Adequate Penetration of Daptomycin Into Bone Tissue

After a single high dose of (8 or 10 mg/kg BW) of daptomycin IV, bone levels were measured in plasma and trabecular bone obtained during hip or knee surgery of 16 patients.[1]

At the time of surgery, mean concentrations in plasma and synovial fluid were 39 and 22 µg/mL, respectively.  For femoral and tibial bone samples, the mean concentrations were 3.3 and 3.4 µg/mL.


The median penetration into synovial fluid was calculated as 54%, and into bone as 9%.

The study showed that daptomycin reliably achieves bone levels above the MIC breakpoint for Staphylococci (1 µg/mL) with a high dose regimen.

There was 1 serious adverse event (bullous pemphigoid) which occurred 28 days after surgery.  It was considered possibly related to study drug.


Prosthetic joint infections (PJI) caused by S. aureus and post-operative osteomyelitis, esp. vertebral, are notoriously difficult to treat.  With higher doses of daptomycin found to be reasonably safe, this study shows that a 8-10 mg/kg intravenous dose can provide adequate bone penetration.  With animal data showing efficacy in acute osteomyelitis models, this study builds the case for use in recent bone infections, post-surgical osteomyelitis, and PJI.

It stands to reason that other long-acting (lipo)glycopeptide, i.e., dalbavancin (Dalvance®) and oritavancin (Orbactiv®), will try to replicate these results in their quest to expand the market beyond skin/skin structure infections.  We should soon see a flurry of osteomyelitis studies.

This is a challenging arena as good clinical bone infection studies have not been done for a very long time and FDA Guidance is lacking.  Entering uncharted territory should not frighten Cubist which has tackled similar challenges successfully in the past: Just think of their brilliant endocarditis program orchestrated by Francis Tally.  Let’s hope his spirit is still alive and well.


[1] Montange.  Antimicrob Agents Chemother 58: 3991; 2014

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