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Chapter 12 - Antimicrobial Drugs
I. History of Chemotherapy –
A hundred years ago, in U.S., 1 out of 3 children was expected to die from an infectious disease before the
age of 5. Modern antimicrobial drugs were introduced in the 1930’s – thought to be “miracle drugs”.
Antimicrobial drugs have greatly reduced the incidence of certain diseases, but not all infectious diseases
can be eradicated. Growing resistance among organisms to antimicrobial drugs is presenting new challenges
in the fight against infectious diseases.
Humans have been taking medicines to try to control diseases for thousands of years Chemotherapy - the use of a chemical substance to treat a disease
Antibiotic - a substance produced by microorganisms that in small amounts inhibits other
microorganisms
A. Paul Erlich - Father of modern chemotherapy; coined the term "chemotherapy"; "magic bullet"
Antimicrobial effect of dyes; Salvarsan – arsenic compound for syphiilis
B. Sulfa drugs (sulfonamides) – Germany 1930’s
C. Fleming - discovered (accidentally) the first antibiotic - "penicillin"
Source: mold, Penicillium notatum
D. Howard Florey; Ernst Chain – large-scale production of penicillin
Terminology of Chemotherapy –– Be able to define:
Chemotherapeutic drug
Antimicrobial Chemotherapy
Prophylaxis
Antibiotics
Semisynthetic drugs
Synthetic Drugs
Narrow Spectrum
Broad Spectrum
The Origins of Antimicrobial Drugs
Sources of antibiotics:
Bacteria - Streptomyces ( more than 1/2 of our antibiotics come from this genus)
Bacillus species
Molds - Penicillum sp. and Cephalosporium species
II. Interactions Between Drug and Microbe
1. selective toxicity – You need to choose a drug that kills or inhibits the pathogen, but does not harm
the normal host cell
 identifying unique targets in prokaryotic cells is easy
 If the pathogen is a eukaryote, it is harder to find a unique target; these organisms more
closely resemble human cells
2. The Spectrum of microbial activity = the range of different microbes a drug affects
 Narrow spectrum - affects only a narrow range of organisms

Broad spectrum - affects a broad range of gram positive and gram negative organisms
advantage - can be used before you're sure what the pathogen is; covers a wide range of
possible pathogens; saves time
disadvantage 1. can also destroy the body's normal flora; this may allow some pathogenic organisms
to overgrow and cause a superinfection
2. overuse can lead to development of antibiotic resistant strains of bacteria
III. How Do Antimicrobial Drugs Work? (The Mechanisms of Drug Action) –
cidal - kill microbes directly
static - prevent microbes from growing
A. Inhibition of Cell Wall Synthesis –
1. Penicillins and cephalosporins prevent peptidoglycan from linking up to form a stable cell wall
 The cell undergoes osmotic lysis because of the weakened cell wall.
 not usually toxic to human cells (they contain no peptidoglycan )

actively growing cells are more susceptible

more effective against gram positive than against gram negative because of problems
penetrating the outer membrane of gram negatives
 the broad spectrum cephalosporins ( e.g., ceftriaxone) can access the cell wall of gram
negatives
B. Inhibition of Protein Synthesis –Some antibiotics target the 70S ribosomes of prokaryotes
1. Eukaryotes have 80S ribosomes, but do have some 70S ribosomes in the mitochondria –
2. sometimes these types of antibiotics can damage human cells ( especially chloramphenicol,
which can cause aplastic anemia)
3. protein synthesis inhibitors: chloramphenicol, erythromycin; streptomycin, tetracyclines and
aminoglycosides ( such as gentamycin)
C. Injury to the Plasma Membrane
1. change the permeability of the plasma membrane ; cell loses important proteins, ions, etc.
2. microbes vary in the types of lipids found in the membrane; different drugs act specifically
against different lipids
3. Most are also toxic to human cells
4. antifungal drugs - bind to ergosterol on the fungal plasma membrane
don't affect bacterial membranes ( they have no sterols)
will affect human membranes ( can bind to cholesterol)
Some, like amphotericin-B can be highly toxic
D. Inhibition of Nucleic Acid Synthesis
1. block synthesis of nucleotides; inhibit DNA synthesis; inhibit the DNA replication ; stop
transcription
2. these processes are very similar in bacteria and humans, so these drugs have a limited
usefulness
3. Quinolones ( e.g. ciprofloxacin) ; Chloroquine (antimalarial drug) ; Antiviral drugs ( e.g. AZT)
E. Drugs that Inhibit Folic Acid Synthesis
1. If the drug acts as a competitive inhibitor of an enzyme, it can stop an essential metabolic
pathway
2. In bacteria, PABA gets converted to folic acid by an enzyme.
3. Sulfonamides and trimethoprim act as competitive inhibitors; they compete with PABA for
the enzyme; They tie up the enzyme, so no folic acid is produced; bacterial growth is
inhibited
4. These two drugs are often given together to achieve a synergistic effect
5. Safe for humans because we don't make our own folic acid (we get it from our food)