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Community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) is an established pathogen in several areas of the United States, but experience with clindamycin for the treatment of invasive MRSA infections is limited. We compared the outcome of therapy for MRSA with that of methicillin-susceptible (MSSA) invasive infections in children treated with clindamycin, vancomycin or beta-lactam antibiotics.The demographics, hospital course and outcome of children at Texas Children’s Hospital between February and November 2000 and between August 2001 and August 2002 with invasive S. aureus infections were reviewed from medical records in this retrospective study.CA-MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused invasive infections in 46 and 53 children, respectively. The median ages (range) of the children were: MRSA, 3.5 years (2 months to 18.6 years); MSSA, 4.8 years (3 months to 19.8 years). The sites of infection for MRSA vs. MSSA isolates, respectively, were: bacteremia, 3 vs. 6; osteomyelitis, 14 vs. 14; septic arthritis, 5 vs. 7; pneumonia, 11 vs. 3; lymphadenitis, 7 vs. 14; other, 5 vs. 8. Among MRSA patients 39 (20 received clindamycin only, 18 had vancomycin initially and 8 were treated with a beta-lactam initially) received clindamycin and 6 received vancomycin as primary therapy. Among MSSA patients, clindamycin, nafcillin or other beta-lactam antibiotics were used in 24, 18 and 9, respectively. The median number of febrile days was 3 (0 to 14) and 2 (0 to 6) for MRSA and MSSA patients, respectively (P = 0.07). The median number of days with positive blood cultures was 2 for the MRSA (n = 16) and 1 for the MSSA (n = 18) patients (P = 0.04).Clindamycin was effective in treating children with invasive infections caused by susceptible CA-MRSA isolates.