CHAPTER
10
Controlling Microbial
Growth in the Body:
Antimicrobial Drugs
Chapter Outline
The History of Antimicrobial Agents (pp. 287–288)
Mechanisms of Antimicrobial Action (pp. 288–296)
Inhibition of Cell Wall Synthesis
Inhibition of Protein Synthesis
Disruption of Cytoplasmic Membranes
Clinical Considerations in Prescribing Antimicrobial Drugs (pp. 296–300)
Spectrum of Action
Effectiveness
Routes of Administration
Safety and Side Effects
Resistance to Antimicrobial Drugs (pp. 301–315)
Interactive Microbiology: Antibiotic Resistance—Selection
The Development of Resistance in Populations
Mechanisms of Resistance
Chapter Summary
The History of Antimicrobial Agents (pp. 287–288)
Chemicals that affect physiology in any manner are called drugs. Chemotherapeutic agents are
drugs used to treat diseases. Among them are antimicrobial agents (antimicrobials), which are
drugs used to treat infections.
Chapter 10 Controlling Microbial Growth in the Body: Antimicrobial Drugs
The use of these drugs began with German scientist Paul Ehrlich (1854–1915), who
discovered that arsenic compounds are effective against trypanosome parasites and syphilis. He
also proposed the term chemotherapy. Unfortunately, Ehrlich’s arsenic compounds were toxic to
Mechanisms of Antimicrobial Action (pp. 288–296)
The key to successful chemotherapy against microbes is selective toxicity; that is, an effective
antimicrobial agent must be more toxic to a pathogen than to the pathogen’s host. Selective
toxicity is possible because of differences in structure or metabolism between the pathogen and
its host. Because there are many differences between the structure and metabolism of pathogenic
Inhibition of Cell Wall Synthesis
Bacteria and fungi have cell walls that protect them from the effects of osmotic pressure.
The macromolecule peptidoglycan is the major component of bacterial cell walls.
Peptidoglycan is composed of chains of N-acetylglucosamine (NAG) and N-acetylmuramic acid
(NAM). NAM molecules are in turn cross-linked by short peptide bridges. Many common
antibacterial agents act by preventing the cross-linkage of peptidoglycan NAM subunits in the
bacterial cell wall. Most prominent among these drugs are the beta-lactams, such as penicillins
and cephalosporins. Their functional beta-lactam rings irreversibly bind to the enzymes that
cross-link NAM subunits.
Vancomycin and cycloserine disrupt cell wall formation by interfering with alanine-alanine
Instructor’s Manual for Microbiology with Diseases by Taxonomy, 5e
Inhibition of Protein Synthesis
Many antimicrobials take advantage of the differences between prokaryotic and eukaryotic
ribosomes to target bacterial protein translation. Various structures and functions within the
ribosome are targets. Antimicrobials that inhibit protein synthesis include aminoglycosides such
loading isoleucine to tRNA in Gram-positive bacteria such as Staphylococcus and
Streptococcus.
Video Tutor: Actions of Some Drugs That Inhibit Prokaryotic Protein Synthesis
Disruption of Cytoplasmic Membranes
Some antimicrobial agents, such as gramicidin and the polyenes, disrupt the cytoplasmic
membrane of a targeted cell, often by forming a channel through the membrane and damaging
its integrity. The polyenes nystatin and amphotericin B are fungicidal because they attach to
Inhibition of Metabolic Pathways
Antimetabolic agents target differences between the metabolic processes of a pathogen and its
host. The targets include:
electron transport. Atovaquone is effective on protozoa and fungi.
enzyme activity, blocked by heavy metals
Chapter 10 Controlling Microbial Growth in the Body: Antimicrobial Drugs
glucose uptake
activation of viruses
metabolic antagonists like sulfanilamide
Sulfonamides, including sulfanilamide, are structural analogs of para-aminobenzoic acid
Inhibition of Nucleic Acid Synthesis
Several drugs function by blocking either the replication of DNA or its transcription into RNA.
Drugs such as actinomycin bind DNA and inhibit DNA synthesis in both eukaryotic and
prokaryotic cells. Because both eukaryotic and prokaryotic DNA replication is affected,
actinomycin is used for research applications and to slow replication in cancer cells.
The synthetic quinolones and fluoroquinolones are active against prokaryotic DNA
specifically because they inhibit DNA gyrase, an enzyme necessary for correct coiling of
Prevention of Virus Attachment, Entry, or Uncoating
Attachment of viruses to host cells can be blocked by peptide and sugar analogs of either
attachment or receptor proteins. The use of such attachment antagonists is a new area of
antimicrobial drug development. Pleconaril is an attachment antagonist specific to the
Picornaviruses. Drugs that prevent attachment of the virus also prevent its entry.
Instructor’s Manual for Microbiology with Diseases by Taxonomy, 5e
Clinical Considerations in Prescribing Antimicrobial Drugs
(pp. 296–300)
The ideal antimicrobial agent would be readily available, inexpensive, chemically stable, easily
administered, nontoxic and nonallergenic, and selectively toxic against a wide range of
pathogens. No such agent exists, so drugs are selected for infections by a variety of criteria.
Spectrum of Action
The number of different kinds of pathogens a drug acts against is known as its spectrum of
action. Drugs that work against only a few kinds of pathogens are narrow-spectrum drugs,
Effectiveness
To ascertain the efficacy of antimicrobials for treatment, microbiologists conduct a variety of
tests, including, but not limited to, the following:
A Diffusion susceptibility test, also known as a Kirby-Bauer test, is a simple test used to
reveal which drug is most effective against a particular pathogen. The procedure involves
inoculating a Petri plate uniformly with a standardized amount of the pathogen in question
Minimum inhibitory concentration (MIC) attempts to quantify the smallest amount of a
drug that will inhibit growth and reproduction of a pathogen. This is typically determined by
Routes of Administration
For external infections, topical or local administration is effective. For internal infections, drugs
are administered orally, intramuscularly (IM), or intravenously (IV). Each route has advantages
Safety and Side Effects
Physicians must consider the possibility of adverse side effects of chemotherapy, including
toxicity, allergic reaction, and disruption of normal microbiota.
Toxicity
Many drugs have toxic effects on kidneys, liver, and nerves. Some side effects are unpleasant,
for example the “black hairy tongue” caused by metronidazole. Toxicity is especially important
to consider for pregnant women because many drugs that are safe for adults can have adverse
Allergies
Some drugs trigger allergic immune responses in sensitive patients. Although relatively rare,
such reactions can be life threatening, especially when they result in anaphylactic shock.
Disruption of Normal Microbiota
Many drugs, especially broad-spectrum antibiotics, also disrupt normal antagonism between
benign normal microbiota and opportunistic pathogens and thus prompt secondary infections.
For example, broad-spectrum antibiotics taken for prolonged periods of time can lead to an
Resistance to Antimicrobial Drugs (pp. 301–315)
Pathogens developing resistance to antimicrobial agents is a growing challenge.
Interactive Microbiology: Antibiotic Resistance—Selection
The Development of Resistance in Populations
Bacterial cells acquire resistance to antibiotics in two ways: through new mutations of
chromosomal genes or by acquiring resistance genes on extrachromosomal pieces of DNA
Instructor’s Manual for Microbiology with Diseases by Taxonomy, 5e
Mechanisms of Resistance
Interactive Microbiology: Antibiotic Resistance—Mechanisms
Microorganisms may resist a drug by one of at least seven mechanisms:
2. Inducing changes in the cytoplasmic membrane that prevent entry of the drug
4. Altering the cell’s metabolic pathways
6. Growing within a biofilm that retards drug diffusion and results in altered metabolic rates in
bacteria, reducing the effectiveness of antimicrobials
7. Protecting the target of an antimicrobial drug to inhibit its binding, as in the case of M.
tuberculosis MfpA protein, which protects DNA gyrase from antimicrobial agents.
Multiple Resistance and Cross Resistance
Pathogens can acquire resistance to more than one drug at a time, especially when resistance is
conferred by R plasmids. Multiple-drug-resistant pathogens (erroneously called superbugs) are
Retarding Resistance
Resistance can be retarded in one or more of four ways:
2. Using antimicrobials in combination, promoting synergism, the interaction between drugs
that results in effectiveness that exceeds the effectiveness of either drug alone. For example,
3. Limiting the use of antimicrobials to necessary cases, avoiding indiscriminate prescribing and
uncontrolled use.
4. Developing new variations of existing drugs and searching for entirely new antimicrobials.