Abstract
BackgroundIncreasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited.MethodsA retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan.ResultsA total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3–53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg.ConclusionsTreatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.
Highlights
Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics
Among patients suffering from infections in the intensive care units (ICU), S. aureus, predominantly MRSA, remains one of the most common causative organism [4]
Audit by an infectious diseases physician is necessary to prescribe daptomycin at National Taiwan University Hospital (NTUH), all patients receiving daptomycin during the study period could be identified at onset of therapy
Summary
Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. Clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited. Daptomycin, a cyclic lipopeptide antibiotic, has a rapid, concentration-dependent bactericidal activity against clinically relevant gram-positive organisms, such as Staphylococcus aureus (including methicillinresistant S. aureus, MRSA) and enterococci (including vancomycin-resistant enterococci, VRE). S. aureus isolates with reduced daptomycin susceptibility, especially after receiving prior glycopeptitide therapy, have been described and were associated with clinical failure [5,6,7]. Increased activity with higher doses, especially against isolates with reduced susceptibility, was demonstrated in some in vitro and animal studies [8,9,10]. Increasing doses of daptomycin seems attractive for severe infections, critically ill patients, or prior treatment failure with glycopeptides [12]. The experience with high dose daptomycin (> 6 mg/kg) is still limited worldwide, and it is unclear whether this strategy improves outcomes [13,14,15,16,17]
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