Chapter 15: Antimicrobial Drugs ChemotherapyThe use of drugs to treat a disease Antimicrobial drugsInterfere with the growth of microbes within a host Antibiotic Inhibits “bacterial” growth; usually produced by bacteria or fungi Selective toxicityKills harmful microbes without damaging the host

Broad-spectrum antibiotic Superinfection Bactericidal antibiotic Bacteriostatic antibiotic

1928 – Fleming discovered penicillin; produced by Penicillium (a fungus) – 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 Drugs Nucleoside and Nucleotide Analogs Figure 20.16a

Antiviral Drugs Nucleoside 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