Linezolid-Induced Lactic Acidosis in Two Liver Transplant Patients with the Mitochondrial DNA A2706G Polymorphism

Pozo, J.L. del; Fernández-Ros, Nerea; Sáez, Elena; Herrero, J.I.; Yuste, José Ramón

doi:10.1128/aac.02856-14

Cited by 28 publications

(7 citation statements)

References 12 publications

(26 reference statements)

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“…Therefore, we suggest lactate monitoring during linezolid therapy within day 7. Elevation of serum lactate was more prevalent in patients with other comorbidities, [ 12 , 13 ] but in our study, such elevation also occurred in patients without comorbidities. Therefore, we suggest lactate monitoring for all patients, and not the at-risk group alone.…”

Section: Discussioncontrasting

confidence: 48%

Effect of a serum lactate monitoring recommendation policy on patients treated with linezolid

Lee

Chung³

et al. 2021

Medicine

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Lactic acidosis is one of the most fatal adverse effects of linezolid, an antibiotic used to treat serious infections caused by antibiotic-resistant bacteria. However, the measures to prevent lactic acidosis have not been well established. We performed a retrospective study to analyze the impact of applying a serum lactate monitoring recommendation policy in patients treated with linezolid. Since September 2011, we have recommended inpatient monitoring of serum lactate levels in patients treated with linezolid at our hospital. Patients were divided into two groups according to whether they were seen during the non-recommendation or recommendation periods. The frequency of serum lactate monitoring, linezolid-induced lactatemia, lactic acidosis, critical illness, and death were compared between the two periods. After September 2011, adherence to the recommendation to monitor serum lactate increased from 6.1% to 60.1%. No difference was observed in the incidence of linezolid-induced lactatemia and lactic acidosis between the two periods. However, there was a significant difference in the incidence of linezolid-induced critical illness between the non-recommendation and recommendation periods (3 vs 0 cases, P = .044). In patients treated with linezolid, serum lactate monitoring led to early detection of lactatemia, thus enabling rapid rescue. We recommend regular monitoring of serum lactate in all patients treated with linezolid.

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Section: Discussioncontrasting

confidence: 48%

Effect of a serum lactate monitoring recommendation policy on patients treated with linezolid

Lee

Chung³

et al. 2021

Medicine

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“…One case–control study and several case reports, including a total of 7 patients, suggested an association between linezolid mitochondrial toxicity and the mitochondrial ribosomal RNA polymorphisms A2706G or G3010A ( Palenzuela, L, et al, 2005 , Carson, J, et al, 2007 , Velez, JC and Janech, MG, 2010 , Del Pozo, JL, et al, 2014 ). In our analysis, we did not find any association between mitochondrial toxicity adverse events and these or any other mitochondrial RNA polymorphism ( Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis

et al. 2015

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Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23–7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P < 0·0001). Increasing mean linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = − 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

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“…Likewise, other drugs may prevent ATP production (antibiotics such as oligomycin or local anaesthetic drugs), inhibit protein synthesis (antibiotics including chloramphenicol, tetracycline, erythromycin, eperezolid, linezolid and aminoglycosides) [ 19 , 58 ], decrease electron transfer (anticholesterolemics) or membrane potential, impair mitochondrial lipid metabolic pathways (barbiturates) or increase apoptosis (including benzodiazepines) [ 59 ]. Such mitochondrial disturbances have been reported to cause adverse effects including deafness [ 60 ], peripheral neuropathy [ 61 ], hyperlacatemia, lactic acidosis [ 62 ] and gastrointestinal, dermatological or hematological alterations, myopathic syndrome or gastrointestinal disturbances, among others [ 63 ]. Specific safety and mitochondrial toxic studies in human pregnancies are lacking for most of these drugs.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Toxicity in Human Pregnancy: An Update on Clinical and Experimental Approaches in the Last 10 Years

Morén

Hernández

Guitart‐Mampel

et al. 2014

IJERPH

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Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

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Linezolid-Induced Lactic Acidosis in Two Liver Transplant Patients with the Mitochondrial DNA A2706G Polymorphism

Cited by 28 publications

References 12 publications

Effect of a serum lactate monitoring recommendation policy on patients treated with linezolid

Effect of a serum lactate monitoring recommendation policy on patients treated with linezolid

Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis

Mitochondrial Toxicity in Human Pregnancy: An Update on Clinical and Experimental Approaches in the Last 10 Years

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