From the Guidelines
A delayed hypersensitivity reaction to Bactrim (Trimethoprim/Sulfamethoxazole) is most likely caused by a cell-mediated immune response, where the immune system's T-cells recognize the drug as foreign, triggering an inflammatory response that typically appears 48-72 hours after exposure. This reaction is different from immediate IgE-mediated allergic reactions, and its diagnosis and management should be approached accordingly 1.
Key Considerations
- The reaction is typically mild and self-limiting, but can be severe in some cases, and therefore requires prompt medical attention.
- Treatment involves discontinuation of the medication, antihistamines, topical corticosteroids, and in severe cases, oral prednisone 1.
- The immune system's recognition of the drug as foreign triggers an inflammatory response, which is a key factor in the development of delayed hypersensitivity reactions.
- Updating medical records and wearing a medical alert bracelet indicating the Bactrim allergy is crucial to prevent accidental re-exposure.
Management and Prevention
- Alternative antibiotics such as doxycycline, fluoroquinolones, or cephalosporins should be used for future infections, depending on the type of infection 1.
- A single-day challenge may be sufficient to detect delayed reactions, and multiple-day challenges are not recommended after negative single-day challenges 1.
- Resensitization after oral treatment with penicillins is rare, and routine repeat penicillin skin testing is not indicated in patients with a history of penicillin allergy who have tolerated one or more courses of oral penicillin 1.
Important Notes
- Delayed hypersensitivity reactions to Bactrim can occur even after a single therapeutic dose, and extended challenges may be necessary to exclude delayed reactions 1.
- The majority of delayed reactions are mild and easily treated, but severe reactions can occur, and therefore, prompt medical attention is essential 1.
From the FDA Drug Label
Fatalities and serious adverse reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including sulfamethoxazole and trimethoprim Thrombocytopenia Sulfamethoxazole and trimethoprim-induced thrombocytopenia may be an immune-mediated disorder.
The cause of a delayed hypersensitivity reaction to Bactrim (Trimethoprim/Sulfamethoxazole) is likely immune-mediated.
- Key points:
- The reaction may be related to the development of thrombocytopenia, which is thought to be an immune-mediated disorder 2.
- Other severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS may also occur 2 2. However, the exact cause of the delayed hypersensitivity reaction is not explicitly stated in the drug label.
From the Research
Delayed Hypersensitivity Reaction to Bactrim (Trimethoprim/Sulfamethoxazole)
The cause of a delayed hypersensitivity reaction to Bactrim (Trimethoprim/Sulfamethoxazole) can be attributed to several factors, including:
- Genetic susceptibility, with certain genetic variants of HLA loci and drug metabolic enzymes increasing the risk of delayed drug hypersensitivity 3
- Molecular recognition, involving the interaction between the drug antigen, endogenous peptide, HLA presentation, and T cell receptor (TCR) interaction 3
- Immune mediators, including the activation of cytotoxic proteins, cytokines, and chemokines 3
- High drug doses, polypharmacy, long treatment duration, female gender, and acute or chronic infections, which can predispose individuals to drug hypersensitivity reactions 4
Mechanism of Delayed Hypersensitivity Reactions
Delayed hypersensitivity reactions to Bactrim (Trimethoprim/Sulfamethoxazole) are thought to involve T lymphocyte recognition of the drug antigens and cell activation, leading to a range of clinical presentations, from mild reactions such as maculopapular exanthema (MPE) and fixed drug eruption (FDE), to severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) 3
Clinical Presentations
The clinical presentations of delayed hypersensitivity reactions to Bactrim (Trimethoprim/Sulfamethoxazole) can vary, and may include:
- Maculopapular exanthema (MPE)
- Fixed drug eruption (FDE)
- Drug-induced liver injury (DILI)
- Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) 3
- Drug reaction with eosinophilia and systemic symptoms (DRESS) 5, 3
- Acute generalized exanthematous pustulosis (AGEP) 5, 3