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Skin and soft-tissue abscesses, a common problem among injection drug users (IDUs), result in serious morbidity for the patient and costly hospitalizations for incision and drainage; however, there has been little etiologic or preventive epidemiologic research on this problem. We performed a case-control study that enrolled 151 IDUs who had been given a new diagnosis of abscess requiring incision and drainage (cases) and 267 IDUs who did not have abscess or other bacterial infection during the previous year and who were stratum-matched to cases according to age, sex, and race (controls). Subcutaneous or intramuscular, instead of intravenous, injection is a major risk factor for abscess among IDUs. The injection of a cocaine and heroin mixture, or “speedball,” may predispose patients to develop abscess by inducing soft-tissue ischemia. Cleaning the skin with alcohol before injection was found to have a …