Tedizolid Versus Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infection: A Systematic Review and Meta-Analysis

Abstract

This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were accessed until 18 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of tedizolid with linezolid for adult patients with ABSSSIs were included. The outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of four RCTs involving 2056 adult patients with ABSSSI were enrolled. The early clinical response rate was 79.6% and 80.5% for patients receiving tedizolid and linezolid, respectively. The pooled analysis showed that tedizolid had a non-inferior early clinical response rate to linezolid (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.77–1.19, I2 = 0%). The early response rate was similar between tedizolid and linezolid among patients with cellulitis/erysipelas (75.1% vs. 77.1%; OR = 0.90, 95% CI = 0.64–1.27, I2 = 25%), major cutaneous abscess (85.1% vs. 86.8%; OR = 0.93, 95% CI = 0.42–2.03, I2 = 37%) and wound infection (85.9% vs. 82.6%; OR = 1.29, 95% CI = 0.66–2.51, I2 = 45%). For methicillin-resistant Staphylococcus aureus patients, tedizolid had a favorable microbiological response rate of 95.2% which was comparable to linezolid (94%) (OR = 1.19, 95% CI = 0.49–2.90, I2 = 0%). In addition to the similar risk of treatment-emergent AEs (a serious event, the discontinuation of the study drug due to AEs and mortality between tedizolid and linezolid), tedizolid was associated with a lower risk of nausea, vomiting and abnormal neutrophil count than linezolid. In conclusion, once-daily tedizolid (200 mg for six days) compared to linezolid (600 mg twice-daily for 10 days) was non-inferior in efficacy in the treatment of ABSSSI. Besides, tedizolid was generally as well tolerated as linezolid, and had a lower incidence of gastrointestinal AEs and bone marrow suppression than linezolid.

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

“…We hypothesise that the increase of haemoglobin values during TZD treatment represents a restoration process after blood spoliation secondary to the surgical intervention, while the decrease of platelets and WBC during TZD treatment might be related to the resolution of the infectious process. The incidence of digestive disorders reported in our patients is close to the results of a meta-analysis by Lan et al, noting, however, that the duration of TZD therapy in the studies included was six days, as recommended for the treatment of acute bacterial skin and skin structure infections [ 29 ].…”

Safety and Tolerability of More than Six Days of Tedizolid Treatment

“…Gastrointestinal (GI) disorders (nausea, diarrhea, and vomiting) and myelotoxicity were less frequent in tedizolid than in the linezolid arm (3,4). A recent meta-analysis of four randomized CTs involving 2,056 patients, comparing the efficacy of linezolid versus tedizolid for the treatment of ABSSSI, reconfirmed the previous results (5). The potent activity against Gram-positive cocci (6)(7)(8), high oral bioavailability, improved dosage profile (once daily), the expected lower risk of drug-drug interactions (9,10), and a better safety profile at 6 days of treatment compared to linezolid makes tedizolid an attractive alternative for infections that require longer periods of antibiotic treatment, such as bone and joint infections or mycobacterial infections, among others.…”

“…In line with this, our study included a heterogeneous population of patients, very different from that evaluated in the pivotal clinical trials of tedizolid. The main reason for selecting tedizolid instead of linezolid was toxicity (4,5,12). Interestingly, 22 patients (27.2%) had previous linezolid-associated toxicities that motivated the tedizolid prescription, and 20 did not report AEs.…”

Comparative Efficacy and Safety of Vancomycin, Linezolid, Tedizolid, and Daptomycin in Treating Patients with Suspected or Proven Complicated Skin and Soft Tissue Infections: An Updated Network Meta-Analysis

“…Although some clinical studies have been performed to investigate the role of linezolid, daptomycin, and tedizolid in treating SSTIs [11][12][13], conflicting results directly limited the clinical decision. Several meta-analyses have also been conducted to systematically determine the optimal regime for SSTIs; however, a conclusive finding has not yet been generated [1,[14][15][16]. Compared to traditional head-tohead meta-analysis, which only can perform a single comparison at a time, network metaanalysis has been developed and then extensively applied in practice because this method can simultaneously combine multiple evidence including direct and indirect evidence estimated from the available direct comparisons to generate more reliable and robust findings [17].…”