Efficacy and safety of linezolid in liver transplant patients

Abstract

Bacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug-resistant gram-positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration-approved oxazolidinone, offers a valuable novel treatment option for serious gram-positive infections. Linezolid is relatively non-toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram-positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n = 8), blood stream infection (n = 30), and surgical site/abdominal infection (n = 3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin-resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin-resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram-positive infections.

Emergence of linezolid resistance in hepatobiliary infections caused by E nterococcus faecium

“…Data on bloodstream infections with VRE reveal microbiological cure rates at 83%‐97% after treatment with linezolid . Despite its good biliary penetration, safety, and effectiveness in general in liver transplant patients, linezolid is a bacteriostatic agent and may not achieve sufficient concentrations in the abscess fluid in these patients when intra‐abdominal collections develop . The addition of gentamicin improved the efficacy of linezolid against VRE in an in vivo survival assay .…”

Multidrug-resistant bacteria in solid organ transplant recipients

“…Linezolid does not cause direct nephrotoxicity, but several cases of acute interstitial nephritis have been described , one of them in a renal transplant patient . A study performed in 46 liver transplant patients with Gram‐positive bacterial infections treated with linezolid during a mean of 11 days showed neither significant haematological abnormalities nor any other relevant side‐effects . A subgroup analysis of patients who received treatment for 15 or more days did not show any relevant side‐effects .…”

“…A study performed in 46 liver transplant patients with Gram‐positive bacterial infections treated with linezolid during a mean of 11 days showed neither significant haematological abnormalities nor any other relevant side‐effects . A subgroup analysis of patients who received treatment for 15 or more days did not show any relevant side‐effects . One multicentre trial of compassionate use of linezolid for the treatment of VRE included 85 SOT patients with demonstrated VRE infection (liver, kidney, heart, lung and multivisceral), of whom 43 were bacteraemic, and reported an incidence of thrombocytopenia of 4.7% and decreased leukocyte count in 3.5% of patients .…”

Multidrug‐resistant organisms in liver transplant: Mitigating risk and managing infections

“…(15,29) Treatment of VRE in organ transplantation has been extensively reviewed, (4) and the 2 most commonly used antibiotics, daptomycin and linezolid, are safe and well tolerated in this population. (32,33) Linezolid-resistant VRE has been described in LT recipients in the setting of linezolid exposure as well as horizontal transmission. (34,35) Daptomycin-nonsusceptible enterococci have been recovered in LT recipients with and without prior exposure to daptomycin.…”