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MEKANISME RESISTENSI

ANTIMIKROBA
Dr. Marijam Purwanta, Dra., M.Sc., Apt.
Departemen Mikrobiologi Kedokteran
Fakultas Kedokteran Unair

www.who.int/campaigns/world-antibiotic-
awareness-week/quiz/en/
www.who.int..quiz:how

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The development of Antimicrobial Resistance
(AMR)

Overuse
In mild infection

Misuse
Less supporting
Facility A.B. Abuse AMR

Underuse
Less funding WHO Global Strategy for containment of
antimicrobial Resistance. 2001
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- Too higher dose


Overuse
In mild infection - Too long regiment

- No evidence based empiric


Misuse therapy
Less supporting
Facility - No support data for definitive
therapy

Underuse - Self Antibiotic


Less funding
Usage
- Under dose
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Overuse of
3rd GEN CEPHALOSPORIN
(in Hospital)

ESBL Producing bacteria:


- MDR
- Resistant  3rd Gen Cephalosporin
- Co-resistant  Ciprofloxacin
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MECHANISM OF BACTERIAL
RESISTANCE TO ANTIBIOTICS

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MECHANISM OF BACTERIAL RESISTANCE


TO ANTIBIOTICS

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MECHANISMS OF ANTIMICROBIAL RESISTANCE :
1. Decreased Cell Permeability.
 Tetracyclines Resistance.
2. Inactivation by Enzyme
 Inactivation of Beta-Lactam Antibiotics.
 Inactivation of Aminoglycosides Antibiotics.
 Inactivation of Chlorampenicol.
3. Alteration target molecule/Modification of Antimicrobials
Receptor side.
 Streptomycin Resistance.
 Erythromycin Resistance.
 Rifampicin Resistance.
 Penicillin Resistance.
4. Synthesis of Resistance Pathway.
 Sulfonamide Resistance.
 Trimethoprim Resistance.

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Mechanism of Resistance

Intrinsic/ Innate

Mechanism of
Resistance
Mutation

Acquired
Resistance
Vector (Plasmid)

Adaptation ?

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Natural / Intrinsic Resistant
 Innate Antimicrobial Resistance
 Characteric of All or almost all Isolate
 Antimicrobial Susceptibility testing
Unnecessary
 If the test is “sensitive”, the drug its Clinically
Useless
 Some cases, may be Expressed at low level
MIC

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Natural / Intrinsic Resistant


 Enterobacteriaceae: Glycopeptide or
linezolid
 Proteus mirabilis: Nitrofurantoin and
Colistin
 Serratia marcescens: colistin
 Stenotrophomonas maltophilia: carbapenem
 Gram positif : Aztreonam
 Enterococcus: Fusidic Acid

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Acquired Resistant
 Acquired Antimicrobial Resistance
 Characteric of Not All Isolate
 Antimicrobial Susceptibility testing
Necessary
 Mechanism of Resistant: Mutation,
Resistant Vector or Adaptation

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Resistensi bakteri terhadap Antimikroba


1. Non Genetik
 Bakteri yang proses metabolismenya tidak aktif  resisten terhadap
antimikroba.
Misal : Mycobacterium yang tidak mengadakan multiplikasi dalam
sel inang (Dormant)  resisten terhadap Antimikroba.
 Bakteri kehilangan target spesifik untuk Antimikroba.
Misal : Bakteri L-form karena tidak mempunyai dinding sel  Resisten
terhadap Penicillin / Cephalosporin.
2. Genetik
Mikroorganisme sering resisten terhadap Antimikroba  karena adanya
perubahan genetik:
● Chromosome
● Extra Chromosome

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Perubahan Genetik:

● Chromosome Resistance
Terjadi karena Mutasi spontan  perubahan struktur receptor
untuk antimikroba.
Misal : Perubahan receptor spesifik pada Ribosome.

● Extra Chromosome Resistance


Bakteri mempunyai elemen genetik extra chromosome yang
terletak didalam cytoplasma  disebut Plasmid.
R-factor  Plasmid yang mengatur resistensi terhadap
antimikroba

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Elemen Genetik dapat ditransfer dari satu sel
bakteri ke sel bakteri lain dengaan cara:

● Konjugasi
Misal : Bakteri Gram negatif  melalui Pili
● Transduksi
Misal : Staphylococcus  plasmid ß – lactamase
● Transformasi
Misal : H. influenzae

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Mechanism of resistant
Kelas AB Natural Acquired
Beta lactam Impermeability PBP alteration
Efflux, hydrolysis Hydrolysis
Impermeability
Glycopeptide Impermeability Target Alteration
Different target

Aminoglycoside Non penetration Enzymatic


Enzymatic modification
modification Impermeability
Target alteration

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