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4.2 Medical Microbiology > Non-Fermenters Resistance Mechanisms > Flashcards

Non-Fermenters Resistance Mechanisms Flashcards

1
Q

What NFOs are we concerned with?

A

Acinetobacter baumannii
Pseudomonas aeruginosa
Stenotrophomas maltophilia

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2
Q

NFO MDR associated with what classes

A

Aminoglycosides - vancomycin
Fluoroquinolones
Carbapenems

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3
Q

Talk about MDR P. aeruginosa

A

Major HCA worldwide pathogen
Relative resistance varies globally but high in USA -> unknown for IE and UK yet
Resistant to ciprofloxacin and levofloxacin (fluoros)
Listed under serious threat list on CDC
Mortality up to 60%

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4
Q

Talk about MDR PA in USA

A

1’ cause of VAP in long term acutre care hospitals and hospital wards
2’ cause of VAP in ICU
3’ cause of catheter related UTI

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5
Q

What is the rate of MDR PA in USA

A

Between 10-30%

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6
Q

What is MDR-PA resistant to

A

Fluoroquinolones such as ciprofloxacin and levofloxacin

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7
Q

Mortality of MDR-PA

A

up to 60%

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8
Q

Mechanisms of carbapenem resistance in PA

A

Plasmid or integron mediated -> Class B or class A (class D rare)

increased expression of efflux systems

Reduced porin expression

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9
Q

Talk about plasmid or integron mediated carbapenemases in a class B P. aeruginosa

A

Most clinically important for PA
Metallo-beta lactamases such as IMP or VIM most comon
Genes are found as gene cassettes in integrons and are thus transferrable
IMP and VIM have spread globally

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10
Q

What is IMP active on

A

Imipenem

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11
Q

What is VIM

A

Verona integron encoded MBL

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12
Q

Talk about plasmid or integron mediated carbapenemases in class A PA

A

KPC in P. aeruginosa
First reported in colombia
Hasnt spread outside latin america
Enzymes include GES and IBC which have carbapenemase activity which become clinically important when combined with either diminished outer membrane permeability or efflux over expression

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13
Q

What is GES in KPC

A

Guiana extended spectrum
GES-2 P. aeruginosa has been reported in south africa

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14
Q

What is IBC in KPC

A

Integron-borne cefalosporinase
Has been reported in P. aeruginosa in greece

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15
Q

Talk about plasmid or integron mediated carbapenemases in class D PA

A

Class D such as OXA-198 are rare in P. aeruginosa

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16
Q

Increased expression of efflux systems in MDR P. aeurginosa

A

overexpression of the MexAB-OprM efflux pump

confers resistance to most beta-lactam drugs with the exception of imipenem

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17
Q

Spread of CR PA

A

Highest in USA
In Europe highest rate in Greece >50% and other Eastern european countries
Ireland only 6.6%

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18
Q

Distribution of CR.PA across the world

A

ireland = 6.6% which is 25/29 in euroope

highest proportions are in eastern europe

greece>50%

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19
Q

Epidemiology of PA infections

A

Number of invasive PA decreasing from by 8% between 2022 and 2023. However 5 year trend is stationary

Carbapenem resistance has decreased from 8.6% in 2022 to 6.6% in 2023. Stationary 5 year trend

MDR has decreased from 5.5% in 2022 to 4.3% in 2023. However slight increase in notifications over 5 year period.

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20
Q

Talk about A. baumannii

A

Opportunistic pathogen that causes HAI worldwide
Hospitalised and immunocompromised patients are at higher risk as it can penetrate through skin and airway defects
Most commonly detected in ICU
Treatment often hampered by MDR
High mortality with infection

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21
Q

Talk about Carbapenem resistant A. baumanii

A

Known as CRAB
A priority 1 critical pathogen according to WHO 2017
Responsible for most of the HCAI caused by Acinetobacter spp
Very few treatments effective
Ventilated, ICU and catheterised at high risk
Bacteria have genetically evolved to protect themselves from carbapenems

22
Q

How does A. baumannii present in the community?

A

Increasingly recongnised as an uncommon but important cause of CA pneumonia

Most reported cases in those with underlying conditions

High incidence of bacteraemia

High mortality ranging from 40 to 64%

Colonisation also seen

23
Q

What is the mortality associated with A. baumannii

A

High mortality ranging from 40 to 64% if BSI occurs

24
Q

Talk about MDR A. baumanii

A

Most infections are MDR strains in ICU
Resistance to carbapenems, Fluroquinolones, Aminoglycosides
Tranposons, plasmids or integrons, resistant cassettes have a major role in acquisition of resistance and dissemination of MDR strain

25
Q

Resistance in MDR A. baumannii

A

Resistance to carbapenems, Fluroquinolones, Aminoglycosides

26
Q

Mechanisms of resistance in A. baumannii

A

Antibiotic modifyin enzymes
Efflux pumps
Porins
Drug targets
Aminoglycoside modifying enzymes (AMEs)
AmpC = Ambler class C cephalosporinases
ESBLs
MBLs - CPO
LPS = lipopolysaccharide
Penicillin binding protein

27
Q

List the 4 mechanisms of carbapenem resistance in A. baumannii

A

Enzymatic modification of antibiotics
Modification in membrane permeability
Altered penicillin-binding proteins
Efflux pumps

28
Q

Enzymatic modification of antibiotics in carbapenem resistant A. baumanii

A

Oxacillinase (OXA B-lactamases)
-> Class D
-> OXA 23/24/51/58/143

Metallo-B-lactamases (MBLs)
-> class C
-> NDM-1 commonly founf in CRAB after OXA-23

KPC
-> class A
-> very few ever found -> KPC-2 and KPC3

29
Q

modification in membrane permeability in carbapenem resistant A. baumanii

A

modified porin chanels
Reduced expression of porins like Omp22-36, omp33-36, omp37, omp44, onp47 etc

30
Q

altered penicillin-binding proteins in carbapenem resistant A. baumanii

A

overexpression of pbps resulting in imipenem resistance

31
Q

efflux pumpss in carbapenem resistant A. baumanii

A

4 class associated with CRABs
- MFS = major facillitator superfamily
- RND = resistance nodulation division superfamily
- MATE = multidrug and toxic compound extrusion
- SMR = small multidrug resistance family transporters

32
Q

MATE efflux pumps

A

AbeM efflux pump and Emr-AB-TolC efflux pump convey resistance against imipene,

adeABC effluxs carbapenems out of cytoplasm

33
Q

Epidemiology of CRAB

A

Increasing all across the world particularly in Asia

Pathogen of urgent priority by WHO -> ever since notifications rapidly increasing

> 70% in Asia, Latin America and middle east

50% in American regions

Relative frequency varies greatly 0% in Ireland but 96% in Croatia

34
Q

Carbapenem resistance in Irealnd

A

71 cases of Acinetobacter species in ireland in 2023

0% of these were Carb resistant

35
Q

Why is CRAB cirtical

A

Major problem in Eastern and Southern Europe
9 countries have proportions >50%
WHO has listed these as a critical priority

36
Q

Epidemiology of MDR Acinetobacter species

A

Invasive Acinetobacter spp infections ahve decreased from 80 in 2022 to 71 in 2023

Resistance to all key antibiotics including carbas remain low at <3%

No MDR or CRAB in Irealnd in 2023

MDR and CR major problem in Southern and Eastern European countries -> 16 countries report 75% MDR/CR in 2022

37
Q

Rising threat of NFOs MDR_GNBs in HAI

A

NFOS make up a large majority of ICU HAI infections caused by GNBS (about 70%)

NFOS make up about 30% of all GNB HAI infections

38
Q

Risk factors and those At risk for Enterobacteriacaea

A

Pations in acute settings, especially with recent travel to areas of high prevalence
Potential for community spread

LOS
ICU stay
Catheters and devices
Ventilators
Prior antibiotics
Travel

39
Q

Risk factors and those at risk for non fermenters

A

High risk patients in the ICU and burns units
Rare causes of comminity acquired infection

LOS
ICU stay
Catheters/devices
Ventilators
Prior antibiotics
Trauma esp burns

40
Q

Screening for carbapenemase

A

Population screening on admission and in some instances repeat screening e.g. haematology or oncology etc

Rectal swab or faeces
Culture
Molecular
- KPC, MBLs, OXA enzymes

41
Q

What are the genetic markers for resistance in Acinetobacter species

A

blaOXA51 like gene
blaOXA23 like gene
-> these cover 90% of German isolates

42
Q

What are the common CRAB sites of colonisation??

A

80% tracheal aspirate
69% rectal
69% sternal skin
25% urine

43
Q

Detection methods for Acinetobacter

A

Coris Resist 5
Coris Resist OXA-23 K-SeT for blaOXA23
RAPIDEC CARBA NP test from culture -> oxa23
RAPIDEC CARBA NP test from blood culture -> oxa23
GeneXpert CarbaR
LightMix Roche

We dont have great methods for acinetobacter

44
Q

Talk about Agar for acinetobacter

A

Same CRE agar as for normal CPEs
: CHROMID - CARBA SMART selective chromogenic media bi plate

will screen for OXA-48 on one side and other CPEs such as KPC and NDM-1 on the other

Brilliance CRE Agar
- not for acinetobacter

45
Q

Talk about the Coris Resist OXA-23 K-SeT

A

Detects blaOXA-23 like

100% specificity and senstivity compared to PCR

Low cost only 8 euro per test

15 mins test

Test direct from colony

Only for oxa-23 in Acinetobacter species or P. mirobailis

46
Q

Talk about RAPIDEC CARBA NP test

A

Detects blaOXA-23-like

Straight from culture

100% sensitivity
100% specificity at 120 mins

Only 7 organisms tested though but does include acinetobacter

Will also detect OXA-48, NDM-1, KPC-2, VIM type, OXA-40 and OXA-23

47
Q

Talk about RAPIDEC CARBA NP

A

From blood cultures
Detects bla-OXA-23 like
Enrichment needed -> 50% increase in number of detections - 2 vs 4
P. aeruginosa cannot be detected

Also detects KPC and VIM in K, pneumoniae

48
Q

Talk about GeneXpert CarbaR for Acinetobacter

A

For rectal swabs
Wont detect OXA-23
Will detect blaIMP gene

Not great

IMP, VIM, NDM, KPC, OXA-48 only detected

49
Q

Talk about the light mix for Acinetobacter

A

Can be used to detect OXA-48 or OXA-23

50
Q
A

4.2 Medical Microbiology (20 decks)

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