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Staphylococcus aureus remains one of the most common and troublesome of bacteria causing disease in humans, despite the development of effective antibacterials and improvement in hygiene. The organism is responsible for over 70% of all skin and soft tissue infections in children and accounts for up to one-fifth of all visits to pediatric clinics. Skin and soft tissue infections that are predominantly caused by S. aureus include bullous and non-bullous impetigo, folliculitis, furunculosis, carbunculosis, cellulitis, surgical and traumatic wound infections, mastitis, and neonatal omphalitis. Other skin and soft tissue infections may also be caused by S. aureus but are often polymicrobial in origin and require special consideration. These include burns, decubitus ulcers (particularly in the perianal region), puncture wounds of the foot, as well as human and mammalian bites. Treatment of staphylococcal skin infections varies from topical antiseptics to prolonged intravenous antibacterials, depending on severity of the lesions and the health of the child. The treatment of choice for oral antibacterials remains the penicillinase-resistant penicillins such as flucloxacillin. Cefalexin and erythromycin are suitable cost-effective alternatives with broader cover, although care must be taken with the use of macrolides because of development of resistance to multiple families of antibacterials, particularly the lincosamides. Other cephalosporins such as cefadroxil and cefprozil are also effective, can be given once daily and have a better tolerability profile -- while azithromycin has a further advantage of a 3-day course. However, all of these agents are more expensive. Although the antibacterials have been given for 10 days in most clinical trials, there is no evidence that this duration is more effective than a 7-day course. In children requiring intravenous therapy, ceftriaxone has a major advantage over other antibacterials such as sulbactam/ampicillin and cefuroxime in that it can be given once daily and may, therefore, be suitable for outpatient treatment of moderate-to-severe skin infections. Newer-generation cephalosporins and loracarbef are also effective and have a broader spectrum of activity, but do not offer any added benefit and are significantly more expensive. Skin and soft tissue infections due to methicillin-resistant S. aureus (MRSA) are still relatively uncommon in children. Well children with community-acquired MRSA infections can be treated with clindamycin or trimethoprim-sulfamethoxazole (cotrimoxazole), but must be observed closely for potentially severe adverse effects. In severe infections, vancomycin remains the treatment of choice, while intravenous teicoplanin and clindamycin are suitable alternatives. Linezolid and quinupristin/dalfopristin are currently showing great promise for the treatment of multi-resistant Gram-positive infections. While the choice of antibacterial is important, supportive management, including removal of any infected foreign bodies, surgical drainage of walled-off lesions, and regular wound cleaning, play a vital role in ensuring cure.