Antimicrobial resistance Flashcards
T/F:
VISA uses the same mechanism VRSA?
F
VRSA changes the vancomycin target (glycopeptide target is changed from D-alanine-D-alanine to low-affinity D-alanine-D-lactate or D-alanine-D-serine) This is van gene mediated.
VISA provides many decoy (false) targets
What are the commonest porin loss gens ?
1- OmpF loss - resistance to β-lactams, chloramphenicol, Tetracyclines, Lincosamides, steroids, and Quinolones
2- fadL - Rifampicin
3- pgaA - Streptomycin
4- lamB - Vancomycin
5- yddB - Novobiocin
6- OprD porin loss leads to resistance to Imipenem and some increase in the MIC of Meropenem.
What are the 6 families of Bacterial drug efflux pumps?
the ATP-Binding Cassette (ABC) superfamily- gram +
the Major Facilitator Superfamily (MFS)- gram +
the Multidrug And Toxic compound Extrusion (MATE)
the Small Multidrug Resistance (SMR) family
The resistance Nodulation Division (RND) superfamily mainly gram negative
the Drug Metabolite Transporter (DMT) superfamily
What is the clinical importance of MefA and MefE genes?
MefA and MefE are associated with Macrolide resistance in:
1- Strep pneumoniae
2- group A Streptococcus
What is the clinical significance of :
1- gyrA- gyrB encode for DNA gyrase and :
2- parC- parE genes encode for topoisomerase IV?
These are targets of the fluoroquinolone antibiotics.
Mutation in these genes may lead to altered targets and resistance
Note also:
qnr gene-mediated target protection leading to Fluoroquinolone resistance
What is the clinical significance of rpoB mutation ?
leading to altered target site for Rifampicin leading resistance.
what are the 7 common examples of target modification mechanism of antimicrobial resistance ?
MRSA - PBP2 in S aureus is changed to low-affinity PBP2a due to mecA or mecC gene.
VRSA/VRE - The target for glycopeptide is changed from D-alanine-D-alanine to low-affinity D-alanine-D-lactate or D-alanine-D-serine. This is van gene mediated.
erm gene mediated methylation of the N(6) position of adenine 2058 in 23S rRNA - this confers resistance to Macrolides, Lincosamide, and Streptogramin.
tetO or tetM gene-mediated Tetracycline resistance. Bacteria produce a ribosomal protection protein that does not allow antibiotics to bind to their targets.
qnr gene-mediated target protection leading to Fluoroquinolone resistance.
gyrA-gyrB and parC-parE genes encode for DNA gyrase and topoisomerase IV, respectively (targets of the fluoroquinolone antibiotics). Mutation in these genes may lead to altered targets and resistance.
rpoB mutation leading to altered target site for Rifampicin leading resistance.
What is responsible gene and mechanism of MRSA?
PBP2 in S aureus is changed to low-affinity PBP2a due to mecA or mecC gene.
What is the mechanism of resistance and gene for VRSA/VRE??
The target for glycopeptide is changed from D-alanine-D-alanine to low-affinity D-alanine-D-lactate or D-alanine-D-serine.
This is van gene mediated.
what are the 3types of Aminoglycoside Modifying Enzymes (AMEs)??
This is the primary mechanism of Aminoglycoside resistance.
3 types of AMEs:
1- Aminoglycoside ACetyl transferase [AAC]
2- adeNyl Transferase [ANT]
3- PHospho transferase [APH].
What are the ESCAPE organisms ?
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.
Ambler Class A inhibitor ?
Boronic acid
Ambler class B inhibitor?
EDTA
Dipicolonic acid
Ampler class C inhibitor?
Cloxacillin
What are the meropenem MIC and zone diameter cut-off for carbapenemases screening?
MIC > 0.125
Zone diameter of <28
Meropenem MIC /zone diameter for enterobacterales ?
for non-meningitis :
MIC 2-8 Zone diameter S >22 R<16
for meningitis : MIC 2-2 Zone diameter S<22 R>22
T/F
AZT is stable to MBLs but not ESBL and Amp C ?
T
T/F
Ceftazidime is stable to Oxa48 but not ESBL and AmpC ?
T
What is the mechanism of isolated meropenem resistance?
is due to an upregulated efflux pump MexAB-OprM or MexEF-OprN.
What is the mechanism of isolated R to imipenem but not to other beta-lactams in PSA ?
it is due to OprD porin loss
what is SME carbapenemase?
This is a carbapenemase specific for Serratia.
SME-1, SME 2, SME-3, etc.
It hydrolyses penicillin, aztreonam, and first-gen cephalosporins in addition to imipenem
Intrinsic R of Morganella morganii?
Amoxicillin
coamoxiclav
ampicillin-sulbactam
1st generation cephalosporin
Tetracycline
polymyxin/colistin
nitrofurantoin
What are the possible mechanisms of R seen in Morganella morganii?
- ESBL
- inducible ampC
- Beta-lactamase hyperproduction (mutations at ampD locus) = leading to R to : amox/coamoxiclav/ampi-sulbactam/1GC/2GC/3GC resistant but sensitive to pip-taz
T/F:
Proteus UTI can be treated with temocillin ?
F
proteus peneri and vulgaris are usaully R to Temocillin
Klebseilla aerogenes has inducible Amp c ?
T
and it has intrinsic R to Coamoxiclav
