Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
16(4), P. 459 - 459
Published: March 26, 2024
The
purpose
of
the
present
study
was
to
investigate
anti-staphylococcal
activity
liposomal
daptomycin
against
four
biofilm-producing
S.
aureus
and
epidermidis
clinical
strains,
three
which
are
methicillin-resistant.
Neutral
negatively
charged
daptomycin-loaded
liposomes
were
prepared
using
methods,
namely,
thin-film
hydration
(TFH),
a
dehydration–rehydration
vesicle
(DRV)
method,
microfluidic
mixing
(MM);
moreover,
they
characterized
for
drug
encapsulation
(EE%),
size
distribution,
zeta-potential,
stability,
release,
integrity.
Interestingly,
whilst
loading
in
THF
DRV
nanosized
(by
extrusion)
vesicles
around
30–35,
very
low
(~4%)
possible
MM
vesicles,
requiring
further
explanatory
investigations.
Liposomal
protected
from
degradation
preserved
its
bioactivity.
Biofilm
mass
(crystal
violet,
CV),
biofilm
viability
(MTT),
growth
curve
(GC)
assays
evaluated
antimicrobial
neutral
daptomycin-liposomes
towards
planktonic
bacteria
biofilms.
exhibited
dramatically
enhanced
inhibition
bacterial
(compared
free
drug)
all
species
studied,
while
totally
inactive.
prevention
treatment
studies
revealed
high
antibiofilm
daptomycin.
more
active
negative
charge
ones
treating
established
Planktonic
as
well
matured
biofilms
daptomycin-susceptible,
methicillin-resistant
Staphylococcus
(MRSA)
(MRSE)
strains
almost
completely
eradicated
by
liposomal-daptomycin,
indicating
need
their
exploration
therapeutics.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 23, 2025
Abstract
This
novel
study
leveraged
advanced
machine
learning
techniques
to
elucidate
the
molecular
mechanisms
of
antimicrobial
resistance
(AMR)
in
300
Staphylococcus
aureus
isolates
across
six
critical
antibiotics.
Employing
a
diverse
array
deep
and
ensemble
models,
we
conducted
an
in-depth
analysis
genetic
markers
allelic
variations
characterize
determinants.
Our
investigation
revealed
that
XGBoost
model
demonstrated
most
exceptional
performance,
achieving
remarkable
95%
test
accuracy,
100%
training
unprecedented
ROC
AUC
0.9855.
Comparative
multiple
approaches,
including
Long
Short-Term
Memory
(LSTM),
Convolutional
Neural
Network
(CNN),
Multi-Layer
Perceptron
(MLP),
Decision
Tree,
Stochastic
Gradient
Descent
(SGD)
provided
detailed
insights
into
prediction.
The
SHAP
(SHapley
Additive
exPlanations)
unveiled
markers,
with
“cat_allele_Cluster_1015_Allele_8”
emerging
as
influential
feature
driving
predictions.
Notably,
models
exhibited
varying
performance
different
antibiotics,
consistently
high
accuracy
F1-scores
for
ciprofloxacin,
clindamycin,
gentamicin,
sulfamethoxazole/trimethoprim.
findings
not
only
demonstrate
potential
predicting
but
also
provide
crucial
underlying
S.
drug
resistance.
By
identifying
key
determinants
their
relative
importance,
this
offers
sophisticated
approach
understanding
patterns,
potentially
guiding
future
diagnostic
strategies,
targeted
therapies,
stewardship
practices
clinical
settings.
Frontiers in Microbiology,
Journal Year:
2025,
Volume and Issue:
16
Published: March 14, 2025
Background
Staphylococcus
is
a
genus
of
bacteria
responsible
for
various
infections
ranging
from
mild
skin
to
severe
systemic
diseases.
Methicillin-resistant
aureus
(MRSA)
and
coagulase-negative
staphylococci
(CoNS)
are
significant
challenges
owing
their
resistance
multiple
antibiotics,
including
macrolides,
such
as
erythromycin,
clarithromycin,
azithromycin.
Objective
This
study
aimed
systematically
review
synthesize
data
on
the
prevalence
macrolide
in
spp.,
identify
trends
changes
patterns
over
time,
assess
how
testing
methods
guidelines
affect
reported
rates.
Methods
The
conducted
systematic
search
Scopus,
PubMed,
Web
Science,
EMBASE
databases.
Studies
have
proportion
macrolide-resistant
spp.
Two
authors
independently
extracted
analyzed
using
random-effects
model.
Heterogeneity
was
assessed,
subgroup
analyses
were
performed
based
country,
continent,
species,
AST
guidelines,
methods,
period.
Results
In
total,
223
studies
76
countries
included.
pooled
azithromycin
57.3,
52.6,
57.9%,
respectively.
Significant
heterogeneity
observed
across
(I
2
>
95%,
p
<
0.001).
Oceania
(72%)
had
highest
erythromycin
resistance,
whereas
Europe
lowest
(40.7%).
Subgroup
revealed
variations
with
higher
MRSA
than
MSSA
CoNS
other
species.
Over
slight
decrease
has
been
(59.6%
2015–2019
55%
2020–2023).
Conclusion
emphasizes
high
its
notable
regional
variation.
These
findings
highlight
necessity
standardized
methodologies
global
surveillance
manage
effectively.
Controlling
antibiotic
should
prioritize
enhancing
public
health
measures
updating
treatment
guidelines.
Systematic
registration
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=557756
,
CRD42024557756.
Antibiotics,
Journal Year:
2025,
Volume and Issue:
14(4), P. 339 - 339
Published: March 26, 2025
Background:
Staphylococcus
aureus
is
a
highly
lethal
Gram-positive
bacterium
that
responsible
for
over
one
million
deaths
annually.
As
member
of
the
ESKAPE
pathogens,
its
methicillin-resistant
strains
(MRSA)
are
prevalent
worldwide
and
exhibit
significant
antimicrobial
resistance
(AMR).
Bacterial
efflux
pumps
play
pivotal
role
in
development
AMR
by
facilitating
expulsion
range
agents.
Methods:
The
S.
strain
SA-1199B,
which
overexpresses
NorA
carries
GrlA
mutation,
was
utilized
to
comprehensively
profile
mechanism
compounds
PQQ16P
PQK4F.
To
assess
toxicity
genotoxicity
these
compounds,
RAW
macrophages,
HEK
293T,
HepG2
cell
lines
were
utilized.
Female
BALB/c
mice
vivo
synergism
EPIs
with
CPX,
Results:
pump
inhibitors
(EPIs),
PQK4F,
enhanced
efficacy
antibacterial
ciprofloxacin
(CPX)
against
resistant
strains.
involved
inhibition
pump,
without
compromising
bacterial
membrane
permeability,
ATP
levels,
or
mammalian
calcium
channels.
Moreover,
significantly
augmented
bactericidal
post-antibiotic
effects
elevating
mutation
prevention
concentration
manifesting
substantial
human
cells.
Furthermore,
reduced
invasiveness
indicating
virulence.
Notably,
CPX
observed
mouse
infection
model.
Conclusions:
This
study
provides
evidence
potential
employing
combination
counteract
AMR,
both
vitro
vivo.