Lipopeptide antibiotic · S. aureus
Daptomycin is a cyclic lipopeptide antibiotic made by fermentation of the bacterium Streptomyces roseosporus. Given intravenously, it treats complicated skin infections and Staphylococcus aureus bloodstream infections, including right-sided heart-valve infection in adults, caused by gram-positive bacteria such as MRSA1,3.
Daptomycin binds to the cell membranes of gram-positive bacteria and causes a rapid loss of the membrane's electrical potential. Without that potential, the bacterium can no longer make DNA, RNA or protein, and it dies3. One quirk matters clinically: daptomycin is bound and inactivated by pulmonary surfactant, the film lining the lung's air sacs. Laboratory work linked this to its failure to match the comparator in a severe pneumonia trial, and the label says it is not for pneumonia2,3. Bacteria can become less susceptible during treatment, and the label states that the mechanisms of resistance are not fully understood1,3.
In a randomized human trial of 246 patients with S. aureus bacteremia, with or without endocarditis, daptomycin was noninferior to standard therapy (an antistaphylococcal penicillin or vancomycin, plus initial gentamicin). Success 42 days after treatment was 44% versus 42%1. Clinically significant kidney problems were less common with daptomycin (11% versus 26%), but microbiologic failures were more frequent (19 versus 11 patients, not statistically significant), and isolates from some failing patients showed reduced susceptibility1. The trial supported use in bacteremia and right-sided endocarditis; the label excludes left-sided S. aureus endocarditis3. Laboratory work showed that lung surfactant inhibits the drug, and in animal models it was inactive against a common pneumonia bacterium, consistent with its failure to meet noninferiority in a severe community-acquired pneumonia trial2.
First approved by the FDA in 2003 as Cubicin; Drugs@FDA now lists Cubicin and Cubicin RF as discontinued, while generic daptomycin remains marketed. It is indicated for complicated skin and skin-structure infections in adults and children, and Staphylococcus aureus bloodstream infections in adults (including right-sided endocarditis) and children from age one3.
The label warns of muscle damage (myopathy and rhabdomyolysis), so CPK levels are monitored, plus eosinophilic pneumonia, DRESS (a severe drug rash), tubulointerstitial nephritis, peripheral neuropathy and serious allergic reactions. In adult skin-infection trials, common effects included diarrhea, headache, dizziness, rash, abnormal liver tests and raised CPK. It is not recommended for infants under one year because of muscle and nerve effects seen in newborn dogs3.
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