Addition of ceftaroline to daptomycin after the emergence of daptomycin-nonsusceptible Staphylococcus aureus during therapy improves anti-bacterial activity.
Antimicrob Agents Chemother. 2012 Aug 6;
Authors: Rose WE, Schulz LT, Andes D, Striker R, Berti AD, Hutson PR, Shukla SK
Antistaphylococcal beta-lactams enhance daptomycin activity and have been used successfully in combination for refractory MRSA infections. Ceftaroline possesses MRSA activity, but it is unknown if it improves daptomycin potency comparable to that of other beta-lactams. We report a complex patient case of endocarditis treated with daptomycin in combination with ceftaroline, which resulted in clearance of a daptomycin-nonsusceptible strain. An in vitro pharmacokinetic/pharmacodynamic model of renal failure was used to simulate the development of daptomycin resistance and evaluate the microbiologic effects of daptomycin plus ceftaroline treatment.Combination therapy with daptomycin and ceftaroline restored daptomycin sensitivity in vivo and resulted in clearance of persistent blood cultures. Daptomycin susceptibility in vitro was increased in the presence of either ceftaroline or oxacillin. Daptomycin 6mg/kg every 48h was bactericidal in the model but resulted in regrowth and daptomycin resistance (MIC 2-4 ?g/ml) with continued monotherapy. The addition of ceftaroline 200mg every 12h after the emergence of daptomycin resistance enhanced bacterial killing. Importantly, daptomycin plus ceftaroline as the initial combination therapy produced rapid and sustained bactericidal activity and prevented daptomycin resistance. Both in vivo- and in vitro-derived daptomycin resistance resulted in bacteria with more fluid cell membranes. After ceftaroline was added in the model, fluidity restored to the level of the initial in vivo isolate. Daptomycin resistant isolates required high daptomycin exposures (at least 10 mg/kg) to optimize cell membrane damage with daptomycin alone.Ceftaroline combined with daptomycin was effective in eliminating daptomycin resistant MRSA, and further justifies the potential use of daptomycin plus beta-lactam therapy for these refractory infections.
PMID: 22869564 [PubMed - as supplied by publisher]Link to Article at PubMed