Daptomycin: Uses, Side Effects & Dosage

Daptomycin, a novel cyclic lipopeptide antibiotic produced by supplying decanoic acid to the growth media of Streptomyces roseosporus during fermentation. Daptomycin was approved for clinical use in the USA in 2003 and in Europe in 2006 for complicated skin and skin-structure infections caused by methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and vancomycin-susceptible Enterococcus faecalis; in the same year, approval was extended to bacteraemia and right-sided endocarditis caused by MSSA and MRSA. ^[1]

Although many cyclic lipopeptide antibiotics have been discovered, daptomycin remains the only member of this class approved for clinical use. It exhibits in vitro bactericidal activity against Gram-positive pathogens, including strains for which therapeutic alternatives are limited, and this activity does not seem to be related to an inoculum effect. Daptomycin has also been used as a treatment option for paediatric infections, including meningitis, bacteraemia, sepsis, endocarditis and urinary tract infections caused by VRE. However, reports of daptomycin resistance in S. aureus, Enterococcus faecium and E. faecalis isolates are increasing.^[2]

Side Effect & Dosage

The recommended dosing of daptomycin for cSSSIs is 4 mg/kg once daily for 7 to 14 days; the recommended dose of daptomycin for bacteremia and/or endocarditis is 6 mg/kg once daily for 2 to 6 weeks. The dosing interval should be extended to 48 hours in patients with severe renal insufficiency (CrCl < 30 mL/min, including hemodialysis or peritoneal dialysis). Daptomycin is NOT indicated for the treatment of pneumonia. Phase III trials of community acquired pneumonia (CAP) treated with daptomycin resulted in a higher incidence of death and serious cardiorespiratory adverse events versus CAP treated with comparator agents.

Daptomycin shows low occurrence of side effects comparable to other standard antibiotics. The most frequently experienced potential side effects were gastrointestinal disturbances (ie, constipation, nausea and vomiting and diarrhea), reactions at the injection sites and headache. All these effects were observed in frequencies similar to the comparator drugs (ie, 3%–6%). Although not frequent, the primary toxicity associated with daptomycin use is myopathy, manifested as muscle pain or weakness and associated with elevations in creatine phosphokinase (CPK). Such as, patients receiving daptomy cin should be monitored for elevations in CPK and skeletal muscle dysfunction namely development of muscle pain or weakness, particularly of the distal extremities.^[1]

Reference

[1] Vilhena, C., & Bettencourt, A. (2012). Daptomycin: a review of properties, clinical use, drug delivery and resistance. Mini Reviews in Medicinal Chemistry, 12 3, 202–209. https://doi.org/10.2174/1389557511209030202 

[2] Heidary, M., Khosravi, A. D., Khoshnood, S., Nasiri, M. J., Soleimani, S., & Goudarzi, M. (2018). Daptomycin. The Journal of Antimicrobial Chemotherapy, 1–11. https://doi.org/10.1093/jac/dkx349