Frontiers in Cellular and Infection Microbiology,
Journal Year:
2024,
Volume and Issue:
14
Published: July 16, 2024
Patients
with
severe
carbapenem-resistant
Acinetobacter
baumannii
(CRAB)
infections
currently
face
significant
treatment
challenges.
When
patients
display
signs
of
infection
and
the
clinical
suspicion
CRAB
is
high,
appropriate
should
be
immediately
provided.
However,
current
plans
data
for
are
limited.
Inherent
acquired
resistance
mechanisms,
as
well
host
factors,
significantly
restrict
options
empirical
medication.
Moreover,
inappropriate
drug
coverage
can
have
detrimental
effects
on
patients.
Most
existing
studies
limitations,
such
a
restricted
sample
size,
predominantly
observational
or
non-randomized,
which
report
variability
in
patient
severity
comorbidities.
Therefore,
gold-standard
therapy
remains
lacking.
Current
future
due
to
were
described
this
review.
The
dose
considerable
side
polymyxins,
high
doses
ampicillin-sulbactam
tigecycline
appear
best
option
at
time
initial
treatment.
new
drugs
durlobactam
cefiderocol
substantial
therapeutic
capabilities
may
effective
salvage
treatments.
Bacteriophages
antimicrobial
peptides
serve
alternative
near
future.
advantages
combination
regimen
predominate
those
single
regimen.
Despite
its
nephrotoxicity,
colistin
considered
primary
often
used
antimicrobials,
tigecycline,
ampicillin-sulbactam,
meropenem,
fosfomycin.
Infectious
Diseases
Society
America
(IDSA)
has
deemed
high-dose
typically
combined
polymyxin,
other
antibacterial
agents,
treating
serious
infections.
A
rational
use
exploration
alleviate
prevent
infections,
shorten
hospital
stays,
reduce
mortality.
Antibiotics,
Journal Year:
2023,
Volume and Issue:
12(12), P. 1729 - 1729
Published: Dec. 14, 2023
Infections
caused
by
carbapenem-resistant
Acinetobacter
baumannii
(CRAB)
remain
a
clinical
challenge
due
to
limited
treatment
options.
Recently,
cefiderocol,
novel
siderophore
cephalosporin,
and
sulbactam-durlobactam,
bactericidal
β-lactam-β-lactamase
inhibitor
combination,
have
been
approved
the
Food
Drug
Administration
for
of
A.
infections.
In
this
review,
we
discuss
mechanisms
action
resistance
cefiderocol
antimicrobial
susceptibility
isolates
these
drugs,
as
well
effectiveness
sulbactam/durlobactam-based
regimens
against
CRAB.
Overall,
sulbactam-durlobactam
show
an
excellent
activity
The
review
studies
evaluating
efficacy
therapy
CRAB
indicates
it
is
non-inferior
colistin/other
treatments
infections,
with
better
safety
profile.
Combination
not
associated
improved
outcomes
compared
monotherapy.
Higher
mortality
rates
are
often
prior
patient
comorbidities
severity
underlying
infection.
Regarding
current
data
from
pivotal
trial
case
reports
suggest
antibiotic
combination
could
be
valuable
option
in
critically
ill
patients
affected
particular
where
no
other
appears
effective.
Frontiers in Microbiology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 27, 2024
We
studied
the
Escherichia
coli
outer
membrane
protein
Fiu,
a
presumed
transporter
of
monomeric
ferric
catecholates,
by
introducing
Cys
residues
in
its
surface
loops
and
modifying
them
with
fluorescein
maleimide
(FM).
Fiu-FM
bound
iron
complexes
tricatecholate
siderophore
enterobactin
(FeEnt)
glucosylated
(FeGEnt),
their
dicatecholate
degradation
product
Fe(DHBS)
2
(FeEnt*),
monocatecholates
dihydroxybenzoic
acid
(FeDHBA)
dihydroxybenzoyl
serine
(FeDHBS),
antibiotics
cefiderocol
(FDC)
MB-1.
Unlike
high-affinity
ligand-gated
porins
(LGPs),
had
only
micromolar
affinity
for
complexes.
Its
apparent
K
D
values
FeDHBS,
FeDHBA,
FeEnt*,
FeEnt,
FeGEnt,
FeFDC,
FeMB-1
were
0.1,
0.7,
1.0,
0.3,
0.4,
4
μM,
respectively.
Despite
broad
binding
abilities,
transport
repertoires
E.
as
well
those
Cir
FepA,
less
broad.
Fiu
transported
FeEnt*.
FeEnt*
FeDHBS
(weakly);
FepA
FeDHBA.
Both
albeit
lower
affinity.
Related
transporters
Acinetobacter
baumannii
(PiuA,
PirA,
BauA)
similarly
moderate
specificity
di-
or
catecholates.
microbiological
radioisotopic
experiments
showed
Fiu’s
exclusive
rather
than
monocatecholate
compounds.
Molecular
docking
molecular
dynamics
simulations
predicted
three
sites
FeEnt*in
external
vestibule
fourth
site
deeper
interior.
Alanine
scanning
mutagenesis
outermost
(1a,
1b,
2)
decreased
much
20-fold
reduced
eliminated
uptake.
Finally,
suggested
pathway
movement
through
that
may
generally
describe
process
metal
TonB-dependent
receptors.
European Journal of Clinical Microbiology & Infectious Diseases,
Journal Year:
2024,
Volume and Issue:
43(6), P. 1171 - 1179
Published: April 23, 2024
This
study
aimed
to
determine
the
in
vitro
efficacy
of
cefiderocol
carbapenem-resistant
Acinetobacter
baumannii
(CRAB)
isolates
and
evaluate
disk-diffusion
(DD)
method
as
an
alternative
broth-microdilution
(BMD).
Microorganisms,
Journal Year:
2025,
Volume and Issue:
13(2), P. 356 - 356
Published: Feb. 7, 2025
Acinetobacter
baumannii
complex
(ABC)
can
result
in
a
panoply
of
severe
syndromes,
including
pneumonia
and
septic
shock.
Options
available
for
treating
infections
caused
by
ABC
and,
more
importantly,
carbapenem-resistant
(CRAB)
are
limited
because
the
increasing
prevalence
antimicrobial
resistance.
Furthermore,
many
older
agents,
such
as
polymyxin
colistin,
have
lung
penetration
associated
with
significant
toxicities.
These
factors
underscore
urgent
need
new
paradigms
to
address
CRAB.
Two
cefiderocol
sulbactam-durlobactam,
now
treat
CRAB
infections.
In
addition,
several
anti-infectives
that
target
later-stage
clinical
trials.
order
place
these
newer
molecules
context
help
clinicians
appreciate
emerging
potential
drug
development
pipeline,
we
describe
vitro
activity,
mechanisms
action,
trial
data
not
only
commercially
alternatives,
but
also
review
topics
undergoing
phase
II
III
Specifically,
discuss
analyze
related
four
novel
drugs
from
ABC:
BV-100,
cefepime-zidebactam,
zosurabalpin,
OMN6.
JAC-Antimicrobial Resistance,
Journal Year:
2025,
Volume and Issue:
7(2)
Published: March 4, 2025
Carbapenem-resistant
Acinetobacter
baumannii
(CRAB)
is
characterized
as
a
critical
priority
pathogen
with
restricted
therapeutic
options.
To
date,
the
most
effective
antimicrobial
treatment
against
this
difficult-to-treat
bacterial
strain
has
not
been
established.
Sulbactam
β-lactamase
inhibitor
intrinsic
activity
pathogen,
however,
β-lactam,
it
can
be
hydrolysed
by
β-lactamases
produced
A.
baumannii.
High-dose,
extended-infusion
sulbactam
overcome
hydrolysis
and
considered
an
strategy
CRAB.
The
aim
of
review
to
analyse
primary
secondary
research
studies
that
compare
sulbactam-based
other
regimens,
such
polymyxin-containing
tigecycline-containing
regimens
combinations
CRAB
infections,
especially
ventilator-associated
pneumonia
(VAP),
hospital-acquired
(HAP)
bacteraemia.
Our
findings
suggest
results
are
conflicting,
mostly
because
high
heterogeneity
among
studies.
However,
in
studies,
have
demonstrated
comparable,
several
more
favourable
contrast
treatments
respect
clinical
cure
mortality
CRAB-associated
pneumonia,
yet
without
reaching
statistical
significance
cases.
auspicious
novel
β-lactam/β-lactamase
combination
sulbactam/durlobactam
also
discussed,
although
real-world
data
regarding
its
efficacy
infections
still
scarce.
More
randomized
controlled
trials
comparing
warranted
determine
infections.
Nevertheless,
current
could
play
major
role
treatment.
JAC-Antimicrobial Resistance,
Journal Year:
2024,
Volume and Issue:
6(5)
Published: Sept. 3, 2024
Abstract
Background
Cefiderocol
exhibits
potent
in
vitro
activity
against
carbapenem-resistant
Acinetobacter
baumannii
(CRAb),
but
this
has
not
consistently
translated
to
improved
outcomes
among
patients.
heteroresistance,
or
the
presence
of
a
resistant
subpopulation,
been
proposed
as
one
possible
explanation.
The
objective
study
was
explore
associations
between
heteroresistance
and
patients
with
CRAb
infections.
Methods
Baseline
isolates
were
collected
from
27
consecutive
USA
Italy.
susceptibility
tested
by
broth
microdilutions
triplicate.
Heteroresistance
defined
population
analysis
profiling
duplicate.
Resistance
mechanisms
strain
relatedness
evaluated
through
comparative
genomic
analysis.
Results
Overall,
59%
infecting
identified
cefiderocol-heteroresistant;
rates
higher
Italy
(79%)
than
(38%).
median
Charlson
Comorbidity
SOFA
scores
4
5,
respectively;
44%
had
pneumonia,
which
most
common
infection
type.
Rates
28-day
clinical
success
survival
30%
73%,
respectively.
By
microdilution,
cefiderocol
MICs
≥1
mg/L
associated
failure
≤0.5
(81%
versus
55%).
numerically
infected
cefiderocol-heteroresistant
compared
susceptible
Whole-genome
sequencing
premature
stop
codon
TonB-dependent
receptor
gene
piuA
six
isolates,
all
heteroresistant.
Conclusions
This
pilot
supports
hypothesis
that
treatment
may
be
and/or
heteroresistance.
Further
studies
are
needed
confirm
these
findings.
Expert Review of Anti-infective Therapy,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 18, 2024
Several
novel
agents
are
in
advanced
stages
of
clinical
development,
potentially
expanding
our
treatment
options
against
third-
and
fourth-generation
cephalosporin-resistant
carbapenem-resistant
Gram-negative
bacteria
(GNB),
including
those
pathogens
for
which
the
current
number
effective
treatments
is
limited.
Microorganisms,
Journal Year:
2025,
Volume and Issue:
13(3), P. 493 - 493
Published: Feb. 22, 2025
Acinetobacter
baumannii
is
one
of
the
most
successful
and
feared
nosocomial
pathogens.
A.
considered
a
global
threat
in
healthcare
setting,
mainly
owing
to
its
ability
acquire
multidrug
resistance
phenotypes.
The
pathogenesis
guided
by
environmental
persistence,
as
well
production
numerous
virulence
factors.
In
several
bacteria,
pigments,
such
melanin,
has
indeed
been
linked
with
pathogenicity.
Melanin
brownish
pigment,
rarely
observed
baumannii,
that
potentially
reduces
susceptibility
bacteria
host
defense
mechanisms
insults.
This
study
reports
first
outbreak
Europe
pyomelanin-producing
strains,
tertiary-care
university
hospital
Pisa,
Italy.
Phenotypic
molecular
analyses
were
performed.
