Prolonged use of linezolid in bone and joint infections: a retrospective analysis of adverse effects

Abstract

Objectives Antibiotic treatment for bone and joint infections generally lasts for 6 weeks or longer. Linezolid may be a good option for treating bone and joint infections, but there is an increased risk of potential serious adverse drug events (ADEs) when used for more than 28 days. The aim of this study was to obtain detailed information on the type and time to occurrence of the patient-reported ADEs, the dynamics of haematopoiesis over time, and the reasons for early discontinuation of linezolid when used for an intended maximum duration of 12 weeks. Methods This single-centre retrospective study was conducted at the Sint Maartenskliniek in The Netherlands. Patients were included if they were planned to use linezolid for more than 28 days. The main reason for discontinuation of linezolid, the ADE according to the Naranjo score, and the time to occurrence of ADEs were analysed. Results Among 78 patients, drug toxicity led to early discontinuation of linezolid in 11 (14%) patients before and nine (12%) after 28 days of therapy. The median treatment duration was 42 days. Gastrointestinal intolerance (42%) and malaise (32%) were the most common ADEs. In 75% of the cases the ADE occurred within 28 days of therapy. Sixty-seven patients were able to continue linezolid beyond 28 days, 87% of whom completed therapy as scheduled. Severe cytopenia, according to the Common Terminology Criteria for Adverse events (CTCA), was observed in four patients and was reversible after discontinuation of linezolid. One patient suffered optic neuropathy related to linezolid use. Conclusions Linezolid could be considered an alternative option to the current standard of IV glycopeptides for the treatment of bone and joint infection for up to 12 weeks. If patients pass the first 28 days of therapy, the likelihood of successful completion of therapy is high with a low risk of serious ADEs.

Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database

“…Most importantly, we provide a comprehensive study of the specific time of onset following linezolid administration in each organ system. Previous researchers have reported the median time to occurrence of some specific ADEs for linezolid dosing (Matsumoto et al, 2014;Jaspard et al, 2020;Veerman et al, 2023). Although these results may not reflect the actual TTO given the population in the clinical trial, our results are close to the findings and provide a more detailed and concrete list.…”

“…Gastrointestinal-related symptoms (nausea, vomiting, and diarrhea) were the most common reasons for discontinuation of the drug (Moise et al, 2002;Noel et al, 2012). Nausea (Shorr et al, 2015), gastrointestinal intolerance (Veerman et al, 2023), diarrhea, and vomiting (Shi et al, 2023) were the most common side effects reported in previous studies. A single-center retrospective observational study (Tsutsumi et al, 2022) found that female gender is an independent risk factor for linezolid-induced vomiting, which may be associated with multiple signaling pathways including D2, 5-HT3, and neurokinin-1 receptors (Navari and Aapro, 2016).…”

Modern Microbiological Methods to Detect Biofilm Formation in Orthopedy and Suggestions for Antibiotic Therapy, with Particular Emphasis on Prosthetic Joint Infection (PJI)

“…For patients allergic to penicillin, intravenous high-dose vancomycin or daptomycin are alternatives. The only oral alternative is linezolid, yet its toxicity profile may constrain its long-term usage [ 145 ].…”