Successful Treatment of Vertebral Osteomyelitis with Linezolid in a Patient Receiving Hemodialysis and with Persistent Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus Bacteremias

Sir—We read with interest a recent report describing the use of linezolid (PNU-100766) to treat a methicillin-resistant Staphylococcus aureus (MRSA) graft infection in a renal transplant recipient [1] and a report of persistent vancomycin-resistant Enterococcus (VRE) bacteremias in a patient with neutropenia [2]. In addition, a recent case series reported microbiological cure in two-thirds of patients treated with linezolid, in conjunction with surgical intervention or device removal [3]. In our hospital, significant numbers of patients are colonized with MRSA and VRE and, occasionally, they become infected. We recently used linezolid successfully to treat a patient with persistent MRSA and VRE bacteremias secondary to osteomyelitis and, possibly, endocarditis after treatment failure with other antibiotics. A 64-year-old male immigrant from Hong Kong was admitted to the hospital because of a history of acute back pain, rigors, and fever. He had chronic renal failure of unknown etiology and had been hemodialysis-dependent for 5 years. Examination revealed a temperature of 39°C and systolic and diastolic heart murmurs consistent with mitral and aortic valve regurgitation. A blood culture yielded VRE that was susceptible to amoxicillin, rifampin, and gentamicin, and MRSA that was susceptible to vancomycin, fusidic acid, and tetracycline, as determined by disc diffusion testing. The following day his right subclavian venous catheter was removed. He was treated with iv vancomycin (1 g) postdialysis and with oral rifampin (300 mg twice daily), and 48 h later his temperature had returned to normal. Culture of the venous catheter tip yielded no organisms. A bone scan was within normal limits and a transthoracic echocardiogram revealed mitral valve regurgitation but no vegetations. The patient continued antibiotics as an outpatient and continued to dialyze via a new right femoral venous catheter. One week later, while he was an outpatient, 8 of 8 cultures of the patient's blood yielded VRE. The patient was readmitted to the hospital, all lines were removed, and peritoneal dialysis was commenced. The MIC of the VRE to amoxicillin, rifampin, and linezolid were 1 mg/L, 0.25 mg/L, and 0.5 mg/L, respectively; otherwise, the organism was highly resistant. Therapy was changed to iv amoxicillin 1 g q.i.d. and iv gentamicin, 160 mg postdialysis. Three additional blood cultures yielded no pathogens. A transesophageal echocardiogram demonstrated mitral and aortic valve regurgitation and a small echodense structure attached to the aortic valve, suggestive, but not typical, of endocarditis. From a cardiovascular standpoint, the patient remained stable and he was apyrexial, although his back pain persisted and his C-reactive protein level (CRP, 358 mg/L) and WBC count (14.2 × 109/L) remained elevated. An MRI of his lumbar spine demonstrated images consistent with L3 and L4 osteomyelitis. Two further blood cultures yielded MRSA with vancomycin, fusidic acid, and linezolid MIC of 2 mg/L, 1 mg/L, and 0.5 mg/L, respectively. The organism was resistant to other antibiotics commonly used to treat MRSA infections. Therapy was changed to iv vancomycin, oral amoxicillin (1 g t.i.d.), and fusidic acid (500 mg t.i.d.). Two weeks later, a repeated MRI revealed progressive destruction of his L3–4 disc. Intravenous linezolid (600 mg twice daily) was commenced, and all other antibiotics were discontinued. A multidisciplinary discussion followed involving his family, the renal physicians, the orthopedic surgeons, and ourselves and, despite the risks, spinal surgery was planned. During surgery 3 weeks later, gross destruction of his L3–L4 intervertebral disc and adjacent vertebral endplate was observed. Necrotic bone was debrided and an iliac crest graft was performed. Cultures of the debrided bone did not yield any organisms, although the concentration of linezolid detected was 9.0 mg/g, as measured by HPLC (Antibiotic Reference Unit, Bristol, UK). After a total of 6 weeks treatment and 3 weeks following his operation, linezolid was discontinued. Two months after surgery, the patient was mobile and free of pain. He was afebrile, his WBC count was within normal limits, and his CRP level was 17 mg/L. It is highly likely this patient had osteomyelitis and possibly endocarditis. Blood cultures repeatedly yielded MRSA and VRE, and no organisms were ever grown from dialysis lines. Surgical specimens failed to yield MRSA or VRE, although a high concentration of linezolid was detected in the debrided bone. We are unaware of other reports where linezolid has been successful as therapy for vertebral osteomyelitis. Despite renal failure, the drug was well tolerated and no dose adjustments were required. Our case supports the argument of those who advocate linezolid as a safe and effective antibiotic to treat serious infections caused by resistant gram-positive organisms such as MRSA and VRE.