Daptomycin

• Brand names: Cubicin
• Route: Intravenous

Daptomycin inserts its lipid tail into the bacterial membrane in a calcium-dependent way, then clusters to distort the membrane and cause rapid loss of the potassium gradient.

The cell dies quickly without bursting, so relatively little inflammatory toxin is released. It is one of the fastest bactericidal agents available against MRSA.

Lung surfactant binds and inactivates daptomycin, which is why it must never be used to treat pneumonia.

• 6 mg/kg once daily intravenously for bacteraemia and right-sided endocarditis; 4 mg/kg once daily for complicated skin and soft-tissue infection.
• Many specialists now use 8–10 mg/kg daily for persistent MRSA bacteraemia or deep-seated infection, often in combination with ceftaroline.
• Dose interval is extended to every 48 hours when creatinine clearance falls below 30 mL/min or during intermittent haemodialysis.
• Creatine kinase should be checked at baseline and at least weekly.

Doses listed are typical adult regimens quoted for reference. The actual dose, route and duration are decided by a clinician for the individual patient.

Daptomycin was discovered by Eli Lilly in the early 1980s in a fermentation broth of Streptomyces roseosporus collected from soil on Mount Ararat, Turkey.

Lilly shelved it after muscle toxicity appeared in trials using twice-daily dosing. Cubist Pharmaceuticals licensed the compound in 1997 and showed that once-daily dosing gave the same efficacy with far less muscle effect.

It was approved by the FDA in 2003 for skin infection and in 2006 for S. aureus bacteraemia and right-sided endocarditis.

• Muscle toxicity: raised creatine kinase, muscle pain and weakness, and rarely rhabdomyolysis. Statins are often paused during treatment.
• Eosinophilic pneumonia — a rare but serious reaction presenting with fever, breathlessness and new lung shadowing after a week or more of therapy.
• Peripheral neuropathy, gastrointestinal upset, headache, rash, and raised liver enzymes.

• Vancomycin-resistant enterococcal infection, usually at higher doses.
• Prosthetic joint and device-related Gram-positive infection, frequently with rifampicin.
• An alternative for patients with vancomycin allergy or vancomycin-induced kidney injury.