Tetracyclines

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, calcium, magnesium, iron); thus, tetracyclines cannot be taken with preparations containing these substances (eg, antacids, many vitamin and mineral supplements).Tetracyclineand omadacycline should be taken with plenty of water on an empty stomach. Food decreases absorption of other tetracyclines as well, but this effect is less significant fordoxycycline and minocycline.

Tetracyclines penetrate into most body tissues and fluids. All are concentrated in unobstructed bile. However, cerebrospinal fluid levels are not reliably therapeutic. Minocycline is the only tetracycline that reaches high concentrations in tears and saliva.

Tetracycline and minocyclineare excreted primarily in urine. Doxycycline, eravacycline, and omadacycline are 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 species

• Yersinia pestis

• Francisella tularensis

• Brucella species

• Bacillus anthracis

• Plasmodium vivax

• Plasmodium falciparum

• Mycoplasma species

• Chlamydia and Chlamydophila species

• Some methicillin-resistant Staphylococcus aureus

About 5 to 10% of pneumococcal strains and many group A beta-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-resistantS. aureus infections.

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

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

• Acute exacerbations of chronic bronchitis

• Lyme disease

• Brucellosis

• Anthrax

• Plague

• Tularemia

• Granuloma inguinale

• Syphilis

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

Tetracyclines are contraindicated in patients who have had an allergic reaction to them.

Use had been restricted in children doxycycline. Therefore, most experts now consider short-term (< 21 days) use ofdoxycycline acceptable for all ages (1). A study of children < 8 years of age who were treated with a short course of doxycycline for suspected Rocky Mountain spotted fever found no evidence of tooth staining or enamel defects compared to children who had not received doxycycline (2, 3).

Tetracyclines have been avoided in pregnancy because of the risk of accumulation in fetal bones and teeth; however, short courses of doxycycline (≤ 10 days) do not seem to increase risk of tooth discoloration. Nevertheless, pregnant and breastfeeding women should avoid tetracyclines when safer alternatives are available.

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.

Adverse effects of tetracyclines include

• Gastrointestinal disturbances

• 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 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 (not observed with short-term use of doxycycline; seeContraindications), hypoplasia of dental enamel, and abnormal bone growth in children < 8 years. 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 ofminocycline has been associated with development of autoimmune disorders such as systemic lupus erythematosus 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.

Tetracyclines (except for doxycycline) can exacerbate azotemia, hyperphosphatemia, and metabolic acidosis in patients with renal insufficiency. Although doxycyclinehas many of the metabolic properties of the tetracycline group, it usually does not cause toxic blood levels because of its extrarenal route of excretion.

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

Doxycycline, eravacycline, and omadacycline are excreted primarily in the intestinal tract and require no dose reduction in renal insufficiency, whereas tetracycline and minocycline require dose adjustment in patients with reduced kidney function.

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