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The tetracyclines (see Table 13: Bacteria and Antibacterial Drugs: Tetracyclines ) are bacteriostatic antibiotics that bind to the 30S subunit of the ribosome, thus inhibiting bacterial protein synthesis.
Pharmacology:
About 60 to 80% of tetracycline and ≥ 90% of doxycycline and minocycline are absorbed after oral administration. Because absorption is decreased by metallic cations (eg, aluminum, Ca, Mg, and iron), tetracyclines cannot be taken with preparations containing these substances (eg, antacids, many vitamin and mineral supplements). Food decreases absorption of tetracycline but not of doxycycline or minocycline .
Tetracyclines penetrate into most body tissues and fluids. All are concentrated in unobstructed bile. However, CSF levels are not reliably therapeutic. Minocycline is the only tetracycline that penetrates into tears and saliva in levels sufficient to eradicate the meningococcal carrier state. Tetracycline and minocycline are excreted primarily in the urine, may exacerbate azotemia, and should be avoided in patients with renal insufficiency. In renal failure, doxycycline is primarily excreted in the intestinal tract and requires no dose reduction. Tetracyclines cross the placenta to accumulate in fetal bones and teeth and are excreted in milk.
Indications:
Tetracyclines are effective in infections caused by rickettsiae, spirochetes (Treponema pallidum
, Borrelia burgdorferi), Helicobacter pylori
, Vibrio sp, Yersinia pestis
, Francisella tularensis
, Brucella sp, Bacillus anthracis
, Plasmodium vivax
, Plasmodium falciparum
, Mycoplasma, and Chlamydia and Chlamydophila. About 5 to 10% of pneumococcal strains and substantial numbers of group A β-hemolytic streptococci, many gram-negative bacillary uropathogens, and penicillinase-producing gonococci are resistant.
Tetracyclines are interchangeable for most indications, although minocycline has been most studied for methicillin-resistant Staphylococcus
aureus infections. Doxycycline is usually preferred because of its better tolerability and twice-daily administration for infections caused by rickettsiae, Chlamydia and Chlamydophila
, Mycoplasma, and Vibrio sp; acute exacerbations of chronic bronchitis; Lyme disease; brucellosis; anthrax; plague; tularemia; granuloma inguinale; and syphilis. Doxycycline is used for prophylaxis of malaria caused by chloroquine -resistant P. falciparum. Minocycline is an alternate to rifampin for eradicating the meningococcal carrier state.
Toxicity:
All orally administered tetracyclines produce nausea, vomiting, and diarrhea and can cause Clostridium difficile colitis and Candida superinfections. They can cause esophageal erosions if not swallowed with water. Tetracyclines can cause photosensitivity. They can cause staining of teeth, hypoplasia of dental enamel, and abnormal bone growth in children ≤ 8 yr and in fetuses. Therefore, tetracyclines should be avoided after
the 1st trimester of pregnancy, in mothers who are breastfeeding,
and in children < 8 yr. In infants, idiopathic intracranial hypertension and bulging fontanelles may occur.
Excessive blood levels from large doses or renal insufficiency may lead to fatal acute fatty degeneration of the liver, especially during pregnancy. Minocycline commonly causes vestibular dysfunction, particularly in women, limiting its use. Tetracyclines may decrease the efficacy of oral contraceptives and potentiate the effects of oral anticoagulants.
Older formulations of expired tetracycline pills can degenerate, causing Fanconi syndrome if ingested.
Last full review/revision November 2005
Content last modified November 2005
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