Linezolid-induced Lactic Acidosis Research Articles

Linezolid-Induced Lactic Acidosis

Linezolid-Induced Lactic Acidosis

Mitochondrial toxicity induced by linezolid causing lactic acidosis

Linezolid-induced lactic acidosis is a rare, but life-threatening complication of a commonly used drug. Patients present with persistent lactic acidosis, hypoglycaemia, high central venous oxygen saturation and shock. Linezolid causes mitochondrial toxicity due to impaired oxidative phosphorylation. This is evidenced by cytoplasmic vacuolations in the myeloid and erythroid precursors of bone marrow smear as illustrated in our case. Discontinuation of the drug, administration of thiamine and haemodialysis reduces lactic acid levels.

Severe lactic acidosis after re-exposure to linezolid in a person living with HIV and multidrug resistant tuberculosis: a case report

Abstract Linezolid-induced lactic acidosis is rare and portends a poor prognosis. The mechanism of toxicity may be related to inhibition of mitochondrial ribosomes. We present the first case in the literature of a patient with HIV and multidrug resistant tuberculosis with fatal lactic acidosis secondary to linezolid re-exposure. The index case relates to a 37-year-old lady with a background medical history of HIV, on fixed combination antiretroviral therapy. In addition, she had multidrug resistant pulmonary tuberculosis and was being treated on a salvage antituberculosis regimen containing linezolid. She presented with a 1-day history of backpain, nausea and vomiting. Clinically she was severely acidotic with a lactate of 12 mmol/L, which peaked at 19 mmol/L. A presumptive diagnosis of lactic acidosis was made based on the history and exclusion of other causes. The patient demised despite management in the intensive care unit with continuous veno-venous haemodialysis (CVVH) and mechanical ventilation. The diagnosis of linezolid-induced lactic acidosis requires a high index of suspicion and exclusion of other causes. In the absence of definitive treatment, early diagnosis, drug discontinuation and prompt supportive management including continuous veno-venous haemodiafiltration are key in helping to reduce the high mortality associated with this toxicity.

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 < 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 < 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.

Linezolid-Induced Lactic Acidosis.

Linezolid-Induced Lactic Acidosis.

Linezolid-induced Lactic Acidosis

Lactic acidosis is a known complication of long-term linezolid therapy. We present a case where lactic acidosis developed only after 2 doses of linezolid. A review of literature revealed only 2 cases in which lactic acidosis developed soon after linezolid treatment was commenced. Both patients had underlying immunocompromising conditions. Our patient, like the previous 2 reports had an underlying immunocompromising condition – acute myeloid leukemia. It seems that linezolid has the propensity of inducing lactic acidosis soon after its commencement in immunocompromised patients.

Incidence and risk factors of linezolid-induced lactic acidosis

The use of linezolid has increased with the emergence of multidrug-resistant bacteria. Serum lactic acidosis has been reported as a serious side effect of linezolid use, therefore we evaluated the incidence and characteristics of linezolid-related lactic acidosis. Patients admitted to an 860-bed university hospital were enrolled. The patients were divided into two groups, those who used linezolid and those who used teicoplanin (control group). The study was conducted by review of the medical charts. Seventy-two patients were included in the linezolid group. The control group comprised 72 patients matched to those in the linezolid group for age and indication for antibiotic use. Lactic acidosis occurred in five cases (6.8%) in the linezolid group. None of the patients who used teicoplanin developed lactic acidosis, which was a comparable result. The median change in anion gap in the linezolid group was -0.8 mmol/l (interquartile range (IQR) -3.55 to 1.28 mmol/l), which was significantly higher than in the teicoplanin group, 0.05 mmol/l (IQR -1.75 to 2.3 mmol/l) (p=0.026). The number of increased anion gap events in patients who used linezolid for more than 6 weeks was higher than in the group who used linezolid for less than 6 weeks (p=0.0014). However, no statistically significant difference was observed according to age, estimated glomerular filtration rate, or diabetes. Linezolid showed an association with treatment-related lactic acidosis. A longer duration of linezolid use (>6 weeks) was one of the risk factors for metabolic acidosis. We suggest checking serum lactate concentrations regularly, especially in those on long-term use.

Linezolid-Induced Lactic Acidosis followed by Severe Hypophosphatemia after Discontinuation of Linezolid

Surgical InfectionsVol. 14, No. 2 Letters to Surgical InfectionsLinezolid-Induced Lactic Acidosis followed by Severe Hypophosphatemia after Discontinuation of LinezolidAtsushi Miyawaki, Takahiro Ueda, Atsunori Nakao, Masaru Adachi, Munehiko Ohya, Isamu Yamada, Yoshio Takesue, and Joji KotaniAtsushi MiyawakiSearch for more papers by this author, Takahiro UedaSearch for more papers by this author, Atsunori NakaoSearch for more papers by this author, Masaru AdachiSearch for more papers by this author, Munehiko OhyaSearch for more papers by this author, Isamu YamadaSearch for more papers by this author, Yoshio TakesueSearch for more papers by this author, and Joji KotaniSearch for more papers by this authorPublished Online:25 Apr 2013https://doi.org/10.1089/sur.2012.081AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Linezolid-Induced Lactic Acidosis followed by Severe Hypophosphatemia after Discontinuation of Linezolid." , 14(2), pp. 229–230FiguresReferencesRelatedDetailsCited byThe risk factors of linezolid-induced lactic acidosisMedicine, Vol. 97, No. 36Role of Mitochondrial Dysfunction in Linezolid-Induced Lactic Acidosis23 February 2018Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes1 June 2017 | Expert Opinion on Drug Safety, Vol. 16, No. 7Incidence and risk factors of linezolid-induced lactic acidosisInternational Journal of Infectious Diseases, Vol. 31Miscellaneous Antibacterial DrugsLinezolid1 June 2013 | Reactions Weekly, Vol. 1454, No. 1 Volume 14Issue 2Apr 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Atsushi Miyawaki, Takahiro Ueda, Atsunori Nakao, Masaru Adachi, Munehiko Ohya, Isamu Yamada, Yoshio Takesue, and Joji Kotani.Linezolid-Induced Lactic Acidosis followed by Severe Hypophosphatemia after Discontinuation of Linezolid.Surgical Infections.Apr 2013.229-230.http://doi.org/10.1089/sur.2012.081Published in Volume: 14 Issue 2: April 25, 2013Online Ahead of Print:March 6, 2013PDF download

Rapid-onset, linezolid-induced lactic acidosis in MELAS

Due to their prokaryotic origins, mitochondria are susceptible to a number of antibiotics that target the bacterial ribosome, and this vulnerability is exacerbated by certain mutations of the mitochondrial genome.MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome is characterised by biochemical and structural abnormalities of the muscle mitochondria, in which episodes of lactic acidosis stem from dysfunction of assembled respiratory complex I.Linezolid is an oxazolidinone antibiotic that has been reported to induce lactic acidosis, especially after prolonged administration, through inhibition of the mitochondrially synthesised components of oxidative phosphorylation.We report a patient with longstanding MELAS who suffered a severe lactic acidosis of rapid onset, with associated features of mitochondrial failure, shortly after the commencement of linezolid therapy and in the context of an otherwise improving clinical picture.This case emphasises the importance of circumspection when utilising drugs known to be toxic to the mitochondrion in patients with mitochondrial disease. In particular, given the biochemically plausible interaction, it would seem prudent to avoid the use of linezolid in patients with MELAS whenever possible.

Lactic Acidosis after Treatment with Linezolid

Linezolid is currently indicated to treat vancomycin-resistant Enterococcus faecium infections, nosocomial pneumonia caused by Staphylococcus aureus or Streptococcus pneumoniae, complicated and uncomplicated skin and skin structure infections, and community-acquired pneumonia. We report a case of linezolid-induced lactic acidosis during treatment of vancomycin-resistant enterococcal bacteremia after mitral valve replacement and permanent pacemaker implantation. We also review the current literature describing other cases of linezolid-associated hyperlactatemia.