Daptomycin

Day 1: #daptomycin was discovered in the late 1980s, when Streptomyces roseoporus bacteria was isolated from a Turkish soil sample. Adverse effects led to delays in clinical trials (muscle/neurotoxicity), until research into dosing regimens afforded safe and effective once-daily use. Licensed in 2003.

Day 2: #daptomycin is used in those over 1 year by iv infusion for complicated skin and soft tissue infections, endocarditis and bacteraemia from a broad range of gram +ve bacteria, eg S.aureus/MRSA/VRSA/VRE. Therapeutic range depends on infection and age, eg child 2-17yrs range 5-12 mg/kg; adult 4-6 mg/kg.

Day 3: #daptomycin kinetics; no oral absorption therefore iv infusion once/day for 7–14 days. Low Vd and unknown metabolism processes. Renal excretion with around 50% unchanged drug. T½ ~7–9 hrs, which is increased if renal impairment. Monitor renal function and if severe, decrease the dose or change dose interval to alternate days.

Day 4: #daptomycin is a bactericidal cyclic lipopeptide antibiotic, which has a fatty acid ‘tail’. Full mode of action is unclear, but known to insert the ‘tail’ into the bacterial cell membrane, complexing with Ca+. This causes changes in fluidity and membrane potential, leading to leakage and cell death.