Drugs in this class are broad-spectrum bacteriostatic antibiotics that have only minor differences in their activities against specific organisms.
Oral absorption is variable, especially for the older drugs, and may be impaired by foods and multivalent cations (calcium, iron, aluminum). Tetracyclines have a wide tissue distribution and cross the placental barrier. All the tetracyclines undergo enterohepatic cycling. Doxycycline is excreted mainly in feces; the other drugs are eliminated primarily in the urine. The half-lives of doxycycline and minocycline are longer than those of other tetracyclines. Tigecycline, formulated only for IV use, is eliminated in the bile and has a half-life of 30–36 h.
Tetracyclines are broad-spectrum antibiotics with activity against gram-positive and gram-negative bacteria, species of Rickettsia, Chlamydia, Mycoplasma, and some protozoa.
However, resistance to most tetracyclines is widespread. Resistance mechanisms include the development of mechanisms (efflux pumps) for active extrusion of tetracyclines and the formation of ribosomal protection proteins that interfere with tetracycline binding. These mechanisms do not confer resistance to tigecycline in most organisms, with the exception of the multidrug efflux pumps of Proteus and Pseudomonas species.
Tetracyclines are recommended in the treatment of infections caused by Mycoplasma pneumoniae (in adults), chlamydiae, rickettsiae, vibrios, and some spirochetes. Doxycycline is currently an alternative to macrolides in the initial treatment of community-acquired pneumonia.
Tetracyclines are alternative drugs in the treatment of syphilis. They are also used in the treatment of respiratory infections caused by susceptible organisms, for prophylaxis against infection in chronic bronchitis, in the treatment of leptospirosis, and in the treatment of acne.
Specific tetracyclines are used in the treatment of gastrointestinal ulcers caused by Helicobacter pylori (tetracycline), in Lyme disease (doxycycline), and in the meningococcal carrier state (minocycline). Doxycycline is also used for the prevention of malaria and in the treatment of amebiasis (Chapter 52). Demeclocycline inhibits the renal actions of antidiuretic hormone (ADH) and is used in the management of patients with ADH-secreting tumors (Chapter 15).
Unique features of this glycylcycline derivative of minocycline include a broad spectrum of action that includes organisms resistant to standard tetracyclines. The antimicrobial activity of tigecycline includes gram-positive cocci resistant to methicillin (MRSA strains) and vancomycin (VRE strains), beta-lactamase–producing gram-negative bacteria, anaerobes, chlamydiae, and mycobacteria. The drug is formulated only for intravenous use.
Effects on the gastrointestinal system range from mild nausea and diarrhea to severe, possibly life-threatening enterocolitis. Disturbances in the normal flora may lead to candidiasis (oral and vaginal) and, more rarely, to bacterial superinfections with S aureus or Clostridium difficile.
Bony Structures and Teeth
Fetal exposure to tetracyclines may lead to tooth enamel dysplasia and irregularities in bone growth. Although usually contraindicated in pregnancy, there may be situations in which the benefit of tetracyclines outweigh the risk. Treatment of younger children may cause enamel dysplasia and crown deformation when permanent teeth appear.
High doses of tetracyclines, especially in pregnant patients and those with preexisting hepatic disease, may impair liver function and lead to hepatic necrosis.
One form of renal tubular acidosis, Fanconi's syndrome, has been attributed to the use of outdated tetracyclines. Though not directly nephrotoxic, tetracyclines may exacerbate preexisting renal dysfunction.
Tetracyclines, especially demeclocycline, may cause enhanced skin sensitivity to ultraviolet light.
Dose-dependent reversible dizziness and vertigo have been reported with doxycycline and minocycline.