Safest Antibiotic for Acute Tonsillitis in G6PD Deficiency
Penicillins, specifically amoxicillin, are the safest first-line antibiotics for acute tonsillitis in patients with G6PD deficiency, as they are not among the contraindicated medications and can be used in normal therapeutic doses. 1
Recommended Antibiotic Choice
Use penicillins (amoxicillin or penicillin V) as first-line therapy for acute tonsillitis in G6PD-deficient patients. 1 These beta-lactam antibiotics have no evidence contraindicating their use in G6PD deficiency and represent the standard treatment for bacterial tonsillitis. 2
Medications to Absolutely Avoid
Only seven medications have solid evidence for causing hemolysis in G6PD deficiency and must be avoided: 2
- Dapsone - potent oxidant causing methemoglobinemia and hemolysis 3
- Methylthioninium chloride (methylene blue) - causes severe hemolytic anemia 1, 3
- Nitrofurantoin 2
- Phenazopyridine 2
- Primaquine 1, 3
- Rasburicase 1
- Tolonium chloride (toluidine blue) 2
None of these medications are used for tonsillitis, so this list is primarily for awareness of absolute contraindications. 2
Alternative Antibiotics That Are Safe
Fluoroquinolones
Fluoroquinolones (ciprofloxacin, ofloxacin) can be used safely in G6PD-deficient patients. 4, 5 A retrospective study of 59 G6PD-deficient patients receiving fluoroquinolone prophylaxis during chemotherapy showed no episodes of acute hemolytic anemia. 4 Real-world data from 31,962 G6PD-deficient patients demonstrated safe prescription of ciprofloxacin and ofloxacin to hundreds/thousands of patients. 5
Macrolides
Macrolides (azithromycin, clarithromycin) have no evidence contraindicating their use in G6PD deficiency. 2 These are appropriate alternatives for penicillin-allergic patients with tonsillitis.
Cephalosporins
Cephalosporins can be used safely, as no evidence contraindicates their use in normal therapeutic doses. 2
Important Clinical Caveats
Infection-Related Hemolysis
The infection itself (bacterial tonsillitis) can trigger hemolysis in G6PD-deficient patients, independent of medication exposure. 6, 5 In a real-world study, 8.5% of major hemolytic episodes in G6PD-deficient patients were caused by infection alone. 5 This means hemolysis occurring during antibiotic treatment may be due to the infection rather than the antibiotic.
Variant-Specific Risk
The severity of G6PD deficiency varies by genetic variant. 3 The Mediterranean variant (Gdmed) causes more severe reactions than the African variant (GdA-). 1, 3 However, this primarily affects risk with known oxidant drugs, not standard antibiotics for tonsillitis.
Monitoring Recommendations
Monitor for signs of hemolysis (jaundice, dark urine, pallor) when starting any new medication in G6PD-deficient patients. 1 This is particularly important during acute infections, which themselves can precipitate hemolysis.
Medications Previously Suspected But Now Considered Safe
Sulfonamides (sulfamethoxazole/trimethoprim, sulfasalazine) were historically considered risky but real-world data shows safe use in thousands of G6PD-deficient patients. 5 However, for acute tonsillitis, penicillins or macrolides remain preferred over sulfonamides given the availability of safer alternatives.
Chloroquine/hydroxychloroquine in standard doses appears relatively safe in most G6PD-deficient patients. 3 While not used for tonsillitis, this demonstrates that many historically suspected medications lack evidence for causing hemolysis.
Clinical Bottom Line
Prescribe amoxicillin or penicillin V as first-line treatment for acute tonsillitis in G6PD-deficient patients. 1 For penicillin-allergic patients, use macrolides (azithromycin or clarithromycin) or fluoroquinolones. 2, 4 Avoid the seven definitively contraindicated medications, but recognize that standard antibiotics for tonsillitis are not on this list and can be used safely. 2