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Published in: Trials 1/2019

Open Access 01-12-2019 | Flucloxacillin | Study protocol

CASSETTE—clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: study protocol for a randomised controlled trial

Authors: Ravindra Dotel, Steven Y. C. Tong, Asha Bowen, Jane N. Nelson, Matthew V. N. O’Sullivan, Anita J. Campbell, Brendan J. McMullan, Philip N. Britton, Joshua R. Francis, Damon P. Eisen, Owen Robinson, Laurens Manning, Joshua S. Davis

Published in: Trials | Issue 1/2019

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Abstract

Background

Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking.

Methods

An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to β-lactams or lincosamides will be excluded.
The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed.

Discussion

This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12617001416​381p. Registered on 6 October 2017.
Appendix
Available only for authorised users
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Metadata
Title
CASSETTE—clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: study protocol for a randomised controlled trial
Authors
Ravindra Dotel
Steven Y. C. Tong
Asha Bowen
Jane N. Nelson
Matthew V. N. O’Sullivan
Anita J. Campbell
Brendan J. McMullan
Philip N. Britton
Joshua R. Francis
Damon P. Eisen
Owen Robinson
Laurens Manning
Joshua S. Davis
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-019-3452-y

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