Telavancin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis

Sir, With a rapid increase in invasive infections caused by methicillinresistant Staphylococcus aureus (MRSA), there is a demand for antimicrobials with enhanced activity against MRSA. The concentration-dependent, bactericidal lipoglycopeptide telavancin was approved in 2009 for treatment of complicated skin and skin-structure infections due to susceptible organisms. The emergence of glycopeptide resistance and clinical failures of vancomycin therapy in invasive MRSA infections, including osteomyelitis, has led to the unlabelled use of alternatives to vancomycin for treatment of these infections. We report four patients with MRSA osteomyelitis who failed standard vancomycin therapy and were successfully retreated with telavancin and surgical intervention. A patient was admitted with inability to ambulate for 1 day. This was preceded by a 4 day history of progressive leg weakness and a 2 month history of lower back pain. There also was a history of multiple carbuncles of the face, neck and buttocks, but no antimicrobial therapy had been administered for these. No fever was present. White blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated. Magnetic resonance imaging (MRI) revealed T4–7 vertebral osteomyelitis as well as T5–6 discitis with an anterior epidural phlegmon and stenosis with spinal cord compression. T5–6 laminectomy with drainage of the epidural abscess and decompression of the spinal cord was performed. Treatment with cefepime 2 g intravenously (iv) every 8 h and vancomycin 18 mg/kg iv every 12 h was begun. Blood cultures were negative, but MRSA was identified from culture of the abscess 72 h later. Vancomycin MIC was 2 mg/L, linezolid MIC was 2 mg/L and daptomycin MIC was 1 mg/L. Therapy was changed to daptomycin 6 mg/kg iv daily. After the back pain and WBC were noted to have improved, the patient was discharged to a physical rehabilitation centre to complete a planned 8 week course of daptomycin. Two weeks later, because of progressive leg weakness, fever and re-elevation of WBC, ESR and CRP values, the patient was readmitted. MRI showed recurrent epidural abscess at T5–6. T4–6 laminectomy was performed with drainage of the recurrent abscess and cord decompression. Culture of the abscess again grew MRSA (vancomycin MIC 2 mg/L, daptomycin MIC 1 mg/L and telavancin MIC 0.38 mg/L). Treatment was changed to telavancin 10 mg/kg iv daily. While receiving 10 weeks of telavancin therapy, there was resolution of fever and leucocytosis and normalization of ESR and CRP values. Gradual recovery of leg strength and ability to ambulate was noted. There was no evidence of recurrent infection 4 months after completion of telavancin. A patient with the sudden onset of leg weakness and urinary incontinence was transferred from another hospital after a lengthy hospitalization with MRSA bacteraemia (vancomycin MIC 1 mg/L, linezolid MIC 2 mg/L and daptomycin MIC ≤0.5 mg/L) from cellulitis complicated by sepsis, respiratory failure with pneumonia, renal dysfunction and hepatic encephalopathy. Despite sequential treatment with adequate doses of vancomycin (14 days), linezolid (7 days) and daptomycin (14 days), the MRSA bacteraemia persisted with unchanged MIC values. Fever was absent. WBC, ESR and CRP values were elevated. Transthoracic echocardiography and transoesophageal echocardiography (TOE) did not reveal valvular vegetations. MRI showed an epidural abscess extending from T6 to L2, L1 vertebral osteomyelitis and a left psoas abscess. Telavancin 10 mg/kg iv daily was begun. T6–7 decompressive laminectomy was performed and the abscess was evacuated. Cultures of the blood and abscess grew MRSA with unchanged MIC values of vancomycin, linezolid and daptomycin. Telavancin MIC was 0.25 mg/L. Telavancin was administered for 8 weeks with improvement in leg weakness and normalization of WBC, ESR and CRP values. There was no evidence of recurrence 7 months after completion of telavancin. A patient presented with a 1 week history of right hip pain after a fall. Fever and leucocytosis were present. There was a remote history of a gunshot wound to the right hip. CT revealed a 2 cm mass in the left upper lung and a large right hip effusion. MRI was consistent with right hip septic arthritis and osteomyelitis of the right acetabulum, femoral head, femoral neck and lesser trochanter. Blood cultures grew MRSA (vancomycin MIC 1 mg/L, linezolid MIC 1 mg/L and daptomycin MIC ≤0.5 mg/L). Ceftriaxone 2 g iv daily and vancomycin 13 mg/kg iv every 12 h were begun and continued for 5 days. Research letters