What is the treatment for a patient with a history of Penicillin (PCN) allergy, who has failed Doxycycline treatment, and presents with sinusitis, a single kidney, and normal renal function?

Treatment Recommendation for PCN-Allergic Patient with Sinusitis After Doxycycline Failure

For this patient with penicillin allergy, one kidney (but normal renal function), and sinusitis that failed doxycycline, prescribe a respiratory fluoroquinolone—specifically levofloxacin 500 mg once daily for 10 days—as the most appropriate second-line therapy. 1

Why Fluoroquinolones Are the Correct Choice Here

The American Academy of Otolaryngology-Head and Neck Surgery explicitly recommends respiratory fluoroquinolones (levofloxacin or moxifloxacin) as second-line therapy when initial treatment fails, providing 90-92% predicted clinical efficacy against both drug-resistant Streptococcus pneumoniae and β-lactamase-producing Haemophilus influenzae. 1

Doxycycline has a predicted bacteriologic failure rate of 20-25% for acute bacterial sinusitis, which is significantly higher than first-line agents, making treatment failure unsurprising. 1 The limited activity against H. influenzae due to pharmacokinetic limitations explains why this patient did not respond. 1

The Single Kidney Is Not a Contraindication

With normal kidney function, levofloxacin can be safely prescribed at standard dosing (500 mg once daily). 1 No dose adjustment is required when renal function is preserved. The presence of a single kidney alone does not contraindicate fluoroquinolone use when the remaining kidney maintains normal function.

Alternative Option: Third-Generation Cephalosporins

If the penicillin allergy was non-severe (mild rash, gastrointestinal upset rather than anaphylaxis), third-generation cephalosporins are safe alternatives. 1, 2

• Cefpodoxime has only 0.1% cross-reactivity with penicillin due to its distinct chemical structure. 2
• Cefdinir is another third-generation option with excellent coverage. 1
• The FDA label for cefdinir notes that cross-hypersensitivity among β-lactam antibiotics may occur in up to 10% of patients with penicillin allergy history, but this applies primarily to Type I (anaphylactic) reactions. 3

For non-Type I penicillin allergy (rash, mild reactions), cephalosporins are safe to use. 1 However, for documented severe/anaphylactic penicillin allergy, fluoroquinolones remain the safest choice. 1

Treatment Algorithm Based on Allergy Severity

If Non-Severe Penicillin Allergy (Rash, GI Upset):

• First choice: Cefpodoxime 200 mg twice daily for 10 days 1, 2
• Alternative: Cefdinir 300 mg twice daily for 10 days 1

If Severe/Anaphylactic Penicillin Allergy:

• First choice: Levofloxacin 500 mg once daily for 10 days 1
• Alternative: Moxifloxacin 400 mg once daily for 10 days 1

What NOT to Use

• Azithromycin is explicitly contraindicated due to resistance rates exceeding 20-25% for both S. pneumoniae and H. influenzae. 1
• Trimethoprim-sulfamethoxazole should not be used due to 50% resistance for S. pneumoniae and 27% resistance for H. influenzae. 1
• First-generation cephalosporins (cephalexin) have inadequate coverage against H. influenzae, with nearly 50% of strains being β-lactamase producing. 1
• Clindamycin monotherapy lacks activity against H. influenzae and M. catarrhalis, causing failure in 30-40% of cases. 1

Essential Adjunctive Therapies to Maximize Success

Add intranasal corticosteroids (mometasone, fluticasone, or budesonide twice daily) to reduce mucosal inflammation and improve symptom resolution—this has strong evidence from multiple randomized controlled trials. 1

Additional supportive measures include:

• Saline nasal irrigation for symptomatic relief and mucus removal 1
• Analgesics (acetaminophen or NSAIDs) for pain management 1
• Adequate hydration 1

Critical Monitoring and Reassessment

Reassess at 3-5 days: If no improvement, consider switching antibiotics or re-evaluating the diagnosis. 1

Reassess at 7 days: If symptoms persist or worsen, reconfirm the diagnosis and exclude complications (orbital cellulitis, meningitis, brain abscess). 1 Refer to ENT if no improvement after 7 days of appropriate second-line therapy. 1

Common Pitfall to Avoid

Do not continue ineffective therapy beyond 3-5 days. 1 The 3-5 day reassessment is specifically designed to catch early treatment failures and prevent delayed recognition of complications. 1