A 62-year-old man is hospitalized with severe abdominal pain and diarrhea after a recent urinary tract infection. Six months ago, the patient had an episode of Clostridium difficile colitis after being treated for pneumonia. Medical history is also significant for diverticulitis and upper gastrointestinal tract bleeding. The patient is allergic to penicillin. An appropriate workup confirms C difficile colitis. The patient is placed on an oral macrocyclic antibiotic that inhibits the sigma subunit of RNA polymerase. Which of the following agents was most likely administered to this patient?

Question

A 62-year-old man is hospitalized with severe abdominal pain and diarrhea after a recent urinary tract infection.  Six months ago, the patient had an episode of Clostridium difficile colitis after being treated for pneumonia.  Medical history is also significant for diverticulitis and upper gastrointestinal tract bleeding.  The patient is allergic to penicillin.  An appropriate workup confirms C difficile colitis.  The patient is placed on an oral macrocyclic antibiotic that inhibits the sigma subunit of RNA polymerase.  Which of the following agents was most likely administered to this patient?

Quizplus · Accepted Answer

Treatment options for Clostridium difficile infection (CDI) typically include oral vancomycin or fidaxomicin. Fidaxomicin is a macrocyclic antibiotic (related to macrolides) that inhibits the sigma subunit of RNA polymerase, leading to protein synthesis impairment and cell death (bactericidal activity against C difficile). It is administered orally and has minimal systemic absorption, resulting in high fecal concentrations. It also has a narrow spectrum of activity with a lesser effect on normal colonic flora than vancomycin. (Choice A) Doxycycline binds to the 30S ribosomal subunit and is effective in clostridial skin infections (eg, C perfringens, C septicum), but it is not effective for treatment of CDI. (Choice C) Metronidazole interacts with DNA in anaerobic organisms, disrupting DNA structure and causing strand breakage. Intravenous metronidazole can be a useful adjunct in patients with severe CDI (eg, megacolon, ileus, hypotension), since these patients often have delayed passage of oral antibiotics. (Choice D) Neomycin is a bactericidal aminoglycoside that inhibits the 30S ribosomal subunit. It can be used to treat hepatic encephalopathy or diarrhea due to Escherichia coli and as surgical prophylaxis for gastrointestinal procedures. However, it is not effective against C difficile. (Choice E) Oral vancomycin has minimal systemic absorption and is often used to treat initial or recurrent CDI. It inhibits cell wall synthesis and is bacteriostatic against C difficile at the concentrations typically used for CDI treatment. Educational objective: Clostridium difficile infection can be treated with oral vancomycin or fidaxomicin. Fidaxomicin is a macrocyclic antibiotic that inhibits RNA polymerase. It is bactericidal against C difficile. __________ References: Fidaxomicin: a novel macrocyclic antibiotic approved for treatment of Clostridium difficile infection. (http://www.ncbi.nlm.nih.gov/pubmed/22156854) Bactericidal activity of telavancin, vancomycin and metronidazole against Clostridium difficile. (http://www.ncbi.nlm.nih.gov/pubmed/20044011) Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). (http://www.ncbi.nlm.nih.gov/pubmed/29562266)

A 62-Year-Old Man Is Hospitalized with Severe Abdominal Pain and Diarrhea