linezolid-induced lactic acidosis

Q; 73 years old nursing home resident with previous multiple ICU admissions is admitted again with MRSA-sepsis. Due to documented previous good responses, two weeks of Linezolid is prescribed. Patient is again showing good response with Linezolid. On 9th day of ICU admission, patient ABG is showing mild lactic acidosis (LA). Your next step? (select one)

A) Continue Linezolid as transient LA is common

B) Discontinue Linezolid immediately

Answer: B

Linezolid induced LA can be deadly with mortality up to 25 percent. Linezolid should be discontinued immediately at any sign of unexplained LA. It may take up to 2 weeks for LA to be resolved. The biggest risk factor is the prolonged or recurrent use of linezolid, but may occur as early as at first week. It is due to mitochondrial toxicity, given similarity between human mitochondrial 16S RNA and bacterial 23S rRNA.

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References:

1. Palenzuela L, Hahn NM, Nelson RP Jr, et al. Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis? Clin Infect Dis 2005; 40:e113.

2. Santini A, Ronchi D, Garbellini M, et al. Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes. Expert Opin Drug Saf 2017; 16:833.

3. Wiener M, Guo Y, Patel G, Fries BC. Lactic acidosis after treatment with linezolid. Infection 2007; 35:278.

4. Mao Y, Dai D, Jin H, Wang Y. The risk factors of linezolid-induced lactic acidosis: A case report and review. Medicine (Baltimore) 2018; 97:e12114.