Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

4.2 Medical Microbiology > CPEs - Resistance Mechanisms > Flashcards

CPEs - Resistance Mechanisms Flashcards

1
Q

Talk about Carbapenems

NB: theres a good piece on the clinical significance at the end of the lecture

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the big 5

A

KPC
OXA-48
IMP
VIM
NDM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

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

A

KPC

Resistance against penicillins, cephalosporins, carbapenems and aztreonam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What inhibits class A such as KPC

A

Boronic acid and avibactam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

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

A

VIM
NDM
IMP

Resistant agains all B lactams but aztreonam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

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

A

EDTA and dipicolonic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

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

A

CMY -> not noe of big five

Penicillins, cephalosporins and aztreonam -> not reistant to carbapenems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What inhibits class C such as CMY

A

Cloxacillin
Borionic acid
Avibactam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A

All the OXAs, 48, 23, 51, 24, 58 etc

Resistance to penicillins, cephalosporins, carbapenems and aztreonam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What inhibits class D such as OXA-48

A

Avibactam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does KPC stand for?

A

K. pneumoniae carbapenemase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is KPC found in?

A

Initially found in K. pneumoniae

Has spread to Enterobacterales, P. aeruginosa and acinetobacter spp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Comment on spread of KPC

A

First reported in USA in 1996 but now worldwide spread

First isolate in Greece in 2007 now spread to most acute-care facilities within 2 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What clone of KPC is responsible for worldwide spread?

A

ST-258

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are KPCs resistant to?

A

Mediates resistance to carbapenems, penicillin, cephalosporins and aztreonam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Mortality of KPC

A

50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

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

A

VIM/IMP

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What organisms are VIM/IMP found in?

A

Spread to Enterobacterales, Pseudomonas and Acinetobacter sp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Talk about the spread of VIM/IMP

A

Discovered in Japan in 1990s now reported worldwide

Higher prevalence in southern Europe and Asia

Spread to many Enterobacterales, Pseudomonas and Acinetobacter species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the mortality associated with VIM/IMP

A

Pseudomonas and Acinetobacter sp
Death rates between 18 and 67%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is VIM/IMP resistant against?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the telltale sign of a VIM/IMP
NB: SUSCEPTIBLE TO AZTREONAM -> indicator on vitek
26
Talk about NDM
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
27
How is NDM spread
Plasmid mediated
28
Talk about spread of NDM
Originally in New Dehli in 2008 Now in 40 countries Hotspots in India and Pakistan Common in UK Outbreak in 2019 in Tuscany of 227 cases Mostly in E. coli and K. pneumoniae
29
What is NDM found in
E. Coli K. pneumoniae
30
What is NDM resistant to
Resistant to carbapenems, penicillins, cephalosporins
31
What is the telltale sign of NDM
Susceptible to aztreonam
32
Talk about OXA-48 type
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
33
How is OXA spread
Plasmid and transposons
34
How has OXA spread
Oringially from turkey reports alarmingly increasing in europe Fastest growing CP in Europe Endemic in malta and turkey Associated with E. coli and K. pneumo
35
Mortality for OXA
Unkown
36
Associated organisms with OXA
E. coli and K, pneumo
37
Resistance mediated by OXA
Mediates resistance to carbapenems and first generation cephalosporins Little activity against broad spectrum cephalosporins or aztreonam
38
Telltale sign of OXA
Little activity against broad spectrum cephalosporins or aztreonam
39
Talk about transmission of carpanemases
CP enzyme carried on mobile genetic elements such as plasmids or transpons HGT -> sharing of plasmid amongst gut flora NB in infection control Confers resistance to multiple organims, limiting treatment
40
How might you identify an OXA-48
May be fully susceptible to cephalosporins unless an ESBL or AMPC also present
41
How would you identify an metallo-B-lactamase producer such as VIM/IMP or NDM
Susceptible to aztreonam unless ESBL or AMPC also present
42
What are the resistance profiles of CPEs
They all hydrolyse penicillins, most cephalosponrsins and some carbapenems and aztreonam - depends on group OXA-48 CPs may be fully susceptible to cephalosporins unless also an ESBL or AmpC MBLs are suscpetible to aztreonam unless ESBL or AMPC However resistance phenotype can vary depending on the level of expression and association with other resistance methods e.g. effllux or permeability - MDR etc
43
What are the problems with identifying carbapenemase producers
Not all CP producers are resistant to carbapanems ESBLs/AmpC + porin loss can appear like a CP producer but isnt actually (CPOs vs CREs)
44
Other methods of Carbapenemase resistance other than carbapenemases
Intrinsic resistance to CPs Intrinsic Carbapenemases Loss of porin and/or efflux ESBL or AmpC + impermeability
45
Where is intrinsic resistance seen
Non-fermenters resistant to ertapenem only Serratia species and proteeae -> poor susceptibility to imipenem
46
Intrinsic carbapenemase
Stenotrophomonas maltophilia Aeromonas spp Acinetobacter baumannii
47
Loss of porin and/or efflux
P.aeruginosa
48
ESBL or AMP C + impermeability
Mostly Enterobacter and Klebseilla Rarely in E. coli
49
Talk about trends in Carbapenem resistance in Europe
Resistance increased by more than 50% compared to 2019 ST23-K1 K. pneumoniae rapidly increasing - these are hyper virulent and invasive
50
Talk about trends in Carbapenem resistance in ireland
1.5% increase since 2019 Lots of different outbreakd - associated with travel small outbreaks e.g. oxa-48 in tallagh hsopital k. pneumo
51
List the different outbreaks of CPOs in ireland - from beginning to 2022
2022: 26 outbreaks of CPE in healtchare - all OXA-48 2016-2017 largest outbreak in Dublin (OXA-48 >180 cases in 1 year) 2016 small outbreaks of VIM in mayo and NDM in waterford 2012-2016 -> regional spread, rise in CPE cases in general 2011: OXA-48 K. pneumoniae in Dublin - 12 patients 2011: first outbreak (KPC) in two hospitals, 9 patients in the midwest 2009: first sporadic CPE cases in Ireland - most linked to travel - KPC, VIM, NDM
52
Results from surveillance
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
Most common CPE in Ireland?
OXA-48 73% in 2022
54
How are CPEs changing in Ireland over the years (2018-2022)
OXA-48 increasing by 12% KPC decreasing by 25% NDM increasing by 185% VIM increasing by 200%
55
Public Health Emergency statement
Minister Harris addressed CPE in 2017
56
Importance of detection
Need a catch all method - diversity of enzymes, variation, expression etc, no ideal indicator Have to screen, confirm and characterise CRE producers Distinguish from AmpC b -lactamases
57
Who are we screening
ICU Haematology/oncology/transplant renal dialysis transfers previoius cpe or contact with cpe
58
How do we identify KPC in the lab
Meropenem resistant Synergy with boronic acid only = KPC or other class A CPO
59
How do we identify an AmpC CPE
Meropenem resistant Synergy with boronic acid and cloxacillin (a derivative of oxacillin - a penicillin) = AmpC + porin loss
60
How do we identify an MBL
Meropenem resistant Synergy with dipicolinic acid only = Metallo-B-lactamase (MBL) e.g. VIM/IMP or NDM
61
How do we identify an OXA-48
Meropenem resistant No synergy with any of the acids NB: Temocillin resistant
62
Telltale lab ID of OXA-48
Temocillin resistant
63
How do we ID a ESBL with porin loss
Meropenem resistant No synergy Temocillin susceptible =ESBL plus porin loss
64
What would Mero R but synergy with boronic acid indicate?
KPC or another class A CPO
65
What would mero R but synergy with boronic acid and cloxacillin indicate
AmpC plus porin loss
66
What would mero R but synergy with dipicolinic acid indicate?
MBL such as VIM/IMP or NDM
67
What would Temocillin resistant indicate
OXA-48
68
What would Mero resistance but no synergy and temocillin susceptible indicate?
ESBL with porin loss
69
How do we select the right carbapenem to use fot testing
use of eucast defined screening cut offs Meropenem and ertapanem are used - poor sensitivity with imipenem so its not used
70
Method used
need a method that will catch all
71
List the different methods of detecting CPEs
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
Talk about the different agars for CPEs
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
Talk about the combination disk tests
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
List the Rosco disks
Meropenem + boronic acid = KPC Meropenem + cloxacillin = AmpC Meropenem + dipicolonic acid = IMP, NDM, VIM Temocillin = R = Oxa48
75
What will the Rosco discs be labelled as
MRP10 = meropenem MRPBO = mero + boronic acid MRPDP = mero + dipicolonic acid MRPCX = mero + cloxacillin TEMOC = temocillin 30ug
76
Talk about the gradient strips for CPEs
Imipenem on one end Imipenem plus EDTA on other end Any synergy = positive
77
For the inhibitor combination disc test what is used
Carbapenem only Carbapenem + MBL inhibitor Carbapenem + KPC inhibitor Carbapenem + AMPC inhibitor
78
What are the pros of inhibitor based tests for CPEs
Cheap easy to perform Most extensively evaluated - recommended by eucast for labs without special expertise in B-lactamase detection
79
What are the cons of inhibitor based tests
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
List some of the colorimetric tests for CPEs
CarbaNP and Blue-Carba test B CARBA test
81
What are the pros and cons of colorimetric tests for CPEs
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
Talk about MALDI to detect CPEs, pros and cons
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
Talk about immunochromatographic tests for CPEs
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
Talk about check direct for CPEs
Identifies CPE carriers directly from rectal swabs or cultures in 2 hours Detects clinically prevalent carbapenemases (IMP excluded) More sensitive then culture
85
Talk about GeneXpert Cepheid Carba-R for CPE
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
Talk about the LightMix for CPEs
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
Clinical implications for CPEs
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
Talk about the general mortality with CPEs
x3-x6 times higher with CRE infection mortality between 30 and 75% 65% of CRE BSIs Delays in treatment or treatment unavailable
89
Talk about CPE carriage and infection link
17% carriage overall but 90% linked to infection
90

4.2 Medical Microbiology (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions