Antimicrobial resistance

Question 1

T/F:

VISA uses the same mechanism VRSA?

Answer 1

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

Question 2

What are the commonest porin loss gens ?

Answer 2

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.

Question 3

What are the 6 families of Bacterial drug efflux pumps?

Answer 3

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

Question 4

What is the clinical importance of MefA and MefE genes?

Answer 4

MefA and MefE are associated with Macrolide resistance in:
1- Strep pneumoniae
2- group A Streptococcus

Question 5

What is the clinical significance of :
1- gyrA- gyrB encode for DNA gyrase and :
2- parC- parE genes encode for topoisomerase IV?

Answer 5

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

Question 6

What is the clinical significance of rpoB mutation ?

Answer 6

leading to altered target site for Rifampicin leading resistance.

Question 7

what are the 7 common examples of target modification mechanism of antimicrobial resistance ?

Answer 7

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.

Question 8

What is responsible gene and mechanism of MRSA?

Answer 8

PBP2 in S aureus is changed to low-affinity PBP2a due to mecA or mecC gene.

Question 9

What is the mechanism of resistance and gene for VRSA/VRE??

Answer 9

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.

Question 10

what are the 3types of Aminoglycoside Modifying Enzymes (AMEs)??

Answer 10

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].

Question 11

What are the ESCAPE organisms ?

Answer 11

Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.

Question 12

Ambler Class A inhibitor ?

Answer 12

Boronic acid

Question 13

Ambler class B inhibitor?

Answer 13

EDTA
Dipicolonic acid

Question 14

Ampler class C inhibitor?

Answer 14

Cloxacillin

Question 15

What are the meropenem MIC and zone diameter cut-off for carbapenemases screening?

Answer 15

MIC > 0.125
Zone diameter of <28

Question 16

Meropenem MIC /zone diameter for enterobacterales ?

Answer 16

for non-meningitis :
MIC 2-8 Zone diameter S >22 R<16

for meningitis : MIC 2-2 Zone diameter S<22 R>22

Question 17

T/F

AZT is stable to MBLs but not ESBL and Amp C ?

Answer 17

T

Question 18

T/F

Ceftazidime is stable to Oxa48 but not ESBL and AmpC ?

Answer 18

T

Question 19

What is the mechanism of isolated meropenem resistance?

Answer 19

is due to an upregulated efflux pump MexAB-OprM or MexEF-OprN.

Question 20

What is the mechanism of isolated R to imipenem but not to other beta-lactams in PSA ?

Answer 20

it is due to OprD porin loss

Question 22

what is SME carbapenemase?

Answer 22

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

Question 23

Intrinsic R of Morganella morganii?

Answer 23

Amoxicillin
coamoxiclav
ampicillin-sulbactam
1st generation cephalosporin
Tetracycline
polymyxin/colistin
nitrofurantoin

Question 24

What are the possible mechanisms of R seen in Morganella morganii?

Answer 24

• 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

Question 25

T/F: Proteus UTI can be treated with temocillin ?

Answer 25

F proteus peneri and vulgaris are usaully R to Temocillin

Question 26

Klebseilla aerogenes has inducible Amp c ?

Answer 26

T and it has intrinsic R to Coamoxiclav

Question 27

What are the 2 membrane ass betalactamase enzymes that produced by Moraxella catarrhalis?

Answer 27

BRO-1 and BRO-2 Can hydrolyze penicillin, ampicillin, methicillin, and cefaclor

Question 28

What is Synercid ?

Answer 28

#It is a combination of quinupristin-dalfopristin #A semisynthetic streptogramin #Works by inhibiting protein synthesis #Can be used to treat SSTI with MRSA, GAS or VRE

Question 29

T/F: Enterococcus gallinarum and casseliflavus are intrinsically resistant to vancomycin.

Answer 29

T

Question 30

What is the Enterococcus Van gene-mediated resistance?

Answer 30

It converts D-Alanine-D-Alanine (D-Ala-D-Ala) to either: 1- D-Alanine-D-Lactate (D-Ala-D-Lac) or 2- D- Alanine-D-Serine (D-Ala-D-Ser).

Question 31

What is the gene responsable about ESBL type R in Shigella spp?

Answer 31

blaCTX-M-15

Question 32

Aeromonas intrinsic R to which Abx?

Answer 32

Amoxicillin ampicillin ampicillin-sulbactam

Question 33

What are teh 5 resistence mechanisms in sten mal?

Answer 33

1- L1 metalo-beta-lactamase: Resistance to penicillin, cephalosporin, and carbapenems (but not Aztreonam) 2- L2 serine beta-lactamase - Extended cephalosporinase activity and ability to hydrolyse aztreonam 3-Chromosomal acyl-transferase enzyme - intrinsic resistance to aminoglycoside 4-Multidrug efflux pump - resistance to tetracycline and fluoroquinolone 5-Chromosomal Smqnr gene - resistance to fluoroquinolone

Question 35

What are the Unusual resistance patterns in PSA that if present indicate sending the isolate to AMRHAI?

Answer 35

1. Resistance to ALL of imipenem, meropenem, ceftazidime and piperacillin/tazobactam and exhibiting strong imipenem/EDTA synergy (irrespective of susceptibility to aztreonam) 2. Ceftolozane/tazobactam resistance (MIC >2 mg/L) 3. Colisting resistance by broth microdilution.

Question 36

make a panel for sensitivity test of a PSA spp?

Answer 36

- Panel 1: Pip-taz, ciprofloxacin, meropenem, ceftazidime, aztreonam, amikacin - Panel 2: Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, tobramycin - Broth microdilution (if required) - Colistin

Question 37

What is MDS PSA ?

Answer 37

Defined as P. aeruginosa not susceptible to at least one antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility is generally expected: -penicillins -cephalosporins -fluoroquinolones -aminoglycosides -carbapenems

Question 38

What is DTR PSA ?

Answer 38

DTR (Difficult to Treat) is defined as P. aeruginosa exhibiting non-susceptibility to all of the following: -piperacillin-tazobactam -ceftazidime -cefepime -aztreonam -meropenem -imipenem-cilastatin -ciprofloxacin -levofloxacin

Question 40

What is the Multidrug-Resistant Acinetobacter baumannii (MDRAB)?

Answer 40

MDRAB are - Acinetobacter baumannii susceptible to two or fewer of: 1-meropenem or imipenem 2-(third-generation cephalosporins) 3- piperacillin/tazobactam 4-(tigecycline) 5-aminoglycosides 6-quinolones 7- cotrimoxazole 8-colistin where agents in brackets lack EUCAST breakpoints.