Long-Term Use of Tedizolid in Osteoarticular Infections: Benefits among Oxazolidinone Drugs

Abstract

Background: To evaluate the efficacy and safety of long-term use of tedizolid in osteoarticular infections. Methods: Multicentric retrospective study (January 2017–March 2019) of osteoarticular infection cases treated with tedizolid. Failure: clinical worsening despite antibiotic treatment or the need of suppressive treatment. Results: Cases (n = 51; 59% women, mean age of 65 years) included osteoarthritis (n = 27, 53%), prosthetic joint infection (n = 17, 33.3%), and diabetic foot infections (n = 9, 18%); where, 59% were orthopedic device-related. Most frequent isolates were Staphylococcus spp. (65%, n = 47; S. aureus, 48%). Reasons for choosing tedizolid were potential drug-drug interaction (63%) and cytopenia (55%); median treatment duration was 29 days (interquartile range -IQR- 15–44), 24% received rifampicin (600 mg once daily) concomitantly, and adverse events were scarce (n = 3). Hemoglobin and platelet count stayed stable throughout treatment (from 108.6 g/L to 116.3 g/L, p = 0.079; and 240 × 109/L to 239 × 109/L, p = 0.942, respectively), also in the subgroup of cases with cytopenia. Among device-related infections, 33% were managed with implant retention. Median follow-up was 630 days and overall cure rate 83%; among failures (n = 8), 63% were device-related infections. Conclusions: Long-term use of tedizolid was effective, showing a better safety profile with less myelotoxicity and lower drug-drug interaction than linezolid. Confirmation of these advantages could make tedizolid the oxazolidinone of choice for most of osteoarticular infections.

Real-World Use of Tedizolid Phosphate for 28 Days or More: A Case Series Describing Tolerability and Clinical Success

“…It has been shown that tedizolid has lower steady-state tissue/plasma ratios in rat bone and brain in comparison to linezolid, which may be a mechanistic explanation of the observed low incidence of hematological adverse effects and central nervous system interactions [ 3 ]. With a median duration of 188 (IQR, 62–493) days, the tedizolid duration in this report far surpasses both the time period when adverse effects associated with linezolid would be expected to be observed as well as other published reports on long-term tedizolid use [ 6 , 10 , 11 , 13 ]. Two recent studies that evaluated the safety profile of tedizolid exhibited similar rates of adverse effects (11.1% and 5.9%, overall; 8.6% and 0%, hematologic-related); however, the durations of tedizolid exposure in these investigations were shorter compared with those described in this report (median of 28 [IQR, 14–59] and 29 [IQR, 15–44] days) [ 10 , 11 ].…”

Pharmacokinetics and Pharmacodynamics of Tedizolid

“…However, because of the small sample size ( n = 40) of the study, the long-term safety of TDZ necessitates further investigations. Studies with slightly longer durations (mean of 27–29 days) support these findings [ 102 – 104 ]. In ESTABLISH 1 and 2 trials, neurological (~ 9%) and dermatological (~6%) toxicities were almost equally often reported for both TDZ and LNZ, which were well supported in other studies [ 14 , 90 , 91 , 105 ].…”

Antibiotic Approvals in the Last Decade: Are We Keeping Up With Resistance?

“…Tedizolid has been used off-label with a varying degree of success in the treatment of prosthetic joint infections, osteomyelitis, central nervous system infections, mycobacterial infections, and pneumonia. 32,124,125 Unlike linezolid, which is administered twice daily, tedizolid is given once daily. 32,123 Another advantage is that tedizolid appears to cause fewer hematological adverse effects and fewer interactions with serotonergic agents than linezolid; however, long-term safety data are not yet available.…”

“…32,123 Another advantage is that tedizolid appears to cause fewer hematological adverse effects and fewer interactions with serotonergic agents than linezolid; however, long-term safety data are not yet available. 123 -125 Oral tedizolid inhibits the breast cancer resistance protein (BCRP) in the intestine, and caution is required when coadministering oral BCRP substrates. 32…”