Non-Fermenters Resistance Mechanisms Flashcards
What NFOs are we concerned with?
Acinetobacter baumannii
Pseudomonas aeruginosa
Stenotrophomas maltophilia
NFO MDR associated with what classes
Aminoglycosides - vancomycin
Fluoroquinolones
Carbapenems
Talk about MDR P. aeruginosa
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%
Talk about MDR PA in USA
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
What is the rate of MDR PA in USA
Between 10-30%
What is MDR-PA resistant to
Fluoroquinolones such as ciprofloxacin and levofloxacin
Mortality of MDR-PA
up to 60%
Mechanisms of carbapenem resistance in PA
Plasmid or integron mediated -> Class B or class A (class D rare)
increased expression of efflux systems
Reduced porin expression
Talk about plasmid or integron mediated carbapenemases in a class B P. aeruginosa
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
What is IMP active on
Imipenem
What is VIM
Verona integron encoded MBL
Talk about plasmid or integron mediated carbapenemases in class A PA
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
What is GES in KPC
Guiana extended spectrum
GES-2 P. aeruginosa has been reported in south africa
What is IBC in KPC
Integron-borne cefalosporinase
Has been reported in P. aeruginosa in greece
Talk about plasmid or integron mediated carbapenemases in class D PA
Class D such as OXA-198 are rare in P. aeruginosa
Increased expression of efflux systems in MDR P. aeurginosa
overexpression of the MexAB-OprM efflux pump
confers resistance to most beta-lactam drugs with the exception of imipenem
Spread of CR PA
Highest in USA
In Europe highest rate in Greece >50% and other Eastern european countries
Ireland only 6.6%
Distribution of CR.PA across the world
ireland = 6.6% which is 25/29 in euroope
highest proportions are in eastern europe
greece>50%
Epidemiology of PA infections
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.
Talk about A. baumannii
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
Talk about Carbapenem resistant A. baumanii
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
How does A. baumannii present in the community?
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
What is the mortality associated with A. baumannii
High mortality ranging from 40 to 64% if BSI occurs
Talk about MDR A. baumanii
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
Resistance in MDR A. baumannii
Resistance to carbapenems, Fluroquinolones, Aminoglycosides
Mechanisms of resistance in A. baumannii
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
List the 4 mechanisms of carbapenem resistance in A. baumannii
Enzymatic modification of antibiotics
Modification in membrane permeability
Altered penicillin-binding proteins
Efflux pumps
Enzymatic modification of antibiotics in carbapenem resistant A. baumanii
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
modification in membrane permeability in carbapenem resistant A. baumanii
modified porin chanels
Reduced expression of porins like Omp22-36, omp33-36, omp37, omp44, onp47 etc
altered penicillin-binding proteins in carbapenem resistant A. baumanii
overexpression of pbps resulting in imipenem resistance
efflux pumpss in carbapenem resistant A. baumanii
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
MATE efflux pumps
AbeM efflux pump and Emr-AB-TolC efflux pump convey resistance against imipene,
adeABC effluxs carbapenems out of cytoplasm
Epidemiology of CRAB
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
Carbapenem resistance in Irealnd
71 cases of Acinetobacter species in ireland in 2023
0% of these were Carb resistant
Why is CRAB cirtical
Major problem in Eastern and Southern Europe
9 countries have proportions >50%
WHO has listed these as a critical priority
Epidemiology of MDR Acinetobacter species
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
Rising threat of NFOs MDR_GNBs in HAI
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
Risk factors and those At risk for Enterobacteriacaea
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
Risk factors and those at risk for non fermenters
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
Screening for carbapenemase
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
What are the genetic markers for resistance in Acinetobacter species
blaOXA51 like gene
blaOXA23 like gene
-> these cover 90% of German isolates
What are the common CRAB sites of colonisation??
80% tracheal aspirate
69% rectal
69% sternal skin
25% urine
Detection methods for Acinetobacter
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
Talk about Agar for acinetobacter
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
Talk about the Coris Resist OXA-23 K-SeT
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
Talk about RAPIDEC CARBA NP test
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
Talk about RAPIDEC CARBA NP
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
Talk about GeneXpert CarbaR for Acinetobacter
For rectal swabs
Wont detect OXA-23
Will detect blaIMP gene
Not great
IMP, VIM, NDM, KPC, OXA-48 only detected
Talk about the light mix for Acinetobacter
Can be used to detect OXA-48 or OXA-23
