Correction of Linezolid-Induced Myelotoxicity After Switch to Tedizolid in a Patient Requiring Suppressive Antimicrobial Therapy for Multidrug-Resistant Staphylococcus epidermidis Prosthetic-Joint Infection

Ferry, Tristan; Batailler, Cécile; Conrad, Anne; Triffault-Fillit, Claire; Laurent, François; Valour, Florent; Chidiac, Christian

doi:10.1093/ofid/ofy246

Cited by 17 publications

(7 citation statements)

References 10 publications

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“…The mean age of our patients was 73.3 years, which is quite high with regard to the risk of developing bone marrow toxicity to LZD, as reported by several authors [ 9 , 10 ]. The correction of LZD-induced bone marrow toxicity after switching to TZD observed in one of our patients has already been reported elsewhere [ 27 , 28 ]. Overall, we only recorded a few significant haematological abnormalities which did not result in discontinuation of TZD therapy, except in patients with acute haemorrhage.…”

Section: Discussionsupporting

confidence: 78%

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

et al. 2020

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Objectives: Data on clinical and biological tolerance of tedizolid (TZD) prolonged therapy are lacking. Methods: We conducted a prospective multicentre study including patients with prosthetic joint infections (PJIs) who were treated for at least 6 weeks but not more than 12 weeks. Results: Thirty-three adult patients of mean age 73.3 ± 10.5 years, with PJI including hip (n = 19), knee (n = 13) and shoulder (n = 1) were included. All patients were operated, with retention of the infected implants and one/two stage-replacements in 11 (33.3%) and 17/5 (51.5%/15.2%), respectively. Staphylococci and enterococci were the most prevalent bacteria identified. The mean duration of TZD therapy was 8.0 ± 3.27 weeks (6–12). TZD was associated with another antibiotic in 18 patients (54.5%), including rifampicin in 16 cases (48.5). Six patients (18.2%) had to stop TZD therapy prematurely because of intolerance which was potentially attributable to TZD (n = 2), early failure of PJI treatment (n = 2) or severe anaemia due to bleeding (n = 2). Regarding compliance with TZD therapy, no cases of two or more omissions of medication intake were recorded during the whole TZD treatment duration. Conclusions: These results suggest good compliance and a favourable safety profile of TZD, providing evidence of the potential benefit of the use of this agent for the antibiotic treatment of PJIs.

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Section: Discussionsupporting

confidence: 78%

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

et al. 2020

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“…Safety of long-term use of tedizolid was evaluated in healthy volunteers for 21 days [ 16 ], while most of the information in patients is limited to six days of treatment in ABSSSIs [ 4 , 5 , 21 ], and there is little information with longer therapies where the appearance of thrombocytopenia and anemia was observed in 7.4 and 1.2%, respectively [ 22 ]. In our experience, tedizolid was administered a median of 29 days and was well tolerated without relevant hematologic adverse events appearing or need for withdrawn, even in cases with moderate/severe cytopenia at the start of therapy or those that were switched to tedizolid after developing linezolid myelotoxicity [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Moreover, this drug remains active in MDR staphylococci and could have potential activity against persisters (31). However, PJI is an off-label use of tedizolid, and this antibiotic is a costly option for SAT as a one-year supply of this drug is approximately $127,000 in the United States and e75,000 in France (16).…”

Section: Discussionmentioning

confidence: 99%

“…In patients with multidrugresistant (MDR) coagulase negative staphylococci PJI, linezolid is frequently the only oral active drug. However, its use is associated with a significant toxicity when prescribed for >28 days (15,16). In this context, the use of new adjuvant therapies is of great interest and may improve the stabilization of medical conditions of patient with PJI.…”

Section: Introductionmentioning

confidence: 99%

Arthroscopic “Debridement and Implant Retention” With Local Administration of Exebacase (Lysin CF-301) Followed by Suppressive Tedizolid as Salvage Therapy in Elderly Patients for Relapsing Multidrug-Resistant S. epidermidis Prosthetic Knee Infection

et al. 2021

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Exebacase, a recombinantly produced lysin has recently (i) reported proof-of-concept data from a phase II study in S. aureus bacteremia and (ii) demonstrated antibiofilm activity in vitro against S. epidermidis. In patients with relapsing multidrug-resistant (MDR) S. epidermidis prosthetic knee infection (PKI), the only surgical option is prosthesis exchange. In elderly patients who have undergone several revisions, prosthesis explantation could be associated with definitive loss of function and mortality. In our BJI reference regional center, arthroscopic debridement and implant retention with local administration of exebacase (LysinDAIR) followed by suppressive tedizolid as salvage therapy is proposed for elderly patients with recurrent MDR S. epidermidis PKI with no therapeutic option or therapeutic dead end (for whom revision or transfemoral amputation is not feasible and no other oral option is available). Each use was decided in agreement with the French health authority and in accordance with the local ethics committee. A written consent was obtained for each patient. Exebacase (75 mg/mL; 30 mL) was administered directly into the joint during arthroscopy. Four patients (79–89 years old) were treated with the LysinDAIR procedure. All had several previous prosthetic knee revisions without prosthesis loosening. Three had relapsing PKI despite suppressive antibiotics following open DAIR. Two had clinical signs of septic arthritis; the two others had sinus tract. After the LysinDAIR procedure, no adverse events occurred during arthroscopy; all patients received daptomycin 8 mg/kg and linezolid 600 mg bid (4–6 weeks) as primary therapy, followed by tedizolid 200 mg/day as suppressive therapy. At 6 months, recurrence of the sinus tract occurred in the two patients with sinus tract at baseline. After >1 year follow up, the clinical outcome was favorable in the last two patients with total disappearance of clinical signs of septic arthritis even if microbiological persistence was detected in one of them. Exebacase has the potential to be used in patients with staphylococci PKI during arthroscopic DAIR as salvage therapy to improve the efficacy of suppressive antibiotics and to prevent major loss of function.

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Correction of Linezolid-Induced Myelotoxicity After Switch to Tedizolid in a Patient Requiring Suppressive Antimicrobial Therapy for Multidrug-Resistant Staphylococcus epidermidis Prosthetic-Joint Infection

Cited by 17 publications

References 10 publications

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

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

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

Arthroscopic “Debridement and Implant Retention” With Local Administration of Exebacase (Lysin CF-301) Followed by Suppressive Tedizolid as Salvage Therapy in Elderly Patients for Relapsing Multidrug-Resistant S. epidermidis Prosthetic Knee Infection

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