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Tetracyclines are adequately but incompletely absorbed from the gastrointestinal tract. Approximately 65 percent of a short-acting tetracycline is bound to plasma proteins; the plasma protein binding for intermediate- and long-acting analogues is usually greater.
Penetration of the tetracyclines into most body fluids and tissues is excellent. Tetracyclines are distributed in varying degrees into bile, liver, lung, kidney, prostate, urine, cerebrospinal fluid, synovial fluid, mucosa of the maxillary sinus, brain, sputum, and bone. Tetracyclines cross the placenta and enter the fetal circulation and amniotic fluid.
Following a single oral dose, peak plasma concentrations are achieved in two to four hours.
Tetracyclines are concentrated by the liver in the bile. They are excreted in both the urine and feces at high concentrations in a biologically active form. Since renal clearance of tetracyclines is by glomerular filtration, excretion is significantly affected by the state of renal function. (See WARNINGS.)
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines have a similar antimicrobial spectrum of activity against a wide range of gram-positive and gram-negative organism. Crossresistance of these organisms to tetracyclines is common. In addition, gram-negative bacilli made tetracycline-resistant, may also show cross-resistance to chloramphenicol.
Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are especially recommended:
Because many strains of these gram-positive microorganism have been shown to be resistant to tetracycline, culture and susceptibility testing are recommended. Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Enterococcus faecalis (formerly Streptococcus faecalis) have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for treatment of streptococcal disease unless the organism is known to be susceptible.
Quantitative methods that require measurement of zone diameters give the most precise estimate of the susceptibility of bacteria to antimicrobial agents.
One such standard procedure1 that has been recommended for use with disks to test susceptibility of microorganisms to tetracycline uses the 30-mcg tetracycline disk. Interpretation involves the correlation of the zone diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for tetracycline.
Reports from the laboratory giving results of the standard single- disk susceptibility test with a 30-mcg tetracycline disk should be interpreted according to the following criteria:
|Zone Diameter (mm)||Interpretation|
A report of "Susceptible" indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of "Intermediate" suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissues or fluids in which high antibiotic (or antimicrobial) levels are attained. A report of "Resistant" indicates that achievable concentrations are unlikely to be inhibitory and other therapy should be selected.
Standardized procedures require the use of laboratory control organisms. The 30-mcg tetracycline disk should give the following zone diameters:
|Organism||Zone Diameter (mm)|
|E. coli||ATCC 25922||18-25|
|S. aureus||ATCC 25923||19-28|
Use a standardized dilution method2 (broth, agar, microdilution) or equivalent with tetracycline powder. The MIC values obtained should be interpreted according to the following criteria:
|> 4.0 < 16||Intermediate|
As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard tetracycline pow- der should provide the following MIC values:
|E. coli||ATCC 25922||1-4|
|S. aureus||ATCC 29213||0.25-1|
|E. faecalis||ATCC 29212||8-32|
|P. aeruginosa||ATCC 27853||8-32|
Animal Pharmacology and Animal Toxicology
Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO4 and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO4 and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.
Minocycline, tetracycline PO4, methacycline, doxycycline, tetracycline base, oxytetracycline HCl and tetracycline HCl were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a large goiter with high radioiodine uptake in rats fed a relatively high iodine diet.
Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline), in chickens (chlortetracycline), and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.
1. National Committee for Clinical Laboratory Standards, Perfor- mance Standards for Antimicrobial Disk Susceptibility Tests- Fourth Edition. Approved Standard NCCLS Document M2-A4, Vol. 10, No. 7 NCCLS, Villanova, PA, April 1990.
2. National Committee for Clinical Laboratory Standards, Meth- ods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically-Second Edition. Approved Standard NCCLS Document M7-A2, Vol. 10, No. 8 NCCLS, Villanova, PA, April 1990.
Last reviewed on RxList: 2/8/2008
This monograph has been modified to include the generic and brand name in many instances.
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