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4.2 Medical Microbiology > CPEs > Flashcards

CPEs Flashcards

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USMLE® Step 1 flashcards Biology 101 flashcards
1
Q

Talk about Carbapenems

A

B-lactams with broad spectrum of activity against Gram negative pathogens

Last effective defence against MDR strains e.g. E. Coli or K. pneumoniae

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2
Q

Talk about carbapenemases

A

There are over 2000 classes

Class A: KPC
Class B: metallo B-lactamsases (VIM, NDM, IMP)
Class D: OXA-48 and OXA-181

Genes can be plasmid-located and associated with transposons and integrons - ability to spread

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3
Q

List the big 5

A

KPC
OXA-48
IMP
VIM
NDM

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4
Q

Give some examples of Class A and what do they mediate resistance against

A
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5
Q

What inhibits class A such as KPC

A

Boronic acid and avibactam

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6
Q

Give some examples of Class B and what do they mediate resistance against

A
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7
Q

What inhibits class B such as IMP, NDM and VIM?

A

EDTA and dipicolonic acid

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8
Q

Give some examples of Class C and what do they mediate resistance against

A
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9
Q

What inhibits class C such as CMY

A
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10
Q

Give some examples of Class D and what do they mediate resistance against

A
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11
Q

What inhibits class D such as OXA-48

A

Avibactam

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12
Q

What does KPC stand for?

A

K. pneumoniae carbapenemase

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13
Q

What is KPC, talk about it

A

Most common carbapenemase worldwide
Transposon encoded
Class A
Endemic - worldwide spread
Has spread to Enterobacterales, P. aeruginosa and acinetobacter spp
High mortality 50% or more due to MDR
Mediates resistance to carbapenems, penicillin, cephalosporins and aztreonam

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14
Q

What is KPC found in?

A

Has spread to Enterobacterales, P. aeruginosa and acinetobacter spp

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15
Q

Comment on spread of KPC

A

.

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16
Q

What clone of KPC is responsible for worldwide spread?

A

ST-258

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17
Q

What are KPCs resistant to?

A

Mediates resistance to carbapenems, penicillin, cephalosporins and aztreonam

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18
Q

Mortality of KPC

A

50%

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19
Q

List the Class B: Metallo-B-lactamases were concerned with

A

VIM/IMP

NDM-1 -> New Dehli metallo-B-lactamase 1

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20
Q

Talk about VIM/IMP

A

Class B
51 variants
Integron encoded
Reported worldwide
Spread to Enterobacterales, Pseudomonas and Acinetobacter sp
Death rates between 18 and 67%
High level of production can produce resistance to all carbapenems, penicillins and all cephalosporins
NB: SUSCEPTIBLE TO AZTREONAM

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21
Q

What organisms are VIM/IMP found in?

A

Spread to Enterobacterales, Pseudomonas and Acinetobacter sp

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22
Q

Talk about the spread of VIM/IMP

A
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23
Q

What is the mortality associated with VIM/IMP

A

Pseudomonas and Acinetobacter sp
Death rates between 18 and 67%

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24
Q

What is VIM/IMP resistant against?

A

High level of production can produce resistance to all carbapenems, penicillins and all cephalosporins

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25
Q

What is the telltale sign of a VIM/IMP

A

NB: SUSCEPTIBLE TO AZTREONAM

-> indicator on vitek

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26
Q

Talk about NDM

A

New Dehli metallo-B-lactamase 1
Class B
16 variants
Plasmid-mediated
Originated in New delhi in 2008 but now in 40 countries
Mostly in E. Coli and K. pneumoniae
Major public health concern as it can spread in envirnoment, getting into water etc -> often multiple clones associated in spread
Resistant to carbapenems, penicillins, cephalosporins
Susceptible to aztreonam

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27
Q

How is NDM spread

A

Plasmid mediated

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28
Q

Talk about spread of NDM

A
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29
Q

What is NDM found in

A

E. Coli
K. pneumoniae

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30
Q

What is NDM resistant to

A

Resistant to carbapenems, penicillins, cephalosporins

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31
Q

What is the telltale sign of NDM

A

Susceptible to aztreonam

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32
Q

Talk about OXA-48 type

A

Class D
Many variants e.g. OXA-181 etc
Plasmid and transposon encoded
Originated in Turkey but rapidly spread across Europe
Fastest growing GP in Europe - now endemic in Malta and Turkey
Mortality unknown
Associated with E. Coli and K. pneumoniae
Mediates resistance to carbapenems and first generation cephalosporins
Little activity against broad spectrum cephalosporins or aztreonam
But very difficult to detect so true prevalence understimated

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33
Q

How is OXA spread

A

Plasmid and transposons

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34
Q

How has OXA spread

A
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35
Q

Mortality for OXA

A

Unkown

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36
Q

Associated organisms with OXA

A

E. coli and K, pneumo

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37
Q

Resistance mediated by OXA

A

Mediates resistance to carbapenems and first generation cephalosporins

Little activity against broad spectrum cephalosporins or aztreonam

38
Q

Telltale sign of OXA

A

Little activity against broad spectrum cephalosporins or aztreonam

39
Q

Talk about transmission of carpanemases

A
40
Q

How might you identify an OXA-48

A

May be fully susceptible to cephalosporins unless an ESBL or AMPC also present

41
Q

How would you identify an metallo-B-lactamase producer such as VIM/IMP or NDM

A

Susceptible to aztreonam unless ESBL or AMPC also present

42
Q

What can alter resistance profiles

A
43
Q

What are the problems with identifying carbapenemase producers

A

> > >

44
Q

Other methods of Carbapenemase resistance other than carbapenemases

A
45
Q

Where is intrinsic resistance seen

A
46
Q

Intrinsic

A
47
Q

Loss of porin

A
48
Q

ESBL or AMP C

A
49
Q

Talk about trends in Carbapenem resistance in Europe

A

Resistance increased by more than 50% compared to 2019
ST23-K1 K. pneumoniae rapidly increasing - these are hyper virulent and invasive

50
Q

Talk about trends in Carbapenem resistance in ireland

A

1.5% increase since 2019
Lots of different outbreakd - associated with travel
small outbreaks e.g. oxa-48 in tallagh hsopital k. pneumo

51
Q

List the different outbreaks of CPOs in ireland

A
52
Q

Results from surveillance

A

861 confirmed CPEs in 2022 found through surveillance
88% were colonisation
10% were noninvasive infection
2% were invasive

OXA-48 most common at 73% of all CPEs in Ireland

53
Q

Most common CPE in Ireland?

A

OXA-48

73% in 2022

54
Q

How are CPEs changing in Ireland over the years (2018-2022)

A

OXA-48 increasing by 12%
KPC decreasing by 25%
NDM increasing by 185%
VIM increasing by 200%

55
Q

Public Health Emergency statement

A
56
Q

Importance of detection

A
57
Q

Who are we screening

A
58
Q

How do we identify KPC in the lab

A

Meropenem resistant
Synergy with boronic acid only

= KPC or other class A CPO

59
Q

How do we identify an AmpC CPE

A

Meropenem resistant
Synergy with boronic acid and cloxacillin (a derivative of oxacillin - a penicillin)

= AmpC + porin loss

60
Q

How do we identify an MBL

A

Meropenem resistant
Synergy with dipicolinic acid only

= Metallo-B-lactamase (MBL) e.g. VIM/IMP or NDM

61
Q

How do we identify an OXA-48

A

Meropenem resistant
No synergy with any of the acids
NB: Temocillin resistant

62
Q

Telltale lab ID of OXA-48

A

Temocillin resistant

63
Q

How do we ID a ESBL with porin loss

A

Meropenem resistant
No synergy
Temocillin susceptible

=ESBL plus porin loss

64
Q

What would Mero R but synergy with boronic acid indicate?

A

KPC or another class A CPO

65
Q

What would mero R but synergy with boronic acid and cloxacillin indicate

A

AmpC plus porin loss

66
Q

What would mero R but synergy with dipicolinic acid indicate?

A

MBL such as VIM/IMP or NDM

67
Q

What would Temocillin resistant indicate

A

OXA-48

68
Q

What would Mero resistance but no synergy and temocillin susceptible indicate?

A

ESBL with porin loss

69
Q

How do we select the right carbapenem to use fot testing

A
70
Q

Method used

A
71
Q

List the different methods of detecting CPEs

A

Chromagar and rectal swabs
Combination disk test (Rosco/MAST)
Double disc synergy test
Gradient strip tests e.g. imipenem + imipenem + EDTA
Combination disc tests
Clorimetric tests to detect hydrolysis
MALDI-TOF to detect hydrolysis
Immunochromatographic test to detect carbapenemase antigens
Check Direct CPE
Gene Xpert Carba-R
LightMix modular Kits

72
Q

Talk about the different agars for CPEs

A

Used to screen only as sens poor especially for OXA-48
Brilliance CRE 82% sens
ChromID/Super CARBA >95% sens
-> oxa-48 sens only 30% for both
Split agar combining CARBA with OXA-48 selective agar increases sens to 61% for OXA

73
Q

Talk about the combination disk tests

A

Also known as ROSCO or MAST disks
Comparing meropenem to selective inhibitors to distinguish between carbapenemase ty[es
Confirms CPE if zone size is greated with inhibitor

74
Q

List the Rosco disks

A

Meropenem + boronic acid = KPC
Meropenem + cloxacillin = AmpC
Meropenem + dipicolonic acid = IMP, NDM, VIM
Temocillin = R = Oxa48

75
Q

What will the Rosco discs be labelled as

A

MRP10 = meropenem
MRPBO = mero + boronic acid
MRPDP = mero + dipicolonic acid
MRPCX = mero + cloxacillin
TEMOC = temocillin 30ug

76
Q

Talk about the gradient strips for CPEs

A

Imipenem on one end
Imipenem plus EDTA on other end

Any synergy = positive

77
Q

For the inhibitor combination disc test what is used

A

Carbapenem only
Carbapenem + MBL inhibitor
Carbapenem + KPC inhibitor
Carbapenem + AMPC inhibitor

78
Q

What are the pros of inhibitor based tests for CPEs

A

Cheap
easy to perform
Most extensively evaluated - recommended by eucast for labs without special expertise in B-lactamase detection

79
Q

What are the cons of inhibitor based tests

A

Some MBL inhibitors such as EDTA act non-sepcifically -> will inhibit other CPEs
Can lack sens if enzyme expressed at low levels
Difficult to interpret if multiple resistance mechanisms are present
We have no inhibitor for OXA-48
Overnight incubation required

80
Q

List some of the colorimetric tests for CPEs

A

CarbaNP and Blue-Carba test
B CARBA test

81
Q

What are the pros and cons of colorimetric tests for CPEs

A

Results in less than 2 hours
Good sens and spec
Subjective interpretation based on colour
False negatives with mucoud strains and some enzymes -> K. pneumo
Not all primary culture medium works with test

82
Q

Talk about MALDI to detect CPEs, pros and cons

A

Detects hydrolysis
Uses Bruker MBT STAR Carba IVD kit and software
Pick colonies and resuspend in antibiotic solution then inc for 3 hours
Can be done on isolates and blood/urine
Not for in house as will have to change MALDI settings
Issues with detecting some enzymes

83
Q

Talk about immunochromatographic tests for CPEs

A

Detect carbapenemase antigens
RESIST-4: KPC, OXA48, NDM, VIM
CARBA 5: KPC, OXA-48, NDM, VIM, IMP
Excellent sens and spec from colonies and spiked blood cultures
Results in 15 mins
some issues with false negatives

84
Q

Talk about check direct for CPEs

A

Identifies CPE carriers directly from rectal swabs or cultures in 2 hours
Detects clinically prevalent carbapenemases (IMP excluded)
More sensitive then culture

85
Q

Talk about GeneXpert Cepheid Carba-R for CPE

A

Rectal swabs
All 5 CPEs
High sens, spec, ppv, npc all over 95%
accurate and rapid with less than 5 mins hands on time
55 euros per test

86
Q

Talk about the LightMix for CPEs

A

Uses LightCycler
Direct detection of colonised patients
Used in mater
Rectal swabs or blood cultures
99% sens, 100% spec
TAT about 2 hours
Only ran in batches though
Very cheap only 14 euros per test

87
Q

Clinical implications for CPEs

A

Public health threat

Community

Random outbreaks

High mortality

Carriage linked to infection

Rapid dissemination through mobile genetic determinants

prevention reliant on early active surveillance

Can be difficult to distinguish - special screening methods needed

88
Q

Talk about the general mortality with CPEs

A

x3-x6 times higher with CRE infection

mortality between 30 and 75%

65% of CRE BSIs

Delays in treatment or treatment unavailable

89
Q

Talk about CPE carriage and infection link

A

17% carriage overall but 90% linked to infection

90
Q
A

4.2 Medical Microbiology (12 decks)

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