Graded Escalating Doses of Trimethoprim-Sulfamethoxazole in Immunocompetent Patients with Previous History of Delayed Rash to Sulfa Antimicrobials

Rationale: Allergy to sulfonamide antibiotics often present w/delayed cutaneous reactions ranging from mild exantham to severe exfoliating dermatitis.  Much of the literature demonstrates safety/efficacy of graded challenge/desensitization in immunocompromised patients. However less is known about immunocompetent patients. We present a case series of oral graded dose escalations (GDE) of trimethoprim-sulfamethoxazole (TMP-SMX) in immunocompetent patients.

Methods: Chart review of patients admitted at a tertiary medical center over 2 years. Patients were selected from allergy/immunology consult service w/history of allergy to TMP-SMX with need for resistant infection. Several GDE protocols were used w/some modification based on clinical scenario.

Results: 11 patients: age 12-63yo; 9 w/cystic fibrosis (CF), 1 quadriplegia, 1 COPD. Delayed rash reported in 10 patients; 7 w/ pruritus, 2 nausea/vomiting, 1 skin sloughing. Time of reaction to GDE is < 1 year to decades. Some patients received multiple GDEs resulting in 18/19 successful attempts. 1 unsuccessful GDE had repeat fixed drug eruption w/skin sloughing. There were seven 3-step GDEs, dosed at 1/100 then 1/10 then full dose. 3 patients had > 6-step GDE followed by 3-step GDEs thereafter on readmission. Other GDEs varied between 6-30 steps, with intervals of 15min-12hrs between doses.

Conclusions: CF patients are unique w/frequent need for TMP-SMX but are otherwise immunocompetent. We demonstrate safety/efficacy to a variety of GDEs in these immunocompetent patients w/history of TMP-SMX allergy. 1 patient failed without significant morbidity. This suggests that GDEs to TMP-SMX are generally safe/efficacious and 3-step GDEs may be used more often if the clinical scenario so dictates.