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Background: Intravenous drug abuse (IVDA) is a common problem; there were more than 16 million users worldwide in 2008. Numerous reports highlight the infectious skeletal complication associated with IVDA., Objective: To determine septic arthritis pathogens in IVDA in a U.S. hospital and compare the current causative organisms to a cohort from the 1980s at the same institution., Methods: An institutional review board-approved retrospective cohort study compared a consecutive series of IVDA septic arthritis patients over a 10-year period, 1999-2008 (Group B), with an IVDA septic arthritis database that was collected in the 1980s (Group A). Endpoints were: bacterial species and staph species antibiotic susceptibility., Results: Group B included 58 patients (35 men, 23 women) with a median age of 46.5 years. Group A included 38 patients (30 men, 8 women), with a median age of 32.5 years. The sets were significantly different in pathogens (p = 0.0443). The most common organisms were Staphylococcus (staph) species (B 74.51%, A 52.63%), followed by Streptococcus (strep) species (B 7.84%, A 31.58%), Pseudomonas (B 13.73%, A 13.16%), and Serratia (B 3.92%, A 2.63%). Of the total number of septic joints, methicillin-resistant Staphylococcus aureus (MRSA) made up 39% of Group B and 34% of Group A. However, within the staph species, MRSA made up 53% of Group B and 65% of Group A. Strep species made up 7.84% (Group B) vs. 31.58% (Group A), and Pseudomonas (13%) and Serratia (3-4%) were similar. In the Group B cohort, methicillin-susceptible Staphylococcus aureus (MSSA) had a predilection to infect the knee (94.4%), whereas MRSA was found more often in the hip (57.1%)., Conclusions: In IVDAs, MRSA is the most common pathogen causing septic arthritis. The ratio of staph species in septic joints is increasing, and the ratio of MRSA to MSSA remains high (>50%). Strep species are much less common., (Copyright © 2014 Elsevier Inc. All rights reserved.)