Linezolid and Lactic Acidosis

Su, Erik; Crowley, Kelli; Carcillo, Joseph A.; Michaels, Marian G.

doi:10.1097/inf.0b013e3182186035

Cited by 35 publications

(10 citation statements)

References 10 publications

(13 reference statements)

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“…For patients treated with linezolid, chronic liver disease and impaired liver function are risk factors for thrombocytopenia (26) and for isolated cases of delayed but rapid-onset lactic acidosis (39,40). Linezolid pharmacokinetic changes have not been formally evaluated in subjects with severe hepatic impairment, but an increase in linezolid AUC of approximately1.3-fold was observed in subjects with mild to moderate hepatic impairment (33).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Flanagan

Minassian

Morris

et al. 2014

Antimicrob Agents Chemother

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Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (ϳ8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (ϳ9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].)

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Flanagan

Minassian

Morris

et al. 2014

Antimicrob Agents Chemother

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“…Linezolid has been reported to be associated with lactic acidosis in both adults137 and children 138. It is most commonly reported after prolonged administration of linezolid and resolves when linezolid is stopped133,137 but there have been case reports of lactic acidosis occurring early on during linezolid treatment 139,140.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Clinical update on linezolid in the treatment of Gram-positive bacterial infections

Gould¹

2012

IDR

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Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs.

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“…Linezolid induced lactic acidosis has been described in several case reports in the literature [3][4][5][6][7][8]. One small retrospective study found that 6.8% of patients taking linezolid developed lactic acidosis unexplained by other factors [3].…”

Section: Discussionmentioning

confidence: 99%

Linezolid Induced Lactic Acidosis: The Side Effect, Clinician Should Be Aware of

Nightingale

Austin

Agarwal

et al. 2020

Cureus

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Linezolid is a synthetic antibiotic that functions through the inhibition of bacterial protein synthesis by binding to ribosomal ribonucleic acid (rRNA). Deliverable in both intravenous and oral form, with a low level of resistance amongst Methicillin-resistant Staphylococcus aureus (MRSA) strains, it is recommended for a wide range of gram-positive infections. We present a case of a male patient who underwent endovascular abdominal aortic aneurysm repair complicated by abdominal sepsis due to bowel ischemia; several days after linezolid therapy was initiated, he presented with signs of lactic acidosis. After excluding other sources such as metabolic, hypoxia, or organ damage, the resulting lactic acidosis was determined to be a side effect of linezolid.

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Linezolid and Lactic Acidosis

Cited by 35 publications

References 10 publications

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Clinical update on linezolid in the treatment of Gram-positive bacterial infections

Linezolid Induced Lactic Acidosis: The Side Effect, Clinician Should Be Aware of

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