Tetracyclines inhibit bacterial protein synthesis by binding reversibly to the 30S ribosomal subunit.
Decreased accumulation of drug within bacteria leads to resistance; drug uptake is affected by decreasing influx or increasing efflux.
The tetracyclines are considered broad-spectrum bacteriostatic antibiotics with activity against many aerobic gram-positive and gram-negative bacteria and atypical pathogens, such as mycoplasma and chlamydia.
Absorption of tetracyclines occurs primarily in the proximal small intestine and the stomach with good distribution into tissues and body fluids.
Tetracyclines should generally not be used in pregnant women or children under the age of eight years unless other appropriate drugs are ineffective or contraindicated.
Tetracyclines are generally safe; the most common adverse events are related to gastrointestinal symptoms (eg, epigastric discomfort and nausea).
Chlortetracycline was the first tetracycline discovered, in 1948. Since then five additional tetracyclines have been isolated or derived (oxytetracycline, tetracycline, demeclocycline, doxycycline and minocycline), but only the last four are available for systemic use in the United States. Of these four agents, doxycycline and minocycline are the most frequently prescribed. Research to find tetracycline analogues lead to the development of the glycylcyclines. Tigecycline is the first of this new class of agents and exhibits broad-spectrum antibacterial activity similar to the tetracyclines．
Tigecycline has a broader spectrum of activity when compared to the tetracyclines. Tigecycline has activity against gram-positive pathogens including: Enterococcus spp., vancomycin-resistant enterococci (VRE), Listeria, Streptococcus spp., both methicillin-susceptible and -resistant S. aureus, and S. epidermidis. Its gram-negative activity includes: Acinetobacter baumannii, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Pasteurella multocida, Serratia marcescens, and Stenotrophomonas maltophilia．
Combination of tetracyclines and penicillins
A deleterious effect was observed for the combination of a static and cidal antibiotic when chlortetracycline and penicillin were used together for the treatment of pneumococcal meningitis. The combination of the two drugs was inferior to penicillin alone. Tetracycline administered with ampicillin or amoxicillin may result in diminished bactericidal activity of the penicillin. Thus, combinations of tetracyclines and penicillins should be avoided, if possible.
In general, tetracyclines penetrate into tissues and body fluids fairly well. Among the following agents, the degree of tissue penetration correlates to lipid solubility: minocycline > doxycycline > tetracycline