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Little is known of clinical disease due to Mycobacterium chelonae chelonae. One hundred skin, soft tissue, or bone isolates of this rapidly growing mycobacterium were identified over 10 years. Clinical disease included disseminated cutaneous infection (53%); localized cellulitis, abscess, or osteomyelitis (35%); and catheter infections (12%). Underlying conditions with disseminated infection included organ transplantation, rheumatoid arthritis, and autoimmune disorders; 92% involved corticosteroid use. Trauma and medical procedures were risk factors for localized infections. Corticosteroids and chronic renal failure were risk factors for catheter infections. Overall, 62% of patients were receiving corticosteroids and 72% were immunosuppressed. MICs of six oral antimicrobials were obtained for 180 isolates by broth microdilution. Up to 20% of isolates were susceptible to doxycycline, ciprofloxacin, ofloxacin, and sulfamethoxazole. In contrast, 100% were susceptible to clarithromycin (MICs less than or equal to 1 microgram/mL). Disease due to M. chelonae chelonae usually occurs in the setting of corticosteroid therapy and is often disseminated; the organisms require high MICs of oral antimicrobials other than clarithromycin.