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.
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.
| Original language | English |
|---|---|
| Article number | dlac014 |
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | JAC-Antimicrobial Resistance |
| Volume | 4 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 17 Feb 2022 |
Bibliographical note
Funding Information:This work was supported by a National Health and Medical Research Council HOT NORTH grant (grant number 1131932), a Telethon Kids Institute, Wesfarmers Centre for Vaccines and Infectious Diseases Seed Fund grant, a National Health and Medical Research Council PhD scholarship to A.J.C (grant number APP1133670), National Health and Medical Research Council fellowship to A.C.B (grant number APP1175509) and a National Health and Medical Research Council fellowship to S.Y.C.T. (grant number 1145033).
Publisher Copyright:
© 2022 The Author(s).
