What are tetracycline antibiotics?

What Are Tetracycline Antibiotics

Definition and Mechanism of Action

Tetracycline antibiotics are a class of bacteriostatic antimicrobial agents that inhibit bacterial protein synthesis by reversibly binding to the 30S ribosomal subunit, preventing aminoacyl-tRNA from binding to the ribosomal acceptor site. 1, 2

• These drugs are primarily bacteriostatic rather than bactericidal, meaning they inhibit bacterial growth and replication rather than directly killing bacteria, relying on the host immune system to eliminate the pathogen 3, 1
• Tetracyclines are readily absorbed after oral administration and are concentrated by the liver in bile, then excreted in urine and feces in biologically active form 1, 2

Members of the Tetracycline Class

First-Generation Tetracyclines

• Tetracycline is the original compound in this class, typically dosed at 250-500 mg orally or intravenously every 6 hours in adults 4
• First-generation agents have been in clinical use for over 60 years 5, 6

Second-Generation Tetracyclines (Preferred Agents)

• Doxycycline is the preferred tetracycline agent for most indications due to superior pharmacokinetics with twice-daily dosing (100 mg twice daily), excellent oral absorption even with food, and no renal dose adjustment required 7, 8
• Doxycycline is virtually completely absorbed after oral administration, with peak serum levels of 2.6 mcg/mL at 2 hours following a 200 mg dose 2
• Minocycline represents a reasonable substitute for doxycycline in select scenarios, including skin and soft-tissue infections, community-acquired pneumonia in young healthy patients, and rickettsial diseases when doxycycline is unavailable 7, 8

Antimicrobial Spectrum

Gram-Positive Bacteria

• Active against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Bacillus anthracis, and Listeria monocytogenes 1
• Up to 44% of Streptococcus pyogenes strains and 74% of Streptococcus faecalis strains are resistant to tetracyclines, requiring susceptibility testing before use 2

Gram-Negative Bacteria

• Active against Haemophilus influenzae, Yersinia pestis, Vibrio cholerae, Francisella tularensis, and Brucella species 1
• Many strains of Escherichia coli, Klebsiella species, Enterobacter aerogenes, Shigella species, and Acinetobacter species show resistance, necessitating culture and susceptibility testing 2

Atypical and Intracellular Pathogens

• Highly effective against Chlamydia trachomatis, Chlamydophila psittaci, Mycoplasma pneumoniae, Ureaplasma urealyticum, and Rickettsia species 1, 9
• Active against Borrelia recurrentis (Lyme disease), Treponema pallidum (syphilis), and Treponema pallidum subspecies pertenue 1

Other Organisms

• Active against anaerobes including Bacteroides species, Clostridium species, Fusobacterium fusiforme, and Propionibacterium acnes 1
• Effective against parasites including Entamoeba species, Balantidium coli, and the asexual erythrocytic forms of Plasmodium falciparum 1, 2

Primary Clinical Indications

Respiratory Tract Infections

• Doxycycline is a first-line agent for community-acquired respiratory tract infections, particularly atypical pneumonia syndromes caused by Mycoplasma pneumoniae and Chlamydophila pneumoniae 3, 6
• Adequate activity against penicillin-susceptible pneumococci, though efficacy decreases with penicillin-resistant strains 3

Sexually Transmitted Infections

• First-line treatment for chlamydial genital infections caused by Chlamydia trachomatis 6, 9
• Doxycycline 100 mg orally twice daily for 14 days is the preferred alternative for syphilis in penicillin-allergic patients 7

Rickettsial and Vector-Borne Diseases

• Essential for treating Rocky Mountain spotted fever, typhus, Q fever, ehrlichiosis, and Lyme disease 6, 9
• Doxycycline is the preferred agent for Lyme disease prophylaxis 7

Bioterrorism-Related Infections

• Doxycycline 100 mg twice daily orally or intravenously is the first-choice agent for bioterrorism-related cutaneous and inhalational anthrax, with treatment continued for 60 days due to potential spore persistence 4
• Effective against Yersinia pestis (plague) and Francisella tularensis (tularemia) 1

Dermatologic Conditions

• Doxycycline 100 mg daily for 3-4 months maximum, always combined with topical benzoyl peroxide and/or retinoids, for moderate to severe inflammatory acne 3
• Oral tetracyclines are helpful for patients with meibomian gland dysfunction and blepharitis whose symptoms are not controlled by eyelid cleansing 4

Cholera

• Azithromycin is the first-choice agent for children with cholera, with doxycycline or ciprofloxacin as second-choice alternatives 4

Critical Contraindications and Safety Warnings

Pregnancy and Lactation

• Tetracycline-class antibiotics are contraindicated in pregnancy (Category D) due to permanent tooth discoloration and bone growth inhibition in the fetus. 4, 7
• Tetracyclines are contraindicated for nursing women, though short-term doxycycline use (≤3 weeks maximum without repeated courses) may be acceptable in exceptional circumstances due to low concentrations in breast milk 10
• For life-threatening infections during pregnancy (such as bioterrorism-related anthrax), doxycycline may be indicated despite risks, as adverse effects on developing teeth and bones are dose-related 4

Pediatric Use

• Children under 8 years of age should not receive tetracycline-class agents due to permanent tooth enamel discoloration and bone growth inhibition. 4, 7
• The American Academy of Pediatrics recommends tetracyclines for serious infections in young children (such as Rocky Mountain spotted fever) only in exceptional circumstances 4
• For children requiring tetracycline-class coverage, erythromycin 30-40 mg/kg/day divided over 3 doses for 3 weeks, then twice daily for 4-6 weeks, is the preferred alternative 4, 7

Common Adverse Effects

• Photosensitization occurs with tetracyclines, resulting in greater likelihood of sunburn with sun exposure 4, 6
• Gastrointestinal upset, vaginitis, and rarely azotemia may occur 4
• Tetracyclines have been implicated in cases of pseudotumor cerebri 4
• Minocycline can stain skin, nails, sclera, teeth, conjunctiva, tongue, and bone 4

Drug Interactions

• Tetracyclines may decrease the effectiveness of oral contraceptives and potentiate the effect of warfarin 4
• Tetracyclines are contraindicated in patients with a history of hypersensitivity to tetracyclines 4

Resistance Considerations

• Tetracycline resistance in bacteria can occur by acquisition of ≥1 of 36 different resistance genes, by mutations to host efflux pumps or in 16S rRNA sequences, or by alteration in cell permeability 9
• Cross-resistance among tetracyclines is common, meaning resistance to one tetracycline often confers resistance to others 1, 2
• Bacteriostatic antibiotics should never be used as monotherapy for prolonged durations to prevent resistance development 3
• Culture and susceptibility testing are recommended for many gram-negative organisms due to high resistance rates 2