What are tetracycline antibiotics?

What Are Tetracycline Antibiotics?

Tetracycline antibiotics are a class of broad-spectrum bacteriostatic antimicrobials that work by inhibiting bacterial protein synthesis through binding to the 30S ribosomal subunit, preventing aminoacyl-tRNA molecules from attaching to ribosomal acceptor sites. 1, 2

Mechanism of Action

• Tetracyclines exert their antimicrobial effect primarily by inhibiting protein synthesis in bacteria, specifically by binding to the 30S ribosomal subunit 1, 2
• They are bacteriostatic rather than bactericidal, meaning they prevent bacterial growth rather than directly killing bacteria 3, 1
• This mechanism makes them effective against actively dividing bacteria but requires adequate host immune function to clear infections 4

Antimicrobial Spectrum

Tetracyclines demonstrate activity against a broad range of pathogens:

• Gram-positive bacteria: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Bacillus anthracis, Listeria monocytogenes 1
• Gram-negative bacteria: Haemophilus influenzae, Yersinia pestis, Vibrio cholerae, Neisseria gonorrhoeae 1, 2
• Atypical organisms: Chlamydia trachomatis, Chlamydophila psittaci, Mycoplasma pneumoniae, Ureaplasma urealyticum 1, 2
• Rickettsiae and spirochetes: Rickettsia species, Borrelia recurrentis, Treponema pallidum 1, 2
• Anaerobes: Bacteroides species, Clostridium species, Propionibacterium acnes (now Cutibacterium acnes) 1
• Parasites: Entamoeba species, Balantidium coli, Plasmodium falciparum (asexual forms only) 1, 2

Generations and Specific Agents

First-Generation Tetracyclines

• Tetracycline (the original compound) 5
• Less commonly used today due to pharmacokinetic limitations 6

Second-Generation Tetracyclines

• Doxycycline: The preferred tetracycline for most indications due to its long half-life (18-22 hours), excellent oral absorption even with food, superior tissue penetration, and no dose adjustment needed in renal insufficiency 2, 6
• Minocycline: Has unique properties including activity against methicillin-resistant Staphylococcus aureus (MRSA) but carries higher risk of serious adverse effects (8.8 cases per 100,000 patient-years) 3, 6

Third-Generation Tetracyclines

• Sarecycline: A narrow-spectrum tetracycline specifically effective against Cutibacterium acnes, FDA-approved for acne treatment, dosed at 1.5 mg/kg by weight 3, 7
• Tigecycline, omadacycline, eravacycline: Broader-spectrum agents used for severe resistant infections 7

Pharmacokinetics

• Tetracyclines are readily absorbed orally and bind to plasma proteins in varying degrees 1, 2
• They are concentrated by the liver in bile and excreted in urine and feces in biologically active form 1, 2
• Doxycycline is virtually completely absorbed after oral administration, with peak serum levels of 2.6 mcg/mL at 2 hours after a 200 mg dose 2
• Renal excretion of doxycycline is approximately 40% over 72 hours in patients with normal renal function, but can fall to 1-5% in severe renal insufficiency without significantly affecting serum half-life 2
• Hemodialysis does not alter doxycycline's serum half-life 2
• Tetracyclines cross the placenta and are found in fetal tissues 2

Clinical Applications

Primary dermatologic uses:

• Moderate to severe inflammatory acne vulgaris (first-line systemic therapy) 3, 8
• Rosacea and ocular rosacea 3
• Blepharitis and meibomian gland dysfunction 3

Infectious disease indications:

• Atypical pneumonia syndromes 3, 4
• Chlamydial genital infections 4, 6
• Rickettsial infections (Rocky Mountain spotted fever, ehrlichiosis, anaplasmosis) - doxycycline is the drug of choice 3
• Lyme disease (Borrelia infections) 4, 6
• Sexually transmitted infections 6
• Traveler's diarrhea 6

Dosing Recommendations

For acne treatment:

• Doxycycline: 100 mg twice daily (oral or IV) for adults; 2.2 mg/kg twice daily for children weighing <45.4 kg 3, 8
• Minocycline: 50-100 mg daily for adults; initial dose 4 mg/kg followed by 2 mg/kg every 12 hours for children ≥8 years 9, 2
• Sarecycline: 1.5 mg/kg daily (weight-based dosing) 3

For tickborne rickettsial diseases:

• Doxycycline: 100 mg twice daily for adults; 2.2 mg/kg twice daily for children, continued for at least 3 days after fever subsides, typically 5-7 days minimum 3

Major Adverse Effects and Contraindications

Common Side Effects

• Gastrointestinal disturbances: Nausea, vomiting, diarrhea, abdominal discomfort (more common with doxycycline at higher doses) 3
• Photosensitivity: Particularly with doxycycline (more photosensitizing than minocycline) 3
• Esophagitis: Can be reduced by taking with adequate fluids in upright position 3, 10
• Vaginal candidiasis: Can occur with any tetracycline 3

Serious Adverse Effects

• Pseudotumor cerebri (intracranial hypertension): Rare but serious complication associated with all tetracyclines 3, 10
• Minocycline-specific risks: Autoimmune disorders (drug-induced lupus, DRESS syndrome), tinnitus, dizziness, pigment deposition in skin/mucous membranes/teeth, autoimmune hepatitis 3, 9
• Esophageal perforation: Rare but potentially fatal complication from pill esophagitis 10
• Hypersensitivity reactions: Drug eruptions, Stevens-Johnson syndrome (rare) 3

Absolute Contraindications

• Pregnancy (FDA Category D): Risk of permanent tooth discoloration and bone growth inhibition in fetus 3, 9
• Lactation: Tetracyclines pass into breast milk and can cause tooth discoloration in nursing infants 3
• Children under 8 years of age: Risk of permanent tooth discoloration and interference with bone growth 3, 8
• History of hypersensitivity to tetracyclines 3

Critical Prescribing Considerations

To minimize bacterial resistance:

• Always combine oral tetracyclines with topical benzoyl peroxide when treating acne 3, 8
• Limit treatment duration to 3-4 months for acne 3, 8, 9
• Never use as monotherapy for acne 8, 9

Drug interactions:

• May decrease effectiveness of oral contraceptives 3
• May potentiate warfarin effects 3
• Absorption reduced by dairy products, antacids, and iron supplements (less problematic with doxycycline) 4

Special populations:

• Doxycycline is safe in renal impairment (primarily hepatically metabolized) 3, 8
• For pregnant patients or children <8 years requiring antibiotic therapy, consider macrolides (erythromycin, azithromycin) as alternatives 3, 8

Common Pitfalls to Avoid

• Using tetracyclines in children under 8 years (except in life-threatening situations like Rocky Mountain spotted fever where benefits outweigh risks) 3, 8, 11
• Prescribing during pregnancy or lactation 3, 9
• Failing to counsel patients about photosensitivity risk with doxycycline 8
• Using oral antibiotics as monotherapy for acne, which accelerates resistance 8, 9
• Exceeding 3-4 month treatment duration for acne without compelling indication 3, 8, 9
• Not instructing patients to take doxycycline with adequate fluids while upright to prevent esophagitis 3