Daptomycin for methicillin-resistant Staphylococcus aureus diabetic foot infections.

BACKGROUND: Diabetic foot infection (DFI) is a serious, difficult-to-treat infection, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin has been the standard treatment for MRSA infection, but lower response rates in MRSA skin infections have been reported. This analysis assessed the outcome and safety of daptomycin therapy in patients with a DFI caused by MRSA. METHODS: Using the Cubicin Outcomes Registry and Experience and the European Cubicin Outcomes Registry and Experience (2006-2009), 79 patients with MRSA DFI were identified and included in this analysis. RESULTS: In the 74 evaluable patients, daptomycin was administered at a median dose of 4.8 mg/kg primarily every 24 hours (85.1%) and for a median of 15.0 days. Overall, 77.0% of the patients (57 of 74) received initial therapy with activity against MRSA; however, of patients receiving daptomycin as second-line therapy (n = 31), only 45.2% were treated with an antibiotic agent active against MRSA. The overall clinical success and treatment failure rates were 89.2% and 10.8%, respectively. Success with daptomycin therapy was higher in patients who had surgery and in those whose initial therapy was daptomycin. Eleven patients had 14 adverse events, two of which were possibly related to daptomycin use and led to discontinuation. CONCLUSIONS: In a large real-world cohort of patients with MRSA DFI, daptomycin therapy was shown to be generally well tolerated and effective. The use of an anti-MRSA antibiotic agent should be considered when implementing first-line antibiotic drug therapy for DFI in countries where MRSA is common to avoid inappropriate empirical treatment and potential negative effects on outcomes.

Daptomycin use in patients with osteomyelitis: a preliminary report from the EU-CORE(SM) database.

BACKGROUND: Osteomyelitis 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-CORE(SM)), a large database on real-world daptomycin use. PATIENTS AND METHODS: In total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases. RESULTS: Most 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. CONCLUSIONS: This 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.

Daptomycin for the treatment of infective endocarditis: results from a European registry.

OBJECTIVES: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. PATIENTS AND METHODS: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. RESULTS: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. CONCLUSIONS: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.