What is the appropriate first‑line antibiotic for a healthy 26‑year‑old man with a 10‑day upper‑respiratory infection, improvement for 2 days, then worsening symptoms?

Acute Bacterial Rhinosinusitis Following Viral Upper Respiratory Infection

For a 26-year-old healthy male with a 10-day URI, 2 days of improvement, then worsening symptoms ("double sickening"), prescribe amoxicillin-clavulanate 875 mg/125 mg orally twice daily for 5–10 days as first-line therapy. This clinical pattern meets diagnostic criteria for acute bacterial rhinosinusitis and warrants immediate antibiotic treatment rather than continued observation. 1

Diagnostic Confirmation

• This patient exhibits "double sickening"—initial improvement after a viral URI followed by symptom worsening within 10 days—which is one of three validated patterns that confirm acute bacterial rhinosinusitis (ABRS) and justify antibiotic therapy. 1, 2

• The other two diagnostic patterns are: (1) persistent symptoms ≥10 days with purulent nasal discharge plus obstruction or facial pain/pressure, and (2) severe symptoms ≥3–4 consecutive days with fever ≥39°C, purulent discharge, and facial pain. 1, 2

• Approximately 98–99.5% of acute rhinosinusitis episodes are viral and resolve spontaneously within 7–10 days; however, this patient's biphasic course strongly suggests bacterial superinfection. 1, 2

First-Line Antibiotic Regimen

• Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days provides 90–92% predicted clinical efficacy against the three major sinusitis pathogens: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1, 2

• The clavulanate component is essential because 30–40% of H. influenzae and 90–100% of M. catarrhalis isolates produce β-lactamase, rendering plain amoxicillin ineffective. 1, 2

• Treatment duration of 5–7 days achieves comparable clinical cure rates (74–80%) to 10-day regimens with fewer adverse effects, though most guidelines recommend continuing until symptom-free for 7 consecutive days (typically 10–14 days total). 2

Alternative Regimens (If Penicillin Allergy)

• For non-severe (non-type I) penicillin allergy (e.g., mild rash): use a second- or third-generation cephalosporin—cefuroxime-axetil, cefpodoxime-proxetil, cefdinir, or cefprozil—for 10 days. Cross-reactivity with penicillins is negligible (<1%). 1, 2

• For severe (type I/anaphylactic) penicillin allergy: prescribe a respiratory fluoroquinolone—levofloxacin 500 mg once daily for 10–14 days or moxifloxacin 400 mg once daily for 10 days—both achieving 90–92% predicted efficacy against multidrug-resistant S. pneumoniae. 1, 2

• Doxycycline 100 mg once daily for 10 days is an acceptable but suboptimal alternative (predicted efficacy 77–81% with a 20–25% bacteriologic failure rate) due to limited H. influenzae coverage; reserve for cases where fluoroquinolones are contraindicated. 1, 2

Antibiotics to Avoid

• Macrolides (azithromycin, clarithromycin) should never be used because resistance rates are 20–25% for both S. pneumoniae and H. influenzae; the American Academy of Pediatrics explicitly contraindicates azithromycin for ABRS. 1, 2

• Trimethoprim-sulfamethoxazole exhibits ≈50% resistance in S. pneumoniae and ≈27% in H. influenzae. 1, 2

• First-generation cephalosporins (e.g., cephalexin) are inadequate because ≈50% of H. influenzae strains produce β-lactamase and they have poor activity against penicillin-resistant S. pneumoniae. 1, 2, 3

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution; this recommendation is supported by strong evidence from multiple randomized controlled trials. 1, 2

• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1, 2

• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1, 2

Monitoring and Reassessment Protocol

• Reassess at 3–5 days: if no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch immediately to high-dose amoxicillin-clavulanate (2 g/125 mg twice daily) or a respiratory fluoroquinolone. 1, 2

• Reassess at 7 days: persistent or worsening symptoms warrant confirmation of diagnosis, exclusion of complications (orbital cellulitis, meningitis, intracranial abscess), and consideration of imaging or ENT referral. 1, 2

• Expected timeline: noticeable improvement within 3–5 days of appropriate therapy, with complete resolution by 10–14 days or when symptom-free for 7 consecutive days. 1, 2

Red-Flag Situations Requiring Urgent ENT Referral

• No clinical improvement after 7 days of appropriate second-line antibiotic therapy. 1, 2

• Any worsening at any time (increasing facial pain, fever, purulent drainage). 1, 2

• Signs of complications: severe headache, visual changes, periorbital swelling/erythema, proptosis, diplopia, altered mental status, or cranial nerve deficits. 1, 2

• Recurrent sinusitis (≥3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities. 1, 2

Common Pitfalls to Avoid

• Do not prescribe antibiotics based solely on purulent nasal discharge; this reflects neutrophilic inflammation common to viral disease and does not indicate bacterial infection. 1, 4

• Do not obtain routine imaging (X-ray or CT) for uncomplicated ABRS; up to 87% of viral upper-respiratory infections show sinus abnormalities on imaging, leading to unnecessary interventions. 1, 2

• Ensure adequate treatment duration (≥5 days for adults) to prevent relapse. 1, 2

• Gastrointestinal adverse effects with amoxicillin-clavulanate are common: diarrhea occurs in 40–43% of patients, with severe diarrhea in 7–8%. 1, 2

• Reserve fluoroquinolones for documented severe β-lactam allergy or treatment failure to limit resistance development; they should not be used as routine first-line therapy. 1, 2