Tedizolid phosphate for the treatment of acute bacterial skin and skin-structure infections: an evidence-based review of its place in therapy

Figures & data

Table 1 Core evidence clinical impact summary for tedizolid phosphate for the treatment of ABSSSI

Outcome measure	Evidence	Implications
Disease-oriented evidence Early clinical response	Randomized, doubleblind, noninferiority clinical trial	6-day once-daily oral tedizolid noninferior to 10-day twice-daily oral linezolid for ABSSSI; similar results observed when tedizolid and linezolid administered intravenously, with optional oral stepdown
Patient-oriented evidence Safety	Randomized, doubleblind, noninferiority clinical trial	Most frequent adverse events in randomised clinical trials nausea and headache;serious adverse events rare; pooled data from ESTABLISH-1 and ESTABLISH-2 indicated lower frequency of thrombocytopenia in tedizolid-treated than linezolid-treated patients
Economic evidence Net benefit	High-level evidence still unavailable, although potential saving over line- zolid for the treatment of ABSSSI has been suggested in a simulated cohort	Economic analyses warranted to optimize the use of tedizolid and maximize its advantages for treatment of ABSSSI (eg, short duration of treatment, activity against some linezolid-resistant MRSA isolates, reduced toxicity)

Table 2 Mean (SD) tedizolid pharmacokinetic parameters

Dose	200 mg OD IV/PO
Cmax (mg/L) IV	3±0.7
Cmax (mg/L) PO	2.2±0.7
hours	12
AUC (mg*h/L) IV	29.2±6.2
AUC (mg*h/L) PO	25.6±8.5
Protein binding	70%-90%
Excretion	Inactive metabolite 80% in feces 20% in urine
Need for renal adjustment	No
Need for hepatic adjustment	No

Figure 1 Potential algorithm for considering tedizolid-based early switch (ES) to oral therapy and early discharge (ED) in patients with ABSSI.

Note: Potential predictors of MRSA and factors indicating suitability for ES/ED have been extrapolated from the literature; data from references 54 and 55.

Abbreviations: ABSSSI, acute bacterial skin and skin-structure infection; LRINEC, laboratory risk indicator for necrotizing fasciitis; MRSA, methicillin resistant Staphylococcus aureus; WBCs, white blood cells.

Table 3 Potential use of tedizolid in off-label indications and related preliminary evidence

Off-label indication	Evidence
Pneumonia	• A noninferiority phase III, randomized, double-blind, double-dummy, controlled clinical trial (NCT02019420) comparing once-daily intravenous tedizolid (200 mg) vs twice-daily intravenous linezolid (600 mg) for 10 days for the treatment of presumed Gram-positive hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia has been recently completed, and results are awaited.
	• In neutropenic immunocompetent mice inoculated intranasally with Staphylococcus aureus isolates, simulation of human ELF exposure to tedizolid demonstrated greater bacterial reductions than vancomycin.^62
	• In a rabbit model of MRSA pneumonia, production of α-toxin and Panton-Valentine leukocidin was significantly inhibited when rabbits were treated with tedizolid or linezolid compared with vancomycin.^63
	• Tedizolid and linezolid showed antimicrobial and immunomodulatory properties in a murine model of hematogenous MRSA pulmonary infection.^61
Osteomyelitis and prosthetic joint infections	• A phase II, single-arm, open-label trial evaluating tolerability, safety, and efficacy of oral tedizolid for the treatment of bone and joint infections is ongoing (NCT03009045).
	• A pilot study investigating tolerance, compliance, and efficacy of tedizolid for ≥6 weeks as monotherapy or in combination for orthopedic device infections caused by Gram-positive cocci is currently recruiting patients (NCT03378427).
	• A case of successful treatment of VRE prosthetic joint infection has been reported.^66
	• Although inactive against biofilm-embedded S. aureus infection in the setting of bone and joint infections, tedizolid seems able to prevent biofilm formation.^59
CNS infections	• A successful 6-month course of tedizolid therapy for CNS nocardiosis in a multiple myeloma patient has been described, without additional myelotoxicity being reported.^64
Diabetic foot infection	• Plasma and tissue exposure observed in in hospitalized patients with diabetic foot infections after 200 mg once-daily tedizolid may support further study for this indication.^67
Catheter-related infection	• In a murine model of subcutaneous MRSA and MSSA catheter-related biofilm infection, a better response in terms of decreased S.aureus density and bioluminescent signals after treatment with tedizolid than with linezolid has been observed.^60
Mycobacterial diseases	• Preliminary data on long-term safety in a small sample of 24 patients have been presented in scientific 68congresses.

Bassetti M, Baguneid M, Bouza E, Dryden M, Nathwani D, Wilcox M. European perspective and update on the management of complicated skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid. Clin Microbiol Infect. 2014;20(Suppl 4):3–18. doi:10.1111/1469-0691.12463

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