Professional Documents
Culture Documents
ANTIMICROBIAL DRUGS
DR.DATTEN BANGUN,MSC,SPFK
DEPT.FARMAKOLOGI &TERAPEUTIK
FAKULTAS KEDOKTERAN
UHN
Bacteria
Unicellular, prokaryotes
DNA and RNA
Binary fission
No mitochondria
Rigid cell wall containing peptidoglycan
Eubacteria
Classified according to:
size & shape
cell wall (Gram stain)
aerotolerance
Shape
coccus - round (chains? clusters?)
bacillus - rod
Chemotherapy
Substance produced by a
microbe that, in small amount
inhibits another microbe
Selective toxicity
Features of Antimicrobial
Drugs
Antimicrobial action
Inhibit = bacteriostatic
Kill = bacteriocidal
Adverse effects
Allergic reactions
Allergies to penicillin
Toxic effects
Aplastic anemia--Chloramphenicol
Body cannot make RBC or WBC
Suppression of normal flora
Antibiotic associated colitis,diarrhea
Antimicrobial resistance
Principles / Definitions
Spectrum of Activity:
1.Narrow spectrum :
= drug is effective against a limited number of
species
2.Broad spectrum
= drug is effective against a wide variety of species
- Gram negative agent
- Gram positive agent
- Anti-anaerobic activity
1928
Fleming
discovered
penicillin,
produced by
Penicillium.
1940
Howard Florey
and Ernst
Chain
performed first
clinical trials of
penicillin.
Figure 20.1
Figure 20.2
MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS
Mechanism of action
include:
1.Inhibition of cell wall
synthesis
2.Inhibition of protein
synthesis
3.Inhibition of nucleic acid
synthesis
4.Inhibition of metabolic
pathways
5.Interference with cell
membrane integrity
Figure 20.4
Figure 20.4
Beta-lactams group:
Penicillins and cephalosporins
Part of group of drugs called lactams
Have shared chemical structure called -lactam
ring
Competitively inhibits function of penicillinbinding proteins
Inhibits peptide bridge formation between
glycan molecules
This causes the cell wall to develop weak
points at the growth sites and become fragile.
The cephalosporins
Chemical structures make them resistant to
inactivation by certain -lactamases
Tend to have low affinity to penicillin-binding
proteins of Gram + bacteria, therefore, are
most effective against Gram bacteria.
Chemically modified to produce family of
related compounds
First, second, third and fourth generation
cephalosporins
Cephalosporins
1st generation- mainly gram pos, some gram neg
(cefazolin)
2nd generation- weaker gram pos, better gram neg
(cefuroxime)
3rd generation - excellent gram neg, some gram pos
(ceftriaxone)
4th generation - excellent gram neg, good gram pos
(cefepime)
Spectrum of activity
Narrow spectrum
Broad spectrum
Cefoxitin/cefotetan
Think Haemophilus in
1st generation plusaddition to 1st
anaerobes
generation specturm
A mixed, non-serious
A respiratory drug
infection surgeon drug
Think cefazolin/metro
which is what we
would use
Third-Generation Cephalosporins
Cefotaxime, ceftriaxone (IV)
Enhanced activity against Enterobacteriaceae
Enhanced activity against streptococci, including penicillin resistant
S. pneumoniae.
Long half life favors ceftriaxone
Less diarrhea favors cefotaxime
Ceftazidime (IV)
Active against P. aeruginosa.
Decreased activity against gram positive cocci.
Vancomycin
Inhibits formation of glycan chains
Inhibits formation of peptidoglycans and cell wall construction
Does not cross lipid membrane of Gram Gram - organisms innately resistant
Bacitracin
Interferes with transport of peptidoglycan precursors across
cytoplasmic membrane
Toxicity limits use to topical applications
Common ingredient in non-prescription first-aid ointments
Complexation or chelation;
EX1., Tetracycline interacts with iron preparations
or
Milk (Ca2+ )
Unabsorpable complex
Chloramphenicol
Binds to 50S ribosomal subunit
Prevents peptide bonds from forming and
blocking proteins synthesis
Fluoroquinolones
Inhibit action of topoisomerase DNA gyrase
(Topoisomerase maintains supercoiling of DNA)
Effective against Gram + and Gram
Examples include:
= Ciprofloxacin and
= Oloxacin
Resistance due to alteration of DNA gyrase
Mechanism of action of
TMP-SMX
Side-effects:- rarely:
- Steven-Johnsons Syndrome
Antimicrobial resistance
Resistance: the inability to kill or inhibit the
organism with clinically achievable drug
concentrations
Resistance may be innate (naturally resistant)
Resistance may be acquired
- mutation
- acquisition of foreign DNA
Antibiotic Resistance
A condition where the antimicroba does not
produce its effect anymore
RESISTANCE TO ANTIMICROBIAL
DRUGS
Mechanisms of resistance
1. Drug inactivating enzymes
Some organisms produce enzymes that chemically
modify drug
Penicillinase breaks -lactam ring of penicillin
antibiotics
2. Alteration of target molecule
Minor structural changes in antibiotic target can
prevent binding
Changes in ribosomal RNA prevent macrolids
from binding to ribosomal subunits
RESISTANCE TO ANTIMICROBIAL
DRUGS
Mechanisms of resistance
3. Decreased uptake of the
drug
Alterations in porin
proteins decrease
permeability of cells
Prevents certain
drugs from entering
RESISTANCE TO ANTIMICROBIAL
DRUGS
Mechanisms of resistance
4. Increased elimination of
the drug
Some organisms produce
efflux pumps
Increases overall
capacity of organism to
eliminate drug
Enables organism to
resist higher
concentrations of
drug
Tetracycline
resistance
Antibiotic Resistance,
WHY?
Misuse of antibiotics selects for resistant
mutants.
Misuse includes:
Using outdated, weakened antibiotics
Using antibiotics for the common cold and
other inappropriate conditions
Use of antibiotics in animal feed
Failure to complete the prescribed regimen
Using someone else's leftover prescription
Antimicrobial resistance
Factors which may accelerate the
development of resistance
- inadequate levels of antibiotics at the
site of infection
- duration of treatment too short
- overwhelming numbers of organisms
- overuse / misuse of antibiotics
ANTIMICROBIAL
SUSCEPTIBILITY TESTING
Probably the most
widely used testing
method is the diskdiffusion method, also
known as the KirbyBauer test.
EFFECTS OF COMBINATIONS
OF DRUGS
Principles / Definitions
Treatment vs prophylaxis
= Prophylaxis - antimicrobial agents are administered to
prevent infection
= Treatment - antimicrobial agents are administered to
cure existing or suspected infection