through the rabbit hole(h VISA) , episode 1
.........
one of the most challenging cases in medicine is h-VISA "heterogeneous vancomycin intermediate resistance staph aureus!
=most of cells are sensitive to vancomycin with subset of resistant population ,slowly growing and marginalized ,even though the bacteria look susceptible in routine lab tests
..............
does it matter for doctors "internist ,pulmonologist /cardiologist,intensivist and surgeons"?
it can present as recurrence of signs of septicemia after initial settling (death of the sensitive subtype followed by late catch growing of resistant one) , many doctors can misinterpret it as
(1) false sensitivity test , discarding the results while a good one with refute this possibility due to the initial improvement
(2) poor tissue penetration , increasing the dose while a class A doctor will consider the AUC/MIC rather than the trough concentration 15-20mg/kg , again initial improvement makes it less likely
one can say it is easy search for initial improvement ^_^ , but it is not that easy , vancomycin is relatively slow then apparent failure "inertia" could be expected with high bacterial load ,the scenario here will the typical vancomycin treatment failure (sustained bacteremia for 7 day ) which may be true VISA/VRSA or inaccessible site of infection "abscess ,prosthetic ,..." and the h VISA
NB for surgeon : Mohamed Aziz
when you suspect poor vancomycin penetration ,consider MIC if it higher than 1-1.5 then the risk of vancomycin failure is too high
consider Linezolid as first line and
second line Daptomycin +/-Ceftaroline
(3) new insult "hospital acquired infection"
while it typically matches , the cultures will return either MRSA (s) or (I) to vancomycin , routine escalations to Linezolid /Daptomycin /Ceftaroline can be frequently noticed
........................
vancomycin is used empirically for most ICU patients to cover MRSA ,ideally for 48 h "results of nasal swab" , doctors may wait the final culture and sensitivity result after (3-7 d) to de- escalate
my personal approach is to rely on microscopic finding ( not gram positive cocci = no need for MRSA coverage)
with absence of clinical improvement ,after careful exclusion of abscesses , a non trained doctor may
(1)
: falsely consider resistance very early "with in 48 -72h" switching to another line skipping the culture .he will rely totally on rapid clinical response "Daptomycin is lipophilic while vancomycin is hydrophilic
,however it may be hGISA not just h VISA
I will call this symptom-driven approach and premature switch
moreover hVISA was documented in MSSA ,skipping the necessary culture may lead to unnecessary danger/costy antibiotics instead of simple penicillin /cephalosporin
basic hint : Mohammed Adel Gomaa ,kindly correct any fine mistakes in the following part
When MSSA develops the hVISA phenotype
it is evolutionary, adaptive process rather than a plasmid acquisition
t is completely independent of mec A or mec C gene (= no effect on Penicillin-Binding Proteins PBP2a) ,Instead, it relies on complex cell-wall remodeling
(A) waLKR mutation :encodes a sensor histidine kinase (a histone-like protein kinase that forms part of a two-component regulatory system). It controls the autolysins that break down peptidoglycan. Mutations in this locus lead to the down-regulation of autolytic enzymes, disabling normal autolysis and directly causing a significantly thickened cell wall
(B)graRS (Glycopeptide Resistance Associated) Mutations
This two-component regulatory system controls global cell-wall properties and synthesis.
Clinical Note (Cross-Resistance):
Mutations in graRS frequently lead to the upregulation of the mprF gene (lysyl-phosphatidylglycerol synthetase). This increases the net positive charge of the bacterial cell membrane, repelling positively charged molecules and driving concomitant daptomycin resistance (due to the effect of the positive charge on the bacterial surface).
⬇️⬇️KEEP READING⬇️⬇️
1August 30, 2026 77
