Antimicrobial Drugs

Fading Miracle?
BLS 206 Lecture Hoza, A . S

Ehrlich’s Magic Bullets

• 1906: Paul Ehrlich discovered Salvarsan 606 • 1930s: sulfa drugs discovered

Fleming and Penicillin

TERMINOLOGIES

Terminologies
Chemotherapy • The use of drugs to treat a disease

• Selective toxicity: – A drug that kills harmful microbes without damaging the host

positive and Gnegative bacteria e. oxazolidone . 1-2nd generation cephalosporins. 3-4th generation cephalosporins. penicillin G.g. Carbapenems.Terminologies Antibacterial spectrum Range of activity of an antibiotic A broad spectrum Antibiotic that can inhibit wide range of G. quinolones A narrow spectrum Antibiotic that is active only against a limited number of bacteria e.g.

9% of the bacterial population .Bacteriostatic activity Level of antimicrobial activity that inhibits the growth of bacteria Minimum inhibitory concentration (MIC) The lowest concentration that inhibits the growth of bacterial population Bactericidal activity Minimum bactericidal concentration (MBC) The lowest concentration that kills 99.

2 + 2 = 4) e.g. combination of two ß-lactam antibiotics Antibiotic antagonism Combination in which the activity of one antibiotic interferes with the activity of the other (e.g.g. 2 + 2 < 4) .g.g. 2 + 2 = 6) e. ampicillin+gentamicin in entercoccal carditis Additive effect Combination of antibiotics has an additive effect (e.Antibiotic combinations Antibiotic synergism Combination of antibiotics have enhanced activity when tested together compared with each antibiotic alone (e.

. • Antagonism occurs when the effect of two drugs together is less than the effect of either alone.Effects of Combinations of Drugs • Synergism occurs when the effect of two drugs together is greater than the effect of either alone.

Effects of Combinations of Drugs .

Combined antibacterial therapy .

Antibiotic/Antimicrobial • Antibiotic: – Chemical produced by a microorganism that kills or inhibits the growth of another microorganism • Antimicrobial agent: – Chemical that kills or inhibits the growth of microorganisms .

Antimicrobial Agents • Disinfectant: •antimicrobial agent used only on inanimate objects • Chemotherapeutic agent: •antimicrobial agent that can be used internally • Bactericidal: •agent that kills bacteria • Bacteriostatic: •agent that inhibits the growth of bacteria .

Microbial Sources of Antibiotics .

Antibiotic Spectrum of Activity • No antibiotic is effective against all microbes .

Mechanisms of Antimicrobial Action • Bacteria have their own enzymes for – Cell wall formation – Protein synthesis – DNA replication – RNA synthesis – Synthesis of essential metabolites .

Mechanisms of Antimicrobial Action • Viruses use host enzymes inside host cells • Fungi and protozoa have own eukaryotic enzymes • The more similar the pathogen and host enzymes. the more side effects the antimicrobials will have .

Modes of Antimicrobial Action .

Basic mechanisms of antibiotics .

carbapenems and monobactams. ethinamide. ß-lactamase inhibitor/ßlactam combinations Glycopeptides  Vancomycin Polypeptides Bacitracin. polymyxins Drugs used for treatment of mycobacterial infections Isoniazid. cycloserine . cephalosporins and cephamycins. ethambutol.Basic mechanisms of antibiotic action (1) Disruption of bacterial cell wall  ß-lactam antibiotics Penicillins.

(B) bacteria .Bacterial cell wall of G+ (A) and G.

Gram-positive and Gram-negative bacteria .

Inhibition of protein synthesis Acting at 30S ribosomes Aminoglycosides Tetracyclines Acting at 50S ribosomes Chloramphenicol Macrolides Clindamycin Streptogramins Oxazolidones .2.

Inhibition of nucleic acid synthesis Acting on DNA replication Quinolones Metronidazole Acting on RNA synthesis Rifampin Rifabutin .3.

4. Antimetabolites Sulfonamides Dapsone Trimethoprim Paraaminosalicylic acid .

Antimicrobial Agents .

Antimicrobial Agents .

Antimicrobial Agents .

Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Penicillin (over 50 compounds) – Share 4-sided ring (ß lactam ring) • Natural penicillins • Narrow range of action • Susceptible to penicillinase (ß lactamase) .

Prokaryotic Cell Walls Gram positive cell wall Gram negative cell wall .

Penicillins Figure 20.6 .

Penicillinase (b Lactamase) Figure 20.8 .

resistant penicillins • Carbapenems: very broad spectrum • Monobactam: Gram negative • Extended.spectrum penicillins • Penicillins + b-lactamase inhibitors .Semisynthetic Penicillins • Penicilinase.

3rd. and 4th generations more effective against gram-negatives Figure 20.Other Inhibitors of Cell Wall Synthesis • Cephalosporins – 2nd.9 .

Other Inhibitors of Cell Wall Synthesis • Polypeptide antibiotics – Bacitracin • Topical application • Against gram-positives – Vancomycin • Glycopeptide • Important "last line" against antibiotic resistant S. aureus .

Other Inhibitors of Cell Wall Synthesis • Antibiotics effective against Mycobacteria: – interfere with mycolic acid synthesis or incorporation – Isoniazid (INH) – Ethambutol .

GI tract) – Macrolides: Erythromycin (gram +. kidneys) – Tetracyclines (Rickettsias & Chlamydia. toxicity problems • Examples – Chloramphenicol (bone marrow) – Aminoglycosides: Streptomycin. neomycin. gentamycin (hearing.Inhibitors of Protein Synthesis • Broad spectrum. used in children) .

Injury to the Plasma Membrane • Polymyxin B (Gram negatives) – Topical – Combined with bacitracin and neomycin (broad spectrum) in over-the-counter preparation .

Inhibitors of Nucleic Acid Synthesis • Rifamycin – Inhibits RNA synthesis – Antituberculosis • Quinolones and fluoroquinolones – Ciprofloxacin – Inhibits DNA gyrase – Urinary tract infections .

7 .Competitive Inhibitors – Sulfonamides (Sulfa drugs) • Inhibit folic acid synthesis • Broad spectrum Figure 5.

Antifungal Drugs • Fungi are eukaryotes • Have unique sterols in their cell walls • Pathogenic fungi are often outside the body .

protein capsid.Antiviral Drugs • Viruses are composed of nucleic acid.16a . and host membrane containing virus proteins • Viruses live inside host cells and use many host enzymes • Some viruses have unique enzymes for DNA/RNA synthesis or protein cutting in virus assembly Figure 20.

16a .Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.

Analogs Block DNA Synthesis Figure 20.16b. c .

Antiviral Drugs Enzyme Inhibitors • Inhibit assembly – Indinavir (HIV) • Inhibit attachment – Zanamivir (Influenza) • Inhibit uncoating – Amantadine (Influenza) .

Antiviral Drugs Enzyme Inhibitors • Interferons – prevent spread of viruses to new cells (Viral hepatitis) • Natural products of the immune system in viral infections .

Antiprotozoan Drugs • Protozoa are eukaryotic cells • Many drugs are experimental and their mode of action is unknown .

– hookworms .Antihelminthic Drugs • Helminths are macroscopic multicellular eukaryotic organisms: – tapeworms. – pinworms. – roundworms.

Antihelminthic Drugs • Prevent ATP generation (Tapeworms) • Alters membrane permeability (Flatworms) • Neuromuscular block (Intestinal roundworms) • Inhibits nutrient absorption (Intestinal roundworms) • Paralyzes worm (Intestinal roundworms) .

Measuring Antimicrobial Sensitivity • E Test • MIC: Minimal inhibitory concentration .

Measuring Antimicrobial Sensitivity: Disk Diffusion .

Penicillin .