Chapter 50. Miscellaneous Antimicrobial Agents & Urinary Antiseptics

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.

Metronidazole and Tinidazole

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.

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 require hepatic metabolism, and dosage reduction may be needed in patients with liver dysfunction. Tinidazole has a long elimination half-life permitting once-daily dosing.

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 C 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.

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.

Mupirocin

Mechanisms

Mupirocin is a natural product from Pseudomonas fluorescens. It acts on gram-positive cocci and inhibits protein synthesis by specifically binding to isoleucyl-tRNA synthetase.

Pharmacokinetics and Clinical Use

Mupirocin is used topically and is not absorbed. This drug is indicated for impetigo caused by staphylococci (including methicillin-resistant strains), β-hemolytic streptococci, and Streptococcus pyogenes. It is ...