For an adult with a β‑lactam allergy, what antibiotic regimen provides coverage for Streptococcus species, considering the severity of the allergy and the infection site?

Streptococcal Coverage for β-Lactam Allergic Adults

For adults with β-lactam allergy requiring streptococcal coverage, use clindamycin 300 mg orally three times daily for 10 days if the allergy is severe (Type I/immediate hypersensitivity), or a first-generation cephalosporin such as cephalexin 500 mg twice daily for 10 days if the allergy is non-severe (e.g., rash without anaphylaxis). 1, 2

Severity-Based Algorithm for Antibiotic Selection

Step 1: Classify the Allergy Severity

Non-severe β-lactam allergy (delayed rash, non-urticarial reactions):

• First-generation cephalosporins are the preferred choice 3, 1
• Cephalexin 500 mg orally twice daily for 10 days 2
• Cefadroxil 1 g once daily for 10 days 1
• Cross-reactivity risk with penicillin is <1% for later-generation cephalosporins with distinct side chains 4

Severe β-lactam allergy (Type I immediate hypersensitivity: anaphylaxis, angioedema, urticaria):

• Avoid ALL β-lactam antibiotics including cephalosporins 3, 1, 2
• Clindamycin is the preferred alternative 2, 5
• Clindamycin 300 mg orally three times daily for 10 days 2
• Clindamycin has only ~1% resistance in the US and provides excellent streptococcal coverage 2, 5

Step 2: Consider Macrolides as Second-Line for Severe Allergy

If clindamycin is unavailable or contraindicated:

• Azithromycin 500 mg once daily for 5 days 1, 6
• Clarithromycin 250 mg twice daily for 10 days 1
• Important caveat: Macrolide resistance in Group A Streptococcus ranges from 20-25% with significant geographic variation 1, 2
• Macrolides have lower bacteriologic efficacy (73%) compared to penicillin (91-92%) 3
• Azithromycin does not prevent rheumatic fever as reliably as penicillin-based regimens 6

Step 3: Infection Site-Specific Considerations

For pharyngitis/tonsillitis:

• Non-severe allergy: Cephalexin 500 mg twice daily × 10 days 1, 2
• Severe allergy: Clindamycin 300 mg three times daily × 10 days 1, 2
• Alternative: Azithromycin 500 mg daily × 5 days (only if clindamycin unavailable) 1, 6

For acute bacterial rhinosinusitis:

• Non-severe allergy: Cefuroxime or cefpodoxime 3
• Severe allergy: Doxycycline 100 mg twice daily or respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily) 3
• TMP-SMX has 83% calculated efficacy but should be reserved for mild disease 3

For community-acquired pneumonia:

• Non-severe allergy: Respiratory fluoroquinolone (moxifloxacin, levofloxacin 750 mg, or gemifloxacin) 3
• Severe allergy: Respiratory fluoroquinolone plus azithromycin for hospitalized patients 3
• Doxycycline 100 mg twice daily is acceptable for outpatient mild disease 3

For endocarditis (streptococcal):

• Non-severe allergy: Ceftriaxone 2 g IV daily or cefazolin 2 g IV every 8 hours 3
• Severe allergy: Vancomycin 15 mg/kg IV every 12 hours (target trough 15-20 mcg/mL) plus gentamicin 3 mg/kg/day IV divided every 8 hours for first 2 weeks 3

Critical Treatment Principles

• Always complete a full 10-day course for streptococcal pharyngitis (except azithromycin's 5-day regimen) to prevent acute rheumatic fever 3, 1, 2
• Penicillin remains the only regimen with proven rheumatic fever prevention in controlled trials; alternatives lack this definitive evidence 3
• First-generation cephalosporins have superior streptococcal coverage compared to third-generation agents and should be prioritized when cephalosporins are appropriate 1, 7
• Clindamycin is FDA-approved for serious streptococcal infections and should be reserved for penicillin-allergic patients 5

Common Pitfalls to Avoid

• Do not use cefixime (third-generation cephalosporin) for strep throat—it is explicitly excluded from IDSA guidelines and lacks proven efficacy for streptococcal pharyngitis 7
• Do not assume all "penicillin allergies" are true allergies—over 90% of reported penicillin allergies can be ruled out with proper allergy testing 8
• Do not use TMP-SMX as first-line therapy—it has inconsistent activity against pneumococci and 20-25% failure rates 1, 2
• Do not use fluoroquinolones for routine pharyngitis—reserve them for resistant infections or when other options are contraindicated 1, 2
• Do not prescribe macrolides in regions with high resistance (>25%)—bacteriologic failure rates approach 20-25% 1
• Do not use aztreonam for streptococcal coverage—it has no gram-positive activity and is only appropriate for gram-negative infections in β-lactam allergic patients 3

When to Reassess or Escalate

• If no clinical improvement after 72 hours, switch antibiotic class or re-evaluate for complications (peritonsillar abscess, suppurative lymphadenitis) 3, 1
• Consider allergy testing for patients with reported β-lactam allergy to enable future use of preferred agents—most can safely receive cephalosporins or even penicillins after evaluation 4, 8
• For severe infections requiring β-lactams, consider rapid desensitization protocols rather than accepting inferior alternatives 9, 8