A 45-year-old Japanese man presented to the emergency department with the main complaints of fever and disturbance of consciousness (Glasgow Coma Score of E3V4M6). He had a previous medical history of dissecting aortic aneurysm (Stanford type A), for which he underwent transverse aortic arch replacement 14 months before admission. He had no history of travelling abroad or having his skin pierced. He had previously been treated with vancomycin at 3 g/day (1 g intravenously [IV] three times a day [TID]) and rifampicin at 600 mg/day (300 mg orally [PO] twice a day [BID]) for 2 days before being transferred to our hospital. The patient’s condition was diagnosed as an anterior mediastinal abscess and hemorrhagic cerebral infarction associated with a prosthetic graft infection of the aortic arch. Surgical intervention to remove the infected graft, which required anticoagulant therapy during cardiopulmonary bypass, was not possible because of intracerebral hemorrhage. Initial treatment for the prosthetic graft infection was started with vancomycin at 3 g/day (1 g IV TID) and cefazolin at 6 g/day (2 g IV TID). On the second hospital day, drainage and continuous irrigation were started for treatment of the anterior mediastinal abscess. Because the results of the blood culture performed 2 days before admission revealed an MRSA infection, the treatment was switched to vancomycin at 3 g/day (1 g IV TID) and rifampicin at 600 mg/day (300 mg PO BID); this treatment was continued for 9 days. The isolates from the blood and anterior mediastinal cultures performed on the day of admission also indicated MRSA infection. The vancomycin serum trough levels remained at 9.8–12.2 μg/ml during vancomycin treatment. The vancomycin minimum inhibitory concentration (MIC) of the MRSA strain isolated from the pus in the abscess was 2 μg/ml, and this strain was also susceptible to most non-β-lactam agents except gentamicin. The blood culture became negative for MRSA during the course of vancomycin and rifampicin therapy. However, the patient became feverish again on the 10th hospital day, and the treatment was switched to IV daptomycin at 6 mg/kg/day and rifampicin. On the 40th day, after the patient had remained in a stable condition for several days with daptomycin and rifampicin treatment, his fever returned and the blood culture became positive again for MRSA. Therefore, we suspected nonsusceptibility to daptomycin. Daptomycin was discontinued and treatment with linezolid was initiated at 1200 mg/day (600 mg IV BID). Reconstruction of the acute aortic dissection was carried out on the 61st day because the chest computed tomography scan performed during therapy showed persistence of the anterior mediastinal abscess and gallium scintigraphy showed persistence of prosthetic graft-associated inflammation. The infected prosthetic graft was completely removed and replaced. After the surgery, antimicrobial treatment was switched to linezolid at 1200 mg/day (600 mg PO BID) and clindamycin at 1800 mg/day (600 mg PO TID). The patient’s condition subsequently improved, and recurrence was not observed for 12 months of follow-up. The time course of his body temperature variations and antibiotic treatment regimen are shown in Figure. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Rifampicin susceptibility testing, not routinely included, was performed after the treatment and revealed resistance at an MIC of >2 μg/ml from Isolate 2 in the course of vancomycin and rifampicin dosing. The MRSA isolate from the pus in the abscess on the 55th hospital day (Isolate 4) demonstrated a vancomycin MIC of 4 μg/ml, indicating vancomycin-intermediate S. aureus (VISA). The daptomycin MICs of the MRSA isolates obtained from the blood and anterior mediastinal abscess cultures were evaluated by the broth microdilution method, using MicroScan (Siemens, Tokyo, Japan) and frozen plate (Eiken Chemical Co., Ltd., Tokyo, Japan), and Etest® (bioMérieux, Marcy-l'Étoile, France). The MRSA isolates showed susceptibility to daptomycin at the time of admission, with MICs of ≤0.5 μg/ml, 0.5, and 0.125 μg/ml upon analysis by MicroScan, frozen plate, and Etest®, respectively. Over time, however, these MICs increased to >1, 1.5, and 1.5 μg/ml, respectively, indicating daptomycin nonsusceptibility. The interpretations of the MIC results (susceptible, intermediate, nonsusceptible, or resistant) were determined according to the CLSI guidelines. MRSA isolates with daptomycin MICs of >1 μg/ml, vancomycin MICs of 4 to 8 μg/ml, and rifampicin MICs of >2 μg/ml were defined as daptomycin nonsusceptible, vancomycin-intermediate resistant, and rifampicin resistant, respectively. Pulsed-field gel electrophoresis was performed using a contour-clamped homogeneous electric field dynamic regulation III system (CHEF-DR system; Bio-Rad Laboratories, Hercules, CA, USA) as previously described by McDougal et al. []. The results indicated that the isolates obtained sequentially in this case were derived from the same origin. Multilocus sequence typing (MLST) analysis was performed by sequencing seven housekeeping genes (arcC, aroE, glpF, gmk, pta, tpi, and yqiL) based on the MLST database (), as described by Enright et al. []. The characterization of SCCmec[] and the detection of PVL genes [] were performed by polymerase chain reaction as described previously. Typing of the MRSA isolates revealed that they belonged to ST72 (1-4-1-8-4-4-3), carried SCCmec type IV, and were negative for PVL.