Network meta-analysis and pharmacoeconomic evaluation of antibiotics for the treatment of patients infected with complicated skin and soft structure infection and hospital-acquired or ventilator-associated penumonia

Abstract

Background Infections due to methicillin-resistant Staphylococcus aureus ( MRSA) cause serious health risks and significant economic burdens and the preferred drugs are still controversial. Methods We performed a network meta-analysis (NMA) to compare the efficacy and safety of antibiotics used to treat inpatients with complicated skin and soft structure infections (cSSSI) or hospital-acquired or ventilator-associated pneumonia (HAP/VAP). We also developed a decision tree model to assess the cost-effectiveness of antibiotics. Results Forty-nine randomized controlled trials met the inclusion criteria (34 for cSSSI, 15 for HAP/VAP) and compared the efficacy and safety of 16 antibiotics. For cSSSI, NMA indicated that for clinical cure, linezolid was superior than vancomycin (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.19–2.02), while tedizolid (OR 1.39, CI 0.70–2.76) was similar to vancomycin. In terms of safety, there were no significant differences between any two interventions on total adverse events. Based on drug and hospital costs in America, the incremental cost-effectiveness ratios (ICERs) per life-year saved for linezolid and tedizolid compared with vancomycin were US$2833 and US$5523. For HAP/VAP, there were no significant effects either for clinical cure or for safety endpoints between linezolid and vancomycin in NMA. ICERs per life-year saved for linezolid compared with vancomycin were US$2185. Conclusion In these clinical trials, considering efficacy, safety, and cost-effectivenes, linezolid and tedizolid showed their superiority in MRSA cSSSI; while linezolid might be recommended to treat MRSA pneumonia. Although vancomycin was not cost-effective in pharmacoeconomic evaluation, it is still the first-line treatment for MRSA infection in the clinical practice. This study might provide new insights of therapeutic choices for patients with MRSA infections whilst awaiting the arrival of higher quality evidence. Electronic supplementary material The online version of this article (10.1186/s13756-019-0518-2) contains supplementary material, which is available to authorized users.

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

“…According to the previous meta-analysis [ 16 ], we designed the following selection criteria: (1) adult patients who were diagnosed with suspected or confirmed MRSA-related infections; (2) patients who were instructed to orally or parenterally use antibiotics with anti-MRSA activity; (3) only randomized controlled trials (RCTs) were considered eligible. Moreover, we only considered the latest study with more sufficient data when a series of studies had been published by the same research group based on the same sample.…”

“…Clinical success was evaluated to be cured and improved status at test of cure (TOC) in the modified intention-to-treat (mITT) population, which was defined as the randomized patients receiving at least one dose of the study drug. Cured was defined as resolution of the clinical signs and symptoms of infection compared with baseline; improved was defined as improvement in two or more, but not all, clinical signs and symptoms of infection compared with baseline [ 16 ].…”

“…According to the previous meta-analysis [16], we designed the following selection criteria: (1) adult patients who were diagnosed with suspected or confirmed MRSA-related infections;…”

“…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].…”

“…Compared to traditional head-to-head meta-analysis, which only can perform a single comparison at a time, network meta-analysis 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 ]. Although two network meta-analyses [ 14 , 16 ] have also partially considered this topic, we must recognize that some limitations such as an insufficient number of eligible studies have impaired the reliability and robustness of pooled results. Therefore, we performed this updated network meta-analysis to compare these four different antibiotics including vancomycin, linezolid, tedizolid, and daptomycin used for the treatment of MRSA SSTIs to further determine which should be preferentially prescribed.…”