Class notes Antimicrobial Agents

M
MICROBIOLOGY & PARASITOLOGY
C3
PREFINALS ANTIMICROBIAL AGENTS
ANTIMICROBIAL AGENTS in 1910: The concept of chemotherapy to
- substances produced from microorganisms or treat microbial diseases was born.
synthetically that are capable of inhibiting or - 1935: Sulfa drugs (sulfanilamide) discovered→
destroying microorganisms even at low against gram + bacteria
concentrations. - 1928: Fleming discovered penicillin
Sources - 1940: Howard Florey and Ernst Chain
 Natural performed first clinical trials of penicillin.
o Microorganisms
 Fungi (Antifungal) Sulfanilamide and other Sulfonamides
 Bacteria (Antibacterial) - Inhibit bacterial folic acid synthesis due to
 Synthetic competitive inhibition. No folic acid→ bacteria
 Semi-synthetic die.
- Sulfamethoxazole: example of modern
sulfonamide
- Prescribed against Gram+ bacteria and UTI
- Often combined with Trimethoprim (inhibits
another step in folic acid synthesis) ⇒ Bactrim
(used against pneumocystis pneumonia)
- Allergy possible

Classification of antibiotics
Criterion Types
Spectrum of Activity Broad: with wide
coverage of activity
against wide
spectrum of
ANTIBIOTIC microorganism
- Not same as antimicrobial Narrow: limited
- Only a type of antimicrobial coverage of activity;
- Mainly used to treat infectious disease effective only against
- a substance produced by microorganisms that in limited no. of
small amounts inhibits another microorganism microorganism
Antimicrobial Activity Bacteriostatic: if it can
An ideal antimicrobial agent must possess the only inhibit the growth
following characteristics: of microbes
 It should be able to kill the microbial agent or Bactericidal:
inhibit its growth. completely kill the
 It must have a broad spectrum of activity. microbes
 It should not cause any damage or adverse Absorbability from Locally Acting: limits
effect to the patient. the site of its action at the site
 It should remain stable when stored in either a administration where it is administered
solid or a liquid form. like topical ointments or
 It should be able to remain in specific body eyedrops
tissues long enough for it to be effective. Systematically
 It should be able to kill the organism or inhibit acting: affects several
its growth before it has had a chance to body systems like
mutate and develop resistance. antibiotics administered
 It must exhibit selective toxicity. It must be intramuscularly or
toxic to the microbial cell but not to the host's intravenously
cells.
Classification of Antibiotics According to
Definition of terms mechanism of Action
Chemotherapy - The use of drugs to treat a disease.
Antimicrobial drugs - Interfere with the growth of
microbes within a host.
Antibiotic - Of biological origin; Produced by a
microbe, inhibits other microbes.
Chemotherapeutic agent - synthetic chemicals

Note
Today distinction blurred→ many newer
"antibiotics" are biological products that are
 chemically modified or
 chemically synthesized

HISTORY OF CHEMOTHERAPY
- Paul Ehrlich and Sahachiro Hata developed
Salvarsan (Arsphenamine) against syphilis


Hannah Adan 1

, M
MICROBIOLOGY & PARASITOLOGY
C3
PREFINALS ANTIMICROBIAL AGENTS
o More stable than penicilins to bacterial
B-lactamases, broader spectrum ⇒ used
 Agents that Interfere with the Synthesis of against penicillin-resistant strains.
Bacterial Cell Wall - Incidence of cross-sensitivity with penicillin
Penicillin estimated at 5-16%
- Natural and semisynthetic penicilins Glycopeptides (vancomycin)
contain ß-lactam ring - Inhibit the transglycosylate and transpeptidase
o Natural penicillins produced by enzymes that essential for the completion of the
Penicillium are effective against Gram + synthesis of the peptidoglycan component of the
cocci and spirochetes bacterial cell wall.
o Semisynthetic penicillins: made in Vancomycin
laboratory by adding different side - Vancomycin, the crucial "drug of last resort,"
chains onto ß-lactam ring => inhibits PG synth by binding directly to the D-
penicillinase resistant and broader Ala-D-Ala end of the peptide
spectrum of activity - forms a cap over the end of the chain; blocks
Penicillinase (B- bacterial enzyme that cross-linking
lactamase): destroys natural  inhibits peptidoglycan biosynthesis of
penicillins bacterial cell wall
Penicillinase methicilin replaced by  blocks transglycosylase and trans peptidase
resistant oxacilin and nafcilin activity
penicillins: due to MRSA  prevents transpeptidation linking
Extended-spectrum Ampicilin, amoxicilin;  stops bacterial cell wall maturation
penicilins: new: carboxypenicilins
and ureidopenicillins
(also good against P.
aeruginosa)




Vancomycin and Streptogramins
- Glycopeptide from Streptomyces
o Inhibition of cell wall synthesis
o Used to kill MRSA
o Emerging Vancomycin resistance: VRE
and VRSA
- Streptogramins
o inhibit protein synthesis and may be
used to treat VRE and VRSA:
o SynercidⓇ I.V.: Combination of
quinupristin and dalfopristin in a 3:7
ratio. Bactericidal. Quinupristin binds to
50s ribosomal subunit and prevents
elongation of the polypeptide.
Dalfopristin binds to nearby site,
changes the conformation of the 50s
ribosomal subunit, enhancing the
binding of quinupristin.

 Agents that Alter the Function or
Permeability of the Cell Membrane




Cephalosporins
- Fungi of genus Cephalosporium -> 4
Generations of cephalosporins
- Chemical structure and mode of action
resembles penicilins
- Advantages:




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