A 56-year-old man is admitted to the intensive care unit of a hospital for treatment of community-acquired pneumonia. He receives ceftriaxone and azithromycin upon admission, rapidly improves, and is transferred to a semiprivate ward room. On day 7 of his hospitalization, he develops copious diarrhea with eight bowel movements but is otherwise clinically stable. Clostridioides difficile infection is confirmed by stool testing. What is an acceptable treatment for the patient’s diarrhea? The patient is transferred to a single-bed room. The housekeeping staff asks what product should be used to clean the patient’s old room.
METRONIDAZOLE, FIDAXOMYCIN, RIFAXIMIN, MUPIROCIN, POLYMYXINS, & URINARY ANTISEPTICS
Metronidazole is a nitroimidazole antiprotozoal drug (see Chapter 52) that also has potent antibacterial activity against anaerobes, including Bacteroides and Clostridioides (formerly Clostridium) species.* Metronidazole is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up by anaerobes, it is nonenzymatically reduced by reacting with reduced ferredoxin. This reduction results in products that accumulate in and are toxic to anaerobic cells. The metabolites of metronidazole are taken up into bacterial DNA, forming unstable molecules. This action occurs only when metronidazole is partially reduced, and, because this reduction usually happens only in anaerobic cells, it has relatively little effect on human cells or aerobic bacteria.
Metronidazole is well absorbed after oral administration, is widely distributed in tissues, and reaches serum levels of 4–6 mcg/mL after a 250-mg oral dose. It can also be given intravenously. The drug penetrates well into the cerebrospinal fluid and brain, reaching levels similar to those in serum. Metronidazole is metabolized in the liver and may accumulate in hepatic insufficiency.
Metronidazole is indicated for treatment of anaerobic or mixed intra-abdominal infections and pelvic inflammatory disease (in combination with other agents with activity against aerobic organisms), vaginitis (trichomonas infection, bacterial vaginosis), and brain abscess. While it is no longer a first-line treatment for Clostridioides difficile infection when administered alone, it may be given intravenously, combined with oral vancomycin, to patients with fulminant C difficile infection. The typical dosage for most indications is 500 mg three times daily orally or intravenously (30 mg/kg/d). Vaginitis may respond to a single 2-g dose. A vaginal gel is available for topical use.
Adverse effects include nausea, diarrhea, stomatitis, and peripheral neuropathy with prolonged use. It had been thought that metronidazole has a disulfiram-like effect necessitating the avoidance of alchol, but re-evaluation of available data suggests that this is not the case. Although teratogenic in some animals, metronidazole has not been associated with this effect in humans. Other properties of metronidazole are discussed in Chapter 52.
A structurally similar agent, tinidazole, is a once-daily drug approved for treatment of trichomonas infection, giardiasis, amebiasis, and bacterial vaginosis. It also is active against anaerobic bacteria, but is not approved in ...