What is the management approach for a patient with hematuria (blood in urine) while taking cephalexin (a cephalosporin antibiotic), considering their past medical history, including any previous kidney issues, allergies, or experiences with antibiotics?

Management of Hematuria While Taking Cephalexin

Discontinue cephalexin immediately and evaluate for drug-induced nephrotoxicity, as hematuria is a recognized adverse effect of cephalosporin antibiotics that can indicate renal injury. 1, 2

Immediate Actions

• Stop cephalexin immediately upon recognition of hematuria, as this may represent drug-induced nephropathy or hypersensitivity reaction 2
• Check for concurrent eosinophilia, which when present with hematuria suggests a hypersensitivity-mediated renal injury pattern 2
• Obtain serum creatinine to assess for acute kidney injury, as transient increases can occur with cephalosporin-related nephropathy 2
• Review medication history for probenecid use, which inhibits renal excretion of cephalexin and increases risk of toxicity 1, 2

Clinical Context and Risk Factors

The development of hematuria with cephalexin is well-documented, particularly in specific clinical scenarios:

• High-dose therapy (20-24 g/day) significantly increases risk, especially when combined with probenecid 2
• History of penicillin allergy may predispose to cross-reactive hypersensitivity reactions with cephalosporins 2
• Prior cephalosporin exposure may increase susceptibility to subsequent reactions 2
• Impaired renal function increases drug accumulation and potential for toxicity 1, 3

Diagnostic Evaluation

• Urinalysis with microscopy to confirm true hematuria versus false-positive reactions (cephalexin can cause false-positive glucose tests, suggesting potential for other assay interference) 1
• Complete blood count to evaluate for eosinophilia, which indicates hypersensitivity-mediated injury 2
• Renal function panel including BUN and creatinine to assess for acute tubular necrosis or interstitial nephritis 2, 4
• Consider renal ultrasound if hematuria persists after drug discontinuation to exclude other structural causes 2

Mechanism of Injury

Cephalosporin-related renal injury can manifest through two distinct patterns:

• Toxic nephropathy presenting as acute tubular necrosis with elevated creatinine and hematuria 4
• Hypersensitivity reaction characterized by interstitial nephritis with eosinophilia, rash, and hematuria 2, 4

The FDA label explicitly warns that cephalosporins may cause positive Coombs' tests and require careful monitoring in patients with impaired renal function 1

Alternative Antibiotic Selection

If continued antibiotic therapy is needed:

• Avoid all cephalosporins in this patient, as cross-reactivity within the class is possible 5
• Consider carbapenems as safe alternatives with minimal cross-reactivity (0.3% reaction rate in cephalosporin-allergic patients) 5
• Aztreonam is safe unless the original cephalosporin was ceftazidime or cefiderocol 5
• Penicillins with dissimilar side chains can be used if no penicillin allergy history exists 5

Monitoring After Discontinuation

• Hematuria typically resolves promptly after cephalexin discontinuation 2
• Renal function abnormalities should normalize within days to weeks if drug-induced 2
• Document this reaction as a cephalosporin adverse effect in the medical record to prevent future exposure 1
• Avoid rechallenge with cephalexin or structurally similar cephalosporins 2

Critical Pitfalls to Avoid

• Do not continue cephalexin while investigating hematuria, as this risks progressive renal injury 2
• Do not assume asymptomatic bacteriuria requires treatment if that was the indication, as antimicrobial therapy for asymptomatic bacteriuria causes harm without benefit 5, 6
• Do not use cephalexin for catheter-associated asymptomatic bacteriuria, as this promotes resistance and provides no clinical benefit 5, 6
• Do not overlook probenecid co-administration, which dramatically increases cephalexin levels and toxicity risk 1, 2