MDR in NFOs Flashcards

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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
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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
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19
Q

Epidemiology of MDR PA infections

A

Need to add more info from slide

But decreasing over 5 years in Europe in invasive infections, resistance to carbapenems

MDR has decreased since 2022 but 5 year trend slight increase

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

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
30
Q

altered penicillin-binding proteins in carbapenem resistant A. baumanii

A
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

MFS efflux pumps

A
33
Q

RND efflux pumps

A
34
Q

MATE efflux pumps

A
35
Q

SMR family transporters

A
36
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

37
Q

Carbapenem resistance in Irealnd

A

71 cases of Acinetobacter species in ireland in 2023

0% of these were Carb resistant

38
Q

Why cirtical

A
39
Q

Epidemiology of MDR Acinetobacter species

A

Invasive Acinetobacter spp infections ahve decreased

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

No MDR or CR in Irealnd in 2023

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

40
Q

Rising threat of MDR_GNBs

A
41
Q

Risk factors and those At risk for Enterobacteriacaea

A
42
Q

Risk factors and those at risk for non fermenters

A
43
Q

Screening for carbapenemase

A
44
Q

What are the genetic markers for resistance in Acinetobacter species

A

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

45
Q

What are the common CRAB sites of colonisation??

A

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

46
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

47
Q
A