The tetracyclines are a group of drugs that differ in physical and pharmacologic characteristics but have virtually identical antimicrobial properties and give complete cross-resistance. All tetracyclines are readily absorbed from the intestinal tract and distributed widely in tissues but penetrate into the CSF poorly (except doxycycline). Some can also be administered intramuscularly or intravenously. They are excreted in stool and into bile and urine at varying rates. With doses of tetracycline hydrochloride, 2 g/day orally, blood levels reach 8 μg/mL. Minocycline and doxycycline are excreted more slowly and therefore are administered at longer intervals.

The tetracyclines have the basic structure shown below.

Antimicrobial Activity

Tetracyclines are concentrated by susceptible bacteria and inhibit protein synthesis by inhibiting the binding of amino acyl-tRNA to the 30S unit of bacterial ribosomes. Resistant bacteria fail to concentrate the drug. This resistance is under the control of transmissible plasmids.

The tetracyclines are principally bacteriostatic agents. They inhibit the growth of susceptible Gram-positive and Gram-negative bacteria (inhibited by 0.1–10 μg/mL) and are drugs of choice in infections caused by rickettsiae, Anaplasma, Bartonella, chlamydiae, and Mycoplasma pneumoniae. Tetracyclines are used in cholera to shorten excretion of vibrios. Tetracycline hydrochloride or doxycycline orally for 7 days is effective against chlamydial genital infection. Tetracyclines are sometimes used in combination with streptomycin to treat Brucella, Yersinia, and Francisella infections. Minocycline is often active against Nocardia infections and can eradicate the meningococcal carrier state. Low doses of tetracycline for many months are given for acne to suppress both skin bacteria and their lipases, which promote inflammatory changes.

Tetracyclines do not inhibit fungi. They temporarily suppress parts of the normal bowel microbiota, but superinfections may occur, particularly with tetracycline-resistant pseudomonads, staphylococci, and yeasts.

Side Effects

The tetracyclines produce varying degrees of gastrointestinal upset (nausea, vomiting, diarrhea), skin rashes, mucous membrane lesions, and fever in many patients, particularly when administration is prolonged and dosage high. Photo sensitivity resulting in a rash in sun-exposed areas is also common. Replacement of bacterial microbiota (see earlier) occurs commonly. Overgrowth of yeasts on anal and vaginal mucous membranes during tetracycline administration leads to inflammation and pruritus. Overgrowth of organisms in the intestine may lead to enterocolitis.

Tetracyclines are deposited in bony structures and teeth, particularly in fetuses and during the first 6 years of life. Dis coloration and fluorescence of the teeth occur in newborns if tetracyclines are taken for prolonged periods by pregnant women. Hepatic damage may also occur. Minocycline can cause marked vestibular disturbances.

Bacteriologic Examination

 Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, resistance to tetracycline cannot be used to predict resistance to the other agents.

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