Liver function, quantified by the LiMAx test, as a predictor for the clinical outcome of critically ill patients treated with linezolid

Abstract

BACKGROUND: Critically ill patients commonly suffer from infections that require antimicrobial therapy. In previous studies, liver dysfunction was shown to have an essential impact on the dose selection in these patients. This pilot study aims to assess the influence of liver dysfunction, measured by the novel LiMAx test, on clinical outcomes in critically ill patients treated with linezolid. METHODS: Twenty-nine critically ill patients were included and treated with linezolid. Indications for linezolid therapy were secondary or tertiary peritonitis (46.7%), bloodstream infection (6.7%) and 46.7% were other infections with gram-positive bacteria. Linezolid Cmin, maximal liver function capacity (LiMAx test) and plasma samples were collected while linezolid therapy was in a steady-state condition. Furthermore, potential factors for the clinical outcome were investigated using logistic regression analysis. Clinical cure was defined as the resolution or significant improvement of clinical symptoms without using additional antibiotic therapy or intervention. RESULTS: Cured patients presented lower median linezolid Cmin yet a significantly higher mean LiMAx-value compared to the clinical failure group (1.9 mg/L vs. 5.1 mg/L) (349 μg/kg/h vs. 131 μg/kg/h). In the logistic regression model, LiMAx < 178 μg/kg/h was the only independent predictor of clinical failure with a sensitivity of 77% and specificity of 93%. CONCLUSIONS: The LiMAx test predicts clinical failure more precisely than linezolid trough levels in critically ill surgical patients. Therefore liver failure may have a stronger impact on the outcome of critically ill surgical patients than low linezolid Cmin. While linezolid Cmin failed to predict patient’s outcome, LiMAx results were the only independent predictor of clinical failure.

Expert consensus statement on therapeutic drug monitoring and individualization of linezolid

“…Wicha et al used the maximal liver function capacity (LiMAx test) tool for linezolid dose adjustment in patients with hepatic insufficiency. They suggested that TDM should be performed for LiMAx <100 μg/kg/h to reduce the risk of excessively high target plasma concentrations ( 62 , 63 ).…”

Immunomodulation by Hemoadsorption—Changes in Hepatic Biotransformation Capacity in Sepsis and Septic Shock: A Prospective Study

“…LiMAx ® achieved promising results for the assessment of hepatic function in liver resection, in liver transplantation [ 25 , 34 , 90 , 91 ], in monitoring antibiotics [ 27 , 29 , 92 ] and during sepsis [ 24 , 28 ]. The scope of applications may extend to monitor hepatic function during hemoadsorption with CytoSorb ® .…”

“…The LiMAx ® can serve as a guide and help to correctly assess the severity of SALD at an early stage. This diagnostic tool could make an important contribution to minimizing additional liver cell damage, e.g., by adjusting and monitoring liver toxic drugs such as antibiotics and antimycotics [ 24 , 27 , 28 , 29 , 31 , 92 , 114 , 115 ].…”

Why Product Information Should not be Set in Stone: Lessons from a Decade of Linezolid Therapeutic Drug Monitoring: An Opinion Paper

“…A substantial inverse association between the LiMAx score and high linezolid trough concentration has also been reported. 24,25 They reported that for LiMAx ,100 mg/kg/h, 64% of the linezolid trough concentrations were above the recommended trough concentration of 8 mg/L. Cured patients presented lower median linezolid Cmin, yet a remarkably higher…”

“…A substantial inverse association between the LiMAx score and high linezolid trough concentration has also been reported. 24,25…”