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Pharmacology · Lipopeptides

Daptomycin !

A once-daily IV lipopeptide for S. aureus bacteremia, right-sided endocarditis and skin infections, including MRSA; useless in pneumonia.

Updated 2026-11-01

  • Class: Lipopeptides
  • Target: Cytoplasmic membrane of gram-positive bacteria
  • ATC code: J01XX09

Mechanism of action

Daptomycin binds the bacterial cell membrane and causes rapid depolarization. The loss of membrane potential stops DNA, RNA and protein synthesis, and the bacterium dies. It is bactericidal, concentration-dependent, and active against gram-positives including MRSA and many vancomycin-resistant strains; it lacks useful activity against gram-negatives.

  1. Inserts into the gram-positive membrane
  2. The membrane depolarizes rapidly
  3. DNA, RNA and protein synthesis stop
  4. The bacterium dies

Pharmacokinetics

Absorption
Poorly absorbed by mouth; given IV only (it is toxic to muscle if injected IM).
Distribution
About 90 to 93% bound to albumin; it reaches the lung but surfactant inactivates it.
Elimination
Mostly in the urine; the interval is lengthened in severe kidney failure.
Half-life
About 8 to 9 hours, allowing one dose a day.

Indications

Adverse effects

Common

  • Diarrhoea, headache, dizziness, rash
  • CPK elevation
  • Abnormal liver tests

Contraindications

  • Known hypersensitivity to daptomycin
  • Not used to treat pneumonia

Key interactions

Statins (HMG-CoA reductase inhibitors)
Added risk of myopathy; statins are usually paused during treatment.
Aminoglycosides
Caution because of possible added nephrotoxicity.
Some prothrombin-time reagents (laboratory interaction)
Falsely prolonged PT and raised INR; samples drawn just before a dose reduce the effect.

What is monitored

  • CPK weekly, more often with kidney failure, statins or prior CPK rise
  • Muscle pain or weakness, especially in the distal limbs
  • New fever, cough or dyspnoea (eosinophilic pneumonia)
  • Kidney function

Administration and safety

  • IV injection or infusion after reconstitution, no more than once a day.
  • Never intramuscular.
  • Not compatible with dextrose-containing diluents.

Nursing care

  • Baseline CPK and kidney function; ask about statin use.
  • Assess daily for muscle pain or weakness.
  • Report new breathing problems, rash with fever or numbness.
  • Teaching: report muscle aches, weakness, tingling, cough, shortness of breath or severe diarrhoea.

Pregnancy and breastfeeding

Limited data in pregnant women are insufficient to define a risk; animal studies did not show malformations. It is used if clearly needed.

Test yourself

Think of the answer, then tap the question to see it.

A patient with MRSA pneumonia is prescribed daptomycin. What is the problem?

Daptomycin is inactivated by pulmonary surfactant and is not indicated for pneumonia; vancomycin or linezolid are options.

Why are statins usually paused during daptomycin treatment?

Both can damage muscle; together they raise the risk of myopathy and rhabdomyolysis.

Which bloodstream infection is daptomycin approved for?

Staphylococcus aureus bacteremia, including right-sided infective endocarditis, by MSSA or MRSA.

What lung adverse effect is typical of daptomycin?

Eosinophilic pneumonia: fever, dyspnoea with hypoxia and infiltrates; the drug is stopped.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - DAPTOMYCIN injection, powder, lyophilized, for solution (DailyMed (U.S. National Library of Medicine), 2026); Daptomycin Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 58 (McGraw Hill, 2023).

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Representative model, for educational purposes only.