Table 1.
Clinical characteristics and outcomes of 3 patients with S. aureus endocarditis treated with a combination of high-dose daptomycin and fosfomycin
| Parameter(s) | Patient 1 | Patient 2a | Patient 3 |
|---|---|---|---|
| Age (yr) | 54 | 53 | 71 |
| Gender | Female | Male | Male |
| Chronic underlying diseases | Scleroderma, severe pulmonary artery hypertension, elective aortic and mitral double-valve replacement with mechanical prostheses 11 yr ago, MRSEc prosthetic-valve endocarditis 10 years ago needing an aortic valve homograft | Diabetes mellitus, HIV-HBVb coinfection | Diabetes mellitus, diabetic foot infection, Child-Pugh class B liver cirrhosis, mild mitral regurgitation due to severe valve calcification |
| Drug allergies | Penicillin, vancomycin | None | None |
| Source of infection | Unknown | Left inguinal infection by MRSA 2 weeks after lymph node biopsy | MRSA-infected foot ulcer |
| Clinical characteristics | High-grade fever, cerebral and splenic emboli, coma, additive EuroSCOREe of 18 | High-grade fever, malaise, pain in neck and index finger of left hand | High-grade fever, splenic emboli |
| Blood cultures before treatment | 6/6 positive for MSSA | 6/6 positive for MRSA | 6/6 positive for MRSA |
| Antibiotic susceptibilities (MIC, μg/ml) | Vancomycin, 1; fosfomycin, 8; daptomycin, 1 | Vancomycin, 1.5; fosfomycin, ≤ 32; daptomycin, 1 | Vancomycin, 1.5; fosfomycin, ≤ 32; daptomycin, 1 |
| TEEd findings | 1-cm aortic homograft valve vegetation, 10 by 8 mm perivalvular abscess, no prosthetic valve dysfunction | Calcification of aortic and mitral valves, no evidence of vegetations or perivalvular abscesses | Mitral valve rupture with severe regurgitation, 1-cm mitral valve vegetation, 6 by 8 mm perivalvular abscess |
| Initial i.v. antibiotic therapy (no. of days) | Daptomycin at 10 mg/kg/day (7) | Daptomycin at 4 mg/kg/day (2), daptomycin at 4 mg/kg/day plus gentamicin at 240 mg/48 h (5), daptomycin at 8 mg/kg/day plus gentamicin at 240 mg/48 h (3) | Vancomycin at 15 mg/kg every 12 h; vancomycin trough plasma concentrations, 11 and 20 μg/ml on days 2 and 5, respectively |
| Complications of first-line treatment | None | Progressive renal failure; need for hemodialysis; signs of septic embolization along left sternal margin and on first left metacarpal joint, second and third right toes, right forefoot, and left sternocleidomastoid muscle at day 2; pyomyositis with compression of oropharynx at day 10 | Serum creatinine increase from 1.4 to 3.0 mg/dl (normal, ≤1.3 mg/dl) during first 24 h but return to normal level after 2 days |
| Follow-up blood cultures after initial treatment | Positive at days 3, 7 | Positive at days 3, 7, 10 | Positive at day 5 |
| No. of days from initial treatment to switch to daptomycin plus fosfomycin | 7 | 10 | 5 |
| Doses given i.v. (daptomycin, fosfomycin) | 10 mg/kg/day, 2 g/6 h | 10 mg/kg/day, 2 g/6 h | 10 mg/kg/day, 2 g/6 h |
| Time of first negative blood cultures after switch to daptomycin plus fosfomycin (h) | 72 | 48 | 48 |
| Duration of treatment (wk) | 8 | 6 | 6 |
| Complications of daptomycin plus fosfomycin treatment | None | Transmetatarsal amputation of right foot, chronic hemodialysis | None |
| Follow-up blood cultures after daptomycin plus fosfomycin | Negative at days 14, 42 | Negative at days 14, 28, 42, 90 | Negative at days 30, 90 |
| Clinical follow-up | Alive at 1 yr | Alive at 1 yr | Alive at 6 mo |