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4.2 Medical Microbiology > AMPC and ESBLs > Flashcards

AMPC and ESBLs Flashcards

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USMLE® Step 1 flashcards Biology 101 flashcards
1
Q

What are our ESKAPEE organisms?

A

E. faecium
S. aureus
Klebsiella
Acinetobacter
Pseudomonas
Enterobacter
E. Coli

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2
Q

In general what resistance are we concerned with in gram negatives

A

B-lactamase mediated resistance emerging at an alarming rate

Increased resistance to aminoglycosides and quinolones

MDR GNBs becoming an epidemic public health threat

Clonal spread of resistant phenotypes e.g. epidemic strains of E. coli and klebsiella

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3
Q

Talk about B-lactamase mediated resistance in GNBs

A

ESBLs -> transferable resistance seen in Klebsiella pneumonia and E. coli

Chromosomal AmpC -> E.cloacae, C. fredii, S. marcescens, P. aeruginosa and M. morganii

Plasmid mediated AmpC -> transfers resistance

CPE - ‘Big 5’ -> P. aeruginosa, Enterobacterales

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4
Q

Give the common different resistance mechhanisms in GNBs

A

Porin reduction to decrease permeability

Broad-specificity efflux pumps

Beta-lactamase enzymes

Target site modification - Beta-lactam-insensitive cell-wall transpeptidases

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5
Q

What are the different classifications of B-lactamases?

A

Bush system - Functional classification

Ambler system - Structural classification

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6
Q

Talk about the Bush system of classifying b-lactamases

A

Divided into 4 primary class (1-4) based on functionality

Not really used anymore as organisms could gain mutations which would result in them changing classes

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7
Q

Talk abut the Ambler system

A

Categorised into 4 molecular groups A to D
Offers stability against mutations that may influence enzyme activity

The majority of clinically significant B-lactanases re found in Ambler A and C

This system is used over the Bush system nowadays as these are more stable categories

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8
Q

What are the Ambler class A?

A

Serine beta-lactamases
Works on penicillins, early cephalosporins with ESBLs working on 3rd generation cephalosporins
Inhibited by clavulanate
Examples include ESBLs and carbapenemases such as KPC

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9
Q

Talk about Ambler class B

A

.

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10
Q

Talk about Ambler class C

A

b

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11
Q

Talk about Ambler class D

A

.

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12
Q

What is the mechanism in AmpC B-lactamases

A

A type of Class C, Group 1
They are typically chromosomally encoded but can also be plasmid-mediated -> therefore less likely to see transmission
AmpC enzymes hydrolyse penicillins and cephalopsorins including many third gens

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13
Q

What is the resistance spectrum of AmpC B-Lactamases

A

Active against penicillins, cephalosporins (including cephamycins like cefoxitin) and monobactams

Not inhibited by clavulanic acid but may be inhibited by substances like boronic acids or cloxacillin

Resistant to third-generation cephalosporins like ceftriazone and cefotaxime but are less susceptible to B-lactamase inhibitors

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14
Q

What are the most common AmpC organisms

A

Enterobacterales like Enterobacter spp, Citrobacte freundii, Serratia marcescens and Pseudomonas aeruginosa

Also seen in plasmid-mediated forms in E. coli and Klebsiella species

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15
Q

Talk about the clinical relevance of AmpC B-lactamases, how do we detect it

A

Resistance can emerge via the induction or depression of chromosomal AmpC genes
Use of cefoxitin or cefepime in testing can help identify AmpC producers

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16
Q

Talk about Extended-Spectrum B-lactamases

A

ESBLs are an Ambler clas A B-lactamases

ESBLs are a major public health threat associated with significant morbifity, mortality and increased healthcare cosrs

They hydrolyse most penicillins and cephalosporins including cefuroxime and 3rd and 4th generation cephalosporins

Have no activity on cephamycins or carbapenems

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17
Q

What is the resistance profile of ESBLs

A

Resistant to most penicillins and cephalosporins e.g. cefuroxime, cefotaxime, ceftrazidime and ceftriaxone also aztreonam

No activity against carbapenems or cephamycins such as efoxitin and cefotetan

Inhibited by clavulanic acid, sulboactam and tazobactam

Level of expression nad presence of other mechanisms such as AMP C leads to a variety of resistance phenotypes

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18
Q

What do ESBLs have no activity against?

A

No activity against carbapenems or cephamycins such as efoxitin and cefotetan

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19
Q

What is ESBL inhibited by

A

Inhibited by clavulanic acid, sulboactam and tazobactam

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20
Q

What are some of the different mutants of ESBLs

A

TEM and SHV

CTX-Ms such as CTX-M-15

OXA

VEB

PER

GES

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21
Q

Talk about TEM and SHV mutants, how did the originate

A

Original ESBLs

Mainly drive resistance in healtchare

Arose form mutations in the parent beta-lactamases found in Escherichia coli (TEM) and Klebsiella pneumonia (SHV)

22
Q

What is the mechnism of TEM and SHV ESBLs

A

Mutations in the TEM and SHV genes typicaly result in the substitution of specific amino acids in the beta-lactamase active site, allowing these enzymes to break down a broader range of beta-lactam antibiotics

Ability to hydrolyse exended-spectrum penicillins and 3r and 4th generation cephalosporins

23
Q

Talk about CTX-Ms

A

Dominant ESBL enzymes globally
Resistance in both hospitals and CA infection
Widespread in common pathogens such as:
- E. Coli - most frequent carrier in community infections
- Klebsiella pneumoniae - especially in healthcare-associated infections
Resistance is spread due to plasmid-mediated mobility facilitating horizontal gene transfer

24
Q

Spectrum of CTX-Ms

A

They hhydrolyse third generation cephalosporins e.g. cefotaxime and ceftriaxone

25
Q

How do we detect CTX-Ms

A

Resistant to cefotaxime (marker)

Will also be resistant to ceftriaxone

26
Q

Talk about the mechanism of resistance in CTX-Ms

A

CTX-M genes encoded on plasmids and often co-locate with resistance genes for other antibiotic classes such as aminoglycosides or fluoroquinolones

Mobility of genes allows rapid dissemination across species and geographical boundaries - hence widespread
Mobility also allows co-resistance - MDR through linkage with other resistance determinants

27
Q

What is the most prevalent CTX-M ESBL vaiant?

A

CTX-M-15

global variant - known for its efficient dissemination

28
Q

Talk about the OXA variant of ESBL

A

A type of Class D organism

Primarily oxacillin-hydrolysing enzymes, associated with carbapenem resistance

29
Q

Talk about the VEB, PER variants of ESBLs

A

ESBLs found occasionally in Pseudomonas or Acinetobacter

30
Q

Talk about the GES variant of ESBLs

A

A rare group that can confer resistance to carbapenems in addition to cephalosporins

31
Q

Talk about rates of ESBL E. Coli in Europe

A

Decrease of 3.6% compared to 2019
Ireland consisent at 10% seen over last 5 years
Bulgaria at 40%

32
Q

Talk about 3rd generation cephalosporin resistant KLPN in europe

A

34.8% on average
Bulgaria at 80%

33
Q

How can you distinguish a TEM and SHV ESBL from a CTX-M ESBL

A

TEM and SHV are resistant to ceftazidine but variable to cefotaxime
CTX-M are resistant to cefotaxme but variable to ceftazidine

34
Q

What should you do with a positive ESBL

A

Must distinguish an ESBL from:
- AmpC B-lactamase
- Carbapenem hydolysing B-lactamase

35
Q

How would you screen or an ESBL

A

Put up against cefotaxime and ceftazidine -> if resistant to one or both = ESBL

If AmpC ESBL confirm with cefepime +/- clavulanic acid

If ESBL variant confirm with ceftazidime and cefotaxime +/- clavulanic acid -> if intermediate query AmpC and test accordingly

36
Q

What combination of antibiotics are used fr ESBLs

A

Cefotaxime or ceftriaxone AND ceftrazidime or cefpodoxime

37
Q

Talk about agar for ESBLs

A

ESBL chromagars are available for use with rectal swabs
- Chromagar 98% sens, 72% spec
- ChromID 98% sens, 73% spec
- Brilliance 99% sens, 58% spec

No medium is fully ESBL selective though - derepressed AmpC B-lactamase and P. aeruginosa
Complementary tests needed to confirm

38
Q

What is the marker of all ESBLS

A

Cefpodoxime resistance seen in all ESBLs but low level resistance is common ni the absence of ESBLs

Cefpodoxime most sensitive individual indicator but lacks specificity -> combination of cefotaxime and ceftrazidime allows for better specificty

39
Q

What is the marker for TEM and SHV

A

Ceftazidime resistance

40
Q

What is the marker for CTX-M resistance

A

Cefotaxime resistance

41
Q

What is the molecular detection method for ESBLs

A

Check-Direc ESBL

42
Q

Talk about Check Direct for ESBLs

A

Can identify ESBLs directly from rectal swabs in 2 hours
Covers clinically prevalent ESBLs: CTX-M-1, CTX-M-2, CTX-M-9 and SHV
Early studies show good performanc and greated sensitivity then culture

Detects 80 CTX-M, 160 TEM, 110 SHV variants

43
Q

What are some of the common confirmatory tests for ESBLS

A

Combinaion disk test
Double-disk synergy test
Gradient strips

44
Q

Talk about the combination disk test for ESBLs

A

Ceftazidime + ceftazidime + clavlanic acid

Cefotoxime + cefotozime + clavulanic acid

Cefepime + clavulanic acid or AmpC inhibitor to detect AmpC activity

> 5mm increase in zone indicates an ESBL

45
Q

Talk about double-disk synergy test

A

Expansion of indicator cephalosporin inhibition zon towards amox/clav (augmentin) disk -> augmentin and cefodoxime

Disk spacing is critical -> may be reduced or expaned for strains with high or low level of resistance

Either use of cefepime disc or add clox to agar for AmpC producers

46
Q

Talk about gradient strips for ESBLs

A

Double ended strip - cephalosporin + cephalosporin + clav

> 8 fold reduction in MIC = ESBL
Phantom zone in middle = ESBL
Deformed ellipse = ESBL

Non determinable could be due to AmpC activity - should test cefepime/clav

47
Q

What are the pros and cons of each ESBL confirmatory method?

A

Double disc test: cheap but best disc spacing varies with strain
Combination disc test: cheap, does not require critical spacing, sensitive and specific but batch variation and negative controls critical
Gradiant strip: sensitive, accurate, internally controlled, mor epensivr

48
Q

What bacteria do we not screen for ESBLs for

A

Theres no test developed for Acinetobacter spo and P. aeruginosa

Stenotrophomas maltophilia also causes false positives

49
Q

Why can we not ESBL screen for acinetobacter

A

Acinetobacter spp is often susceptible to clavulanate alone

50
Q

Why do we not have an ESBL screen for P. aeruginosa

A

ESBLs are not common in these and should not be sought routinely

ESBL should only be considered in ceftolozane/tazobactam resistant isolates

51
Q

Why do we not have an ESBL screen for Stenotrophomonas?

A

S. matlophilia can cause positive results due to inhibition of L-2 chromosomal B-lactamase ubiquious in the species

4.2 Medical Microbiology (12 decks)

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