Can cephalexin (Keflex) cause diarrhea?

Can Cephalexin (Keflex) Cause Diarrhea?

Yes, cephalexin can definitely cause diarrhea, ranging from mild gastrointestinal upset to severe, potentially life-threatening Clostridium difficile-associated diarrhea (CDAD). 1

Mechanism and Severity

Diarrhea from cephalexin occurs through two distinct mechanisms:

• Antibiotic-associated diarrhea: Cephalexin alters normal colonic flora, leading to overgrowth of C. difficile, which produces toxins A and B that cause CDAD 1
• Direct gastrointestinal effects: Mild, self-limited diarrhea represents one of the most common adverse effects, typically manifesting as gastrointestinal upset 2

The FDA drug label explicitly warns that CDAD "may range in severity from mild diarrhea to fatal colitis" and can occur even "over two months after the administration" of cephalexin 1

Clinical Presentation and Risk Assessment

When evaluating diarrhea in a patient taking cephalexin, immediately assess for:

• Fever, abdominal pain, or leukocytosis: These suggest colitis rather than simple antibiotic-associated diarrhea 3
• Timing of onset: CDAD can develop during treatment or up to 2 months after discontinuation 1
• Severity markers: Profuse watery diarrhea, bloody stools, or signs of dehydration indicate potentially serious complications 3

Three documented cases of cephalexin-associated colitis presented with profuse diarrhea, vague abdominal pain, fever, and leukocytosis, with one case showing pseudomembrane formation 3

Critical Management Algorithm

For mild diarrhea (no fever, no blood, no systemic symptoms):

• Continue monitoring closely
• Ensure adequate hydration
• Consider symptomatic treatment with loperamide if appropriate 4

For moderate-to-severe diarrhea or any concerning features:

• Discontinue cephalexin immediately 1
• Test for C. difficile toxins
• Institute bowel rest and intravenous hydration 3
• Initiate appropriate fluid and electrolyte management 1
• If CDAD confirmed, start antibiotic treatment directed against C. difficile 1

Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, can be refractory to antimicrobial therapy, and may require colectomy 1

Common Pitfalls to Avoid

• Never dismiss diarrhea as "just a side effect": CDAD must be considered in all patients who develop diarrhea during or after cephalexin use 1
• Don't wait for severe symptoms: Early recognition and discontinuation prevent progression to fulminant colitis 3
• Avoid continuing cephalexin if CDAD suspected: Ongoing antibiotic use not directed against C. difficile must be discontinued 1
• Don't assume negative stool cultures rule out serious pathology: All three reported colitis cases had negative bacterial cultures but still required aggressive management 3

Incidence and Context

While the exact incidence of diarrhea with cephalexin is not precisely quantified in the evidence, adverse gastrointestinal effects including diarrhea are described as "relatively infrequent" in upper respiratory tract infections 2. However, when diarrhea occurs in the context of recent surgery or severe medical comorbidities, the risk of serious complications increases substantially 3