Linezolid-Induced Anemia in a Patient with Osteomyelitis Lee YY1 and Chen HY1,2 Department of Pharmacy, Taipei Medical University -Wanfang Hospital1 School of Pharmacy, Taipei Medical University2 After linezolid was used for one month, the patient presented to the emergency department with dizziness. At that time, his hemoglobin was 10.1 g/dL and hematocrit was 29.7%. He again received blood transfusion and linezolid was held. Two weeks later, his hemoglobin and hematocrit returned to 13.4 g/dL and 39.3%, respectively. Patient’s white blood cell counts and platelet counts were all within normal range. BACKGROUND Linezolid is actively against resistant gram-positive cocci, such as methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Linezolid has both parenteral and oral formulations and is considered an attractive choice for chronic bone and joint infections. It has been reported Tto effectively treat MRSA bone and joint infections. The cure rate is ranged from 57.7% to 79%. However, because it is associated with reversible myelosuppression, such as thrombocytopenia, leukopenia, or anemia, prolonged use of linezolid for chronic osteomyelitis is still controversial. The mechanism of linezolid-induced anemia is believe to be due to bone marrow suppression via inhibition of mitochodrial respiration. Clinical studies suggested it is reversible and time- and dose-dependent. Myelosuppression is more likely to occur if the duration of linezolid therapy is more than 2 weeks. We present a case of a 43-year-old man who received linezolid for treatment of MRSA osteomyelitis developing more than one episode of anemia requiring blood transfusion. 2/8-4/4 linezolid 5/2-6/11 linezolid 3/30 Blood Transfusion 6/11 Blood Transfusion Date Figure 1. Summary of Patient’s Hemoglobin and Hematocrit Values Assessment of this adverse drug reaction (ADR): Severity: Moderate; Causality: Probable, Naranjo score: 7; Preventable CASE REPORT DISCUSSION A 43-year-old man hospitalized for with MRSA endocarditis and chronic osteomyelitis was treated by intravenous vancomycin for eight weeks. However, the patient developed fever by the end of the treatment course and the wound culture from his left shoulder was still positive for MRSA in January 2007. Antibiotics were switched to intravenous teicoplanin 400mg daily and oral co-trimoxazole 800mg Daily. Due to poor clinical response, oral fusidic acid 500mg daily was added about three weeks later. However, under these treatments, patient’s C-reactive protein (CRP) persistent to increase, from 3.09 mg/dL to 7.64 mg/dL. As a result, teicoplanin was switched to intravenous linezolid 600mg twice daily on February 8th 2007. In addition, co-trimoxazole was discontinued because patient had complained of gastrointestinal discomfort from taking it. The patient was discharged on March 20th with oral linezolid 600mg twice daily, oral fusidic acid 500mg daily and oral rifampicin 300mg twice daily. Six weeks after linezolid started, patient’s hemoglobin decreased from 12.9 g/dL to 8.9 g/dL and his hematocrit decreased from 38.5% to 27.4%, and therefore resulted in blood transfusion. At the same time, results of iron tests did not strongly suggest iron-deficiency anemia (serum ferritin level was 605.1ng/mL, iron level was 142mcg/dL, and total iron-binding capacity (TIBC) was 231 mcg/dL). Linezolid-induced anemia was suspected. The patient was then admitted and linezolid was switched to vancomycin while he was hospitalized. One month later, after he was discharged home, his hemoglobin and hematocrit returned to 12.7 g/dL and 38.3%, respectively. Oral linezolid was again restarted. It has been reported in a retrospective study that reversible anemia happened in 31.8% of chronic osteomyelitic patients receiving prolonged linezolid treatment. Median time from treatment iniation to anemia onset was 7.3 weeks. Patients with age > 58 years, alcohol abuse, diabetes mellitus, or low hemoglobin before linezolid treatment are considered more predisposed to myelosuppression. Our patient had low pre-treatment hemoglobin value suggesting that he was at higher risk of linezolid-induced anemia. More than one episode of anemia requiring blood transfusion had happened to him after 4 to 6 weeks of linezolid. In order to ensure patient safety, alternatives should be considered for this patient. CONLCUSION Due to the risk of myelosuppression, chronic use of linezolid should be reserved when other treatment options have failed. If linezolid is needed for more than 2 weeks, weekly hematological monitoring is highly recommended. REFERENCES Gerson S, Kaplan S, Bruss J et al. Hematologic effects of linezolid: summary of clinical experience. Antmicrob Agents Chemother 2002; 46: 2723-6. Senneville E, Legout L, Valette M et al. Risk factors for anaemia in patients on prolonged linezolid therapy for chronic osteomyelitis: a case-control study. J Antimicrob Chemother 2004; 54: 798-802. Bassetti M, Vitale F, Melica G et al. Linezolid in the treatment of Gram-positive prosthetic joint infection. J Antimicrob Chemother 2005;55: 387-90.