Table 1.
Clinical Studies With High-Dose Daptomycin Doses.
| Reference | Study design | Population | Daptomycin regimens | Results and conclusions | Safety |
|---|---|---|---|---|---|
| Huang et al, 2020109 | Retrospective, single center | n = 10; Severe burn injury (>50% BSA), Chinese, 20-50 years, 7 days postburn | 6 mg/kg/d (n = 3) vs 12 mg/kg/d (n = 7). The higher dose was given after 6 mg/kg/d did not reach desired serum concentrations. | Two of 3 MRSA infections in the high-dose group converted to negative cultures, whereas 0 of 2 in the standard-dose group became negative. High-dose daptomycin produced higher concentrations than standard doses through 7 hours after the dose | No significant difference in CPK levels between high doses and standard doses (1 patient showed transient CPK increase after high doses). Albumin was increased with high-dose daptomycin on day 7 compared with baseline |
| Peghin et al, 201947 | Prospective, single center | n = 43; NVE and PVE from enterococcal spp | Daptomycin-based regimen (high-dose ± another agent, n = 16) vs daptomycin-sparing regimen (no daptomycin, n = 27). Mean daptomycin dose: 10.25 mg/kg/d | No difference in mortality rates and/or treatment failure in either group. Shorter antibiotic therapy length was found in the daptomycin-based group (45 vs 56 days; P = 0.02) | No rhabdomyolysis or eosinophilic pneumonia occurred in patients receiving high-dose daptomycin |
| Russo et al, 201939 | Prospective, single center | n = 327 (224 NVE and 103 PVE); Monomicrobial gram-positive endocarditis | Daptomycin-containing regimen (n = 84) vs nondaptomycin regimen (n = 140); daptomycin doses ranged from 4 to ≥8 mg/kg/d | Daptomycin 4-6 mg/kg/d was associated with higher mortality and treatment failure compared with ≥8 mg/kg/d dosing (NVE mortality: 26.1% vs 1.2%; PVE mortality: 6.5% vs 0%). Standard daptomycin doses of 4-6 mg/kg/d were associated with 30-day mortality in daptomycin-treated patients (OR = 2.2; P = 0.02) | No patient receiving daptomycin had an adverse event warranting a change in therapy |
| Chuang et al, 201863 | Prospective, 2-center Taiwanese observational cohort | n = 108; VRE BSI treated with daptomycin or linezolid | Daptomycin <9 mg/kg (58%) vs daptomycin ≥9 mg/kg (14%) vs linezolid (28%) | Daptomycin ≥9 mg/kg cleared bacteremia faster than <9 mg/kg (−0.04 vs −0.56 Δ log10 copies/mL/d). Slower bacterial clearance predicted mortality (aOR = 1.4; P = 0.045 | None reported |
| Britt et al, 201760 | Retrospective, national cohort of Veterans Affairs hospitals | n = 911; BSI with VRE and treated with daptomycin | Daptomycin 6 mg/kg/d (78%), 8 mg/kg/d (16%), or ≥10 mg/kg/d (7%) | Doses ≥10 mg/kg/d were associated with greater survival than both 6 (aHR: 2.58; P = 0.004) and 8 mg/kg/d (aHR: 2.52; P = 0.008). Doses ≥10 mg/kg/d were associated with a lower 30-day mortality risk. Doses of 8 and 10 mg/kg/d were both associated with enhanced microbiological clearance rates than 6 mg/kg/d | CPK elevation occurred in 1.2% of those measured, and no patient in the ≥10-mg/kg/d group experienced CPK elevation. Concurrent statin use was not associated with elevated CPK (1.3% vs 0.7%; P = 0.504) |
| Claeys et al, 201657 | Retrospective, multicenter, propensity matched | n = 262; MRSA BSI treated with daptomycin or vancomycin | Daptomycin 8.2 mg/kg/d (IQR = 6.4-10) vs vancomycin trough target (15-20 mg/L) | All-cause 30-day mortality was lower with daptomycin (6.1% vs 15.3%; P = 0.01). Change in therapy occurred less frequently with daptomycin (15.3% vs 28.2%; P = 0.05) | Adverse drug reactions were reported in 11.5% of patients in both groups. Three patients receiving daptomycin had CPK elevations >2000 U/L, and 2 (1.5%) reported myopathy |
| Guleri et al, 201542 | Retrospective, multicenter, data from EU-CORE | n = 610; At least 1 dose of daptomycin for serious gram-positive IE | Daptomycin doses ≥8 to ≤10 mg/kg/d (n = 109, 17.9%) and doses >10 mg/kg/d (n = 7, 1.1%) | Daptomycin doses ≥8 mg/kg/d had a trend toward higher clinical success rates than doses <8 mg/kg/d (92.2% vs 78.3%) | Blood CPK elevations were reported in 11 of 610 patients (1.8%); myalgia and rhabdomyolysis each occurred in 1 patient |
| Ceron et al, 201448 | Retrospective, single center | n = 32; Patients ≥18 years old with monomicrobial enterococcal IE | Daptomycin 6 to 10 mg/kg/d (n = 6) vs ampicillin/ceftriaxone (n = 21) vs ampicillin or vancomycin ± gentamicin (n = 5); median daptomycin dose: 8.5 mg/kg/d | Daptomycin-treated patients had a longer duration of bacteremia (6 days vs 1 day vs 1 day; P < 0.01). Daptomycin-treated patients needed more frequent therapy changes (66.7% vs 0% vs 20%; P < 0.01 | No differences in adverse events related to antibiotic therapy (0% vs 0% vs 20%) |
| Carugati et al, 201340 | Prospective observational, multicenter | n = 441; Left-sided IE caused by S aureus, Enterococcus faecalis, or coagulase-negative staphylococci | Daptomycin (n = 49) vs other standard of care antibiotics (n = 392); median daptomycin dose: 9.2 mg/kg/d (7.7-10.0) | Daptomycin was associated with faster clearance of MRSA bacteremia (1 vs 5 days; P < 0.01). Daptomycin was used as second-line in 68% of daptomycin-treated patients | Doses ≥8 mg/kg/d were not associated with a difference in adverse events |
| Murray et al, 201346 | Matched retrospective, multicenter | n = 170; MRSA bacteremia (etiologies: IE = 40; bone/joint = 58; SSTI = 56) treated with daptomycin or vancomycin for >72 hours. Patients who received vancomycin for >72 hours prior to daptomycin initiation were excluded | Daptomycin (n = 85) vs vancomycin (n = 85); median daptomycin dose: 8.4 mg/kg/d (IQR = 6.3-9.9) | Daptomycin was associated with lower rates of clinical failure (20% vs 48.2%; P < 0.001), 30-day mortality (3.5% vs 12.9%; P = 0.047), persistent bacteremia (18.8% vs 42.4%; P = 0.001), and duration of bacteremia (3 vs 5 days; P = 0.003) | One patient treated with daptomycin 12 mg/kg/d experienced significant CPK elevation (67-7221 U/L) on day 17 of daptomycin. No musculoskeletal symptoms were observed. Nonsignificant CPK elevations were observed in 30.6% of daptomycin-treated patients (median increase: 92 U/L) after a median of 11 treatment days |
| Kullar et al, 201159 | Retrospective, multicenter | n = 250; Bacteremia, 163; IE, 59. Patients ≥18 years old receiving high-dose daptomycin for >72 hours for S aureus and/or enterococcal infections at any site (complicated bacteremia, 163; IE, 59) | Median daptomycin dose: 8.9 mg/kg/d;89.6% of patients received high-dose daptomycin as salvage therapy | Clinical success occurred in 83.6% of patients with MRSA and VRE; clinical failure occurred in 9 (6%) patients with bacteremia and 5 (8%) patients with IE; 13 patients developed daptomycin nonsusceptibility, usually after prior extensive vancomycin exposure | Three (1.2%) patients experienced an adverse event associated with daptomycin. Of 152 patients with baseline CPK ≤200 U/L, 16 (n = 10.5%) had CPK elevations >200 U/L; 24 patients were taking concomitant statin therapy, and none developed myopathies |
Abbreviations: aHR, adjusted hazard ratio; aOR, adjusted odds ratio; BSA, body surface area; BSI, blood stream infection; CPK, creatinine phosphokinase; EU-CORE, European Cubicin Outcomes Registry and Experience; IE, infective endocarditis; IQR, interquartile range; MRSA, methicillin-resistant Staphylococcus aureus; NVE, native valve endocarditis; PVE, prosthetic valve endocarditis; SSTI, skin and soft tissue infection; VRE, vancomycin-resistant Enterococcus.