Carbapenem resistance

PRESENTER : Dr. AISHIYA

1

Carbapenems are a class

of beta-lactam antibiotics
with very broad activity

 Lactam Antibiotics

Most widely prescribed

drugs

Penicillin

Monobactams
Carbepenems

Penicillins
betalactamases

Ist generation cepalosporins

2nd generation cephalosporins
3rd generation cephalosporins
Extended spectrum
betalactamases

- Lactam Inhibitors & CARBEPENEMS

Resistance

BACTERIAL RESISTANCE
Even in presence of antimicrobials, if

pathogenic microorganisms is multiplying

treatment outcome is compromised.
This phenomenon is referred to as antimicrobial
resistance (AMR).

SURVIVAL OF THE FITTEST

Resistant bacteria survive, susceptible ones die

Mutant emerges
slowly

Sensitive cells
killed by antibiotic

Mutants progeny
overrun
7

BACTERIAL RESISTANCE

GENETIC

CHROMOSOMA
L

EXTRA
CHROMOSOMA
L

BIOCHEMICA
L

EFFLUX
PUMPS

MODIFICATION
OF TARGET
SITES

INACTIVATING
ENZYMES
E,g: Lactamases
8

BACTERIAL RESISTANCE
1.GENETIC
Chromosomal :
CONJUGATION

Extrachromosomal:
Plasmids

TRANSDUCTION
TRANSFORMATION

10

11

12

2.BIOCHEMICAL METHODS
By producing enzymes that inactivate
the antibiotic..for e,g: lactamases

13

EFFLUX PUMPS

14

4. MODIFICATION OF TARGET SITES

15

Carbapenems
The Big Gun
Carbapenems are reserved drugs
and are the last resort for many
bacterial infections
APPROVED

UNAPPROVED/EXPERIMENTAL

Ertapenem
imipenem
meropenem
doripenem
Panipenem/betamipron
biapenem

Razupenem
Tebipenem
Lenapenem
tomopenem

16

Route of
Administra FDA
tion
Status
Drug

Carbapenems
IV

Cleared

Lower respiratory tract

infection
Skin infection
Bone and joint
Complicated UTI

IV

Cleared

Pneumonia
Against enterobacteriaceae ,
pseudomonas spp ,
acinetobacter spp, H.
influenza and anaerobic
bacteria
Serious hospital acquired
infection

Imipenem

Meropene
m

C0mm0n uses

17

MODE
OF ACTION OF CARBAPENEMS
INTERFERS BACTERIAL WALL SYNTHESIS by binding to penicillin-binding pro

18

19

PORIN

Porins are a class of outer membrane protein (OMP)

Porins are involved in the exchange of nutrients ,

also allows the antibiotics to enter the cell

20

Penicillins
betalactamases
Cephalosporins
betalactamases

Ist generation cepalosporins

2nd generation cephalosporins
3rd generation cephalosporins
Extended spectrum
betalactamases

- Lactam Inhibitors & CARBEPENEMS

RESISTANCE
21

MECHANISM OF CARBAPENEM
RESISTANCE

GENETIC

Change in porin
protein gene
cause a
frameshift
mutation-altering
porin structure
and function

EFFLUX
PUMPS

BIOCHEMICA
L

INACTIVATING
ENZYMES
carbapenemase
s
22

23

Carbapenemases

Classification

Enzyme

Most Common
Bacteria

Class A

KPC, SME IMI,

NMCGES

Enterobacteriac
eae
(rare reports in P.
aeruginosa)

Class B
IMP, VIM, GIM, SPM P. aeruginosa
Enterobacteriacea
(metallo--lactamse)
Acinetobacter spp.
Class D

OXA

Acinetobacter spp.
24

LABORATORY
DIAGNOSIS
25

Screening test
Disc diffusion method
Etest for MIC determination
Automated antimicrobial susceptibility systems:

Confirmatory test
Modified Hodge test (MHT)
Ethylene diamine tetraacetic acid (EDTA) impregnated

disc test
2mercaptopropionic acid disc test
Boronic acid disc test.

Molecular methods
Polymerase chain reaction (PCR)
Sequencing.
26

SCREENING TEST
DISC DIFFUSION

27

E test

28

AUTOMATED METHODS
These are used as per
manufacturers

instructions

29

CONFIRMATORY TEST
Modified Hodge test (MHT)
Ethylene diamine tetraacetic acid (EDTA)

impregnated disc test

2mercaptopropionic acid disc test
Boronic acid disc test.

30

Modified Hodge Test

Test isolate
produces the
enzyme

Carbapenem
susceptible strain
(E.coli ATCC
25922) grows
towards
carbapenem
disk.
31

A Positive HMT test

MHT Positive test has a

clover leaf-like
indentation of the E.coli
25922 growing along
the test organism
growth streak within
the disk diffusion zone.
A positive MHT
indicates that this
isolate is producing a
carbapenemase
32

A Negative HMT Test

MHT Negative test has no growth of the

E.coli 25922 along the test organism

growth streak within the disc diffusion.

A negative MHT indicates

that this isolate is not

producing a carbapenemase
33

EDTA DISC TEST

34

Double Disk

Enhancement of inhibition zone towards EDTA disc

35

COMBINED DISK TEST

imipenem

EDTA+imipenem

ceftazidime

EDTA+ceftazidi
me

36

2 MERCAPTOPROPIONIC
ACID
ceftazidime

2-MCP

DOUBLE DISC

ceftazidim
e

2-MCP

Enhancement of inhibition zone towards 2-MCP disc

37

IMIPENEM

Imipenem +
BORONIC ACID

BORONIC
ACID DISC
TEST

38

MOLECULAR TECHNIQUES

Sequencing

39

NEWER Drugs
Colistin
Polymyxin
Fosfomycin
Tigecycline

40

PREVENTION

41

Hand washing still the best

option to prevent spread of CRE

Hand hygiene is a

primary part of
preventing multidrugresistant organism
(MDRO) transmission.

Facilities should

ensure that
healthcare personnel
are familiar with

42

We may not be able to stop the

emergence of Super bugs
but we CAN

43

44