This document discusses various classes of antimicrobial drugs, including their mechanisms of action, spectra of activity, and mechanisms of resistance. It focuses on penicillin, cephalosporins, quinolones, and aminoglycosides. The key points are: 1) Penicillin and cephalosporins inhibit bacterial cell wall synthesis via competitive inhibition of transpeptidase. Resistance can arise via beta-lactamase production or alterations to penicillin binding proteins. 2) Quinolones inhibit DNA gyrase, blocking DNA replication in bacteria. They are well-absorbed and mainly eliminated by the kidneys. 3) Aminoglycosides bind to bacterial ribosomes,

1. ANTIMICROBIAL DRUGS
dr. Dita Hasni, M.Biomed

2. WHAT WE LEARN
Introduction of antimicrobial drugs
Penicillin
Cephalosporin
Quinolon
Aminoglycoside

3. INTRODUCTION TO ANTIMICROBIAL CHEMOTHERAPY
(GENERAL PRINCIPLES)
1.
Mechanisms of actions of different groups of
antibiotics.
Mechanisms by which pathogens acquire and
express resistance to antibiotics.
Combination therapy (use of two or more
drugs concomitantly).
Host determinants that influence the selection
and efficacy of antibiotics.

5. MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS
Inhibit cell wall synthesis
Inhibit protein synthesis
Inhibit nucleic acid synthesis
Injury to plasma membrane
Inhibit synthesis of essential metabolites

6. MECHANISMS OF ACTIONS OF ANTIMICROBIAL DRUGS

7. FEATURES OF ANTIMICROBIAL DRUGS:
ANTIMICROBIAL ACTION
• inhibit growth of
microorganisms
Bacteriostatic:
• Kill microorganismsBactericidal

8. FEATURES OF ANTIMICROBIAL DRUGS:
SPECTRUM OF ACTIVITY
 Some kill only limited range : Narrow-spectrum
antimicrobial
 While others kill wide range of microorganisms: Broad-
spectrum antimicrobial
Antimicrobial medications vary with respect to the range
of microorganisms they kill or inhibit

10. RESISTANCE
Failure to reach the target
The drug is inactivated
The target is altered

12. EFFECTIVENESS OF COMBINATION THERAPY
Synergistic effect
Additive effect
Antagonism effect

13. IMPORTANT HOST DETERMINANTS
Hepatic function
Kidney function
Host defense
mechanism

14. UNTOWARD EFFECTS OF ANTIBIOTICS
Reactions due to toxic properties of
antibiotics.
Hypersensitivity reactions
Superinfection (or also called
Suprainfection)

15. ANTIMICROBIAL DRUGS
Dose-dependent Time-dependent
Antibacterial effect directly
depends on their
concentrations in the locus of
inflammation
(high doses 1-2 times/24h)
Aminoglycosides
Fluoroqinolones
Metronidazol
Amphotericin B
Effectiveness depends on a
period of time, during which
concentration in blood
overwhelms MIC for a
particular causative agent
(constant i.v. infusion or 3-6
times/24h)
Beta-lactames
Glycopeptides
Macrolides
Linkozamides

17. PROPERTIES OF AN IDEAL ANTIBIOTIC
broad spectrum
stable--long
shelf life
soluble in body
fluids
stable toxicity Nonallergenic reasonable cost
selectively toxic
not likely to
induce bacterial
resistance

18. PENICILLIN AND CEPHALOSPORIN

19. PROTOTYPES (-LACTAMS & RELATED AGENTS)
Penicillins: penicillin G; phenoxymethyl penicillin (pen V)
methicillin; oxacillin
ampicillin; amoxicillin; carbenicillin; ticarcillin
Cephalosporins: First Gen.: cephalexin; cephalothin
Second Gen.: cefoxitin; cefaclor
Third Gen.: cefotaxime; cefoperazone;
ceftriaxone
Fourth Gen.: cefepime
-Lactam related agents: Antibiotics: imipenem; aztreonam
-Lactamase inhibitors: sulbactam;
clavulanic acid

22. ANTIMICROBIAL SPECTRUM (THERAPEUTIC USES)
Penicillin G is primarily a narrow spectrum antibiotic, and mainly Gram (+) organisms are
susceptible. However, there are Gram (-) organisms that are very sensitive to the agent.
a) Sensitive G(+) cocci: Pneumococci, Strep.
Pneumoniae,
b) Sensitive G(-) cocci: N. meningitidis N. gonorrhea,
c) Other cocci and G(+) and G(-) bacilli require test for the drug sensitivity
because of frequent resistance to penicillin G. However, Treponema
pallidum (syphillis), Treponema pertenue and Actinomyces israeli etc are still sensitive
to the agent.

23. ANTIBACTERIAL ACTION MECHANISMS OF -LACTAM
• --The last step of peptidoglycan synthesis
1. Competitive inhibition of
TRANSPEPTIDASE.
• --Inhibition of SEPTUM formation
(Penicillin Binding Protein mechanism)
2. Alteration of bacterial
morphology.
• --Stimulation of bacterial cell lysis (PBP
mechanism)
3. Inhibition of availability of
Autolysin Inhibitor.

25. MECHANISMS UNDERLYING BACTERIAL
RESISTANCE TO -LACTAMS
Production of -LACTAMASE
Alteration in penicillin binding proteins
(PBP)
Decreased entry of -lactams (cell
membrane and cell wall structure; porin
mechanism)
Increased efflux of -lactams

26. QUINOLONES (GABA ANTAGONISTS)
 Inhibit DNA gyrase.
 Nalidixic acid – used only for UTIs.
 Ciprofloxin (6-fluoro substituent) that greatly
enhances its effectiveness against both gram- and
gram+ bacteria.
Well-absorbed both orally and i.v.
Eliminated largely unchanged by the kidneys.
Side-effects (headache, vomiting, nausea) are rare; but
convulsions may occur.

28. AMINOGLIKOSIDA

29. aa
A
50S
30S
mRNA
template
Transferase
site
P
Nascent polypeptide
chain
Mechanism of action of Aminoglycosides
AG’s

30. 50S
5’
5’
3’
5’ 3’
AUG
5’ 3’
AUG
30S
3’AUG
X
Blocks initiation
Premature termination
Wrong amino acid is
incorporated
+ aminoglycoside
mRNA translation
Effects of Aminoglycosides
Mature protein
Growing polypeptide

31. 30S
Aminoglycosides on Protein Synthesis
50S
5’ 3’
Blocks initiation
3’5’
Premature termination
5’ 3’AUG
mRNA translation
+
Amino
Glycoside
3’5’
Incorporation of wrong amino acid
X
Mature Protein
Growing Polypeptide

32. AMINOGLYCOSIDES
 Gentamicin – used for acute, life-thretening gram- infections.
Has synergism with pen and van and combo.
 Amikacin – used for bact that are gent-resistant.
 Netilmicin – less toxic than gentamicin.
 Neomycin – too toxic for parenteral use. Used for topically for
skin infections and orally for sterilizing bowel before surgery.
 Streptomycin – active against Mycobacterium tuberculosis.
But bec of its ototoxicity, rifampicin replaces.
 Rifampicin – resistance develops quickly alone; so, with TB,
combine with isoniazid, ethambutol, and pyrazinamide for the
1st 2 mos of treatment, followed by another 4 mos with
rifampicin and isoniazid.

33. TOXICITY
Ototoxicity
(Vestibular and Auditory).
Nephrotoxicity.
Neuromuscular Blockade.