Dian Nurmansyah

Magister Ilmu Biomedik

Kekhususan Ilmu Kedokteran Dasar Mikrobiologi
PPS Universitas Udayana
2016
 Since the first use of antibiotics in the 1930s and 1940s, bacteria quickly
adapted and developed mechanisms to escape their effects

 Over the following decades, new antibiotics were developed to overcome

resistance

 Since the 1990s, new antibiotic development has fallen sharply while
bacterial resistance continues to increase

 Antibiotic resistance is responsible for countless human deaths and billions

of dollars in healthcare expenses
 Antibiotic = A drug that kills or inhibits the growth of microorganisms

 Resistant = Somewhat arbitrary designation that implies that an

antimicrobial will not inhibit bacterial growth at clinically achievable
concentrations

 Susceptible = Somewhat arbitrary designation that implies that an

antimicrobial will inhibit bacterial growth at clinically achievable
concentrations

Barden L.S. Clin Pediatr 1998

 Linezolid

Daptomycin
Linezolid

Barden L.S. Clin Pediatr 1998

 E-test®
Kirby-Bauer
Disk Diffusion
Barden L.S. Clin Pediatr 1998

Agar dilution
 Antibiotic Use Leads to
Antibiotic Resistance

Inpatient

Agriculture

Outpatient
Barden L.S. Clin Pediatr 1998
The doctor >< patient relationship leads to resistance
Overuse of broad-spectrum antibiotics

Antibiotic Prescription Barden L.S. Clin Pediatr 1998

Tortora, 2013
Gillespie and Bamford, 2009
 Bacteria are capable of
becoming resistant through Decreased
several mechanisms Permeability

 One or many mechanisms may

exist in an organism
 Multidrug-resistant bacteria
often have multiple mechanisms
 Genes encoding resistance may
exist on plasmid or chromosome
Alteration
in Target
Gillespie and Bamford, 2009
Molecule
Degrading enzymes will bind to
Blocking enzymes attach side chains to
the antibiotic and essentially degrade it
the antibiotic that inhibit its function.
or make the antibiotic inactive
E.g. -lactamases
 Gram-negative bacteria are relatively more resistant to antibiotics because of the
nature of their cell wall, which restricts absorption of many molecules to
movements through openings called porins

 Some bacterial mutants modify the porin opening so that antibiotics are unable to
enter the periplasmic space
 The synthesis of proteins involves the movement of a ribosome
along a strand of messenger RNA

 Several antibiotics, especially those of the aminoglycoside,

tetracycline, and macrolide groups, utilize a mode of action that
inhibits protein synthesis at this site
 Minor modifications at this site can neutralize the effects of
antibiotics without significantly affecting cellular function

Gillespie and Bamford, 2009

 Certain proteins in the plasma
membranes of gram-negative
bacteria act as pumps that expel
antibiotics, preventing them
from reaching an effective
concentration

 This mechanism was originally

Observed with tetracycline
antibiotics, but it confers
resistance among practically all
major classes of antibiotics
Gillespie and Bamford, 2009
ANTIBIOTIC TARGET MOA MECHANISM
OF RESISTANCE
CELL WALL
b-Lactams Transpeptidases/transglyc Blockade of cross linking b-Lactamases, PBP mutants
osylases (PBPs enzymes in peptidoglycan
layer
Vancomycin D-Ala-D-Ala termini of Sequestration of substrate Reprogramming of D-Ala-
peptidoglycan and of lipid required for cross linking D-Ala to D-Ala-D-Lac od D-
II Ala –D-ser
PROTEIN SYNTHESIS
Macrolides of the Peptidyl transferase, centre Blockade of protein rRNA methylation, drug
erythromycin class of the ribosome synthesis efflux
Tetracyclines Peptidyl transferase Blockade of protein Drug efflux
synthesis
Aminoglycosides Peptidyl transferase Blockade of protein Enzymatic modification of
synthesis drug
Oxazolidinones Peptidyl transferase Blockade of protein unknown
synthesis
DNA replication/repair

Fluoroquinolones DNA gyrase Blockade of DNA Gyrase mutations to drug

replication resistance
GUIDELINES FOR EXTENDING THE USEFUL LIFE OF
ANTIMICROBIAL DRUGS