Nitroimidazoles

Agents: metronidazole, tinidazole

Nitroimidazoles are around to clean up organisms that the big drug classes—penicillins, cephalosporins, fluoroquinolones, macrolides, etc.—for the most part miss. Worried about gut anaerobes?  Metronidazole is there for you. Thinking about parasites in your patient with diarrhea? Try metro-nidazole or its newer cousin tinidazole, which has a spectrum of activity similar to that of metronidazole but is approved only for parasitic infections.  And of course, if you have gone overboard with the antibiotics and your patient has  C. difficile colitis, turn to metronidazole as your first-line therapy. Just remember the limitations of these drugs: they do not have adequate activity against aerobic bacteria— staphylococci, streptococci, E. coli, and such.

Spectrum: metronidazole

Good: Gram-negative and Gram-positive anaerobes, including  Bacteroides,  Fusobacterium,  and  Clostridium species; protozoa, including Trichomonas, Entamoeba, and Giardia

Moderate: Helicobacter pylori

Poor : aerobic Gram-negative and Gram-positive organisms, anaerobes that reside in the mouth  (Peptostreptococcus, Actinomyces, Propionibacterium)

Adverse Effects

Gas trointes tin al: Nausea, vomiting, and diarrhea,  along with a metallic taste, are not uncommon with metronidazole. More severe adverse re-actions such as hepatitis and pancreatitis are rare.

Neurologic: Dose-related, reversible peripheral neuropathy is occasionally reported with metronidazole, as have very rare cases of con-fusion and seizures.

Important Facts

• Metronidazole has a reputation for causing a disulfiram-like reaction with the consumption of alcohol, because of its inhibition of aldehyde dehydrogenase. It is prudent to have patients abstain from alcohol while taking metronidazole. Much more considerable is the interaction with warfarin, whose anticoagulant properties are significantly potentiated by inhibition of warfarin metabolism. Careful monitoring is necessary, because possible warfarin dose re-duction may be required.

• Metronidazole has excellent (~100%) bioavailability and none of the drug-chelating concerns of the fluoroquinolones; thus patients should be switched from IV to oral metronidazole as soon as they are tolerating oral medications.

• Resistance to metronidazole among isolates of C. difficile is uncommon, but treatment failure with this infection is not. The organism can exist as an antibiotic-resistant spore and cause relapses after the end of treatment. Re-treatment with metronidazole is reasonable in most cases of mild or moderate relapsing C. difficile infection, although treatment with oral vancomycin is an alternative. Alternatives are currently being developed for C. difficile infection.

What They’re Good For

Infections with documented or suspected abdominal anaerobic bacteria, with adjunctive coverage of aerobes by a second drug when necessary. They are also used for treatment of vaginal Trichomoniasis and GI infections caused by susceptible protozoa  (amebiasis, giardiasis, etc.). Metronidazole is also a component of therapy for H. pylori GI ulcer disease in combination with other antibacterials and acid-suppressive drugs. It is also a drug of choice for mild to moderate C. difficile infections.

Don’t Forget!

The GI flora of humans is a delicate ecosystem—disturb it at your patient’s peril. Metronidazole’s effect on the normal (primarily anaerobic) GI flora can set up your patients for colonization with nasty bugs such as VRE; determine whether you really need anaerobic coverage.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.