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This chapter includes miscellaneous agents that have antibacterial activity, urinary tract and other antiseptics, and disinfectants.



This group includes imidazoles that have activity against several bacteria and protozoans, a drug that acts only on Gram-positive cocci, and polypeptides that act on Gram-negative bacilli.

A. Metronidazole and Tinidazole

1. Mechanisms

Metronidazole and tinidazole are imidazole derivatives with activity against protozoa and bacteria. The drugs undergo a reductive bioactivation of their nitro group by ferredoxin (present in anaerobic parasites) to form reactive cytotoxic products that interfere with nucleic acid synthesis.

2. Pharmacokinetics

Metronidazole and tinidazole are effective orally and are distributed widely to tissues, achieving cerebrospinal fluid (CSF) levels similar to those in the blood. Metronidazole can also be given intravenously and is available in topical formulations. Elimination of the drugs requires hepatic metabolism, and dosage reduction may be needed in patients with liver dysfunction. Tinidazole has a long elimination half-life permitting once-daily dosing.

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High-Yield Terms to Learn
Antiseptic An agent used to inhibit bacterial growth in vitro and in vivo
Disinfectant An agent used to kill microorganisms in an inanimate environment
Sterilization Procedures that kill microorganisms on instruments and dressings; methods include autoclaving, dry heat, and exposure to ethylene oxide
Chlorine demand The amount of chlorine bound to organic matter in water supplies; unavailable for antimicrobial activity

3. Clinical use

As an antibacterial agent, metronidazole has greatest activity against Bacteroides and Clostridium. It is the drug of choice for treatment of pseudomembranous colitis resulting from Clostridium difficile and is effective in anaerobic or mixed intra-abdominal infections and in brain abscess. Tinidazole has similar activity versus anaerobic bacteria. Metronidazole is also used for infections involving Gardnerella vaginalis and in regimens for the eradication of Helicobacter pylori in gastric ulcers. As antiprotozoal drugs, metronidazole and tinidazole are effective drugs in trichomoniasis, giardiasis, and the treatment of intestinal amebiasis and amebic hepatic abscess.

4. Toxicity

Adverse effects include gastrointestinal irritation, headache, and dark coloration of urine. More serious toxicity includes leukopenia, dizziness, and ataxia. Opportunistic fungal infections may occur during treatment with metronidazole and tinidazole. Drug interactions with metronidazole include a disulfiram-like reaction with ethanol and potentiation of coumarin anticoagulant effects. Although metronidazole and tinidazole are not contraindicated in pregnancy, the drugs should be used with caution.

B. Fidaxomicin

1. Mechanisms

Fidaxomicin is a narrow-spectrum, macrocyclic antibiotic that is active against Gram-positive aerobes and anaerobes. Fidaxomicin inhibits bacterial RNA polymerase.

2. Pharmacokinetics and clinical use

When administered orally, systemic absorption is negligible but ...

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