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ObjectivesTo describe the patient populations and infections being treated with daptomycin, as well as the efficacy and safety outcomes.Patients and methodsData from the European Cubicin Outcomes Registry and Experience (EU-CORESM), retrospectively collected at 118 institutions between January 2006 and August 2008, were analysed.ResultsDaptomycin treatment was documented in 1127 patients with diverse infections, including complicated skin and soft tissue infections (33%), bacteraemia (22%), endocarditis (12%) and osteomyelitis (6%). It was used empirically, before microbiological results became available, in 53% of patients. Staphylococcus aureus was the most common pathogen (34%), with 52% of isolates resistant to methicillin; coagulase-negative staphylococci and enterococci were also frequent, with 22% of Enterococcus faecium isolates resistant to vancomycin. Daptomycin was used as first-line therapy in 302 (27%) patients. When used second line, the most common reasons for discontinuation of previous antibiotic were treatment failure and toxicity or intolerance. The use of concomitant antibiotics was reported in 65% of patients. Most frequent doses were 6 mg/kg (47%) and 4 mg/kg (32%). The median duration of daptomycin therapy was 10 days (range 1–246 days) in the inpatient setting and 13 days (range 2–189 days) in the outpatient setting. The overall clinical success rate was 79%, with a clinical failure rate of <10% for all infection types. Low failure rates were observed in first- and second-line therapy (6% and 8%, respectively). Daptomycin demonstrated a favourable safety and tolerability profile regardless of treatment duration.ConclusionsDaptomycin has a relevant role in the treatment of Gram-positive infections.

Nosocomial infections caused by enterococci present a challenge for clinicians because treatment options are often limited due to the widespread occurrence of strains resistant to multiple antibiotics, including vancomycin. Daptomycin is a first-in-class cyclic lipopeptide that has proven efficacy for the treatment of Gram-positive infections. Although methicillin-resistant Staphylococcus aureus has been the most prominent target in the clinical development of daptomycin, this agent has demonstrated potent bactericidal activity in enterococcal infection models and has been used for the treatment of enterococcal infections in humans. In recent years, large-scale susceptibility studies have shown that daptomycin is active against >98% of enterococci tested, irrespective of their susceptibility to other antibacterial agents. This lack of cross-resistance reflects the fact that daptomycin has a mode of action distinct from those of other antibiotics, including glycopeptides. While there are limited data available from randomized controlled trials, extensive clinical experience with daptomycin in enterococcal infections (including bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and urinary tract infections) has been reported. This growing body of evidence provides useful insights regarding the efficacy of daptomycin against enterococci in clinical settings.

BackgroundOsteomyelitis is a complex and heterogeneous group of infections that require surgical and antimicrobial interventions. Because treatment failure or intolerance is common, new treatment options are needed. Daptomycin has broad Gram-positive activity, penetrates bone effectively and has bactericidal activity within biofilms. This is the first report on clinical outcomes in patients with osteomyelitis from the multicentre, retrospective, non-interventional European Cubicin® Outcomes Registry and Experience (EU-CORESM), a large database on real-world daptomycin use.Patients and methodsIn total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases.ResultsMost patients (76%) received prior antibiotic treatment, and first-line treatment failure was the most frequent reason to start daptomycin. Common sites of infection were the knee (22%) or hip (21%), and the most frequently isolated pathogens were Staphylococcus aureus (33%) and coagulase-negative staphylococci (32%). Overall, 52% of patients had surgery, 55% received concomitant antibiotics and 29% received a proportion of daptomycin therapy as outpatients. Clinical success was achieved in 75% of patients. Among patients with prosthetic device-related osteomyelitis, there was a trend towards higher success rates if the device was removed. Daptomycin was generally well tolerated.ConclusionsThis analysis suggests that daptomycin is an effective and well-tolerated treatment option for osteomyelitis and highlights the importance of optimal surgical intervention and appropriate microbiological diagnosis for clinical outcomes.

For patients with SAB and CLCR <30 mL/min, or receiving HD or CAPD, the dose recommendation of 6 mg/kg every 48 h provides appropriate daptomycin exposure for this indication; this will not be the case for patients receiving 4 mg/kg every 48 h.