Microorganisms,
Journal Year:
2024,
Volume and Issue:
12(6), P. 1193 - 1193
Published: June 13, 2024
This
study
describes
KPC-204,
a
novel
variant
of
Klebsiella
pneumoniae
carbapenemase,
characterized
by
Lys-Asp-Asp
(KDD)
amino
acid
insertion
at
Ambler
position
269
deviates
from
KPC-2.
was
identified
in
an
ST11-type
clinical
isolate
carbapenem-resistant
China.
Notably,
KPC-204
exhibits
resistance
to
both
ceftazidime-avibactam
and
carbapenems.
Genetic
analysis
revealed
that
blaKPC-204
located
on
highly
mobile
IncFII/IncR
plasmid
within
complex
genetic
structure
facilitates
its
spread.
Functional
analysis,
achieved
through
cloning
into
E.
coli
DH5α,
validates
KPC-204’s
contribution
increased
ceftazidime-avibactam.
The
kinetic
parameters
showed
exhibited
similar
affinity
KPC-2
toward
ceftazidime
reduced
sensitivity
avibactam.
Docking
simulations
weaker
interaction
between
avibactam
compared
Mating
experiments
demonstrated
the
resistance’s
transmissibility.
investigation
underscores
evolving
diversity
KPC
variants
affecting
resistance,
highlighting
necessity
for
continuous
monitoring.
Journal of Antimicrobial Chemotherapy,
Journal Year:
2024,
Volume and Issue:
80(2), P. 583 - 592
Published: Dec. 19, 2024
To
evaluate
the
in
vitro
activity
of
ceftazidime/avibactam,
meropenem/vaborbactam,
imipenem/relebactam
and
comparators
against
KPC-producing
Klebsiella
pneumoniae
(KPC-Kp)
clinical
isolates
collected
from
a
multicentre
study
Italy
(2022-23)
genomic
characterization
molecular
mechanisms
causing
resistance.
Consecutive
KPC-Kp
blood
cultures
(n
=
264)
were
14
hospital
centres
period
2022-23.
Antimicrobial
susceptibility
testing
was
performed
using
broth
microdilution.
WGS
used
to
investigate
strains
resistant
new
approved
β-lactam/β-lactam
inhibitor
combinations
(BLICs).
Overall,
meropenem/vaborbactam
(95.1%
susceptible
by
EUCAST
93.9%
CLSI;
MIC50
0.5
mg/L;
MIC90
4
mg/L)
(97%
92.8%
0.25
showed
similar
activity,
followed
ceftazidime/avibactam
(93.9%
both
2
8
mg/L).
Ten
out
13
(76.9%)
carried
blaKPC
variant
including
blaKPC-31,
blaKPC-205,
blaKPC-203
blaKPC-93.
Among
imipenem/relebactam,
90.9%
(10/11)
80%
(4/5)
harboured
WT
carbapenemase
(i.e.
blaKPC-2
or
blaKPC-3),
respectively.
All
and/or
truncated
OmpK35
mutated
(ins135GD)
OmpK36.
New
BLICs
shown
be
most
widely
active
therapeutic
option
Italy.
Ceftazidime/avibactam
resistance
is
mainly
driven
expression
KPC
variants,
whereas
loss
function
OmpK36
porins
appears
play
key
but
not
exclusive
role
development
Microorganisms,
Journal Year:
2024,
Volume and Issue:
12(6), P. 1193 - 1193
Published: June 13, 2024
This
study
describes
KPC-204,
a
novel
variant
of
Klebsiella
pneumoniae
carbapenemase,
characterized
by
Lys-Asp-Asp
(KDD)
amino
acid
insertion
at
Ambler
position
269
deviates
from
KPC-2.
was
identified
in
an
ST11-type
clinical
isolate
carbapenem-resistant
China.
Notably,
KPC-204
exhibits
resistance
to
both
ceftazidime-avibactam
and
carbapenems.
Genetic
analysis
revealed
that
blaKPC-204
located
on
highly
mobile
IncFII/IncR
plasmid
within
complex
genetic
structure
facilitates
its
spread.
Functional
analysis,
achieved
through
cloning
into
E.
coli
DH5α,
validates
KPC-204’s
contribution
increased
ceftazidime-avibactam.
The
kinetic
parameters
showed
exhibited
similar
affinity
KPC-2
toward
ceftazidime
reduced
sensitivity
avibactam.
Docking
simulations
weaker
interaction
between
avibactam
compared
Mating
experiments
demonstrated
the
resistance’s
transmissibility.
investigation
underscores
evolving
diversity
KPC
variants
affecting
resistance,
highlighting
necessity
for
continuous
monitoring.
