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Explore the use of antimicrobial drugs to treat diseases and their impact on microbial growth. Learn about antibiotics, selective toxicity, and the emergence of antibiotic resistance.
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Chapter 15: Antimicrobial Drugs • Chemotherapy The use of drugs to treat a disease • Antimicrobial drugs Interfere with the growth of microbes within a host • Antibiotic Inhibits “bacterial” growth; usually produced by bacteria or fungi • Selective toxicity Kills harmful microbes without damaging the host
Broad-spectrum antibiotic • Superinfection • Bactericidal antibiotic • Bacteriostatic antibiotic
The First Antibiotic • 1928 – Fleming discovered penicillin;produced by Penicillium (a fungus). • 1940 – First clinical trials of penicillin. Figure 20.1
Antimicrobials and Modes of Action • Prevents cell wall synthesis • Prevents protein synthesis • Plasma membrane attack • Prevents nucleic acid synthesis • Disrupts biochemical pathways
Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis • Penicillin • Natural penicillins • Narrow spectrum • Use for Staphylococci, Streptococci, Spirochetes • Vulnerable to penicillinases (beta lactamases)
Some bacteria can disrupt the functioning of penicillin Figure 20.8
Penicillins Figure 20.6
Semisynthetic penicillins • Penicillinase-resistant penicillins • First was methicillin • Extended-spectrum penicillins • Effective against many Gram negatives • Some effective against Pseudomonas aeruginosa • Penicillins + -lactamase inhibitors
Cephalosporins: • more effective against gram-negatives than natural penicillins • Vancomycin: • Used against antibiotic resistant S. aureus (i.e. MRSA) • VRE have emerged Figure 20.9
Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16a
Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16b, c
Antiviral Drugs • Protease inhibitors • Entry and Uncoating inhibitors • Viral release inhibitors • i.e. Tamiflu • Interferons, prevent spread of viruses to new cells • Common treatment for Hepatitis C infection
Kirby-Bauer (Disk-Diffusion) Test • Antibiotic soaked disks are placed on cultured plate • Zone of inhibition is measured and compared to table with known results
E test • Antibiotic gradient strip is placed on cultured plate • Minimal inhibitory concentration (MIC) is determined
E Test Figure 20.18
Broth Dilution Test • Can distinguish between MIC and MBC (minimal bactericidal concentration)
Antibiotic Resistance • Mechanisms of antibiotic resistance • Alteration of drug's target site • Rapid ejection of the drug • Enzymatic destruction of drug • Prevention of penetration of drug
Antibiotic Resistance • A variety of mutations can lead to antibiotic resistance. • Resistance genes are often on plasmids or transposons that can be transferred between bacteria.
Antibiotic Resistance • 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
Effects of Drug Combinations • Synergism: occurs when the effect of two drugs together is greater than the effect of either alone. • Antagonism: occurs when the effect of two drugs together is less than the effect of either alone.
Effects of Combinations of Drugs Figure 20.22