Abstract
Aim
Long term use of antibiotics following surgical debridement are the cornerstone of PJI treatment. Due to increasing resistance of bacteria for many first line antibiotics new options are needed. One such option is linezolid known for its low percentage of resistance against many Gram positive bacteria causing PJI. Success rates up to 86% have been reported. At the same time many adverse events (AE) have been described including anemia, thrombocytopenia, gastrointestinal effects and sometimes neuropathy, e.g. irreversible vision loss [1, 2]. Therefore, linezolid use is advised to be limited to a maximum of 28 days. Literature about the effects of prolonged use is currently lacking and therefore this study will aim to determine the safety of long-term (>28 days) linezolid use in patients with orthopedic infections.
Methods
We performed a retrospective descriptive study on patient records of orthopedic patients who were treated with linezolid between January 2014 and January 2019 for >28 days. Data were collected from medical charts including co-morbidities, pre-existing liver/kidney dysfunctions, diagnosis, treatment, type of prosthesis, pathogens, adverse events associated with linezolid use and follow up laboratory data.
Results
91 patients treated with linezolid were identified. 46 patients (25 male), mean age 64 (SD 11.49) received long-term linezolid with an average treatment duration of 45.3 (range 29 – 91) days. AE were observed in 32 with gastrointestinal AE's (16 patients) being the most frequent following anemia (7 patients) thrombocytopenia (6 patients), leucopenia (2 patients). One patient reported optic neuritis but no association with linezolid could be confirmed. Linezolid treatment was ended in 7 patients (15.2%) due to AE (predominantly anemia) compared to 14 patients (31.1%) who received short-term treatment (predominantly gastrointestinal AE). Decreased post-surgery hemoglobin levels tended to increase during the first two weeks of linezolid use after which hemoglobin levels showed an average decrease of 0.39 mmol/L between week 2 and week 7 of treatment. Leucocyte and thrombocyte levels showed an average decrease between baseline measures and week 7 of treatment of 2.21∗109/L and 89.0∗109/L respectively. AE were resolved after a mean 12 days (range 2–30 days)
Conclusions
Long-term linezolid use was not associated with an increase in serious irreversible AE and can therefore be considered generally safe, provided that patients are well monitored considering high drop out in the first weeks mainly due to gastrointestinal AE and anemia during prolonged treatment. These observations help to fill the gap in knowledge about prolonged linezolid use.