patients.
Another
study
limitation
was
the
inclusion
of
just
three
pathogens,
which
may
make
study
findings
not
generalizable
for
infections
with
rarer
pathogens.
POET
II
was
conducted
in
Denmark,
Sweden,
and
the
U.S.
and
included
adults
with
infective
endocarditis
of
prosthetic
or
native
valves
on
the
heart’s
left
side,
a
group
that
accounts
for
roughly
half
of
all
infective
endocarditis
cases.
After
clinical
stabilization
on
2-4
weeks
of
antibiotics
therapy,
patients
were
randomized
1:1
to
either
stop
antibiotics
or
continue
taking
them
for
a
full
4-6
weeks.
The
cohort
had
a
mean
age
of
70
years,
and
three-quarters
were
men.
Streptococcus
species
were
the
most
common
pathogen,
in
57.3%
of
patients,
followed
by
S.
aureus
(24.2%),
and
E.
faecalis
(18.5%).
Nearly
two-thirds
of
patients
(63.2%)
had
affected
aortic
valves,
while
26.4%
had
prosthetic
valve
infections.
Before
randomization,
one
in
three
people
had
undergone
cardiac
surgery.
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