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Summary Dissemination of methicillin-resistant-Staphylococcus aureus/(MRSA) is a worldwide concern both in hospitals [healthcare-associated-(HA)-MRSA] and communities [community-associated-(CA)-MRSA]. Knowledge on when and where MRSA colonization is acquired and what clones are involved is necessary, to focus efforts for prevention of hospital-acquired MRSA-infections. Methods A prospective/longitudinal cohort study was performed in eight Argentina hospitals (Cordoba/ October-December/2014). Surveillance cultures for MRSA (nose-throat-inguinal) were obtained on admission and at discharge. MRSA strains were genetically typed as CA-MRSAG and HA-MRSAG genotypes. Results Overall, 1419 patients were screened and 534 stayed at hospital for ≥3 days. S. aureus admission prevalence was 30.9% and 4.2% for MRSA. Overall MRSA acquisition rate was 2.3/1000 patient-days-at-risk with a MRSA acquisition prevalence of 1.96% (95%CI: 1.0%-3.4%); 3.2% of patients were discharged back to community with MRSA. CA-MRSAG accounted for 84.6% of imported, 100.0% of hospital-acquired and 94% of discharged MRSA strains. Most imported and acquired MRSA strains belonged to two major epidemic CA-MRSA clones spread in Argentina: PFGEtypeI-ST5-IVa-t311-PVL+ and PFGEtypeN/ST30-IVc-t019-PVL+. Conclusions CA-MRSA clones, particularly ST5-IV-PVL+ and ST30-IV-PVL+, with main reservoir in the community, not only enter but also are truly acquired within hospital, causing healthcare-associated-hospital-onset infections, having a transmission capacity greater or similar than HA-MRSAG. This information is essential to develop appropriate MRSA infection prevention-control programs, considering hospital and community.

Objectives Ceftaroline (active form of the prodrug ceftaroline fosamil) is a novel cephalosporin with activity against pathogens commonly associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and Gram-negative pathogens. This randomized, double-blind, Phase III study evaluated the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ -10%] of clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations. Methods Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 2 registration number NCT00509106 (http://clinicaltrials.gov/ct2/show/NCT00509106). Results The study enrolled 627 patients, 315 of whom received ceftaroline fosamil and 307 of whom received ceftriaxone. Patients in both treatment groups had comparable baseline characteristics. Clinical cure rates were as follows: CE population, 82.1% (193/235) for ceftaroline fosamil and 77.2% (166/215) for ceftriaxone [difference (95% CI), 4.9% (-2.5, 12.5)]; and MITTE population, 81.3% (235/289) for ceftaroline fosamil and 75.5% (206/273) for ceftriaxone [difference (95% CI), 5.9% (-1.0, 12.7)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE (mMITTE) population were 83.3% (35/42) and 70.0% (28/40) for ceftaroline fosamil and ceftriaxone, respectively. Ceftaroline fosamil and ceftriaxone were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations due to an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, hypokalaemia, insomnia and phlebitis, and the most common AEs for ceftriaxone-treated patients were diarrhoea, insomnia, phlebitis and hypertension. Conclusions Ceftaroline fosamil achieved high clinical cure and microbiological response rates in patients hospitalized with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile that is similar to that of ceftriaxone and other cephalosporins. Ceftaroline fosamil is a promising agent for the treatment of CAP.

BACKGROUND: Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone. CASE PRESENTATION: We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (≤ 2 μg/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country. CONCLUSIONS: This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country. This study was supported by the National Council for Scientific Research and Technology of Argentina (CONICET), Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT - PICT 01630 to JLB), Secretaría de Ciencia y Técnica-Universidad Nacional de Córdoba (SECyT-UNC) and Agencia Córdoba Ciencia. Sí