What is the most likely diagnosis for a patient with recent antibiotic use, diarrhea, abdominal cramping, and elevated inflammatory markers, such as C-reactive protein (CRP)?

Clostridioides (Clostridium) difficile colitis is the most likely diagnosis

Given the recent antibiotic use for urinary tract infection, non-bloody diarrhea with increased frequency, elevated inflammatory markers, and leukocytosis, this patient's presentation is most consistent with C. difficile infection (CDI). 1, 2

Key Diagnostic Features Supporting CDI

Recent Antibiotic Exposure

• Recent antibiotic use is the single strongest risk factor for CDI, with one-third of colonized patients developing symptomatic infection within 2 weeks of antibiotic therapy 1, 2
• The diagnosis should be strongly considered in any patient who received antibiotics in the previous 4-6 weeks 1
• The temporal relationship between antibiotic treatment for UTI and onset of diarrhea one week later is highly characteristic 2

Clinical Presentation

• Six episodes of loose, non-bloody diarrhea daily with lower abdominal cramping fits the typical CDI presentation 3, 4
• Mild tachycardia (pulse 100/min) and borderline blood pressure (100/70 mmHg) suggest early volume depletion 4
• Mild diffuse lower quadrant tenderness without peritoneal signs is consistent with CDI 1

Laboratory Findings

• Leukocytosis (13,000) and elevated CRP (4.0) are characteristic inflammatory markers in CDI 1
• The combination of leukocytosis and elevated inflammatory markers strongly supports an infectious/inflammatory colitis 1
• Hemoglobin of 10.0 may reflect chronic disease or early blood loss 1

Why Other Diagnoses Are Less Likely

Ischemic Colitis (Option A)

• Typically presents with bloody diarrhea in 80-90% of cases, which this patient lacks 1
• More common in patients with vascular risk factors or hypotension, though the patient is on apixaban for atrial fibrillation 1
• Usually has sudden onset of abdominal pain followed by bloody diarrhea within 24 hours, not gradual progression over a week 1
• The recent antibiotic use makes CDI far more likely 2

Inflammatory Bowel Disease (Option B)

• While IBD should be considered in elderly patients with diarrhea, the temporal relationship to recent antibiotics strongly favors CDI 1
• IBD flares must have infectious causes (especially C. difficile) ruled out before diagnosis 1
• The acute onset after antibiotic exposure is atypical for new-onset IBD 1
• CRP of 4.0 mg/L is relatively modest for active IBD, which typically shows higher values (>10 mg/L in extensive colitis) 1

Microscopic Colitis (Option C)

• Typically presents with chronic watery diarrhea without elevated inflammatory markers 1
• CRP is usually normal in microscopic colitis, unlike this patient's elevated level 1
• Not associated with recent antibiotic use as a trigger 1
• Leukocytosis is uncommon in microscopic colitis 1

Immediate Management Approach

Diagnostic Testing

• Order stool testing for C. difficile toxin immediately using a two-step algorithm: GDH screening followed by toxin testing, or NAAT followed by toxin confirmation 2
• The first stool specimen has 79% sensitivity, with 97% negative predictive value 5
• If the first specimen is negative but clinical suspicion remains high, test a second specimen (cumulative sensitivity 91%) 5

Critical Medication Review

• Discontinue the causative antibiotic if clinically feasible, as continued use significantly increases recurrence risk 2
• Review methotrexate and apixaban continuation with caution given potential for systemic absorption of oral vancomycin in inflammatory colitis 6
• Absolutely avoid antiperistaltic agents (loperamide) as they worsen disease severity and can precipitate toxic megacolon 2

Empiric Treatment Considerations

• While awaiting test results, given the high pretest probability, consider starting oral vancomycin 125 mg four times daily 1, 2, 6
• Vancomycin has approximately 81% clinical success rate for initial CDI episodes 2
• Oral vancomycin is preferred over metronidazole for all CDI episodes regardless of severity per recent guidelines 1

Infection Control

• Implement strict handwashing with soap and water, as alcohol-based sanitizers do not inactivate C. difficile spores 2
• Mechanical removal through friction and running water is the only effective hand hygiene method 2

High-Risk Features in This Patient

Immunosuppression

• Methotrexate use increases risk of severe CDI and complications 1
• Immunosuppressed patients may have atypical presentations 1

Renal Impairment

• eGFR of 37 indicates stage 3B chronic kidney disease 6
• Patients with renal insufficiency and colitis may have significant systemic absorption of oral vancomycin, requiring monitoring of serum vancomycin levels 6
• Nephrotoxicity risk is increased in patients >65 years, and renal function should be monitored during and after vancomycin treatment 6

Anticoagulation

• Apixaban use requires careful monitoring if CDI progresses to bloody diarrhea or complications 6

Common Pitfalls to Avoid

• Do not wait for bloody diarrhea to consider CDI—most cases present with non-bloody diarrhea 1, 4
• Do not assume normal CRP excludes serious pathology—CRP of 4.0 mg/L is elevated and significant in this context 1
• Do not use single toxin EIA alone due to insufficient sensitivity; use two-step testing algorithm 2
• Do not test formed stool for C. difficile as it is not clinically indicated 1
• Do not give antimotility agents even for symptomatic relief—use opioids or octreotide if needed instead 2