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Inhibiting the Growth
of Pathogens In Vivo
using Antimicrobial
Agents
BY: MC3 INSTRUCTORS
- Introduction
- Characteristics of an Ideal Antimicrobial Agent
- How Antimicrobial Agents Work
- Antibacterial Agents
- Some Major Categories of Antibacterial Agents
- Multidrug Therapy
- Synergism versus Antagonism
- Antifungal Agents chapter outline
After studying this chapter, you should be able to:
- Identify the characteristics of an ideal antimicrobial agent
- Compare and contrast chemotherapeutic agents, antimicrobial agents, and antibiotics as to their intended purpose
- State the five most common mechanisms of action of antimicrobial agents
- Differentiate between bactericidal and bacteriostatic agents
- State the difference between narrow-spectrum and broad-spectrum antimicrobial agents
- Identify the four most common mechanisms by which bacteria become resistant to antimicrobial agents
- State what the initials “MRSA” and “MRSE” stand for
- Define the following terms: β-lactam ring, β-lactam antibiotics, and β lactamase learning objectives
- Name two major groups of bacterial enzymes that destroy the β-lactam ring
- State six actions that clinicians and/or patients can take to help in the war against drug resistance
- Explain what is meant by empiric therapy
- List six factors that a clinician would take into consideration before prescribing an antimicrobial agent for a particular patient
- State three undesirable effects of antimicrobial agents
- Explain what is meant by a “superinfection,” and cite three diseases that can result from superinfections
- Explain the difference between synergism and antagonism with regard to antimicrobial agents learning objectives
paul ehrlich (1854-1915)
- He is the Father of Chemotherapy.
- A German chemist, began his search for chemicals (referred to as “magic bullets”) that would destroy bacteria, yet would not damage normal body cells.
- He discovered an arsenic compound that proved effective in treating syphilis. Because this was the 606th compound Ehrlich had tried, he called it “Compound 606.”The technical name for Compound 606 is arsphenamine, and the trade name was Salvarsan.
- Ehrlich also found that rosaniline was useful for treating African trypanosomiasis.
Alexander fleming (1881-1955)
- He accidentally discovered the first antibiotic
when he noticed that growth of contaminant
Penicillium notatum mould colonies on his
culture plates was inhibiting the growth of
Staphylococcus bacteria. He named it
Penicillin.
Gerhard Domagk
- Earlier—in 1935—a chemist named Gerhard Domagk discovered that the red dye Prontosil, was effective against streptococcal infection in mice. Further research demonstrated that Prontosil was degraded or broken down in the body into sulfanilamide, and that sulfanilamide [a sulfa drug] was the effective agent.
- Although sulfanilamide is an antimicrobial agent, it is not an antibiotic because it is not produced by a microorganism.)
Selman Waksman
- In 1944, Selman Waksman and his colleagues isolated streptomycin (the first antituberculosis drug) and subsequently discovered antibiotics such as chloramphenicol, tetracycline, and erythromycin in soil samples. It was Waksman who first used the term “antibiotic.”
How Antimicrobial Agents Work To be acceptable, an antimicrobial agent must inhibit or destroy the pathogen without damaging the host (i.e., the infected person). To accomplish this, the agent must target a metabolic process or structure possessed by the pathogen but not possessed by the host. The five most common mechanisms of action of antimicrobial agents are as follows:
- Inhibition of cell wall synthesis
- Damage to cell membranes
- Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
- Inhibition of protein synthesis
- Inhibition of enzyme activity
Some Major Categories of Antibacterial Agents
- Penicillins are referred to as β-lactam drugs because their molecular structure includes a four-sided ring structure known as a β-lactam ring. Penicillins interfere with the synthesis of bacterial cell walls and have maximum effect on bacteria that are actively dividing. They are bactericidal drugs.
- The cephalosporins are also β-lactam antibiotics and, like penicillin, are produced by moulds. Also, like penicillins, cephalosporins interfere with cell wall synthesis and are bactericidal. The cephalosporins are classified as first-, second-, third-, fourth-, and fifth-generation cephalosporins.
Some Major Categories of Antibacterial Agents
- Tetracyclines are broad-spectrum drugs that exert their effect by targeting bacterial ribosomes. They are bacteriostatic. Tetracyclines are effective against a wide variety of bacteria, including chlamydias, mycoplasmas, rickettsias, Vibrio cholerae, and spirochetes such as Borrelia spp. and Treponema pallidum.
- Aminoglycosides are bactericidal broad-spectrum drugs that inhibit bacterial protein synthesis. The major factor that limits their use is their toxicity. Aminoglycosides are effective against a wide variety of aerobic Gram-negative bacteria, but are ineffective against anaerobes.
Some Major Categories of Antibacterial Agents
- Macrolides inhibit protein synthesis. They are considered bacteriostatic at lower doses and bactericidal at higher doses. The macrolides include erythromycin, clarithromycin, and azithromycin. They are effective against chlamydias, mycoplasmas, T. pallidum, and Legionella spp.
- Fluoroquinolones are bactericidal drugs that inhibit DNA synthesis. The most commonly used fluoroquinolone, ciprofloxacin, is effective against members of the family Enterobacteriaceae and P. aeruginosa.