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

• 1928 – Fleming discovered penicillin;produced by Penicillium (a fungus).

• 1940 – First clinical trials of penicillin.

Figure 20.1

The First Antibiotic

Table 20.2

Antimicrobials and Modes of Action• Prevents cell wall synthesis

• Prevents protein synthesis

• Plasma membrane attack

• Prevents nucleic acid synthesis

• Disrupts biochemical pathways

• Penicillin

• Natural penicillins

• Narrow spectrum

• Use for Staphylococci, Streptococci, Spirochetes

• Vulnerable to penicillinases (beta lactamases)

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

Figure 20.8

Some bacteria can disrupt the functioning of penicillin

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

Figure 20.9

Vancomycin:• Used against antibiotic resistant S. aureus (i.e. MRSA)

• VRE have emerged

Antiviral DrugsNucleoside and Nucleotide Analogs

Figure 20.16a

Antiviral DrugsNucleoside and Nucleotide Analogs

Figure 20.16b, c

• 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

Antiviral Drugs

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)

• 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

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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.

• 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

Antibiotic Resistance

• 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 Drug Combinations

Effects of Combinations of Drugs

Figure 20.22