Tolerance of Prolonged Oral Tedizolid for Prosthetic Joint Infections: Results of a Multicentre Prospective Study

Senneville, Éric; Dinh, Aurélien; Ferry, Tristan; Beltrand, E.; Blondiaux, Nicolas; Robineau, Olivier

doi:10.3390/antibiotics10010004

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…In terms of efficacy, we found a treatment failure rate of 11%, similar to the rates of 6%–24% reported by others ( 18 – 20 , 23 ). How these treatment failure rates compare to that of other antimicrobial regimens, intravenous or oral, is unclear.…”

Section: Discussionsupporting

confidence: 90%

“…Ferry et al prospectively looked at the safety of suppressive treatment in implant-associated BJIs in 17 patients with multidrug-resistant Gram-positive infections and found tedizolid to be well tolerated ( 19 ). Senneville et al prospectively examined 33 patients with prolonged therapy undergoing surgical intervention for a mean of 8.0 weeks ( 20 ). Two patients (6%) had to stop tedizolid due to intolerance, and two more (6%) due to anemia, although the anemia was felt to be due to bleeding.…”

Section: Discussionmentioning

confidence: 99%

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Safety and tolerability of tedizolid as oral treatment for bone and joint infections

Miller,

Flores,

Launer

et al. 2023

Microbiol Spectr

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Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4–12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash ( n = 1) and urgent surgery ( n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4–12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Safety and tolerability of tedizolid as oral treatment for bone and joint infections

Miller,

Flores,

Launer

et al. 2023

Microbiol Spectr

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“…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 ]. Safety profiles of elderly individuals, adolescents, and children (aged 2–12 years), patients with cystic fibrosis, and renal and hepatically impaired patients were comparable to that of the adult population [ 15 , 19 , 20 , 25 , 106 , 107 ]. The overall safety pattern of TDZ in post-marketing surveillance in the ADR reports (2014–20) in the worldwide US Food and Drug Administration Adverse Events Reporting System was in line with the above results where no serious adverse effect was directly associated with TDZ [ 108 ].…”

Section: Pharmacodynamicsmentioning

confidence: 97%

“…For long-term safety, less structured data are available. Yet, in a recent study in patients with bone and joint infections (n = 33) where TDZ was administered for a mean duration of 8 weeks at 200 mg/day, an overall high ADR rate (60%) was reported, and 18% of the patients discontinued the TDZ because of intolerance or severe anemia due to hemorrhage [109]. The results were comparable with overall ADR rates reported in non-tuberculosis mycobacterial infections after an average of 101 days of TDZ administration [110].…”

Section: Safety Profilementioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Tedizolid

2022

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Tedizolid is an oxazolidinone antibiotic with high potency against Gram-positive bacteria and currently prescribed in bacterial skin and skin-structure infections. The aim of the review was to summarize and critically review the key pharmacokinetic and pharmacodynamic aspects of tedizolid. Tedizolid displays linear pharmacokinetics with good tissue penetration. In in vitro susceptibility studies, tedizolid exhibits activity against the majority of Gram-positive bacteria (minimal inhibitory concentration [MIC] of ≤ 0.5 mg/L), is four-fold more potent than linezolid, and has the potential to treat pathogens being less susceptible to linezolid. Area under the unbound concentration-time curve (fAUC) related to MIC (fAUC/MIC) was best correlated with efficacy. In neutropenic mice, fAUC/MIC of ~ 50 and ~ 20 induced bacteriostasis in thigh and pulmonary infection models, respectively, at 24 h. The presence of granulocytes augmented its antibacterial effect. Hence, tedizolid is currently not recommended for immunocompromised patients. Clinical investigations with daily doses of 200 mg for 6 days showed non-inferiority to twice-daily dosing of linezolid 600 mg for 10 days in patients with acute bacterial skin and skin-structure infections. In addition to its use in skin and skin-structure infections, the high pulmonary penetration makes it an attractive option for respiratory infections including Mycobacterium tuberculosis. Resistance against tedizolid is rare yet effective antimicrobial surveillance and defining pharmacokinetic/pharmacodynamic targets for resistance suppression are needed to guide dosing strategies to suppress resistance development.

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“…Also recently, the results of a French prospective multi-centre study reassured the good tolerance of prolonged oral tedizolid therapy for PJI. This study included patients with PJI who were treated for at least 6 weeks but not more than 12 weeks [ 8 ]. Thirty-three adult patients with PJI [hip (n = 19), knee (n = 13) and shoulder (n = 1)] were included.…”

mentioning

confidence: 99%

Tedizolid: new data and experiences for clinical practice

Lletí

García-Bustos²,

Ruiz³

et al. 2021

Rev Esp Quimioter

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The most relevant information on the clinical uses of tedizolid from studies published in the last 18 months is presented in this brief review. The most important data indicate better tolerance and safety profile of long-term therapeutic regimes in off-label indications, such as osteoarticular infections and those caused by mycobacteria. Its lower risk of hazardous interactions compared to linezolid should be emphasized. Furthermore, tedizolid in its combination with rifampicin shows a more favourable way of acting as demonstrated in vitro and in vivo studies. A recent trial also opens the door for its potential use in nosocomial pneumonia caused by Gram-positive bacteria.

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Tolerance of Prolonged Oral Tedizolid for Prosthetic Joint Infections: Results of a Multicentre Prospective Study

Cited by 13 publications

References 31 publications

Safety and tolerability of tedizolid as oral treatment for bone and joint infections

Safety and tolerability of tedizolid as oral treatment for bone and joint infections

Pharmacokinetics and Pharmacodynamics of Tedizolid

Tedizolid: new data and experiences for clinical practice

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