Antibiotics That Can Cause Mouth Sores
While antibiotics themselves rarely directly cause mouth sores, certain antibiotics—particularly broad-spectrum agents and those used in immunocompromised patients—can predispose to oral mucositis through secondary fungal superinfections (oral candidiasis/thrush) or, less commonly, through direct drug-induced ulceration.
Primary Mechanism: Secondary Fungal Infections
The most common pathway by which antibiotics cause mouth sores is through disruption of normal oral flora, leading to opportunistic fungal overgrowth:
Broad-spectrum antibiotics including ampicillin, amoxicillin, amoxicillin-clavulanate, cephalosporins (cephalexin, cefuroxime), tetracyclines, and clindamycin can all cause oral candidiasis as a superinfection 1, 2, 3.
Penicillins and cephalosporins are particularly implicated in causing gastrointestinal disturbances and superinfections, with oral candidiasis being a frequent manifestation 2.
Immunocompromised patients are at substantially higher risk for persistent and severe fungal infections, with oral candidosis being particularly common in this population 4, 5.
Direct Drug-Induced Oral Ulceration
Less commonly, certain antibiotics can cause direct oral ulceration:
Methotrexate (used in rheumatoid arthritis) is associated with solitary oral ulcerations that typically appear after several weeks of treatment and resist conventional treatments until the drug is discontinued 6.
Penicillamine and gold compounds (long-term rheumatoid arthritis therapy) can induce oral ulcerations 6.
Azathioprine (immunosuppressive agent) is associated with oral ulceration 6.
High-Risk Scenarios
Patients with the following characteristics face elevated risk:
- History of oral thrush or recurrent candidiasis 4, 5
- Immunocompromised status (HIV, chemotherapy, organ transplant recipients) 4, 5
- Prolonged antibiotic courses, particularly with broad-spectrum agents 2
- Multiple concurrent medications 6
Clinical Recognition and Management
Key diagnostic clues include:
- Oral ulcerations accompanied by burning mouth, metallic taste, dysgeusia, or ageusia strongly suggest a pharmacological origin 6
- White patches or plaques (thrush) developing during or after antibiotic therapy 4, 5
- Ulcerations that resist conventional treatments but heal rapidly after drug discontinuation 6
Management approach:
- For antibiotic-associated oral candidiasis, nystatin remains first-line treatment, with ketoconazole reserved for refractory cases 2
- For suspected direct drug-induced ulceration, consider discontinuing or switching the offending antibiotic if clinically feasible 6
- In immunocompromised patients, maintain high suspicion for fungal infections and consider prophylactic antifungal therapy 4, 5
Common Pitfalls to Avoid
Failing to recognize superinfection: Oral candidiasis during antibiotic therapy is often mistaken for worsening of the primary infection rather than a drug-related complication 2, 4.
Overlooking medication history: In patients on multiple medications, systematically review all agents, paying particular attention to recently initiated drugs 6.
Inadequate antifungal coverage: In immunocompromised patients, simple topical antifungals may be insufficient; systemic therapy may be required 4, 5.