The first French outbreak of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 clone was investigated. After outbreak investigation, hygiene measures were implemented in all family households and childminders' homes. Several decontamination procedures were performed, which used a combination of topical mupirocin, total body application of chlorhexidine, chlorhexidine gargle (if >6 years old) and a course of antibiotic therapy in cases of infection or decontamination failure. Patients were followed up for MRSA skin and soft tissue infections (SSTIs) and carriage. Strains were characterised by antimicrobial drug resistance profile, pulsed-field gel electrophoresis (PFGE) and DNA microarrays. Between June 2011 and June 2012, six children and six adults among the ten corresponding relatives developed 28 SSTIs. None of the family members, including the index case, had any contact with foreigners or individuals known to have SSTIs. After infection control measures and prolonged decontamination have been implemented with a high adherence, six patients remained sustained CA-MRSA USA300 carriers, including one who developed mupirocin resistance and six who experienced minor CA-MRSA-related SSTIs. A baby was identified as an MRSA carrier 2 months after delivery. CA-MRSA decontamination using mupirocin and chlorhexidine in the community setting may also be a questionable strategy, associated with failure and resistance to both agents. Close monitoring of CA-MRSA SSTIs is required in France and in other European countries where MRSA USA300 has recently emerged. We showed that a closed management based on hygiene measures reinforcement, decolonisation and extended screening may fail to suppress CA-MRSA carriage and subsequent infections.