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CASE STUDY
A 22-year-old woman presents to her college medical clinic complaining of a 2-week history of vaginal discharge. She denies any fever or abdominal pain but does report vaginal bleeding after sexual intercourse. When questioned about her sexual activity, she reports having vaginal intercourse, at times unprotected, with two men in the last 6 months. A pelvic examination is performed and is positive for mucopurulent discharge from the endocervical canal. No cervical motion tenderness is present. A first-catch urine specimen is obtained for chlamydia and gonorrhea nucleic acid amplification testing. A urine pregnancy test is also ordered as the patient reports she “missed her last period.” Pending these results, the decision is made to treat her presumptively for chlamydial cervicitis. What are two potential treatment options for her possible chlamydial infection? How does her potential pregnancy affect the treatment decision?
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The drugs described in this chapter inhibit bacterial protein synthesis by binding to and interfering with ribosomes. Most are bacteriostatic, but a few are bactericidal against certain organisms. Tetracycline and macrolide resistance is common. Except for tigecycline and the streptogramins, these antibiotics may be administered orally.
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All of the tetracyclines have the basic structure shown at right:
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Free tetracyclines are crystalline amphoteric substances of low solubility. They are available as hydrochlorides, which are more soluble. Such solutions are acidic and fairly stable. Tetracyclines chelate divalent metal ions, which can interfere with their absorption and activity. Tigecycline is a glycylcycline and a semisynthetic derivative of minocycline.
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Mechanism of Action & Antimicrobial Activity
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Tetracyclines are broad-spectrum bacteriostatic antibiotics that inhibit protein synthesis. Tetracyclines enter microorganisms in part by passive diffusion and in part by an energy-dependent process of active transport. Susceptible organisms concentrate the drug intracellularly. Once inside the cell, tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome, blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex (Figure 44–1). This prevents addition of amino acids to the growing peptide.
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