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Methicillin-resistant Staphylococcus aureus (MRSA) with a narrower antibiotic resistance pattern have emerged. There is a risk for the appearance of resistance during clindamycin therapy of erythromycin-resistant MRSA infections because of the linked resistance mechanisms.We analyzed clindamycin-susceptible MRSA organisms from children (1987 to 2000) along with clinical data. Antibiotic susceptibilities of organisms were tested, pulsed field gel electrophoresis (PFGE) was done and the linked resistance mechanism was detected by the D test.An average of 11 clindamycin-susceptible MRSA per year were obtained from children since 1993. Of 88 isolates 33 (38%) were erythromycin-resistant. The latter were less often community-acquired (45%vs. 69%), more often from infants <1 month of age (24%vs. 4%) and less likely to be in the community acquisition-associated PFGE Group 1 (62%vs. 87%) than those that were susceptible. The D test was positive in 31 of 33 erythromycin-resistant isolates. A 9-month-old boy with pneumonia/empyema caused by a clindamycin-susceptible, erythromycin-resistant, D test-positive MRSA developed a PFGE-identical clindamycin-resistant isolate and clinical relapse during clindamycin treatment. In contrast a 12-year-old girl with abscesses caused by a similar MRSA developed another abscess after clindamycin therapy, but the organism was unchanged in susceptibility.Erythromycin resistance was present in 38% of clindamycin-susceptible MRSA in children, and clindamycin resistance was detected during treatment in one child. Clindamycin remains a treatment option if the clinician is notified of the risk by the microbiology laboratory and the clinical situation is suitable.