Comparative efficacy and safety of antibiotics used to treat acute bacterial skin and skin structure infections: Results of a network meta-analysis

Abstract

ObjectiveThis NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI.MethodsComparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality.ResultsStudy interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline.ConclusionDalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes.

Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases

“…Linezolid, an oxazolidinone antibiotic, is indicated for the treatment of infectious diseases and has become widely used with the increasing prevalence of multidrug‐resistant gram‐positive bacteria . Linezolid‐induced thrombocytopenia is an important side effect to be considered when assessing the safe use of this medication and the associated risks of gastrointestinal and intracranial haemorrhage, and thus, mortality …”

Economic evaluation of the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) from the national payer perspective: introduction of a new treatment to the patient journey. A simulation of three European countries

“…The nephrotoxicity [40]. Dalbavancin has a better potential tolerability profile than other therapies for ABSSSIs, and it has been recommended by a recently published meta-analysis [41].…”

Antibiotic therapy for skin and soft tissue infections: a protocol for a systematic review and network meta-analysis

“…Previous NMAs have had several weaknesses, which limit our confidence in their results and their implications for the clinical management of SSTIs. They were restrictive in their searches (by antibiotics and infection types), had limited generalizability, and were poorly conducted (e.g., screening and data extraction was not completed in duplicate, did not explore potential sources of heterogeneity and bias, and did not assess the overall quality of evidence) [ 18 – 21 ]. The proposed NMA will have several methodological strengths: (1) inclusion of a wider range of antibiotics and infection types; (2) a comprehensive search strategy; (3) screening and data extraction will be completed in duplicate by independent reviewers; (4) inclusion of a wider range of outcomes (e.g., duration of antibiotic treatment and hospital stay); (5) exploration of heterogeneity based on a priori subgroups and meta-regression, if possible; (6) application of GRADE to assess our certainty in the evidence; and (7) ease of interpretability of the comparative effectiveness of antibiotics (e.g., through presentation of results in league tables, cumulative probability rankograms, SUCRA curves, and/or a rank-heat plot).…”

“…We are aware of four related NMAs that have been conducted in the last decade; however, they were limited in the antibiotics and infection types studied, generalizability and methodological rigor [ 18 – 21 ]. To the best of our knowledge, there has been no review as comprehensive as the one proposed.…”