Antimicrobial Stewardship Initiatives and Studies by the Hospital Pharmacist: Study of Linezolid-associated Thrombocytopenia

Abstract

Infectious disease chemotherapy pharmacists should evaluate the appropriate usage of antimicrobial agents within the hospital, support in-patient pharmacists in treating infections, and appropriately use antimicrobial agents throughout the infection treatment course. Hospital pharmacists are required to strive to prevent adverse events and support the appropriateness of antimicrobial use to cure infectious diseases. Our hospital's antimicrobial stewardship team provides support and information on the proper use of antimicrobial agents in collaboration with in-patient pharmacists. Among other things, thrombocytopenia in linezolid therapy can often be an obstacle to treatment. We conducted clinical and basic research on thrombocytopenia, the major adverse event associated with linezolid. We first conducted a retrospective study investigating renal dysfunction and thrombocytopenia associated with vancomycin and linezolid treatments. Renal dysfunction occurred more frequently in patients receiving vancomycin than those receiving linezolid (p=0.032). In contrast, thrombocytopenia occurred more frequently in patients treated with linezolid than those treated with vancomycin (p<0.001). A significantly higher rate of thrombocytopenia was observed in patients with linezolid treatment durations >7.5 days. Secondly, we examined whether the linezolid cytotoxicity to eukaryotic cells was associated with mitochondrial dysfunction and apoptosis-like cell death in U937 human leukemic monocyte lymphoma cells. Apoptosis-like cell death was clearly observed in cells incubated with linezolid in concentration- and duration-dependent manners. Linezolid cytotoxicity was relieved by superoxide dismutase-1 knockdown in U937 cells. These results suggest that mitochondrial damage could be linked to the induction of apoptosis in linezolid-treated U937 cells.