What is the next step in managing a patient with elevated calprotectin levels indicating intestinal inflammation, a negative Clostridioides (C.) difficile test, and a history of Aeromonas sobria infection, currently on antibiotic treatment?

Management of Elevated Calprotectin with Negative C. difficile

In a patient with elevated fecal calprotectin and negative C. difficile testing who is already on antibiotics for Aeromonas sobria, proceed with endoscopic evaluation to assess for inflammatory bowel disease (IBD), as the elevated calprotectin indicates active intestinal inflammation that requires definitive diagnosis and treatment beyond infection management. 1

Immediate Assessment Steps

Rule out other infectious causes first:

• While C. difficile is negative, ensure comprehensive stool testing for other enteric pathogens has been completed, as fecal calprotectin elevates with any intestinal infection 1
• Calprotectin levels are elevated in over 95% of patients with infectious colitis, not just IBD 2
• The history of Aeromonas sobria infection is particularly relevant, as documented cases show progression from acute Aeromonas colitis to chronic ulcerative colitis even after infection clearance 3

Assess symptom severity to guide timing:

• For moderate to severe symptoms (significant abdominal pain, frequent bloody stools, systemic symptoms) with calprotectin >150 μg/g: endoscopic assessment is warranted to establish diagnosis before treatment decisions 1, 4
• For mild symptoms with calprotectin >150 μg/g: endoscopic assessment is recommended before any empiric treatment adjustment 1, 4

Endoscopic Evaluation Protocol

Complete colonoscopy with terminal ileum intubation is the preferred approach:

• Obtain multiple biopsies even from normal-appearing mucosa to establish histologic diagnosis 5
• This distinguishes between post-infectious inflammation, new-onset IBD, or other pathology 5
• The sensitivity of fecal calprotectin at 150 μg/g cutoff is approximately 81% with 72% specificity for detecting moderate to severe endoscopic inflammation 1

Obtain baseline laboratory assessment:

• Complete blood count, C-reactive protein, ESR, and comprehensive metabolic panel to assess systemic inflammation 5
• Evaluate renal function given potential need for IBD medications 6

Post-Infectious IBD Consideration

The Aeromonas history creates a unique clinical scenario:

• Documented cases show that Aeromonas hydrophila and A. sobria can trigger chronic colitis that progresses to ulcerative colitis even after infection elimination 3
• Two of three reported cases responded to anti-inflammatory medication, while one required colectomy 3
• This suggests bacterial infection may contribute to chronic colitis development, making endoscopic evaluation with biopsy essential for definitive diagnosis 3

Treatment Approach Based on Findings

If endoscopy confirms IBD:

• For ulcerative colitis with moderate to severe symptoms: initiate mesalamine 2.4-4.8 g once daily for induction 6
• Ensure adequate hydration due to nephrolithiasis risk with mesalamine 6
• Monitor renal function periodically during treatment 6

If endoscopy shows post-infectious inflammation without IBD:

• Continue current antibiotic course for Aeromonas
• Repeat fecal calprotectin 2-4 months after completing antibiotics to monitor resolution 4
• Consider endoscopic reassessment at 6-12 months if calprotectin remains elevated 4

Monitoring Strategy

Serial calprotectin measurements guide ongoing management:

• Repeat testing 2-4 months after initiating or adjusting therapy 4
• Values <150 μg/g suggest resolution of inflammation and no intervention needed 4
• Persistently elevated values (>150 μg/g) warrant repeat endoscopic assessment 4
• At 250 μg/g cutoff, specificity improves to 74% for detecting active disease 7

Critical Pitfalls to Avoid

Do not assume elevated calprotectin is solely from resolved infection:

• The false negative rate at <150 μg/g cutoff is 8.5% in patients with unknown endoscopic status 7
• Post-infectious IBD is a recognized entity requiring different long-term management than simple infection 3

Do not delay endoscopy in symptomatic patients:

• Fecal calprotectin >150 μg/g with moderate to severe symptoms has only 4.6% false positive rate for endoscopic inflammation 5
• Early diagnosis prevents progression and complications 3

Calprotectin is not specific for IBD:

• Elevations occur with colorectal cancer, NSAID enteropathy, celiac disease, and infections 5
• Histologic diagnosis via endoscopy remains the gold standard 5