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ESKAPE pathogens

&
Antibiogram

Dr. Sreekumary P.K.


Professor & Head
Department of Microbiology
Government medical college Kottayam
E-mail: drsreekumarypk@gmail.com
ESKAPE
E - Enterococcus faecium
S - Staphylococcus aureus
K - Klebsiella pneumoniae
A - Acinetobacter baumannii
P - Pseudomonas aeruginosa
E - Enterobacter species
ESKAPES

• Stenotrophomons maltophilia

• Escherichia coli
Infections - ESKAPE
• Health – care associated pneumonia

• Urinary tract infections

• Wound & skin infections

• Infection in the site of surgery

• Bacteremia & endocarditis


1. Enterococcus faecium

• Gram - positive cocci


• Present in gastrointestinal tract of human
• Develop biofilm – medical device associated infections
• Vancomycin – resistant strains of E. faecium

• VRE - major cause of device associated infections


Catheter – associated UTIs
Surgical wound infections
Blood stream infections
2. Staphylococcus aureus
• Gram positive cocci

• Most abundant normal flora of the skin & nasal cavity

• Opportunistic pathogen – skin infections


bacteremia & sepsis
RTIs
• Biofilm formation – majority of HCAIs worldwide

• Serious threat in hospital settings – increase mortality


Methicillin- resistant Staphylococcus aureus (MRSA)

• Superbug – Skin & soft tissue infections


UTIs
Sepsis
• 50 % of Staphylococcal infections
3.Klebsiella pneumoniae
• Gram – negative rod belongs to family Enterobacteriaceae
• Human body - in low numbers
• Most common pathogen Bacterial
pneumonia in patients on ventilators & ICUs
UTIs
Catheter –associated infections Surgical
wound infections

• Carbapenem – Resistant K. pneumoniae ( CRKP ) :


urgent threat list
4. Acinetobacter baumannii
• Gram negative Cocco-bacilli

• Normally found in soil & water

• Transient flora in human skin

• RTIs , UTIs , wound infections

• Carbapenem Resistant A . baumannii (CRAB)


Ventilator associated pneumonia
5. Pseudomonas aeruginosa
• Non - fermenting Gram - negative rod
• Opportunistic pathogen
• Hospitalised patients especially with impaired immune
function
Hospitalised – Acquired pneumonia
Blood stream infection
UTIs – 30 to 40 %
of all HCAI
Wound infection - burns unit
Pseudomonas aeruginosa - contd

• Multidrug- resistant strains of P. aeruginosa -


increasing globally - mortality rate up to 60%
Intrinsically resistant to many antimicrobial agents

• Listed under serious threat list of CDC


6. Enterobacter species
• Gram negative lactose fermenting rod
• Recent surveillance –
2nd /3rd most common Enterobacteriaceae spp
associated with Carbapenemases (NDM in India)
• Enterobacter aerogenes : E. cloacae , E. sakazakii
• Common - UTIS & RTIS
• MDR spp – resistant to beta- lactams & Cephalosporins

hard to treatment
Mechanism of resistance in ESKAPE
pathogens

• Antimicrobial inactivation/ Alteration


production of enzymes that irreversibly destroy or
modify the antimicrobial molecules resulting in their
inactivation/ alternation
GNB – Pseudomonas
, Acinetobacter
Klebsiella
Enterobacter
Mechanism of resistance in ESKAPE pathogens - contd

 β –Lactamases
main mechanism in GNB ESKAPE pathogen
resistance against lactam antibiotics by hydrolyzing
β lactam ring of antibiotics

Clinically important BL produced by ESKAPE pathogen :


Extended spectrum β -
Lactamases (ESBLs) Amp C β
Lactamases (ABLs)
Carbapenamases
Metallo-β Lactamases
Mechanism of resistance in ESKAPE pathogens - contd

 Aminoglycoside Modifying Enzymes (AMEs)


resistant against aminoglycoside
reduce affinity to bind with bacterial ribosomes
escape from the actions of AK , Tobra , Neomycin & Genta

Aminoglycoside acetyl transferase (AACs) –


main Aminoglycoside phosphor transferases (APHs)
Aminoglcoside nucleotidyl tranferases (ANTs)
Mechanism of resistance in ESKAPE pathogens - contd
• Antimicrobial ’s Target Modification reduces
affinity to bind with bacterial component

modification of target enzymes/protein :


Penicillin binding proteins - β –Lactam
DNA gyrase & Topoisomerase IV – quinoline & fluroquinolones

modification of ribosomal target sites :


methylation of A2058 residue of 23S r RNA of 50S ribosome resistance against
macrolides eg:- S.aureus & Enterococcus spp
methylation of A2503 residue of 23S r RNA of 50S ribosome resistance to
Linezolid (S. aureus & Enterococcus spp) methylation of 16S r
RNA residue decreases affinity of aminoglycoside binding to the bacterial
ribosome

modification in Cell-wall Precursors :


provides resistance against glycopeptides to gram positive ESKAPE pathogen
Mechanism of resistance in ESKAPE pathogens - contd

• Modification in membrane permeability


reduction in uptake of antibiotics – low intracellular
concentration of
antibiotics Reduce
membrane permeability :
modification in porins
down regulation
loss of porins channels in outer membrane

eg : resistance to β-Lactam & fluroquinolones


Mechanism of resistance in ESKAPE pathogens - contd

• Efflux pumps : extrude intracellular antibiotics


six classes of efflux pumps – present in ESKAPE

Resistance nodular division (RND) : MDR in GNB in ESKAPE


P.aeroginosa & A. baumannii
Aminoglycosides ,Fluroquinolones
Carbapenems
Major facilitator superfamily (MSF)
Multidrug and toxic compound extrusion (MATE)
ATP-binding cassette(ABC)
Proteobacterial
antimicrobial compound efflux (PACE)

AcrAB efflux pump –


Imi, Tetre , Chlor , Fluro resistance in
Mechanism of resistance in ESKAPE pathogens - contd

• Biofilm formation by ESKAPE


S. aureus P.
aeruginosa A. baumannii
K. pneumoniae

increases chance of survival in


medical devices
provides resistance to antibiotics :
restricting antibiotic penetration
modifying antibiotics
increasing interaction between different bacterial spp
upregulating effluxes
enhancing horizontal gene transfer
ENTEROCOCCUS
ACINETOBACTER
• RESISTANCE

• Highlights of data 2021:
● Escherichia coli was the most commonly isolated pathogen followed by the
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas
aeruginosa
Staphylococcus aureus.
● Imipenem susceptibility of
E. coli has dropped steadily from 86% in 2016 to 64% in 2021
Klebsiella pneumoniae dropped steadily from 65% in 2016
45% in 2020
43% in 2021.
● Resistance to carbapenems in Acinetobacter baumannii was recorded as 87.5%
● In Pseudomonas aeruginosa, more than 60% susceptibility was
observed for various aminoglycosides and fluoroquinolones in 2021.
There is a consistent increase insusceptibility to all the
major antipseudomonal drugs in the last few
years.
● In Staphylococcus aureus:
MRSA rates are increasing each year from 2016 to 2021
(28.4% to 42.6%).
The anti MRSA antibiotics such as vancomycin and daptomycin showed
excellent in vitro activity (100% against MRSA isolates).
Linezolid resistance was encountered in both MRSA and CoNS
isolates at very low rates of 0.1%.
● Vancomycin resistance in enterococci (E. faecalis and E. faecium)
was 14.9%,
the rate was 6 times higher in E. faecium compared to E. faecalis

37.5% of Enterococcus faecium causing blood stream infections


(BSIs) were Vancomycin
resistant.
THANK
YOU

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