Tigecycline, formulated for intravenous administration only, is given as a 100-mg loading dose, then 50 mg every 12 hours. As with all tetracyclines, tissue and intracellular penetration is excellent; consequently, the volume of distribution is quite large and peak serum concentrations are low. Elimination is primarily biliary, and no dosage adjustment is needed for patients with renal insufficiency. In addition to the tetracycline class effects, the chief adverse effect of tigecycline is nausea, which occurs in up to one third of patients, and occasionally vomiting. Neither nausea nor vomiting usually requires discontinuation of the drug.
Tigecycline is approved for treatment of skin and skin-structure infection, intra-abdominal infections, and community-acquired pneumonia. However, in a meta-analysis of clinical trials, tigecycline was associated with a small but significant increase in the risk of death compared with other antibiotics used to treat these infections. The increased risk was most apparent in hospital-acquired and ventilator-associated pneumonia but was also seen in other infections. This has led the U.S. Food and Drug Administration (FDA) to issue a black box warning that tigecycline should be reserved for situations where alternative treatments are not suitable. Because active drug concentrations in the urine and serum are relatively low, tigecycline may not be effective for urinary tract infections or primary bacteremia. Tigecycline has in vitro activity against a wide variety of multidrug-resistant pathogens (eg, methicillin-resistant S aureus, extended-spectrum β-lactamaseproducing Gram-negatives, and Acinetobacter sp); however, its clinical efficacy in infections with multidrug-resistant organisms, compared with other agents, is unproven.
A. Oral Dosage
The oral dosage for rapidly excreted tetracyclines, equivalent to tetracycline hydrochloride, is 0.25–0.5 g four times daily for adults and 25–50 mg/kg/d for children (8 years of age and older). For severe systemic infections, the higher dosage is indicated, at least for the first few days. The dosage for doxycycline is 100 mg once or twice daily; the minocycline dose is 100 mg twice daily. Doxycycline is the oral tetracycline of choice for most indications because it is generally well tolerated, it can be given twice daily, and its absorption is not significantly affected by food. All tetracyclines chelate with metals, and none should be orally administered with milk, antacids, or ferrous sulfate. To avoid deposition in growing bones or teeth, tetracyclines should be avoided in pregnant women and children younger than 8 years.
B. Parenteral Dosage
Doxycycline and minocycline are available for intravenous injection at the same doses as the oral formulations. Intramuscular injection is not recommended because of pain and inflammation at the injection site.
Hypersensitivity reactions (drug fever, skin rashes) to tetracyclines are uncommon. Most adverse effects are due to direct toxicity of the drug or to alteration of microbial flora.
A. Gastrointestinal Adverse Effects
Nausea, vomiting, and diarrhea are the most common reasons for discontinuing tetracyclines. These effects are attributable to direct local irritation of the intestinal tract. Oral tetracyclines can rarely cause esophageal ulceration, so patients should be instructed to take them with 8 ounces of water and remain upright for at least 30 minutes after each dose.