What is the first‑line antibiotic for an adult with acute bacterial bronchitis (or acute exacerbation of chronic bronchitis) who has a mild penicillin allergy and resides in an area with low macrolide resistance?

Antibiotic Selection for Acute Bacterial Bronchitis with Mild Penicillin Allergy

For an adult with acute bacterial bronchitis (or acute exacerbation of chronic bronchitis) who has a mild penicillin allergy in an area with low macrolide resistance, a macrolide antibiotic—specifically azithromycin or clarithromycin—is the first-line choice. 1

Critical Diagnostic Distinction: Acute vs. Chronic Bronchitis

Before prescribing any antibiotic, you must first determine whether this is truly acute bacterial bronchitis or an acute exacerbation of chronic bronchitis (AECB), because the management differs fundamentally:

For Uncomplicated Acute Bronchitis in Otherwise Healthy Adults

• Antibiotics should NOT be prescribed routinely, as 89–95% of cases are viral and antibiotics provide no meaningful benefit (reducing cough by only ~0.5 day while increasing adverse events). 1
• Purulent sputum occurs in 89–95% of viral cases and does not indicate bacterial infection. 1
• The only exception is confirmed or suspected pertussis, which requires a macrolide (azithromycin or erythromycin) immediately. 1

For Acute Exacerbation of Chronic Bronchitis (AECB)

• Antibiotics are indicated when the patient has at least 2 of the 3 Anthonisen criteria (increased dyspnea, increased sputum volume, increased sputum purulence) plus at least one risk factor (age ≥65 years, FEV₁ <50% predicted, ≥4 exacerbations per year, or significant comorbidities). 1, 2
• This is the scenario where antibiotic selection becomes clinically relevant.

First-Line Antibiotic for AECB with Mild Penicillin Allergy

Macrolides (Preferred in Low-Resistance Areas)

In areas with low macrolide resistance, a newer macrolide is the appropriate first-line choice for patients with mild penicillin allergy:

• Azithromycin 500 mg once daily for 3 days achieves 85% clinical cure rates in AECB and is well-tolerated. 3
• Clarithromycin extended-release 1000 mg once daily for 5–7 days achieves 90–97% clinical cure rates, or clarithromycin immediate-release 500 mg twice daily for 7–14 days. 1
• Macrolides provide excellent coverage against the three most common AECB pathogens: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 2, 4

Alternative: Doxycycline

• Doxycycline 100 mg twice daily for 7–10 days is recommended as a first-line option for moderate-severity exacerbations, particularly in patients with beta-lactam allergy. 1
• Doxycycline is appropriate for infrequent exacerbations in patients without severe airflow obstruction. 2

Stratification by Severity

Moderate-Severity Exacerbations (Uncomplicated AECB)

For patients with infrequent exacerbations (≤3 per year) and FEV₁ ≥35%:

• First-line options: Azithromycin, clarithromycin, or doxycycline 1, 2
• These agents are appropriate when macrolide resistance is low in your area. 1

Severe Exacerbations (Complicated AECB)

For patients with frequent exacerbations (≥4 per year) or FEV₁ <35%:

• Respiratory fluoroquinolones (levofloxacin 750 mg once daily for 5 days or moxifloxacin) should be considered instead of macrolides, even with penicillin allergy. 1, 5, 6
• Fluoroquinolones are recommended as first-line therapy for patients with risk factors due to superior activity against resistant pathogens and Pseudomonas aeruginosa. 5, 4

Critical Resistance Considerations

Macrolide Resistance Patterns

• 30–40% of S. pneumoniae strains are resistant to macrolides, and this resistance is often associated with beta-lactam resistance. 7
• 25% of H. influenzae and 50–70% of M. catarrhalis produce β-lactamase, making simple aminopenicillins ineffective, but macrolides remain active. 1
• The question specifies low macrolide resistance in your area, which makes macrolides appropriate first-line agents. 1

When to Avoid Macrolides

• If local macrolide resistance is high (>25% for S. pneumoniae), consider doxycycline or a respiratory fluoroquinolone instead. 1
• Older-generation macrolides (erythromycin) should be avoided due to increasing resistance. 1

Practical Dosing Regimens

Antibiotic	Dose	Duration	Clinical Cure Rate
Azithromycin	500 mg once daily	3 days	85% [3]
Clarithromycin ER	1000 mg once daily	5–7 days	90–97% [1]
Clarithromycin IR	500 mg twice daily	7–14 days	82% [3]
Doxycycline	100 mg twice daily	7–10 days	Comparable [1]

Common Pitfalls to Avoid

• Do not prescribe antibiotics for acute bronchitis based on purulent sputum alone—this occurs in 89–95% of viral cases. 1
• Do not assume bacterial infection based on cough duration—viral cough typically lasts 10–14 days and may persist up to 3 weeks. 1
• Do not use aminopenicillins alone (amoxicillin without clavulanate) due to high β-lactamase production rates. 1
• Do not use first-generation cephalosporins or cotrimoxazole due to increasing resistance. 1
• Obtain sputum cultures when possible before starting empirical antibiotics, then adjust therapy based on sensitivity results if no clinical improvement occurs. 1

When to Escalate Therapy

• If fever persists >3 days, consider bacterial superinfection or pneumonia and reassess. 1
• If no clinical improvement occurs after 48–72 hours of appropriate antibiotic therapy, obtain sputum culture and consider switching to a respiratory fluoroquinolone. 1, 5
• For patients with documented Pseudomonas aeruginosa infection, inhaled colistin plus oral azithromycin is recommended. 8