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Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1.
[legionellosis]
The
activity
of
solithromycin
was
evaluated
against
clinical
Legionella
pneumophila
serogroup
1
(
Lp
1
)
isolates
(
n
=
196
)
collected
in
Ontario
,
Canada
,
from
1980
to
2011
.
Its
in
vitro
activity
was
compared
to
that
of
azithromycin
(
AZM
)
using
the
broth
microdilution
method
.
Solithromycin
had
a
MIC
50
of
≤
0
.
015
μg
/
ml
and
a
MIC
90
of
0
.
031
μg
/
ml
,
making
its
activity
at
least
8
-
fold
to
32
-
fold
higher
than
that
of
AZM
(
MIC
50
and
MIC
90
,
0
.
125
μg
/
ml
and
1
μg
/
ml
,
respectively
)
.
Ninety
-
nine
percent
of
the
isolates
had
MICs
for
solithromycin
ranging
from
≤
0
.
015
μg
/
ml
to
0
.
031
μg
/
ml
,
whereas
83
.
6
%
of
the
isolates
showed
MICs
for
AZM
ranging
from
0
.
062
μg
/
ml
to
0
.
25
μg
/
ml
.
Interestingly
,
96
.
7
%
(
30
out
of
31
clinical
isolates
)
identified
with
higher
AZM
MICs
(
0
.
5
μg
/
ml
to
2
μg
/
ml
)
belonged
to
the
clinically
prevalent
sequence
type
1
.
To
investigate
the
intracellular
activity
of
solithromycin
,
in
vitro
invasion
assays
were
also
performed
against
a
subset
of
representative
Lp
1
isolates
internalized
within
human
lung
epithelial
cells
.
Solithromycin
and
AZM
both
inhibited
growth
of
all
intracellular
Lp
1
isolates
at
1
×
or
8
×
MICs
,
displaying
bacteriostatic
effects
,
as
would
be
expected
with
protein
synthesis
inhibitor
rather
than
bactericidal
activity
.
Solithromycin
demonstrated
the
highest
in
vitro
and
intracellular
potency
against
all
Lp
1
isolates
compared
to
AZM
.
Given
the
rapid
spread
of
resistance
mechanisms
among
respiratory
pathogens
and
the
reported
treatment
failures
in
legionellosis
,
the
development
of
this
new
fluoroketolide
,
already
in
phase
3
oral
clinical
studies
,
constitutes
a
promising
alternative
option
for
the
treatment
of
legionellosis
.
Diseases
Validation
Diseases presenting
"oral clinical studies"
symptom
legionellosis
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