A Triad of Linezolid Toxicity: Hypoglycemia, Lactic Acidosis, and Acute Pancreatitis

Johnson, Patrick Connor; Vaduganathan, Muthiah; Phillips, Kristy M.; O’Donnell, Walter J.

doi:10.1080/08998280.2015.11929310

Cited by 18 publications

(19 citation statements)

References 16 publications

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“…A review of PubMed using the MeSH terms “linezolid” and “hypoglycemia” yielded two articles reporting findings of hypoglycemia associated with linezolid therapy [ 6 , 7 ]. Additional review of articles that have cited these publications or articles considered to be similar to these publications yielded one additional report of hypoglycemia associated with linezolid therapy [ 8 ]. Because of this evidence, linezolid medication labeling has recently been mandated by the Food and Drug Administration to contain a warning that a relationship between linezolid and hypoglycemia has been demonstrated, particularly in patients on concomitant hypoglycemic therapies [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Linezolid-Associated Hypoglycemia

Johannesmeyer

Bhakta

2017

Drug Saf - Case Rep

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Our case describes a 77-year-old, African American male who was experiencing recurrent hypoglycemic episodes, which resulted in two emergency department (ED) visits and a subsequent inpatient admission during his second ED visit. He was prescribed linezolid 600 mg twice daily for 14 days for the treatment of a Staphylococcus hominis urinary tract infection. Nine and a half days into therapy, the patient began having recurrent hypoglycemic episodes. These episodes persisted despite repeated intravenous dextrose boluses. The patient’s linezolid was discontinued during the second day of his inpatient admission. After a brief lag period after the final linezolid administration, the patient’s blood glucose level stabilized within normal limits. He was later discharged home. The Naranjo scale scores the causality of this reaction between 4 and 8, indicating possible to probable causality. The patient had a follow-up appointment with his primary care physician 2 weeks after discharge, with no noted blood glucose complications. Two months after discharge, he entered hospice care for his advancing heart failure and later expired due to causes unrelated to blood glucose complications.

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Section: Introductionmentioning

confidence: 99%

Linezolid-Associated Hypoglycemia

Johannesmeyer

Bhakta

2017

Drug Saf - Case Rep

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“…Linezolid may increase the levels of dopamine via its MAO inhibition activity, hence leading to hypoglycemia [23]. Another mechanism of the hypoglycemia is from linezolid induced mitochondrial dysfunction leading to pancreatic beta-cell related insulin secretion dysregulation [8].…”

Section: Discussionmentioning

confidence: 99%

“…It is imperative to recognize the cluster of adverse events to guide optimal treatment. A rare triad of toxicity of the hypoglycemia, lactic acidosis, and acute pancreatitis from linezolid has been reported [8]. We present a novel case of the linezolid toxicity presenting with a rare constellation of adverse events in the form of thrombocytopenia, lactic acidosis, hypoglycemia, and warfarin toxicity.…”

Section: Introductionmentioning

confidence: 94%

A Case of Linezolid Toxicity Presenting as a Sepsis Mimic

Mishra

Patel

Goel

et al. 2019

Case Reports in Critical Care

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Linezolid is an efficacious and well tolerated antimicrobial but can have serious adverse effects including myelo-suppression, serotonin syndrome, neuropathy, hypoglycemia, liver dysfunction, and lactic acidosis. The side effects are generally duration dependent; linezolid use is not recommended for more than 28 days. Case. A 59-year-old female presented with malaise, loss of appetite, and altered mentation. She had multiple medical comorbidities and required long-term anticoagulation with warfarin for venous thromboembolism. She had multiple medication allergies. Prior to admission, she was on linezolid for cellulitis of foot due to Methicillin-resistant Staphylococcus aureus (MRSA). On physical exam, she was drowsy and required endotracheal intubation for airway protection. Initial laboratory parameters showed lactic acidosis, thrombocytopenia, supra-therapeutic coagulation profile, low blood glucose, and transaminitis. Her altered mentation was due to hypoglycemia. The interaction with warfarin led to altered coagulation profile. She developed shock and vasopressors were initiated. Given her presentation, she was managed as severe sepsis. There were no active infectious foci attributing to decline of her clinical status. Linezolid was discontinued and she was managed with intravenous polymyxin B, aztreonam, and vancomycin. Her hemodynamic status improved within one day. She was extubated on Day 5 of her presentation. Her laboratory parameters showed gradual improvement over 12 days after discontinuation of linezolid. Retrospective evaluation revealed linezolid toxicity as possible cause of presentation. Linezolid toxicity can present as sepsis mimic and should be considered as a differential diagnosis while managing sepsis with other antimicrobial agents.

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“…It has been reported that linezolid caused hypoglycemia, lactic acidosis, and acute pancreatitis [ 28 , 30 ]. Based on our study, the hypoglycemia and lactic acidosis may well be the subsequent damage of ATP energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method

Huang

Wang

et al. 2018

BioMed Research International

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Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens. However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome. In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9). The rats of low-group and high-group were given by gavage with linezolid 60 and 120 mg/kg/day for 7 days, respectively. The serum concentration of linezolid was determined by high performance liquid chromatography (HPLC); blood metabolic change was analyzed by gas chromatography-mass spectrometer (GC-MS). Adenosine triphosphate (ATP) concentration in HepG2-C3A after being cultured with linezolid was determined by HPLC. The results showed that there were six metabolites and nine metabolites had statistical differences in low-group and high-group (P<0.05). The trimethyl phosphate was the most significant indicator in those changed metabolites. Except for d-glucose which was slightly increased in low-group, octadecanoic acid, cholest-5-ene, hexadecanoic acid, α-linolenic acid, eicosapentaenoic acid, 9,12-Octadecadienoic acid, and docosahexaenoic acid were all decreased in low-group and high-group. ATP concentration was decreased in HepG2-C3A after cultured with linezolid. In conclusion, the toxicity of linezolid is related to its serum concentration. Linezolid may inhibit the synthesis of ATP and fatty acid.

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A Triad of Linezolid Toxicity: Hypoglycemia, Lactic Acidosis, and Acute Pancreatitis

Cited by 18 publications

References 16 publications

Linezolid-Associated Hypoglycemia

Linezolid-Associated Hypoglycemia

A Case of Linezolid Toxicity Presenting as a Sepsis Mimic

Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method

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