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By Hans P. Schlecht, MD, MSc, Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine ; Christopher Bruno, MD, Assistant Professor of Medicine, Division of infectious Diseases & HIV Medicine, Drexel University College of Medicine

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Tetracyclines (see Table: Tetracyclines) are bacteriostatic antibiotics that bind to the 30S subunit of the ribosome, thus inhibiting bacterial protein synthesis.






About 60 to 80% of tetracycline and 90% of doxycycline and minocycline are absorbed after oral use. However, absorption is decreased by metallic cations (eg, aluminum, Ca, Mg, iron); thus, 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 reaches high concentrations in tears and saliva.

Tetracycline and minocycline are excreted primarily in urine. Doxycycline is excreted primarily in the intestinal tract.


Tetracyclines are active against infections caused by the following:

  • Rickettsiae

  • Spirochetes (eg, Treponema pallidum, Borrelia burgdorferi)

  • Helicobacter pylori

  • Vibrio sp

  • Yersinia pestis

  • Francisella tularensis

  • Brucella sp

  • Bacillus anthracis

  • Plasmodium vivax

  • Plasmodium falciparum

  • Mycoplasma sp

  • Chlamydia and Chlamydophila sp

  • Some methicillin-resistant Staphylococcus aureus

About 5 to 10% of pneumococcal strains and many 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 S. aureus infections.

Doxycycline is usually preferred for all of the following because it is better tolerated and can be given twice/day:

  • Infections caused by rickettsiae or Anaplasma, Chlamydia, Chlamydophila, Ehrlichia, Mycoplasma, or Vibrio spp

  • Acute exacerbations of chronic bronchitis

  • Lyme disease

  • Brucellosis

  • Anthrax

  • Plague

  • Tularemia

  • Granuloma inguinale

  • Syphilis

  • Prophylaxis of malaria caused by chloroquine-resistant P. falciparum

Because of its high concentration in tears and saliva, minocycline is the only tetracycline that can eradicate meningococci in carriers and is an alternate to rifampin for this indication.


Tetracyclines are contraindicated in patients who have had an allergic reaction to them, patients with renal insufficiency (except for doxycycline, which has no dosage adjustment for renal insufficiency), and children < 8 yr (except sometimes for inhalational anthrax or other severe illnesses when the benefit outweighs the potential risk of tooth staining).

Use During Pregnancy and Breastfeeding

Tetracyclines are in pregnancy category D (there is evidence of human risk, but clinical benefits may outweigh risk). Tetracyclines cross the placenta, enter fetal circulation, accumulate in fetal bones, and, if used during the 2nd or 3rd trimester, may cause permanent discoloration of teeth.

Hepatotoxicity may occur in pregnant women, particularly after IV administration and in those with azotemia or pyelonephritis. Taking high doses during pregnancy can lead to fatty degeneration of the liver, which may be fatal.

Tetracyclines enter breast milk, but usually in small amounts (particularly tetracycline). Use during breastfeeding is usually discouraged.

Adverse Effects

Adverse effects include

  • GI disturbances

  • Clostridium difficile–induced diarrhea (pseudomembranous colitis—see Clostridium difficile –Induced Diarrhea)

  • Candidiasis

  • Photosensitivity

  • Bone and dental effects in children

  • Fatty liver

  • Vestibular dysfunction (with minocycline)

All oral tetracyclines cause nausea, vomiting, and diarrhea and can cause C. difficile–induced diarrhea (pseudomembranous colitis) and candidal superinfections. If not swallowed with water, tetracyclines can cause esophageal erosions. Photosensitivity due to tetracyclines may manifest as an exaggerated sunburn reaction. Bone and dental effects include staining of teeth, hypoplasia of dental enamel, and abnormal bone growth in children < 8 yr and in fetuses. In infants, tetracyclines may cause idiopathic intracranial hypertension and bulging fontanelles.

Excessive blood levels due to use of high doses or renal insufficiency may lead to fatal acute fatty degeneration of the liver, especially during pregnancy.

Minocycline commonly causes vestibular dysfunction, limiting its use. Use of minocycline has been associated with development of autoimmune disorders such as SLE and polyarteritis nodosa, which may be reversible. Minocycline may also cause drug reaction with eosinophilia and systemic symptoms (DRESS), which is characterized by fever, rash, lymphadenopathy, hepatitis, atypical lymphocytosis, eosinophilia, and thrombocytopenia.

Tetracycline can exacerbate azotemia in patients with renal insufficiency.

Expired tetracycline pills can degenerate and, if ingested, cause Fanconi syndrome. Patients should be instructed to discard the drugs when they expire.

Dosing Considerations

Doxycycline, excreted primarily in the intestinal tract, requires no dose reduction in renal insufficiency.

Tetracyclines may decrease the effectiveness of oral contraceptives and potentiate the effects of oral anticoagulants.

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