Worldwide Assessment of Linezolid's Clinical Safety and Tolerability: Comparator-Controlled Phase III Studies

Abstract

Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against grampositive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (>2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P ‫؍‬ 0.074), nausea (3.4 and 2.3%, respectively; P ‫؍‬ 0.036), and headache (2.2 and 1.3%, respectively; P ‫؍‬ 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.

Clinical Outcomes of Linezolid Treatment for Extensively Drug-Resistant Tuberculosis in Beijing, China: A Hospital-Based Retrospective Study

“…Peripheral neuropathy occurred in 3 patients; however, all 3 continued the linezolid treatment under careful monitoring. Lactic acidosis and serotonin syndrome, known side effects of linezolid (7,8), were not seen in our study.…”

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…A key issue with linezolid, however, is toxicity. Although a number of large postmarketing studies have found linezolid toxicity rates to be similar to those of comparator drugs (140,145,285,382), high rates of toxicity have been found for complex patients, and prolonged therapy should be used with caution in these cases (24).…”

Pancytopenia due to linezolid treatment

“…During the follow-up in the intensive care unit, supportive treatment was administered, because development of anemia and thrombocytopenia was not initially linked to the drug. The blood counts should be monitored during use of linezolid (17).…”