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

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.

Hematological side effect analysis of linezolid in MDR-TB patients with individual therapy

Objectives This study aimed to estimate the prevalence and analyze the risk factors for linezolid-induced hematological side effects in multidrug-resistant tuberculosis (MDR-TB) patients. Methods Data were collected from medical records of MDR-TB patients who received linezolid between January 2018 and May 2020. Statistical significance analysis and multivariate analysis were performed with SPSS version 24 software. Results Hematological side effects were identified in 27 out of 93 patients (29.0%). The most prevalent effect was anemia (29.0%), while the less prevalent effects were thrombocytopenia (3.2%) and leukopenia (2.2%). These side effects were reported after 2 weeks of linezolid treatment. The drug dose was more than 11 mg/kgBW/day or patient weighing less than 54 kg was identified as an independent risk factor for anemia in multivariate analysis. Conclusions Anemia was the most prevalent of linezolid-induced hematological side effects in MDR-TB patients. Therefore, hemoglobin monitoring might be recommended in patients weighing less than 54 kg and after receiving linezolid therapy for at least 2 weeks.

Development and Validation of a Risk Prediction Model of Linezolid-induced Thrombocytopenia in Elderly Patients

Background Linezolid is an oxazolidinone antimicrobial agent developed for treating multi-drug-resistant gram-positive bacterial infections. Objective This study aimed at investigating risk factors of linezolid (LI)-induced thrombocytopenia (LI-TP) and establishing a risk predictive model for LI-TP.Setting ZhongShan Hospital, FuDan University, China. Method A retrospective study was performed in patients aged ≥ 65 years receiving linezolid therapy from January 2015 to April 2021. Clinical characteristics and demographic data were collected and compared between patients with LI-TP and those without.Main outcome measures Incidence and risk factors of LI-TP in elderly patients.Results A total of 343 inpatients were included as the train set from January 2015 to August 2020. Among them, 67 (19.5%) developed LI-TP. Multivariate logistic regression analysis revealed that baseline platelet counts < 150×109·L-1 (OR=3.576; P< 0.001), age ≥ 75 years (OR=2.258; P=0.009), eGFR< 60 mL·(min·1.73m2)-1 (OR=2.553; P=0.002), duration of linezolid therapy ≥ 10 d (OR=3.218; P<0.001), ICU admittance (OR=2.682; P=0.004), and concomitant with piperacillin-tazobactam (PTZ) (OR=3.863; P=0.006) were independent risk factors for LI-TP. The risk predictive model was established and exhibited a moderate discriminative power, with an AUC of 0.795 [95%CI 0.740-0.851] and 0.849 [95%CI 0.760-0.939] in train set (n=343) and validation set (n=90), respectively.Conclusion The risk factors of LI-TP in elderly patients were duration of linezolid therapy, age, eGFR, ICU admittance, baseline platelet counts, and concomitant with PTZ. A risk predictive model based on these risk factors may be useful to identify patients with high risk of LI-TP.

Hemoadsorption with CytoSorb® and the early course of linezolid plasma concentration during septic shock

Hemoadsorption with CytoSorb® becomes increasingly established in treatment of various, predominantly inflammation-associated diseases. In septic shock, results suggest improvements in hemodynamics and organ function. However, little is known about the in vivo adsorption properties for various antibiotics. We present the case of a 61-year-old female patient with known Ulrich Turner syndrome who treated supportively with CytoSorb® and with linezolid due to a Staphylococcus epidermidis bloodstream infection as part of her intensive care treatment for septic shock. After establishment of a new adsorber, 600 mg of linezolid administered over 1 h. Linezolid levels measured before adsorber inlet (cpre) and after adsorber outlet (cpost) at 0, 15, 60, 120 and 480 min after starting infusion. Out of the ten samples, only the cpre samples 60 min (3.25 mg/l) and 120 min (4.7 mg/l) showed sufficiently high linezolid levels (therapeutic range 3–9 mg/l). After 480 min, cpre decreased to 2.8 mg/l, cpost increased to 1.85 mg/l, and thus clearance decreased to 67.86 ml/min (from 200 ml/min at 60 min), with greatly reduced adsorption capacity of CytoSorb® after 8 h. A loading dose (additional 600 mg) would have been urgently needed. Linezolid therapy under hemadsorption with CytoSorb® requires a clear indication and close monitoring of levels to avoid underdosing.

Incidence and Associated Risk Factors for Lactic Acidosis Induced by Linezolid Therapy in a Case–Control Study in Patients Older Than 85 Years

Background: Serum lactic acid is considered a prognostic indicator in critically ill patients. However, studies on linezolid-induced lactic acidosis (LILA) are still limited. Individuals older than 85 years old (very elderly) have limited capacity for organ compensation, and LILA data from these patients are lacking. In this study, we evaluated the risk factors for LILA in patients older than 85 years and established a risk prediction model for geriatric practice.Methods: In this retrospective cohort study, blood gas analysis data and arterial lactate levels were monitored in patients older than 85 years during the use of teicoplanin or linezolid. After propensity score matching analyses, we compared the incidence of lactic acidosis between the teicoplanin and linezolid therapy groups and identified the risk factors of LILA.Results: The incidence of lactic acidosis was found to be much lower in the group receiving teicoplanin than those receiving linezolid therapy (0 vs. 35.7%; p &lt; 0.0001). A duration of linezolid therapy ≥ 9 days [odds ratio (OR), 3.541; 95% confidence interval (CI), 1.161–10.793; p = 0.026], an arterial blood glucose level ≥ 8 mmol/L (OR, 4.548; 95% CI, 1.507–13.725; p = 0.007), and a high sequential organ failure assessment score (OR, 1.429; 95% CI, 1.213–1.685; p &lt; 0.0001) were risk factors for LILA. The constructed risk model could be used to predict LILA (area under the curve, 0.849; specificity, 65.1%; sensitivity, 91.4%, with a negative predictive value of 93.2% and a positive predictive value of 59.3%).Conclusions: LILA can occur in patients older than 85 years after a relatively shorter duration of linezolid therapy. Therefore, close monitoring of blood gas and arterial lactate levels during linezolid therapy in the very elderly population is necessary.

The Use of Moxisaxin for Treatment of a Decompensated Cirrhosis Patient with Severe Pulmonary Infection

Introduction: Moxifloxacin is recommended for empirical antibiotic treatment of patients with cirrhosis. However, due to a lack of clinical safety data on moxifloxacin in Child-Pugh C patients, it is unknown how to use moxifloxacin in clinical practice. Case Presentation: A 76-year-old female with decompensated cirrhosis developed pneumonia during hospitalization. She had an initial failure to respond to imipenem/cilastatin + linezolid therapy. After three-day therapy with imipenem/cilastatin + moxisaxin, her infection symptoms rapidly improved. At this time, she presented a poor response with suspected hepatic encephalopathy. Given the worsening clinical symptoms caused by drug hepatotoxicity, moxisaxin was discontinued. Then, her body temperature rapidly raised. Conclusions: Moxisaxin may be a potentially useful antibiotic for hospital-acquired pneumonia in patients with decompensated cirrhosis, but further studies are needed to validate its hepatotoxicity.