There is an urgent need to optimize therapeutic options in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who have failed conventional therapy. Two clinical isolates were obtained from a 68-year-old male with persistent MRSA bacteremia before and after the development of daptomycin nonsusceptibility. The pharmacodynamic activity of monotherapies and combinations of ceftaroline, daptomycin, cefoxitin, nafcillin and vancomycin were evaluated in time-kill experiments versus 10 CFU/mL of the pre- and post-daptomycin nonsusceptible MRSA isolates. Cefoxitin, nafcillin and vancomycin alone or in combination with ceftaroline failed to generate prolonged bactericidal activity against the post-daptomycin nonsusceptible isolate whereas a ceftaroline-daptomycin combination resulted in 6, 24 and 48 h log(CFU/mL) reductions of 3.90, 4.40 and 6.32. Population analysis profiles revealed a daptomycin heteroresistant subpopulation of the pre-daptomycin nonsusceptible MRSA isolate that expanded by >10,000× on daptomycin agar containing 2-16 mg/L in the post-daptomycin nonsusceptible isolate. Daptomycin and ceftaroline combinations may be promising against persistent MRSA bacteremia.
Purpose
We present a case of a 55-year-old man post right lung transplantation receiving ECMO for treatment of respiratory failure secondary to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.
Summary
Extracorporeal membrane oxygenation (ECMO) is a frequently utilized support therapy for patients with cardiac and/or respiratory failure. Dosing of medications during ECMO can be challenging due to several factors, including sequestration of medications within ECMO circuits, alterations in volume of distribution, and changes in drug clearance. The patient was initiated on empiric antibiotics, then switched to linezolid at a dose of 600 mg every 8 hours. Linezolid plasma concentrations were collected 30 minutes prior to the sixth administered dose and 30 minutes following the 1-hour infusion of the sixth dose, which resulted in values of 0.4 and 1.7 μg/mL, respectively. The ratio of 24-hour area under the curve (AUC0-24) to minimum inhibitory concentration (MIC), assuming a MIC of 2 μg/mL, was calculated using the extrapolated maximum concentration (1.9 μg/mL) and minimum concentration (0.35 μg/mL), resulting in an AUC0-24/MIC value of 10.8. Due to subtherapeutic linezolid plasma concentrations, ceftaroline was initiated and continued for a total of 18 days. To our knowledge, this is the second report to describe inadequate plasma concentrations of linezolid during ECMO.
Conclusion
In the case described here, linezolid at a dose of 600 mg every 8 hours did not achieve target plasma concentrations in a patient receiving concomitant venovenous ECMO support.
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