Oral minocycline plus rifampicin versus oral linezolid for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus : The AIDA open label, randomized, controlled Phase 4 trial.
| Autor: | Kotsaki A; 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Hellenic Institute for the Study of Sepsis, Athens, Greece., Tziolos N; 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Hellenic Institute for the Study of Sepsis, Athens, Greece., Kontopoulou T; 5th Department of Internal Medicine, Evangelismos Athens General Hospital, Athens, Greece., Koutelidakis IM; 2nd Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece., Symbardi S; 1st Department of Internal Medicine, Thriasio General Hospital of Eleusis, Magoula, Greece., Reed V; Micron Research Ltd, 109B Lancaster Way, Ely CB6 3NX, United Kingdom., O'Hare M; Micron Research Ltd, 109B Lancaster Way, Ely CB6 3NX, United Kingdom., Alexiou Z; 2nd Department of Internal Medicine, Thriasio General Hospital of Eleusis, Magoula, Greece., Sambatakou H; 2nd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Toutouzas K; 1st Department of Propedeutic Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Akinosoglou K; Department of Internal Medicine, Medical School, University of Patras, Rion, Greece., Lada M; 2nd Department of Internal Medicine, Sismanogleion General Hospital, Athens, Greece., Giamarellos-Bourboulis EJ; 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Hellenic Institute for the Study of Sepsis, Athens, Greece., MacGowan A; Bristol Centre for Antimicrobial Research & Evaluation (BCARE), Infection Sciences, Science Quarter, Southmead Hospital, Bristol BS10 5NB, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | EClinicalMedicine [EClinicalMedicine] 2022 Dec 26; Vol. 56, pp. 101790. Date of Electronic Publication: 2022 Dec 26 (Print Publication: 2023). |
| DOI: | 10.1016/j.eclinm.2022.101790 |
| Abstrakt: | Background: The need for oral, cost-effective treatment for complicated skin and skin structure infections (cSSSIs) due to methicillin-resistant Staphylococcus aureus (MRSA) was addressed by the non-inferiority comparisons of oral minocycline plus rifampicin with linezolid. Methods: In the AIDA multicenter, open label, randomized, controlled clinical trial, hospitalized adults with cSSSI and documented MRSA were randomly assigned at a 2:1 ratio to either oral 600 mg rifampicin qd plus 100 mg minocycline bid or oral 600 mg linezolid bid for 10 days. The primary endpoint was the clinical cure rate in the clinically evaluable (CE) population at the test-of-cure visit (14 days). Non-inferiority was confirmed if the lower confidence limit (CI) did not fall below the accepted error margin of 15%. The study is registered with EudraCT number 2014-001276-56. Findings: 123 patients recruited between November 2014 and January 2017 were randomly assigned to treatment (81 patients to minocycline plus rifampicin and 42 patients to linezolid). Cure rates were 78.% (46/59, 90% CI 67.3-86.5) and 68.6% (24/35, 90% CI 53.4-81.3), respectively ( P = 0.337). The percent difference in cure rates was 9.4% (90% CI -7.2 to 26.8%). Minocycline plus rifampicin combination was deemed non-inferior to linezolid as the lower CI was -7.2% i.e. smaller than the accepted error margin of -15%. Although statistically not significant, the overall rate of adverse events was higher in the linezolid group (47.6%, 20/42 versus 38.3%, 31/81). Interpretation: Oral minocycline plus rifampicin was non-inferior to oral linezolid treatment providing alternative oral treatment for cSSSI. Funding: The EU Seventh Research Framework Programme. Competing Interests: Helen Sambatakou has received honoraria from MSD Greece, Elpen Hellas, Mylan Hellas and Pfizer Greece. E.J. Giamarellos-Bourboulis has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and XBiotech Inc; independent educational grants from Abbott CH, AxisShield, bioMérieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi and XBiotech Inc.; and funding from the Horizon2020 Marie Skłodowska-Curie International Training Network “the European Sepsis Academy” (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis). Alasdair MacGowan has research grants/activities with the following: Merck, Shionogi, Venatorx, InfectoPharm, GSK, Bioversys, MRC (UK), NIHR (UK). All other authors declare no competing interests. (© 2022 The Authors.) |
| Databáze: | MEDLINE |
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