Vancomycin, metronidazole, and tetracyclines.
Over the last 30 years, the impurities in the vancomycin product have been reduced, perhaps resulting in a lower rate of adverse reactions. Vancomycin is bactericidal against most susceptible organisms, but is bacteriostatic against the enterococcus. Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus. Vancomycin attains good tissue and bone penetration and must be administered intravenously for systemic infections. It is eliminated renally with a half-life of about 6 hours; this half-life is prolonged with advanced age and reduced renal function. Significant adverse reactions can be minimized with careful attention to administration technique. Metronidazole has excellent tissue penetration; its antibacterial site of action is within anaerobic bacterial cells. Metronidazole is cleared by hepatic metabolism with a half-life of about 7 to 8 hours. The half-life is unchanged with renal dysfunction but is prolonged in patients with hepatic function impairment. Although adverse effects are relatively minor, there is an important interaction with warfarin. For podiatric infections, metronidazole can be used in skin- and soft-tissue infections; anaerobes in bone and joint infections are rare. Topical metronidazole has been used successfully in the treatment of decubitus ulcers, and this needs further evaluation. The most commonly used tetracyclines are tetracycline, doxycycline, and minocycline. The tetracyclines are broad spectrum antimicrobial agents, but their usefulness is limited by resistant strains. Tetracycline's absorption is significantly impaired by food, and it is cleared renally and fecally. Doxycycline has the highest protein binding and the longest half-life; it is cleared both renally and fecally without hepatic metabolism. Minocycline has the best absorption and tissue penetration; the unchanged drug is cleared renally and fecally, and it also undergoes hepatic metabolism. All tetracyclines have important adverse reactions with respect to teeth and bones, and they are contraindicated during pregnancy and for children under age eight.