High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS

BackgroundTrimethoprim/sulfamethoxazole (TMP/SMX) is currently the most effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS. The major drawback is the frequent occurrence of adverse reactions (ADRs).The current study was designed to determine the frequency and risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS.MethodsA retrospective study was conducted in adult patients with PJP and AIDS who were admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January 2006 and December 2011. Charts were reviewed to determine the effect of age, risk behaviors, severity of illness, viral load, CD4 cell counts, use of corticosteroids, and dosage and duration of TMP/SMX on ADRs during hospitalization. Patients who received TMP/SMX for ≤ 5 days or with an incomplete medical record were excluded. Multivariate logistic regression was used to calculate the hazard ratio (HR) for ADRs.ResultsFifty two of 75 patients with PJP and AIDS met the study criteria. Of these patients, 21/52 (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms in three (14.3%). Most of the ADRs occurred within the 1st 2 weeks of TMP/SMX therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX of ≥ 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40–10.35; p = 0.009) and age 34 years (HR, 4.30; 95% confidence interval, 1.52–12.14; p = 0.006) were independently associated with ADRs.ConclusionWe found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.