Tetracyclines
GENERAL PRINCIPLES
• Tetracyclines are bacteriostatic antibiotics that bind to the 30S ribosomal subunit and block protein synthesis.
• These agents have unique roles in the treatment of Rickettsia, Ehrlichia, Chlamydia, and Mycoplasma infections.
They are used as therapy for most tick-borne infections, including Lyme disease-related arthritis, alternate therapy for syphilis, and therapy for P. multocida infections in PCN-allergic patients. The tetracycline derivatives also have activity against some multidrug-resistant (MDR) gram-negative pathogens and may be used in this setting based on results of susceptibility testing.TREATMENT
• Tetracycline (250-500 mg PO q6h) is commonly used for severe acne and in some H. pylori eradication regimens. It has largely been replaced by doxycycline for other infections (see below).
• Doxycycline (100 mg PO/IV q12h) is the most commonly used tetracycline and is standard therapy for C. trachomatis, Rocky Mountain spotted fever, ehrlichiosis, and psittacosis. This agent also has a role in the treatment of CAP and uncomplicated skin and skin structure infections (including infections caused by MRSA, but not S. pyogenes), as well as malaria prophylaxis.
• Minocycline (200 mg IV/PO ? 1 dose, then 100 mg IV/PO q12h) is similar to doxycycline in its spectrum of activity and clinical indications. Among the tetracyclines, minocycline is most likely to provide coverage against Acinetobacter. Minocycline can also be used for treating pulmonary nocardiosis, cervicofacial actinomycosis, and S. maltophilia infections.
• Tigecycline (100-200 mg IV ? 1 dose, then 50-100 mg IV q12h) is a tetracycline derivative further classified as a glycylcycline. Tigecycline has broad spectrum of activity against most gram-positive, gram-negative, and anaerobic bacteria, except P. aeruginosa and some Proteus spp.
It may be used for treatment of infections due to susceptible strains of VRE and some MDR gram-negative bacteria, including CRE. Owing to a high volume of distribution and low achievable blood concentrations, tigecycline should not be used to treat primary bacteremia. Tigecycline should generally be avoided when alternative options are available due to a noted increase in all-cause mortality based on a metaanalysis of phase 3 and 4 clinical trial data. Dose adjustment in severe hepatic impairment is indicated.• Omadacycline (200 mg IV ? 1 dose, then 100 mg IV q24h or 450 mg PO daily ? 2 doses, then 300 mg PO q24h) is a tetracycline derivative FDA-approved for CAP and skin and skin structure infections. This agent can overcome some tetracycline resistance mechanisms, resulting in broad-spectrum activity against gram-positive (including MRSA and VRE), gram-negative, and atypical organisms, as well as anaerobes.
• Eravacycline (1 mg/kg IV q12h) is another tetracycline derivative FDA-approved for complicated intra-abdominal infections. This agent has a broad spectrum of activity similar to omadacycline, including activity against MDR and other tetracycline-resistant pathogens; however, eravacycline has better activity against Acinetobacter compared to omadacycline. Eravacycline should not be used for the treatment of UTI owing to poor urinary concentrations and subsequent failure to demonstrate noninferiority in clinical trials. This agent is a minor substrate of CYP3A4, resulting in the potential for drug interactions. Dose adjustment is indicated in severe hepatic impairment.
SPECIAL CONSIDERATIONS
• Adverse events: Nausea, vomiting, and photosensitivity are common side effects, so patients should be warned about direct sun exposure. Rarely, these medications are associated with pseudotumor cerebri and pancreatitis. They should not routinely be given to children or to pregnant or lactating women because they can cause tooth enamel discoloration in the developing fetus and young children. Minocycline is also associated with vestibular disturbances. Oral formulations of tetracyclines may cause esophageal ulceration if not properly swallowed.
• Aluminum- and magnesium-containing antacids and preparations that contain oral calcium, oral iron, or other metallic cations can significantly impair oral absorption of tetracycline and other oral tetracycline derivatives and should be avoided within 2 hours of each dose.