Thrombocytopenia and Tedizolid: A new ally in hematologic patients? Brief literature review and a clinical case

Thrombocytopenia and Tedizolid: A new ally in hematologic patients? Brief literature review and a clinical case | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Thrombocytopenia and Tedizolid: A new ally in hematologic patients? Brief literature review and a clinical case Luca Montanari, Melissa Bergnach, Chiara Cattaneo, Francesco Marchesi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7809956/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Tedizolid (TDZ) is a second-generation oxazolidinone with potent activity against multidrug-resistant Gram-positive pathogens and a favorable hematologic safety profile compared to linezolid (LNZ). This review summarizes current evidence on TDZ pharmacokinetics, pharmacodynamics, and its reduced risk of thrombocytopenia. We also report a clinical case of a hematologic patient treated with TDZ for fasciitis after hematopoietic stem cell transplantation, achieving complete infection resolution without adverse hematologic effects. These findings support TDZ as a valuable therapeutic option in hematologic patients, where treatment choices are often limited by drug-induced cytopenias. Figures Figure 1 Figure 2 Introduction Oxazolidinone antibiotics are distinguished by their effectiveness against multidrug-resistant Gram positive organisms. Both linezolid (LNZ) and tedizolid (TDZ) inhibit bacterial protein synthesis, interfering with the translation process. Currently, LNZ is approved for the treatment of nosocomial pneumonia and skin and soft tissue infections, whereas TDZ is authorized just for the latter. However, the use of LNZ is often associated with significant side effects, including serotonin syndrome, hyperlactatemia, and myelosuppression. In particular, myelosuppression (most frequently thrombocytopenia) limits its use in hematologic patients, making it a less favorable choice in this population. In contrast, TDZ appears to have a better tolerability profile, with a lower incidence of adverse effects, representing a potentially safer alternative. We submitted a brief questionnaire regarding the use of TDZ to 18 hematologists from the SEIFEM group: 27.8% had used tedizolid in clinical practice, 27.8% for skin and soft tissue infections, and 11.1% for Gram-positive bacteremia. In 100% of these cases, administration was free from side effects. Pharmakokinetics Oxazolidinones act by inhibiting protein synthesis binding to the 23S ribosomal RNA of the 50S subunit, preventing the formation of the 70S initiation complex. The molecular formula of TDZ phosphate is C₁₇H₁₆FN₆O₆P. The structure of TDZ is very similar to that of LNZ; however, the most important differences include the presence in TDZ of: a side chain at the C-5 hydroxymethyl position, which improves solubility and enhances oral bioavailability. a para-oriented (D-ring) structure that increases the number of hydrogen bonds and, consequently, strengthens ribosomal binding. [ 1 ] In vitro studies suggest that TDZ phosphate undergoes dephosphorylation at the intestinal brush border membrane, allowing it to enter enterocytes without accumulating in the intestinal lumen, where is converted into its active form by phosphatases. TDZ is rapidly absorbed, achieving an oral bioavailability of approximately 91% following therapeutic administration. Peak plasma concentrations are reached about 3 hours after oral administration and about 1 hour after intravenous administration of TDZ phosphate. Although TDZ can be taken with or without food, some studies have shown that a fed state reduces Cmax and delays Tmax, likely due to delayed gastric emptying associated with a solid meal, the low permeability of TDZ, and the absence of phosphatases within gastric cells. In the blood, TDZ binds to plasma proteins at a rate of 70–90%, and its volume of distribution in healthy adult patients ranges between 68 and 80 liters [ 1 , 2 ]. It has been demonstrated that TDZ is capable of accumulating in peripheral blood, pulmonary lining fluid (ELF), and alveolar macrophages. The penetration ratio of TDZ is approximately 40 times higher in ELF and 20 times higher in alveolar macrophages [ 3 ]. TDZ is mostly eliminated through the liver; its inactive metabolite is excreted 82% in the feces and 18% in the urine. The mean half-life (t½) of tedizolid was about twice that of linezolid, allowing for the more convenient administration of once-daily dosing [ 1 ]. Pharmacodynamics TDZ is a second-generation oxazolidinone, similar to LNZ, whose activity is against a wide range of Gram positive pathogens, including resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and linezolid - resistant cfr-positive strains [ 2 , 4 ]. As demonstrated by animal models, the best parameter for predicting TDZ activity is the area under the curve/minimum inhibitory concentration ratio (AUC/MIC), confirming that TDZ acts as a time-dependent antibiotic. Several studies have shown that, compared to LNZ, TDZ exhibits lower MIC₅₀ and MIC₉₀ values against Staphylococci , Streptococci , and Enterococci [ 4 ], TDZ has been shown to be 4 to 6 times more potent in vitro than LNZ. It can be observed that while the MICs of LNZ are generally higher than TDZ’, the AUC of LNZ is typically at least twice high. This results in similar AUC/MIC ratios being achievable with lower exposure to TDZ, thereby potentially limiting cumulative toxicity [ 2 ]. Thrombocytopenia: TDZ vs LNZ Unlike LNZ, where hematological toxicity is a significant concern, TDZ appears to have a better hematological safety profile, with a lower risk of thrombocytopenia. In 2006, a study conducted by T. P. Lodise et al. demonstrated that the incidence of reversible thrombocytopenia was markedly lower in the group of patients treated with TDZ administered at the therapeutic dose of 200 mg; conversely, the incidence of thrombocytopenia in the LNZ group was comparable to that observed in patients receiving high-dose TDZ, suggesting a dose-dependent adverse event (TDZ 300 mg: 12.5%, TDZ 400 mg: 25%) [ 5 ]. Although the study involved a small number of healthy subjects, the incidence of thrombocytopenia related to TDZ at its therapeutic dose was 0%. Thrombocytopenia rates in large comparative studies of LNZ vs. TDZ (ESTABLISH-1 and ESTABLISH2, NCT01170221 and NCT01421511, registered on ClinicalTrials.gov), while higher in the LNZ groups, were not statistically significant [ 6 ]. The ESTABLISH-1 study aimed to evaluate the efficacy and safety profile of TDZ administered for 6 days at a therapeutic dose of 200 mg/day versus LNZ administered for 10 days at a dose of 600 mg twice daily in patients with skin and soft tissue infections. Low platelet counts (< 115,000/mm³) (defined as 75% of the lower limit of normal or 75% of a patient's abnormally low baseline count) were observed in 2.3% of patients treated with TDZ and in 4.9% of patients in the LNZ group [ 7 ]. Although approximately half of the patients enrolled in the study were affected by hepatitis C, no data were published regarding the association between thrombocytopenia and hepatitis C infection [ 7 , 8 ]. In the ESTABLISH-2 safety study, although a higher platelet limit (PLT < 150,000/mm³) was considered, thrombocytopenia rates between the two groups were still not statistically significant: 9% (27/314) in the TDZ group versus 13% (41/305) in the LNZ group [ 9 ]. However, when combining data from ESTABLISH-1 and ESTABLISH-2, it was noted that between days 11 and 13, the rates of thrombocytopenia (defined as platelet counts < 150,000 or < 100,000/mm³) were significantly lower in the TDZ group compared to the LNZ group. In contrast, the incidence of thrombocytopenia between the two groups was not relevant between days 7 and 9 of treatment [ 10 ]. An important limitation of this analysis is that it was based on aggregated data from clinical trials and that TDZ therapy ended on day 6, while LNZ therapy continued until day 10. Possible explanations for the observed difference in thrombocytopenia rates are likely related to differences in dosage and administration schedules [ 11 ]. The role of LNZ exposure in the context of renal insufficiency remains a topic of discussion. Clinical case A 67-year-old patient diagnosed with myelodysplastic syndrome without blasts excess, presenting with grade 3 bone marrow fibrosis at onset, very high M-IPSS risk, with del(5q) and TP53 mutation (VAF 77%). The patient underwent treatment with 5 cycles of lenalidomide, followed by one cycle of azacitidine. After conditioning with treosulfan, thiotepa, and fludarabine, the patient received an allogeneic hematopoietic stem cell transplantation (HSCT) from a fully HLA-matched, ABO-compatible family donor using peripheral blood stem cells on 18/02/2025 (day 0). GVHD prophylaxis was initiated with anti-thymocyte globulin (Grafalon), methotrexate on days + 1, +3, and + 6, and cyclosporine starting from day − 1, adjusted according to therapeutic drug monitoring (TDM). On day + 4, during the aplastic phase, the patient developed fever. Blood cultures were obtained, and empiric broad-spectrum antibiotic therapy with piperacillin/tazobactam was initiated. Blood cultures were found positive for Corynebacterium striatum ; piperacillin/tazobactam was discontinued, and vancomycin monotherapy was started. On day + 9, a new febrile episode occurred, associated with erythema, warmth, swelling, and pain in the right lower limb, accompanied by elevated inflammatory markers and CPK (Fig. 1 ). Doppler ultrasound excluded deep vein thrombosis (DVT). An urgent contrast-enhanced CT scan was performed with evidence of fascitis. Based on the imaging, vancomycin was continued and combined with meropenem and tedizolid (preferred over linezolid to minimize the risk of thrombocytopenia while maintaining inhibition of bacterial protein synthesis). The patient was evaluated multiple times by orthopedic specialists, who found no indication for surgical intervention. Transthoracic echocardiography showed no evidence of endocarditis. On day + 30, a follow-up CT scan revealed a newly developed irregular fluid collection with loculated components in the posterolateral compartment of the right leg, measuring approximately 14×25×150 mm. Given the marked clinical and laboratory improvement, antibiotic therapy was discontinued on day + 35 (Fig. 2). Despite concurrent antibiotic treatment with tedizolid, hematologic recovery occurred as follows: neutrophil count > 1000/mm³ on day + 20, platelet count > 20,000/mm³ on day + 21, >50,000/mm³ on day + 26, and > 100,000/mm³ on day + 40. On day + 36, the patient developed acute graft-versus-host disease (aGVHD) grade I, involving the skin (stage 2), which subsequently progressed to grade II (skin stage 3). Treatment with methylprednisolone 2 mg/kg/day for 5 days led to a partial response. An ultrasound performed on day + 44 showed resolution of the previously described collection. The patient was discharged home on day + 49 Conclusions TDZ is a second generation oxazolidinone whose hematological safety profile appears to be improved compared to LNZ. Indeed, current literature shows that TDZ administra tion is associated with a lower incidence of thrombocytopenia compared to LNZ. In the clinical case presented, the patient, who had undergone HSCT, was treated with TDZ for more than two weeks following the diagnosis of fasciitis, without any adverse effects. In this context, TDZ may represent a valuable therapeutic alternative, particularly in complex clinical scenarios such as hematologic patients, where the risk of drug induced cytopenias is a major concern and treatment options are often limited by hematological toxicity. Ethics declaration Ethical approval was not required for this study as it describes a single clinical case. Written informed consent for publication was obtained from the patient. Declarations Funding: This research received no external funding. Author Contribution Luca Montanari: main author wrote the manuscriptCarlo Tascini: authorMelissa Bergnah: author, prepare pictures 1 e 2Francesca Patriarca: reviewed the manuscriptChiara Cattaneo: reviewed the manuscriptFrancesco Marchesi: reviewed the manuscriptLivio Pagano: reviewed the manuscriptRenato Fanin: reviewed the manuscript References McBride D, Krekel T, Hsueh K, Durkin MJ (2017) Pharmacokinetic drug evaluation of tedizolid for the treatment of skin infections. Expert Opin Drug Metab Toxicol 13(3):331–337 1080/17425255 (2017) 2017.1290080. Epub 2017 Feb 16. Erratum. Expert Opin Drug Metab Toxicol 13(4):491. 10.1080/17425255.2017.1303975 PMID: 28140693; PMCID: PMC8007045 Burdette SD, Trotman R, Tedizolid (2015) The Firs tOnce-Daily Oxazolidinone Class Antibiotic. Clin Infect Dis 61(8):1315–1321. 10.1093/cid/civ501 Epub 2015 Jun 23. PMID: 26105167 Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, Kuti JL, Nicolau DP (2012) Pulmonary disposition of tedizolid following administration of once-daily oral 200-milligram tedizolid phosphate in healthy adult volunteers. Antimicrob Agents Chemother 56(5):2627–2634. doi: treatment options are often limited by hematological toxicity10.1128/AAC.05354-11Epub 2012 Feb 13. PMID: 22330925; PMCID: PMC3346604 Shaw KJ, Poppe S, Schaadt R, Brown-Driver V, Finn J, Pillar CM, Shinabarger D, Zurenko G (2008) In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains. Antimicrob Agents Chemother 52(12):4442–4447. 10.1128/AAC.00859-08 Epub 2008 Oct 6. PMID: 18838596; PMCID: PMC2592863 Lodise TP, Bidell MR, Flanagan SD, Zasowski EJ, Minassian SL, Prokocimer P (2016) Characterization of the haematological profile of 21 days of tedizolid in healthy subjects. J Antimicrob Chemother 71(9):2553–2558. 10.1093/jac/dkw206 Epub 2016 Jun 17. PMID: 27317442 Iqbal K, Milioudi A, Wicha SG (2022) Pharmacokinetics and Pharmacodynamics of Tedizolid. Clin Pharmacokinet 61(4):489–503. 10.1007/s40262-021-01099-7 Epub 2022 Feb 7. PMID: 35128625; PMCID: PMC8975765 Prokocimer P, De Anda C, Fang E, Mehra P, Das A (2013) Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA 309(6):559–569. 10.1001/jama.2013.241 Lee EY, Caffrey AR (2017) Thrombocytopenia with Tedizolid and Linezolid. Antimicrob Agents Chemother. ;62(1):e01453-17. 10.1128/AAC.01453-17 . PMID: 29038274; PMCID: PMC5740346.PMID: 23403680 Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P (2014) Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin- structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 14(8):696–705. 10.1016/S1473-3099(14)70737-6 Epub 2014 Jun 5. PMID: 24909499 Lodise TP, Fang E, Minassian SL, Prokocimer PG (2014) Platelet profile in patients with acute bacterial skin and skin structure infections receiving tedizolid or linezolid: findings from the Phase 3 ESTABLISH clinical trials. Antimicrob Agents Chemother 58(12):7198–7204. 10.1128/AAC.03509-14 Epub 2014 Sep 22. PMID: 25246392; PMCID: PMC4249542 Bai AD, McKenna S, Wise H, Loeb M, Gill SS (December 2022) Safety Profile of Linezolid in Older Adults With Renal Impairment: A Population-Based Retrospective Cohort Study. Open Forum Infect Dis 9(12):ofac669 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 02 Dec, 2025 Reviews received at journal 01 Dec, 2025 Reviews received at journal 01 Dec, 2025 Reviewers agreed at journal 17 Nov, 2025 Reviewers agreed at journal 17 Nov, 2025 Reviewers invited by journal 17 Oct, 2025 Editor assigned by journal 13 Oct, 2025 Submission checks completed at journal 13 Oct, 2025 First submitted to journal 08 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7809956","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":535662643,"identity":"bb1f6ea1-c2ed-4fc0-b3f5-16d5af05fcce","order_by":0,"name":"Luca Montanari","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYNCCAgsGNvbmgw8+ANls7ITVMzYwGEgw8PEcSzacAdLCTKwWOYkcM2keEJ+QFt323uMPPhhIJLZJpKVJ2/zaJs/HzMD44WMObi1mZ84lNs4AaeF5fNg6t++2YRszA7PkzG14tNzIMWzmAWlhT0u8ndtzmxGohY2ZlygtDDkG0pY9t+1J0MKRYyTN8ON2ImEtZ84YzgT6xbgNFMi9DbeT25gZm/H75XiPwYcPFTay89uBUfnjz21bEOPDRzxaYMCxAUQytoHJBsLqgcAeQv0hSvEoGAWjYBSMMAAAcGFRsLnKN2wAAAAASUVORK5CYII=","orcid":"","institution":"Azienda Sanitaria Universitaria Friuli Centrale","correspondingAuthor":true,"prefix":"","firstName":"Luca","middleName":"","lastName":"Montanari","suffix":""},{"id":535662644,"identity":"6285d5f6-7949-43a4-8f9c-d82604638dd5","order_by":1,"name":"Melissa Bergnach","email":"","orcid":"","institution":"Università di Udine, Azienda Sanitaria Universitaria Friuli Centrale","correspondingAuthor":false,"prefix":"","firstName":"Melissa","middleName":"","lastName":"Bergnach","suffix":""},{"id":535662645,"identity":"67e19258-7146-4677-b798-7fdb1cf6b5f2","order_by":2,"name":"Chiara Cattaneo","email":"","orcid":"","institution":"ASST-Spedali Civili","correspondingAuthor":false,"prefix":"","firstName":"Chiara","middleName":"","lastName":"Cattaneo","suffix":""},{"id":535662646,"identity":"f16f5bb0-bcbc-4aca-bb6f-fca29aedfd0b","order_by":3,"name":"Francesco Marchesi","email":"","orcid":"","institution":"IRCCS Regina Elena National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Francesco","middleName":"","lastName":"Marchesi","suffix":""},{"id":535662647,"identity":"ad3a25c9-d6ec-4565-88d0-35a466cf94fa","order_by":4,"name":"Francesca Patriarca","email":"","orcid":"","institution":"Università di Udine, Azienda Sanitaria Universitaria Friuli Centrale","correspondingAuthor":false,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Patriarca","suffix":""},{"id":535662655,"identity":"c7ee4f6a-37f1-4e53-8175-dee18c0def89","order_by":5,"name":"Livio Pagano","email":"","orcid":"","institution":"Fondazione Policlinico Universitario A. 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2","display":"","copyAsset":false,"role":"figure","size":28127,"visible":true,"origin":"","legend":"\u003cp\u003eright limb after antibiotic treatment\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7809956/v1/db36f72f462f663d1118a613.jpg"},{"id":94827319,"identity":"1bc95435-13e7-42be-9fc0-06afe54f17b0","added_by":"auto","created_at":"2025-10-31 06:57:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":402125,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7809956/v1/a7eb7c52-c2bd-49bf-9077-447fb5d38375.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Thrombocytopenia and Tedizolid: A new ally in hematologic patients? Brief literature review and a clinical case","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOxazolidinone antibiotics are distinguished by their effectiveness against multidrug-resistant Gram positive organisms. Both linezolid (LNZ) and tedizolid (TDZ) inhibit bacterial protein synthesis, interfering with the translation process. Currently, LNZ is approved for the treatment of nosocomial pneumonia and skin and soft tissue infections, whereas TDZ is authorized just for the latter. However, the use of LNZ is often associated with significant side effects, including serotonin syndrome, hyperlactatemia, and myelosuppression. In particular, myelosuppression (most frequently thrombocytopenia) limits its use in hematologic patients, making it a less favorable choice in this population. In contrast, TDZ appears to have a better tolerability profile, with a lower incidence of adverse effects, representing a potentially safer alternative. We submitted a brief questionnaire regarding the use of TDZ to 18 hematologists from the SEIFEM group: 27.8% had used tedizolid in clinical practice, 27.8% for skin and soft tissue infections, and 11.1% for Gram-positive bacteremia. In 100% of these cases, administration was free from side effects.\u003c/p\u003e"},{"header":"Pharmakokinetics","content":"\u003cp\u003eOxazolidinones act by inhibiting protein synthesis binding to the 23S ribosomal RNA of the 50S subunit, preventing the formation of the 70S initiation complex. The molecular formula of TDZ phosphate is C₁₇H₁₆FN₆O₆P. The structure of TDZ is very similar to that of LNZ; however, the most important differences include the presence in TDZ of:\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003ea side chain at the C-5 hydroxymethyl position, which improves solubility and enhances oral bioavailability.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ea para-oriented (D-ring) structure that increases the number of hydrogen bonds and, consequently, strengthens ribosomal binding. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn vitro studies suggest that TDZ phosphate undergoes dephosphorylation at the intestinal brush border membrane, allowing it to enter enterocytes without accumulating in the intestinal lumen, where is converted into its active form by phosphatases. TDZ is rapidly absorbed, achieving an oral bioavailability of approximately 91% following therapeutic administration. Peak plasma concentrations are reached about 3 hours after oral administration and about 1 hour after intravenous administration of TDZ phosphate. Although TDZ can be taken with or without food, some studies have shown that a fed state reduces Cmax and delays Tmax, likely due to delayed gastric emptying associated with a solid meal, the low permeability of TDZ, and the absence of phosphatases within gastric cells. In the blood, TDZ binds to plasma proteins at a rate of 70–90%,\u003c/p\u003e\u003cp\u003eand its volume of distribution in healthy adult patients ranges between 68 and 80 liters [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It has been demonstrated that TDZ is capable of accumulating in peripheral blood, pulmonary lining fluid (ELF), and alveolar macrophages. The penetration ratio of TDZ is approximately 40 times higher in ELF and 20 times higher in alveolar macrophages [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. TDZ is mostly eliminated through the liver; its inactive metabolite is excreted 82% in the feces and 18% in the urine. The mean half-life (t½) of tedizolid was about twice that of linezolid, allowing for the more convenient administration of once-daily dosing [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e"},{"header":"Pharmacodynamics","content":"\u003cp\u003eTDZ is a second-generation oxazolidinone, similar to LNZ, whose activity is against a wide range of Gram positive pathogens, including resistant strains such as methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\u003cp\u003e(MRSA), vancomycin-resistant enterococci (VRE), and linezolid - resistant cfr-positive strains [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAs demonstrated by animal models, the best parameter for predicting TDZ activity is the area under the curve/minimum inhibitory concentration ratio (AUC/MIC), confirming that TDZ acts as a time-dependent antibiotic. Several studies have shown that, compared to LNZ, TDZ exhibits lower\u003c/p\u003e\u003cp\u003eMIC₅₀ and MIC₉₀ values against \u003cem\u003eStaphylococci\u003c/em\u003e, \u003cem\u003eStreptococci\u003c/em\u003e, and \u003cem\u003eEnterococci\u003c/em\u003e\u003c/p\u003e\u003cp\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e4\u003c/span\u003e],\u003c/p\u003e\u003cp\u003eTDZ has been shown to be 4 to 6 times more potent in vitro than LNZ. It can be observed that while the MICs of LNZ are generally higher than TDZ’, the AUC of LNZ is typically at least twice high. This results in similar AUC/MIC ratios being achievable with lower exposure to TDZ, thereby potentially limiting cumulative toxicity [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e"},{"header":"Thrombocytopenia: TDZ vs LNZ","content":"\u003cp\u003eUnlike LNZ, where hematological toxicity is a significant concern, TDZ appears to have a better hematological safety profile, with a lower risk of thrombocytopenia. In 2006, a study conducted by T. P. Lodise et al. demonstrated that the incidence of reversible thrombocytopenia was markedly lower in the group of patients treated with TDZ administered at the therapeutic dose of 200 mg; conversely, the incidence of thrombocytopenia in the LNZ group was comparable to that observed in patients receiving high-dose TDZ, suggesting a dose-dependent adverse event (TDZ 300 mg: 12.5%, TDZ 400 mg: 25%) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Although the study involved a small number of healthy subjects, the incidence of thrombocytopenia related to TDZ at its therapeutic dose was 0%. Thrombocytopenia rates in large comparative studies of LNZ vs. TDZ (ESTABLISH-1 and ESTABLISH2, NCT01170221 and NCT01421511, registered on ClinicalTrials.gov), while higher in the LNZ groups, were not statistically significant [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The ESTABLISH-1 study aimed to evaluate the efficacy and safety profile of TDZ administered for 6 days at a therapeutic dose of 200 mg/day versus LNZ administered for 10 days at a dose of 600 mg twice daily in patients with skin and soft tissue infections. Low platelet counts (\u0026lt;\u0026thinsp;115,000/mm\u0026sup3;) (defined as 75% of the lower limit of normal or 75% of a patient's abnormally low baseline count) were observed in 2.3% of patients treated with TDZ and in 4.9% of patients in the LNZ group [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Although approximately half of the patients enrolled in the study were affected by hepatitis C, no data were published regarding the association between thrombocytopenia and hepatitis C infection [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the ESTABLISH-2 safety study, although a higher platelet limit (PLT\u0026thinsp;\u0026lt;\u0026thinsp;150,000/mm\u0026sup3;) was considered, thrombocytopenia rates between the two groups were still not statistically significant: 9% (27/314) in the TDZ group versus 13% (41/305) in the LNZ group [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, when combining data from ESTABLISH-1 and ESTABLISH-2, it was noted that between days 11 and 13, the rates of thrombocytopenia (defined as platelet counts\u0026thinsp;\u0026lt;\u0026thinsp;150,000 or \u0026lt;\u0026thinsp;100,000/mm\u0026sup3;) were significantly lower in the TDZ group compared to the LNZ group. In contrast, the incidence of thrombocytopenia between the two groups was not relevant between days 7 and 9 of treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. An important limitation of this analysis is that it was based on aggregated data from clinical trials and that TDZ therapy ended on day 6, while LNZ therapy continued until day 10. Possible explanations for the observed difference in thrombocytopenia rates are likely related to differences in dosage and administration schedules [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The role of LNZ exposure in the context of renal insufficiency remains a topic of discussion.\u003c/p\u003e"},{"header":"Clinical case","content":"\u003cp\u003eA 67-year-old patient diagnosed with myelodysplastic syndrome without blasts excess, presenting with grade 3 bone marrow fibrosis at onset, very high M-IPSS risk, with del(5q) and TP53 mutation (VAF 77%). The patient underwent treatment with 5 cycles of lenalidomide, followed by one cycle of azacitidine. After conditioning with treosulfan, thiotepa, and fludarabine, the patient received an allogeneic hematopoietic stem cell transplantation (HSCT) from a fully HLA-matched, ABO-compatible family donor using peripheral blood stem cells on 18/02/2025 (day 0). GVHD prophylaxis was initiated with anti-thymocyte globulin (Grafalon), methotrexate on days\u0026thinsp;+\u0026thinsp;1, +3, and +\u0026thinsp;6, and cyclosporine starting from day \u0026minus;\u0026thinsp;1, adjusted according to therapeutic drug monitoring (TDM). On day\u0026thinsp;+\u0026thinsp;4, during the aplastic phase, the patient developed fever. Blood cultures were obtained, and empiric broad-spectrum antibiotic therapy with piperacillin/tazobactam was initiated. Blood cultures were found positive for \u003cem\u003eCorynebacterium striatum\u003c/em\u003e; piperacillin/tazobactam was discontinued, and vancomycin monotherapy was started.\u003c/p\u003e\u003cp\u003eOn day\u0026thinsp;+\u0026thinsp;9, a new febrile episode occurred, associated with erythema, warmth, swelling, and pain in the right lower limb, accompanied by elevated inflammatory markers and CPK (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Doppler ultrasound excluded deep vein thrombosis (DVT). An urgent contrast-enhanced CT scan was performed with evidence of fascitis. Based on the imaging, vancomycin was continued and combined with meropenem and tedizolid (preferred over linezolid to minimize the risk of thrombocytopenia while maintaining inhibition of bacterial protein synthesis). The patient was evaluated multiple times by orthopedic specialists, who found no indication for surgical intervention. Transthoracic echocardiography showed no evidence of endocarditis. On day\u0026thinsp;+\u0026thinsp;30, a follow-up CT scan revealed a newly developed irregular fluid collection with loculated components in the posterolateral compartment of the right leg, measuring approximately 14\u0026times;25\u0026times;150 mm. Given the marked clinical and laboratory improvement, antibiotic therapy was discontinued on day\u0026thinsp;+\u0026thinsp;35 (Fig.\u0026nbsp;2). Despite concurrent antibiotic treatment with tedizolid, hematologic recovery occurred as follows: neutrophil count\u0026thinsp;\u0026gt;\u0026thinsp;1000/mm\u0026sup3; on day\u0026thinsp;+\u0026thinsp;20, platelet count\u0026thinsp;\u0026gt;\u0026thinsp;20,000/mm\u0026sup3; on day\u0026thinsp;+\u0026thinsp;21, \u0026gt;50,000/mm\u0026sup3; on day\u0026thinsp;+\u0026thinsp;26, and \u0026gt;\u0026thinsp;100,000/mm\u0026sup3; on day\u0026thinsp;+\u0026thinsp;40. On day\u0026thinsp;+\u0026thinsp;36, the patient developed acute graft-versus-host disease (aGVHD) grade I, involving the skin (stage 2), which subsequently progressed to grade II (skin stage 3). Treatment with methylprednisolone 2 mg/kg/day for 5 days led to a partial response. An ultrasound performed on day\u0026thinsp;+\u0026thinsp;44 showed resolution of the previously described collection. The patient was discharged home on day\u0026thinsp;+\u0026thinsp;49\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTDZ is a second generation oxazolidinone whose hematological safety profile appears to be improved compared to LNZ.\u003c/p\u003e\u003cp\u003eIndeed, current literature shows that TDZ administra tion is associated with a lower incidence of thrombocytopenia compared to LNZ. In the clinical case presented, the patient, who had undergone HSCT, was treated with TDZ for more than two weeks following the diagnosis of fasciitis, without any adverse effects. In this context, TDZ may represent a valuable therapeutic alternative, particularly in complex clinical scenarios such as hematologic patients, where the risk of drug induced cytopenias is a major concern and treatment options are often limited by hematological toxicity.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics declaration\u003c/strong\u003e\u003cp\u003eEthical approval was not required for this study as it describes a single clinical case. Written informed consent for publication was obtained from the patient.\u003c/p\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis research received no external funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLuca Montanari: main author wrote the manuscriptCarlo Tascini: authorMelissa Bergnah: author, prepare pictures 1 e 2Francesca Patriarca: reviewed the manuscriptChiara Cattaneo: reviewed the manuscriptFrancesco Marchesi: reviewed the manuscriptLivio Pagano: reviewed the manuscriptRenato Fanin: reviewed the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcBride D, Krekel T, Hsueh K, Durkin MJ (2017) Pharmacokinetic drug evaluation of tedizolid for the treatment of skin infections. Expert Opin Drug Metab Toxicol 13(3):331\u0026ndash;337\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e1080/17425255 (2017) 2017.1290080. 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Open Forum Infect Dis 9(12):ofac669\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7809956/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7809956/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Tedizolid (TDZ) is a second-generation oxazolidinone with potent activity against multidrug-resistant Gram-positive pathogens and a favorable hematologic safety profile compared to linezolid (LNZ). This review summarizes current evidence on TDZ pharmacokinetics, pharmacodynamics, and its reduced risk of thrombocytopenia. We also report a clinical case of a hematologic patient treated with TDZ for fasciitis after hematopoietic stem cell transplantation, achieving complete infection resolution without adverse hematologic effects. These findings support TDZ as a valuable therapeutic option in hematologic patients, where treatment choices are often limited by drug-induced cytopenias.","manuscriptTitle":"Thrombocytopenia and Tedizolid: A new ally in hematologic patients? 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