What is the likely diagnosis for a patient who develops fever and impaired renal function with eosinophilia after being treated with amoxicillin (amoxicillin) for a urinary tract infection (UTI)?

Acute Tubulointerstitial Nephritis (ATIN)

The most likely diagnosis is D - acute tubulointerstitial nephritis (ATIN), a well-recognized drug hypersensitivity reaction to amoxicillin that presents with fever, eosinophilia, and renal dysfunction occurring days to weeks after antibiotic exposure.

Clinical Reasoning

Why ATIN is the Correct Diagnosis

• Classic temporal relationship: The patient developed symptoms 3 weeks after amoxicillin treatment, which fits the typical delayed type IV hypersensitivity reaction pattern of drug-induced ATIN 1
• Characteristic laboratory findings: Eosinophilia (8%) with normal neutrophils is highly suggestive of drug-induced ATIN, as eosinophilia is a hallmark finding in this condition 2, 3
• Amoxicillin is a well-documented cause: Penicillin-class antibiotics, including amoxicillin, are among the most common drugs causing ATIN 1, 3
• Nonspecific systemic symptoms: Fever and malaise are typical presentations of drug-induced ATIN, though the classic triad of fever, rash, and eosinophilia is present in only a minority of cases 1

Why Other Options Are Less Likely

Pyelonephritis (Option A) is excluded because:

• Laboratory tests are "within normal ranges" except for eosinophilia, suggesting no active bacterial infection 4
• Pyelonephritis would typically show elevated inflammatory markers, positive urine culture, and neutrophilia rather than isolated eosinophilia 4
• The 3-week delay after UTI treatment makes ongoing bacterial infection unlikely 5

Post-streptococcal glomerulonephritis (Option B) is excluded because:

• PSGN typically occurs 1-3 weeks after streptococcal pharyngitis or skin infection, not after amoxicillin treatment for UTI
• PSGN presents with glomerular findings (hematuria, proteinuria, hypertension, edema) rather than tubulointerstitial disease
• Eosinophilia is not a feature of PSGN

Eosinophilic granulomatosis with polyangiitis/Churg-Strauss (Option C) is excluded because:

• EGPA requires evidence of vasculitis and typically presents with asthma, chronic rhinosinusitis with polyps, and multi-organ involvement 4
• The diagnosis requires highly suggestive clinical features beyond isolated eosinophilia and renal dysfunction 4
• The temporal relationship with amoxicillin exposure strongly points to drug-induced rather than primary vasculitic disease 6
• While EGPA can rarely cause tubulointerstitial nephritis with eosinophilic infiltration, this occurs in the context of systemic vasculitis, not as an isolated finding after drug exposure 6

Diagnostic Approach

Essential Immediate Steps

• Discontinue amoxicillin immediately: This is the cornerstone of treatment for drug-induced ATIN 1, 2
• Assess renal function: Measure serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate to determine severity 4
• Urinalysis with microscopy: Look for sterile pyuria, white blood cell casts, eosinophiluria (though not always present), and tubular proteinuria (typically non-nephrotic range) 1, 2
• Monitor for oliguria: This would require inpatient admission for fluid management and potential renal replacement therapy 4

Confirmatory Testing

• Renal biopsy is the gold standard: Shows interstitial infiltrate with lymphocytes, monocytes, and eosinophils, with tubular involvement but no glomerular injury 4, 1, 2
• Consider biopsy if: No improvement after 5-7 days of drug withdrawal, or if diagnosis is uncertain and would change management 4, 1

Exclude Alternative Diagnoses

• Rule out other causes of AKI: Dehydration, recent IV contrast, other nephrotoxic medications, hypotension 4
• Immunological workup if atypical: ANA, ANCA, complement levels, anti-GBM antibodies—but only if clinical picture doesn't fit straightforward drug-induced ATIN 4

Management Algorithm

Initial Conservative Management (Days 1-7)

• Discontinue amoxicillin 1, 2
• Ensure adequate hydration to prevent crystalluria and support renal function 7
• Monitor renal function daily 1
• Avoid other nephrotoxic agents 1

Corticosteroid Therapy (If No Recovery by Day 5-7)

• Initiate methylprednisolone 1 mg/kg/day IV or oral prednisone equivalent if no evidence of kidney function recovery after 5-7 days 4, 1, 2
• Early steroid initiation is critical: Starting corticosteroids promptly decreases inflammatory infiltrates and prevents progression to interstitial fibrosis 1, 2
• Steroid weaning protocol: Once creatinine improves to grade 1, wean over 4 weeks for grade 2 episodes or 4-12 weeks for grade 3-4 episodes 4

Supportive Care During Steroid Treatment (>4 weeks)

• Pneumocystis jiroveci pneumonia prophylaxis 4
• Calcium and vitamin D supplementation 4
• Gastric protection 4
• Monitor for hyperglycemia 4

Critical Pitfalls to Avoid

• Do not delay drug discontinuation: Continued exposure worsens outcomes and increases risk of irreversible fibrosis 1, 2
• Do not wait too long for steroids: If renal function hasn't improved by 5-7 days post-drug withdrawal, initiate corticosteroids promptly to prevent permanent damage 1, 2
• Do not assume infection: The presence of fever and leukocytosis with eosinophilia in the context of recent antibiotic use suggests drug hypersensitivity, not treatment failure 2, 3
• Do not restart amoxicillin or related penicillins: This patient has demonstrated hypersensitivity and rechallenge carries significant risk 3
• Do not overlook baseline creatinine: Pay attention to the patient's baseline renal function, not just laboratory upper limits of normal 4

Prognosis

• Generally favorable with early recognition and treatment: Most patients recover renal function with drug withdrawal alone or with addition of corticosteroids 1, 2, 3
• Risk of chronic kidney disease: Delayed treatment or continued drug exposure increases risk of interstitial fibrosis and permanent renal impairment 1
• Corticosteroid response: Approximately 70% of drug-induced renal toxicities respond to corticosteroids 4