Successful Treatment ofEnterococcus faecalisProsthetic Valve Endocarditis with Linezolid

Sir —Linezolid possesses a broad spectrum of activity against gram-positive organisms, including Enterococcus faecalis [1]. Like other agents used for the treatment of E. faecalis endocarditis, linezolid possesses only bacteriostatic activity [2]. Although the US Food and Drug Administration has not approved linezolid specifically for the treatment of endocarditis, there have been reports of its use both in animals and in patients with endocarditis due to vancomycin-resistant Enterococcus faecium (VREF) [3, 4]. To our knowledge, no cases of E. faecalis endocarditis involving either a native valve or a prosthetic valve have been successfully treated with linezolid. We report the successful use of linezolid therapy for a case of bioprosthetic aortic valve endocarditis due to a strain of E. faecalis with high-level resistance to gentamicin. The patient was a 78-year-old white man who had type II diabetes mellitus and coronary artery disease. In June 2001, he underwent aortic valve replacement with a bioprosthesis and coronary artery bypass. The patient was well until November 2001, when he was admitted to University of Pittsburgh Medical Center South Side (Pittsburgh) with anemia and weakness but without fever, chills, or sweats. Pertinent findings of physical examination included a diastolic murmur of grade 2/4 and guaiac-positive stool specimens. The patient underwent gastrointestinal endoscopy with antibiotic prophylaxis that consisted of ampicillin (2 g iv) plus gentamicin (1.5 mg/kg), both of which were given within 30 min of the start of the procedure, and ampicillin (1 g iv) given 6 h later, as per the 1997 recommendations of the American Heart Association and the Infectious Diseases Society of America [5, 6]. Gastric arteriovenous malformations and rectal telangiectasia were noted and were treated with electrocoagulation and laser ablation. During the patient's hospitalization, he was noted to have a temperature of 38.4 °F, and 6 sets of blood cultures performed during a 6-day period were positive for E. faecalis. Transesophageal echocardiography confirmed the presence of vegetations on the bioprosthetic aortic valve. Ampicillin, 12 g/day, was given in divided doses along with gentamicin, 1 mg/kg per dose adjusted to creatinine clearance. The isolate was found to be susceptible to ampicillin and vancomycin, but it had high-level resistance to gentamicin. Administration of gentamicin was discontinued. The patient was not considered to be a candidate for surgery. By day 4 of hospitalization, the patient developed acute renal failure and experienced an increase in the serum level of creatinine (from 1.3 mg/dL to 4.4 mg/dL). Antimicrobial therapy was changed to linezolid, 600 mg b.i.d. The isolate was found to be susceptible to linezolid (MIC, 1.0 µg/mL). The patient tolerated 6 weeks of the therapy and experienced minimal nausea, which was easily managed with symptomatic treatment. The results of blood cultures performed during and after therapy remained negative. The patient was monitored closely for myelosuppression. His hemoglobin level remained stable, but his WBC count decreased from 7.6 cells/mm3 to 2.4 cells/mm3 and his platelet count decreased from 263 × 103 platelets/ µL to 41 × 103 platelets/ µL on day 42 of therapy. Linezolid therapy was discontinued, and the patient remained asymptomatic. Three weeks after discontinuation of linezolid therapy, the patient's WBC count and platelet count returned to normal. The results of additional blood cultures performed 4 months after discontinuation of linezolid remained negative. The patient has remained hemodynamically stable and has returned to work. To our knowledge, this is the first reported case of prosthetic valve endocarditis due to high-level gentamicin-resistant E. faecalis that has been successfully treated with linezolid. In view of the patient's pathologic gastrointestinal findings, the gastrointestinal tract was the likely source of endocarditis. Linezolid has been shown to be effective in the treatment of VREF endocarditis in experimental settings [3]. Recently, a patient with VREF endocarditis was successfully treated with linezolid after sequential monotherapy with chloramphenicol and quinupristin-dalfopristin failed [4]. A report of the use of linezolid therapy for gram-positive infections described 2 patients with VREF endocarditis, both of whom had a bacteriologic response but died of an unrelated cause while receiving therapy [1]. Linezolid may be an effective alternative for the treatment of enterococcal endocarditis. The 100% bioavailability of the oral formulation of linezolid makes it an attractive alternative option for long-term outpatient treatment. The patient described here received ampicillin for 4 days. It is unlikely, however, that this course of therapy would have cured his prosthetic valve endocarditis. The hematological adverse effects of linezolid, which may be encountered when therapy is prolonged, are usually mild, gradual, and predictable. Such adverse effects can be monitored by weekly assessment of the complete blood count, and reverses in these effects can occur within a few days of discontinuation of the therapy [7, 8]. Linezolid may be an option for the treatment of this challenging disease entity. Additional prospective studies are needed to confirm this observation. We thank Victor Yu and Robert C. Moellering, Jr., for their careful review and comments.