Extended spectrum B-lactamase (ESBL)

Presented By Madan sharma M.Sc Microbiology E.mail: sharmamaddy32@gmail.com

INTRODUCTIONESBL:ESBL’s (extended spectrum beta lactamases) are

enzymes that may be produced by bacteria. They were first reported in 1980

BETA LACTAMASES:Enzymes produced by certain bacteria that provide

resistance to certain antibiotics.Produced by some gram positive bacteria and virtually

all gram negative bacteria.Found on both chromosomes and plasmids.Are primary mode of resistance to beta-lactam

antibiotics.

04/07/2023 2

• The most common ESBL producing organisms include Escherichia coli Klebsiella sp, Enterobacter sp, Acinetobacter.

• The bacteria have become resistant to beta-lactam antibiotics, by their ability to produce an enzyme (beta lactamase) which can break down the antibiotics (eg. penicillin's and cephalosporins).

• ESBL producing organisms not only have the ability to break down beta-lactam antibiotics but they are also able to transfer these resistance enzymes to other microorganisms via plasmids.

• The bacteria may also be resistant to other antibiotics such as aminoglycosides (eg. gentamycin and tobramycin) and quinolones (eg. ciprofloxacin).

04/07/2023 3

• Infection caused by an ESBL producing bacteria is usually referred to as an ESBL infection.

• ESBLs are enzymes that have developed a resistance to some newer antibiotics known as cephalosporins.

• It is this resistance to certain (not all) antibiotics that makes ESBL infections more difficult to treat, due to the restricted treatment options.

•ESBL enzymes are more commonly produced in Klebsiella pneumoniae and Escherichia coli (E. coli) bacteria

04/07/2023 4

MECHANISM OF ACTION:

Hydrolysis of beta-lactam ring of basic penicillin structure.

Hydrolysis = adding a molecule of H2O to C-N bond with enzyme action.

This opens up the ring, thus making the drug ineffective .

04/07/2023 5

04/07/2023 6

TYPES OF ESBL:

TEM-beta Lactamases

SHV- beta Lactamases

CTX-M and Toho- beta Lactamases

OXA-beta- lactamases

DETECTION OF ESBL: • Double disc diffusion test• E-Test

Significance:

•ESBLs have activity against

penicillins

1st & 2nd generation cephalosporins

cefaclor, cefazolin, cefuroxime

and importantly 3rd generation

(extended

spectrum) cephalosporins

ceftriaxone, cefotaxime, ceftazidime

Monobactams

aztreonam04/07/2023 7

•ESBLs do not have activity

againstcarbapenems

ertapenem, imipenem, meropenem

cephamycins

cefoxitin

beta-lactamase inhibitors

clavulanic acid, sulbactam, tazobactam

However these antibiotics may be

inactive due to

other resistance mechanisms

04/07/2023 8

PreventionESBLs are spread from person to person by

direct contact with an infected patient and also when hands are soiled after using the toilet and the bacteria is introduced into the mouth via the soiled hands. The bacterium therefore may have come from another patient who had the infection or the environment.

your personal care they do not need to wear gloves or aprons.

Thorough cleaning should also be undertaken to maintain a clean and safe environment. If you feel this is not being done pleasereport this to the nurse in charge of the ward.

Do not visit other patients elsewhere in the ward or hospital.

Institutions with endemic ESBL-producing organisms need to determine whether there is a high rate of cephalosporin use, especially third generation cephalosporins. Several studies have shown that by limiting the use of these agents alone or in combination with infection control measures, the frequency of ESBL isolates can be reduced substantially. Educational programs for medical staff to increase awareness also should be developed

Methods of DetectionDouble disc synergy test In this test discs of

third generation cephalosporins and augmentin are kept 30 mm apart from center to center on inoculated Mueller-Hinton Agar (MHA). A clear extension of the edge of the inhibition zone of cephalosporin towards augmentin disc is interpreted as positive for ESBL production

Problems in DetectionDue to the variable affinity of these enzymes for

different substrates and inoculum effect, some ESBL isolates may appear susceptible to a third generation cephalosporin in vitro. However, treatment of infections due to an ESBL producing organism with third generation cephalosporins may result in clinical failure if infection is outside the urinary tract Cefpodoxime and ceftazidime have been proposed as indicators of ESBL production as compared to cefotaxime and ceftriaxone. Hence, an institution where only cefotaxime and ceftriaxone are used in the routine sensitivity testing panel may have difficulty in detecting ESBLs.

Treatment While ESBL-producing organisms were previously

associated with hospitals and institutional care, these organisms are now increasingly found in the community.

CTX-M-15-positive E. coli are a cause of community-acquired urinary infections in the UK and tend to be resistant to all oral β-lactam antibiotics, as well as quinolones and sulfonamides.

Treatment options may include nitrofurantoin, fosfomycin,mecillinam and chloramphenicol. In desperation, once-daily ertapenem or gentamicin injections may also be used.

inhibitorsby clavulanic acid& Sulbactam showing clinical

resistance to the beta-lactam—lactamase inhibitor combinations of amoxicillin-clavulanate (Co-amoxiclav), ticarcillin-clavulanate, and ampicillin/sulbactam, they normally remain susceptible to inhibition bytazobactam and subsequently the combination of piperacillin/tazobactam, although resistance has been described. To date, these beta-lactamases have primarily been detected in France and a few other locations within Europe.[13]

[

ConclusionInitially restricted to hospital acquired infections,

they have also been isolated from infections in outpatients. Major outbreaks involving ESBL strains have been reported from all over the world, thus making them emerging pathogens The routine susceptibility tests done by clinical laboratories fail to detect

it is necessary to know the prevalence of ESBL positive strains in a hospital

important is the information on an isolate from a patient to avoid misuse of extended spectrum cephalosporins, which still remain an important component of antimicrobial therapy in high risk wards