Be alert for thrombocytopenia and neutropenia with linezolid

Thrombocytopenia caused by linezolid is common, with a reported prevalence as high as 11.8%. Platelets typically reach normal levels 7 days...

Linezolid (Zyvox) is an antibiotic in the class oxazolidinones and it is effective against all Gram-positive infections. It is usually reserved for resistant Gram-positive organisms, especially vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). It is also sometimes considered if outpatient treatment with oral medicines is required.

Linezolid exhibits a mechanism of action that is different than any other antimicrobial class, thus making cross-resistance with other antibiotics uncommon. The drug works by inhibiting the bacterial translation process. Linezolid binds to the 23S peptidyltransferase of the 50S subunit, thus preventing the formation of a functional 70S initiation complex, an essential step in the bacterial translational process. This prevents bacteria from multiplying.

The most significant side effect of linezolid is myelosuppression, causing thrombocytopenia, neutropenia, and anemia. The thrombocytopenia is reversible upon discontinuation of the drug. Complete blood cell counts (CBCs) should be monitored weekly during linezolid treatment, especially in patients receiving the drug for more than 2 weeks and in those who have preexisting myelosuppression, are receiving concomitant drugs that produce bone marrow suppression, or have a chronic infection that was or is being treated with concomitant anti-infective therapy.

There have also been recent reports of toxic optic neuritis in patients receiving linezolid for longer than the maximum recommended duration of treatment (28 days). These symptoms also resolved with discontinuation of the antibiotic. In addition, since linezolid possesses monoamine oxidase inhibitor (MAOI) activity, it should not be administered with adrenergic and serotonergic agents such as the antidepressant selective serotonin reuptake inhibitors (SSRIs).

If linezolid must be stopped, there are several alternative antimicrobials currently available to treat resistant Gram-positive organisms. Daptomycin was approved in 2003 and has shown good utility. It is a cyclic lipopeptide and is effective against all Gram-positive microbes including VRE, MRSA, and VRSA. Tigecycline was approved in 2005 and has extended spectrum coverage including all Gram positives and resistant Gram positives. It also has activity against anaerobes and Gram negatives, including extended-spectrum beta-lactamases.

REFERENCES

Attassi, K., Hershberger, E., Alam, R. and Zervos, M.J. (2002). Thrombocytopenia Associated with Linezolid Therapy. Clinical Infectious Diseases, [online] 34(5), pp.695–698. Available at: https://academic.oup.com/cid/article/34/5/695/319032

Rao N, Ziran B, Wagener MM, et al. Similar hematologic effects of long term linezolid and vancomycin therapy in a prospective observational study of patients with orthopedic infections. Clin Infect Dis. 2004;38:1058–1064. Available at: https://pubmed.ncbi.nlm.nih.gov/15095207

Senneville E, Legout L. Risk factors for anemia in patients on prolonged linezolid therapy for chronic osteomyelitis: a case-control study. J Antimicrob Chemother. 2004;54:798–802.Available at: https://pubmed.ncbi.nlm.nih.gov/15329363