Tetracyclines are bacteriostatic antibiotics Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more that bind to the 30S subunit of the ribosome, thus inhibiting bacterial protein synthesis. Specific tetracyclines are
Eravacycline (IV only)
Omadacycline (novel aminomethylcycline)
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 withpreparations containing these substances (eg, antacids, many vitamin and mineral supplements). Tetracycline and 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 for doxycycline 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 minocycline are excreted primarily in urine. Doxycycline, eravacycline, and omadacycline are excreted primarily in the intestinal tract.
Indications for Tetracyclines
Tetracyclines are active against infections caused by the following:
Spirochetes (eg, Treponema pallidum Syphilis Syphilis is caused by the spirochete Treponema pallidum and is characterized by 3 sequential clinical, symptomatic stages separated by periods of asymptomatic latent infection. Common manifestations... read more , Borrelia burgdorferi Lyme Disease Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia species. Early symptoms include an erythema migrans rash, which may be followed weeks to months later by neurologic... read more )
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-resistant S. 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 Overview of Rickettsial and Related Infections Rickettsial diseases (rickettsioses) and related diseases (anaplasmosis, ehrlichiosis, Q fever, scrub typhus) are caused by a group of gram-negative, obligately intracellular coccobacilli. All... read more or Anaplasma Ehrlichiosis and Anaplasmosis Ehrlichiosis and anaplasmosis are caused by rickettsial-like bacteria. Ehrlichiosis is caused mainly by Ehrlichia chaffeensis; anaplasmosis is caused by Anaplasma phagocytophilum. Both are transmitted... read more , Chlamydia, Chlamydophila, Ehrlichia Ehrlichiosis and Anaplasmosis Ehrlichiosis and anaplasmosis are caused by rickettsial-like bacteria. Ehrlichiosis is caused mainly by Ehrlichia chaffeensis; anaplasmosis is caused by Anaplasma phagocytophilum. Both are transmitted... read more , Mycoplasma, or Vibrio Cholera Cholera is an acute infection of the small bowel by the gram-negative bacterium Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria... read more species
Prophylaxis of malaria Malaria Malaria is infection with Plasmodium species. Symptoms and signs include fever (which may be periodic), chills, rigors, sweating, diarrhea, abdominal pain, respiratory distress, confusion, seizures... read more caused by chloroquine-resistant P. falciparum
Contraindications to Tetracyclines
Tetracyclines are contraindicated in
Patients who have had an allergic reaction to them
Children < 8 years (except sometimes for inhalational anthrax or other severe illnesses, such as Rocky Mountain spotted fever Rocky Mountain Spotted Fever (RMSF) Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii and transmitted by ixodid ticks. Symptoms are high fever, severe headache, and rash. (See also Overview of Rickettsial... read more , when the benefit outweighs the potential risk of tooth staining)
Use During Pregnancy and Breastfeeding
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 the fetus's 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 of Tetracyclines
Adverse effects of tetracyclines include
Clostridioides (formerly Clostridium) difficile–induced diarrhea Clostridioides (formerly Clostridium) difficile–Induced Diarrhea Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody, rarely... read more (pseudomembranous colitis)
Bone and dental effects in children
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 years 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 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.
Tetracycline can exacerbate azotemia in patients with renal insufficiency.
Expired tetracycline pills can degenerate and, if ingested, cause Fanconi syndrome Fanconi Syndrome Fanconi syndrome consists of multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and bicarbonate wasting. It may be hereditary... read more . Patients should be instructed to discard the drugs when they expire.
Dosing Considerations for Tetracyclines
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.