Mic Bio Chap 20

Selective toxicity

History of Chemotherapy

Selectively finding and destroying pathogens without damaging the host

Chemotherapy

History of Chemotherapy

The use of chemicals to treat a disease

Antibiotic

History of Chemotherapy

A substance produced by a microbe that, in small amounts, inhibits another microbe

Antimicrobial drugs

History of Chemotherapy

Synthetic substances that interfere with the growth of microbes

1932

History

Prontosil red dye used for streptococcal infections

1940

History

First clinical trials of penicillin

1928

History

Fleming discovered penicillin, produced by penicillium

Superinfection

Spectrum of Antimicrobial Activity

Overgrowth of normal microbiota that is resistant to antibiotics

Broad-spectrum

Spectrum of Antimicrobial Activity

Affect a broad range of gram-positive or gram-negative bacteria

Narrow spectrum

Spectrum of Antimicrobial Activity

Drugs that affect a narrow range of microbial types

Bactericidal

Action of Antimicrobial Drugs

Kill microbes directly

Bacteriostatic

Action of Antimicrobial Drugs

Prevent microbes from growing

Inhibiting cell wall synthesis

Action of Antimicrobial Drugs

Penicillins prevent the synthesis of peptidoglycan

Inhibiting protein synthesis

Action of Antimicrobial Drugs

1. Target bacterial 70S ribosomes

2. Chloramphenicol, erythromycin, streptomycin, tetracyclines

Injuring the plasma membrane

Action of Antimicrobial Drugs

1. Polypeptide antibiotics change membrane permeability

2. Antifungal drugs combine with membrane sterols

Inhibiting nucleic acid synthesis

Action of Antimicrobial Drugs

Interfere with DNA replication and transcription

Inhibiting the synthesis of essential metabolites

Action of Antimicrobial Drugs

1. Antimetabolites compete with normal substrates for an enzyme

   1. Sulfanilamide competes with para-aminobenzoic acid (PABA), stopping the synthesis of folic acid

Natural penicillins

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

1. Extracted from Penicillium fungi cultures

   1. Penicillin G (injected) and Penicillin V (oral)

1. Narrow spectrum of activity

2. Susceptible to penicillinases (β-lactamses)

Semisynthetic penicillins

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

Contain chemically added side chains, making them resistant to penicillanses

Penicillinase-resistant penicillin

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

Methicillin and oxacillin

Extended-spectrum penicillins

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

Effective against gram-negatives as well as grampositives (i.e. Aminopenicillins: ampicillin, amoxicillin)

Penicillins plus B-lactamase inhibitors

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

Contain clavulanic acid, a noncompetitive inhibitor of penicillinase

Carbapenems

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

1.  Substitute a C for an S and add a double bond to the penicillin nucleus

   1. Broad spectrum

   2. Primaxin, doripene

Monobactam

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

1. Synthetic; single ring instead of the β-lactam double ring

2. Low toxicity; works against only certain gram-negatives

   1. Aztreonam

Cephalosporins

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

1. Work similar to penicillins

2. β-lactam ring differs from penicillin

3. Grouped according to their generation of development

Penicillin

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

1. Contain a B-lactam ring

   1. Types are differentiated by the chemical side chains attached to the ring.

2. Prevent the cross-linking of peptidoglycans, interfering with cell wall construction (especially gram-positives)

Bacitracin

Polypeptide antibiotics

Topical application; works against gram-positives

Vancomycin

Polypeptide antibiotics

1. Glycopeptide 

2. Last line against antibiotic-resistant MRSA

Teixobactin

Polypeptide antibiotics

A new class of antibiotics; works against grampositives

Isoniazid (INH)

Antimycobacterial Antibiotics

Inhibits the mycolic acid synthesis in mycobacteria

Ethambutol

Antimycobacterial Antibiotics

Inhibits incorporation of mycolic acid into the cell wall

Nitrofurantoin

Inhibitors of Protein Synthesis

1. Converted to intermediates that attack bacterial ribosomal proteins

2. Synthesized chemically

3. Treatment for urinary bladder infections

Chloramphenicol

Inhibitors of Protein Synthesis

1. Inhibits peptide bond formation

   1. Binds to the 50S subunit of the 70S ribosome

2. Synthesized chemically; broad spectrum

3. Can suppress bone marrow and affect blood cell formation

Aminoglycosides

Inhibitors of Protein Synthesis

1. Amino sugars linked by glycoside bonds

2. Change the shape of the 30S subunit of the 70S ribosome

3. Can cause auditory damage

4. Streptomycin, neomycin, gentamici

Tetracyclines

Inhibitors of Protein Synthesis

1. Produced by Streptomyces spp.

2. Interfere with the tRNA attachment to the ribosome

3. Broad spectrum; penetrate tissues, making them valuable against rickettsias and chlamydias

4. Can suppress normal intestinal microbiota

Glycylcyclines

Inhibitors of Protein Synthesis

1. Broad spectrum; bacteriostatic

2. Bind to the 30S ribosomal subunit

3. Inhibits rapid efflux; administered intravenously

4. Useful against MRSA

Macrolides

Inhibitors of Protein Synthesis

1. Contain a macrocyclic lactone ring

2. Narrow spectrum against gram-positives

   1. Erythromycin

Streptogramins

Inhibitors of Protein Synthesis

1. Attach to the 50S subunit

2. Work against gram-positives that are resistant to other antibiotics

Oxazolidinones

Inhibitors of Protein Synthesis

1. Bind to the 50S/30S subunit interface

2. Synthetic; combat MRSA (linezolid)

Pleuromutilins

Inhibitors of Protein Synthesis

Retapamulin: topical and effective against gram-positives

Injury to Membranes

Affects synthesis of bacterial plasma membranes

Daptomycin

Lipopeptides

1. Produced by streptomycetes; used for skin infections

2. Attacks the bacterial cell membrane

Polymyxin B

Lipopeptides

1. Topical; bacteriocidal; effective against gram-negatives

2. Combined with bacitracin and neomycin in nonprescription ointments

Polymyxin E (colistin)

Lipopeptides

Effective against gram-negatives

Rifamycin

Nucleic Acid Synthesis Inhibitors

1. Inhibits mRNA synthesis

2. Penetrates tissues; antitubercular activity

Quinolone and Fluoroquinolones

Nucleic Acid Synthesis Inhibitors

1. Nalidixic acid

   1. Synthetic; inhibits DNA gyrase

2. Norfloxacin and ciprofloxacin

   1. Broad spectrum; relatively nontoxic

Sulfonamides

Competitive Inhibition of Essential Metabolites

1. Inhibit the folic acid synthesis needed for nucleic acid and protein synthesis

2. Competitively bind to the enzyme for PABA production, a folic acid precursor

3. Combination of trimethoprim and sulfamethoxazole (T MP-SMZ) is an example of drug synergism