AssessmentsDNA synthesis inhibitors: Metronidazole
DNA synthesis inhibitors: Metronidazole
USMLE® Step 2 style questions USMLE
A 55-year-old man, who recently moved to the United States from Latin America, comes to clinic because of a 1-week history of bloody diarrhea. Blood tests reveal leukocytosis without eosinophilia, and liver function tests show elevated alkaline phosphatase and transaminases. Physical examination of the abdomen shows fever, right upper quadrant pain, and a palpable mass in the abdomen over the ascending colon. On ultrasound of the liver, there is a round rim-enhancing lesion which looks like a well-defined abscess with low density. Chest X-ray shows an elevated right hemidiaphragm. Which of the following treatments would be most appropriate?
DNA synthesis inhibitors are a group of antibiotics that target the synthesis of DNA in bacteria and other organisms. Metronidazole, a 5-nitroimidazole, prevents the synthesis of nucleic acids, which are the building blocks of DNA, and is effective against many bacteria and protozoans. Metronidazole and related 5-nitroimidazoles are relatively nontoxic to humans. This is because in order to function, they need to be reduced by a protein called ferredoxin, which contains sulfur and iron. This protein is commonly found in anaerobic bacteria and protozoans, but not in humans and aerobic bacteria. Now, this protein can donate an electron to metronidazole, causing it to form free radicals which will damage the DNA, causing it to fragment. Without the DNA as a template, the organism can’t synthesize any more nucleic acids like DNA or mRNA, which will lead to cell death.
Metronidazole can be taken perorally, but it’s also available in an IV form and as topical creams. It penetrates well into body tissues and fluids, including vaginal secretions, seminal fluid, saliva, breast milk, and cerebrospinal fluid, but does not cross over the placenta. This medication can treat many anaerobic bacterial infections like Clostridium difficile, which can cause pseudomembranous enterocolitis in people taking other antibiotics. Another common organism treated by this medication is Helicobacter pylori, a common bacteria that causes gastritis and peptic ulcers. However, it should be used in combination with other antimicrobials and proton pump inhibitors as part of a triple therapy for the best outcome. Next, Lactobacillus species and other anaerobes that can cause bacterial vaginosis are all treated by metronidazole. For protozoan infections, it’s the medication of choice for amoebiasis, an infection of the gut caused by Entamoeba histolytica. It’s the medication of choice against Trichomonas vaginalis as well, which also causes vaginosis. Finally, metronidazole is highly effective against giardiasis, or beaver fever, which is an infection of the gut by Giardia lamblia.
Metronidazole is metabolized in the liver and it’s an inhibitor of CYP450 enzymes, so it can slow down the metabolism of other medications, like warfarin, which are also broken down by this enzyme. Common side effects of metronidazole include decreased appetite, nausea, a metallic taste in the mouth, headaches, and stomach cramps. In high doses, or in chronic treatment, neurological effects, such as seizures, confusion, and peripheral neuropathy can be seen. It is contraindicated during the first trimester of pregnancy as a precaution. Finally, metronidazole is known to cause a disulfiram-like reaction, by inhibiting aldehyde dehydrogenase, so when the person drinks alcohol while taking metronidazole, they will experience severe nausea, vomiting, and headaches.