BL, a 67-year-old female patient, receives a new electronic prescription at your community pharmacy for Dificid 200mg PO BID for 9 days. While speaking with the patient on the phone, you learn that she was discharged from the hospital after receiving one day of treatment. BL is concerned since she’s never had this issue before, and her internet search showed that several medications could increase her risk for this infection.

PMH: Hypertension, GERD, Diabetes (Type II), Cirrhosis

Recent Medication history (within last 90 days):

Moxifloxacin 400 mg PO QD

Lisinopril 10 mg PO QD

Nexium 20 mg PO QD

Metformin 1000 mg PO BID

Dapagliflozin 10 mg PO QD

Insulin glargine 30 units SQ HS

Lactulose 25 mL PO TID

Xifaxan 550 mg PO BID

Based on the patient’s medication list and new prescription, which medications could increase her risk for this infection? Select all that apply. 

A. Moxifloxacin

B. Nexium

C. Metformin

D. Xifaxan

E. Dapagliflozin

Answers with Rationale:

Clostridioides difficile is gram-positive, anaerobic bacterium that can produce toxin mediated gastrointestinal infection. It colonizes the human GI tract after a disruption in normal gut flora, and it is the causative agent in antibiotic-associated colitis. It primarily presents with diarrhea, with 3 or more episodes of loose, watery bowel movements within a 24-hour period. A positive test for the presence of glutamate dehydrogenase (GDH) in stool (indicating presence of the bug itself) along with a test indicating presence of toxin with the 3 or more episodes of diarrhea will confirm the diagnosis of C. difficile infection (CDI). Once confirmed, there are several treatment options with fidaxomicin and vancomycin being first-line options, keeping in mind that only oral vancomycin (not intravenous) is a viable treatment option for CDI.

Although certain classes of antibiotics are known for predisposing patients to CDI, certain classes increase this risk more than others. Clindamycin, fluoroquinolones, 2^nd and 3^rd generation cephalosporins, and carbapenems are some of the primary antibiotics that are cause for concern. Clindamycin, ceftriaxone, and moxifloxacin are of note higher risk due to their pharmacokinetics.  Each of them is significantly excreted through the hepatobiliary tract into the colon, therefore placing high concentrations of antibiotic where flora are then disrupted. Tetracyclines have minimal risk or may even be protective. 

Brands/Generics covered: Dificid (fidaxomicin); Nexium (esomeprazole); Farxiga (dapaglifozin); Xifaxan (rifaximin); Glucophage (metformin); Kristalose (lactulose); Lantus (insulin glargine); Prinivil (lisinopril); Avelox (moxifloxacin)

Answer A is correct: Moxifloxacin is a respiratory fluoroquinolone with activity against gram-positive, gram-negative, anaerobic, and atypical bacteria. It is primarily excreted in the feces, as it is poorly concentrated in the urine. Moxifloxacin’s disruption of normal anaerobic gut flora and increased presence in the intestinal tract contribute to increasing patients’ risk of developing CDI.

Answer B is correct: Nexium is a proton-pump inhibitor, which inhibits gastric acid secretion. Acid suppression therapy increases the gastric pH, which makes a hospitable environment for pathogenic bacteria. While this has yet to be fully elucidated as the mechanism for increasing risk of C. difficile, other mechanisms may be involved. A number of proton pump inhibitors have warnings/precautions not only vs. C. difficile, but also other gastrointestinal infections, such as C jejuni. 

Answer C is incorrect: While metformin is known for causing gastrointestinal issues, including diarrhea, it is not associated with an increased risk of CDI. 

Answer D is incorrect: Xifaxan is a rifamycin-derived antibiotic with activity against gram-positive, gram-negative, aerobic and anaerobic intestinal bacteria. Xifaxan is typically used to treat and help prevent hepatic encephalopathy by killing ammonia producing bacteria. However, it is not associated with increased risk for CDI. Actually, It is used sometimes just after a vancomycin course as a "chaser" for recurrent CDI.

Answer E is incorrect. Farxiga (dapagliflozin) while its spelling almost looks like a FQ, it is actually an SGLT2 inhibitor for diabetes and heart failure management. While Farxiga does not increase your risk for CDI, it does increase the risk for other infections, including vulvovaginal yeast infections, urinary tract infections, and in rare cases life-threating Fournier's gangrene. 

NAPLEX Competencies Covered:

Area 1 (Obtain, Interpret, or Assess Data, Medical, or Patient Information), 1.2 From patients: treatment adherence, or medication-taking behavior; chief complaint, medication history, medical history, family history, social history, lifestyle habits, socioeconomic background; 1.4 From medical records: treatment adherence, or medication-taking behavior; chief complaint, medication history, medical history, family history, social history, lifestyle habits, socioeconomic background.

Area 2 (Identify Drug Characteristics), 2.1 Pharmacology, mechanism of action, or therapeutic class; 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied.

Area 3 (Develop or Manage Treatment Plans), 3.3 Medication reconciliation, indication or therapeutic uses, lack of indication, inappropriate indication, duplication of therapy, omissions; 3.6 Drug contraindications, allergies, or precautions; 3.7 Adverse drug effects, toxicology, or overdose.

Have a great weekend!

Dr. B