Table 2.
High-Dose Daptomycin Considerations.
| Indication | Optimized daptomycin dose | Details |
|---|---|---|
| Endocarditis | ||
| Staphylococcal | ≥9 mg/kg/d | MRSA clearance may be increased by dosing of ≥9 mg/kg |
| Enterococcal | 10-12 mg/kg/d | Higher MICs and in vitro and case series data provide justification for using the highest daptomycin doses in these infections; however, alternative therapy should be considered when MIC is ≥4 mg/L |
| Bacteremia | ||
| Staphylococcal | ≥8 mg/kg/d | Additive benefit may exist when using higher doses early during therapy when vancomycin MIC is >1 mg/L |
| Enterococcal | 10-12 mg/kg/d | Higher doses have improved both survival and bacterial clearance compared with traditional dosing |
| Osteomyelitis | 6-10 mg/kg/d | No differences between doses within the range of 6-10 mg/kg have been shown |
| Meningitis | 8-10 mg/kg/d | No data directly support a specific dose, and most studies suggest poor CNS penetration. Use should err on the side of higher doses because some small reports have obtained success with doses of 8-10 mg/kg in meningitis |
| Special populations | ||
| Obesity | The indication should drive the dosing decision. Adjusted body weight may be used in place of total body weight with concerns for toxicity | Given the limited evidence for any specific practice, exercise caution with any adjustment yielding a lower dose, especially in the setting of indications for high-dose daptomycin. Isolated clinical evidence suggests benefits with high doses over standard doses in overweight and obese populations without compromising safety |
| Intermittent hemodialysis | Doses of 8 mg/kg may warrant conversion to doses as high as 16 mg/kg (50% increase) during 72-hour interdialytic periods when dosed in patients with high-permeability dialyzers but may not warrant increases in 48-hour interdialytic periods | Consider twice-weekly CPK monitoring. Daptomycin exposures are likely to be suboptimal over 24- to 72-hour periods between dialyses, which should be interpreted in the context of organisms’ MICs |
| CRRT | ||
| CVVHD | 8-12 mg/kg/d | Daptomycin 12 mg/kg/24-hours achieves similar PK parameters similar to normal renal function |
| CVVHDF | 8 mg/kg/d | Frequent monitoring of trough concentrations is likely necessary with doses >10 mg/kg/d |
| Burns | 10-12 mg/kg/d | High doses may only achieve drug exposures similar to standard doses because of elevated daptomycin clearance |
Abbreviations: CNS, central nervous system; CPK, creatinine phosphokinase; CRRT, continuous renal replacement therapy; CVVHD, continuous venovenous hemodialysis; CVVHDF, continuous venovenous hemodiafiltration; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; PK, pharmacokinetic.