Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)—an open-labelled pilot randomized controlled trial

Campbell, A.J., Dotel, R., Braddick, M., Britton, P.N., Eisen, D.P., Francis, J.R., Lynar, S., McMullan, B., Meagher, N., Nelson, J., O'Sullivan, M.V.N., Price, D.J., Robinson, J.O., Whelan, A., Tong, S.Y.C., Bowen, A.C., and Davis, J.S. (2022) Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)—an open-labelled pilot randomized controlled trial. JAC-Antimicrobial Resistance, 4 (1). dlac014.

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Abstract

Background: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs).

Objectives: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections.

Methods: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days.

Results: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome—number of days alive and free of systemic inflammatory response syndrome ≤14 days—was similar between groups: clindamycin (3 days [IQR 1–6]) versus standard therapy (4 days [IQR 0–8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes—microbiological relapse, treatment failure or diarrhoea—were similar between groups.

Conclusions: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

Item ID: 77646
Item Type: Article (Research - C1)
ISSN: 2632-1823
Copyright Information: ©The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 1131932, NHMRC APP1133670, NHMRC APP1175509, NHMRC 1145033
Date Deposited: 24 Mar 2023 06:35
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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