Chapter 10Antimicrobial Medications

• Chemotherapy

• Antibiotic

• Synthetic drugs

• Semi-synthetic drugs

• In 1910, Paul Ehrlich discovered Salvarsan– Arsenic derivative used to treat syphilis

• In 1935, Gerhard Domagk discovered a red dye that inhibited G+ bacteria– Prontosil

• In 1936, Ernest Fourneau discovered it was the sulfur portion of the dye that was active – stimulated the development of sulfa drugs

• In 1928, Alexander Flemming -1st true antibiotic– Penicillium mold secretes compound that

inhibits bacterial growth

• Selman Waksman isolated streptomycin from the soil bacteria Streptomyces

• In 1940s, Howard Florey and Ernst Chain performed first clinical trials of penicillin– Developed a method for mass production– Penicillin G

• More than ½ of antibiotics in use come from bacteria– Primarily species of Streptomyces– Some are isolated from species of Bacillus

• Some are isolated from various molds – Penicillium and Cephalosporium

• Most antibiotic producers are spore formers

• Selective Toxicity

• Magic bullet – causes damage to the microorganism without

causing significant harm to the host– Easier with prokaryotic pathogens – Why?

• Chemotherapeutic index – maximum tolerable dose (per kg body weight) /

minimum effective dose (per kg body weight)– Higher the index the safer for host

• Spectrum of activity– range of different microorganisms against which

the drug is effective

– Narrow-spectrum • Example – anti-mycobacterials

– Broad-spectrum• May disturb normal microbiota • May lead to superinfection

• Synergism

– increased effect of two drugs when used together – clavulanic acid and amoxicillin

• Antagonism – reduction of a drug’s desirable effect when

administered with another • penicillin and tetracycline

• Adverse effects of antimicrobials– Allergic reactions– Toxic effects– Suppression of normal flora

Primary Modes of Action

Inhibition of Cell Wall Synthesis

– Bacterial cell walls are composed of the polysaccharide peptidoglycan • Some antibiotics prevent the synthesis of

intact peptidoglycan• Human cells are unaffected

Disruption of Cell Membrane

• changes permeability of the plasma membrane – Results in the loss of important metabolites – May target specific membrane components– Ex. particular sterols in fungi cell membranes

Inhibition of Protein Synthesis

• Common feature of all cells– May target the ribosomes

• Change ribosome shape• Block binding sites for tRNA/rRNA• Inhibit peptide bond formation • Prevent shift of reading frame

– Use is limited

Inhibition of Nucleic Acid Synthesis

• Interfere with DNA or RNA synthesis – May act as nucleoside/nucleotide analogs – Some have an extremely limited usefulness– Others are widely used because they are more

selectively toxic • May act only on bacterial or viral enzymes

Metabolic Antagonists

• Inhibition of the synthesis of essential metabolites– enzymatic activity of microbes can be inhibited

by a substance that closely resembles the normal substrate for the enzyme

– Competitive inhibition

Inhibition of Host Recognition or Attachment

• Depends on chemical reaction between pathogen and host– Pathogen proteins and specific host receptors– Modification of either attachment or receptor

proteins can inhibit attachment and entry

Mechanisms for Administration of Drugs

• Topical

• Orally

• Intramuscularly (IM)

• Intravenously (IV)

Tests to Guide Chemotherapy

• Disk-diffusion method (Kirby-Bauer test)

• Minimum Inhibitory Concentration tests (MIC)

• E-test

• Minimum Bactericidal Concentration tests (MBC)

Kirby-Bauer Test

MIC Test

E Test

MBC Test