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Methicillin-resistant Staphylococcus aureus (MRSA) burden is increasing worldwide in hospitals [healthcare-associated (HA)-MRSA] and in communities [community-associated (CA)-MRSA]. However, the impact of CA-MRSA within hospitals remains limited, particularly in Latin America. A countrywide representative survey of S. aureus infections was performed in Argentina by analyzing 591 clinical isolates from 66 hospitals in a prospective cross-sectional, multicenter study (Nov-2009). This work involved healthcare-onset infections-(HAHO, >48 hospitalization hours) and community-onset (CO) infections [including both, infections (HACO) in patients with healthcare-associated risk-factors (HRFs) and infections (CACO) in those without HRFs]. MRSA strains were genetically typed as CA-MRSA and HA-MRSA genotypes (CA-MRSA G and HA-MRSA G ) by SCC mec - and spa -typing, PFGE, MLST and virulence genes profile by PCR. Considering all isolates, 63% were from CO-infections and 55% were MRSA [39% CA-MRSA G and 16% HA-MRSA G ]. A significantly higher MRSA proportion among CO- than HAHO- S. aureus infections was detected (58% vs 49%); mainly in children (62% vs 43%). The CA-MRSA G /HA-MRSA G have accounted for 16%/33% of HAHO-, 39%/13% of HACO- and 60.5%/0% of CACO-infections. Regarding the epidemiological associations identified in multivariate models for patients with healthcare-onset CA-MRSA G infections, CA-MRSA G behave like HA-MRSA G within hospitals but children were the highest risk group for healthcare-onset CA-MRSA G infections. Most CA-MRSA G belonged to two major clones: PFGE-type N-ST30-SCC mec IVc-t019-PVL + and PFGE-type I-ST5-IV-SCC mec IVa-t311-PVL + (45% each). The ST5-IV-PVL + /ST30-IV-PVL + clones have caused 31%/33% of all infections, 20%/4% of HAHO-, 43%/23% of HACO- and 35%/60% of CACO- infections, with significant differences by age groups (children/adults) and geographical regions. Importantly, an isolate belonging to USA300-0114-(ST8- SCCmec IVa- spa t008-PVL + -ACME + ) was detected for the first time in Argentina. Most of HA-MRSA G (66%) were related to the Cordobes/Chilean clone-(PFGE-type A-ST5-SCC mec I-t149) causing 18% of all infections (47% of HAHO- and 13% of HACO-infections). Results strongly suggest that the CA-MRSA clone ST5-IV-PVL + has begun to spread within hospitals, replacing the traditional Cordobes/Chilean-HA-MRSA clone ST5-I-PVL − , mainly in children. Importantly, a growing MRSA reservoir in the community was associated with spreading of two CA-MRSA clones: ST5-IV-PVL + , mainly in children with HRFs, and ST30-IV-PVL + in adults without HRFs. This is the first nationwide study in Argentina providing information about the molecular and clinical epidemiology of CA-MRSA, particularly within hospitals, which is essential for designing effective control measures in this country and worldwide. [ABSTRACT FROM AUTHOR]