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1.  Community-based outpatient parenteral antimicrobial therapy (CoPAT) for Staphylococcus aureus bacteraemia with or without infective endocarditis: analysis of the randomized trial comparing daptomycin with standard therapy 
Objectives
Administering outpatient parenteral antimicrobial therapy in the community setting (CoPAT) is becoming more common with the increasing emphasis on controlling costs. However, few controlled trials have evaluated this treatment modality.
Methods
Using data from a recent randomized trial comparing daptomycin with standard therapy (semi-synthetic penicillin or vancomycin, each with initial low-dose gentamicin) for Staphylococcus aureus bacteraemia and infective endocarditis (SAB/IE), patient characteristics and outcomes were evaluated. Patients receiving their full course of therapy in the hospital setting were compared with those who received some portion outside of the hospital (CoPAT).
Results
Among the 200 patients, 51.5% received CoPAT. These patients were generally younger (median age 50 versus 54 years, P = 0.028). In the CoPAT group, there tended to be fewer patients with endocardial involvement (8.7% versus 18.6%, P = 0.061) and pre-existing valvular heart disease (7.8% versus 15.5%, P = 0.120). CoPAT patients received longer therapy courses (mean 25.4 versus 13.5 days, P < 0.001) and had higher rates of therapy completion (90.3% versus 45.4%, P < 0.001) and clinical success (86.4% versus 55.7%, P < 0.001). Persisting or relapsing S. aureus was less frequent in the CoPAT group (3.9% versus 15.5%, P = 0.007) and there were fewer deaths (3.9% versus 18.6%, P = 0.001) 6 weeks after the end of therapy. Hospital readmission occurred for 18 of the 103 (17.5%) CoPAT patients. Clinical success rates were similar for CoPAT patients receiving daptomycin (90.0%) or standard therapy (83.0%).
Conclusions
With proper monitoring, stable patients can complete treatment for SAB/IE as outpatients in the community setting. Daptomycin is an appropriate option for this setting.
doi:10.1093/jac/dkp051
PMCID: PMC2667135  PMID: 19264792
outcomes; hospital readmission; OPAT; vancomycin; semi-synthetic penicillin
2.  Associations between the Genotypes of Staphylococcus aureus Bloodstream Isolates and Clinical Characteristics and Outcomes of Bacteremic Patients ▿  
Journal of Clinical Microbiology  2008;46(9):2890-2896.
We investigated associations between the genotypic and phenotypic features of Staphylococcus aureus bloodstream isolates and the clinical characteristics of bacteremic patients enrolled in a phase III trial of S. aureus bacteremia and endocarditis. Isolates underwent pulsed-field gel electrophoresis, PCR for 33 putative virulence genes, and screening for heteroresistant glycopeptide intermediate S. aureus (hGISA). A total of 230 isolates (141 methicillin-susceptible S. aureus and 89 methicillin-resistant S. aureus [MRSA]) were analyzed. North American and European S. aureus isolates differed in their genotypic characteristics. Overall, 26% of the MRSA bloodstream isolates were USA 300 strains. Patients with USA 300 MRSA bacteremia were more likely to be injection drug users (61% versus 15%; P < 0.001), to have right-sided endocarditis (39% versus 9%; P = 0.002), and to be cured of right-sided endocarditis (100% versus 33%; P = 0.01) than patients with non-USA 300 MRSA bacteremia. Patients with persistent bacteremia were less likely to be infected with Panton-Valentine leukocidin gene (pvl)-constitutive MRSA (19% versus 56%; P = 0.005). Although 7 of 89 MRSA isolates (8%) exhibited the hGISA phenotype, no association with persistent bacteremia, daptomycin resistance, or bacterial genotype was observed. This study suggests that the virulence gene profiles of S. aureus bloodstream isolates from North America and Europe differ significantly. In this study of bloodstream isolates collected as part of a multinational randomized clinical trial, USA 300 and pvl-constitutive MRSA strains were associated with better clinical outcomes.
doi:10.1128/JCM.00905-08
PMCID: PMC2546778  PMID: 18596141
3.  Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates 
Objectives
In a prospective, randomized trial, daptomycin was non-inferior to standard therapy for Staphylococcus aureus bacteraemia and right-sided endocarditis. Since rates of infection due to methicillin-resistant S. aureus (MRSA) infection are increasing and treatment outcomes for bacteraemia caused by MRSA are generally worse than those observed with methicillin-susceptible S. aureus bacteraemia, clinical characteristics and treatment results in the trial’s pre-specified subset of patients with MRSA were analysed.
Methods
Clinical characteristics and outcomes of patients receiving daptomycin were compared with those receiving vancomycin plus low-dose gentamicin. Success was defined as clinical improvement with clearance of bacteraemia among patients who completed adequate therapy, received no potentially effective non-study antibiotics and had negative blood cultures 6 weeks after end of therapy.
Results
Twenty of the 45 (44.4%) daptomycin patients and 14 of the 43 (32.6%) vancomycin/gentamicin patients were successfully treated (difference 11.9%; confidence interval −8.3 to 32.1). Success rates for daptomycin versus vancomycin/gentamicin were 45% versus 27% in complicated bacteraemia, 60% versus 45% in uncomplicated bacteraemia and 50% versus 50% in right-sided MRSA endocarditis. Cure rates in patients with septic emboli and in patients who received pre-enrolment vancomycin were similar between treatment groups. However, in both treatment groups, success rates were lower in the elderly (≥75 years). Persisting or relapsing bacteraemia occurred in 27% of daptomycin and 21% of vancomycin/gentamicin patients; among these patients, MICs of ≥2 mg/L occurred in five daptomycin and four vancomycin/gentamicin patients. The clinical course of several patients may have been influenced by lack of surgical intervention.
Conclusions
Daptomycin was an effective alternative to vancomycin/gentamicin for MRSA bacteraemia or right-sided endocarditis.
doi:10.1093/jac/dkn372
PMCID: PMC2583068  PMID: 18782781
MRSA; endovascular infections; bloodstream infections; combination therapy; clinical trial

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