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, ACTRN12617001416381p . Registered on 6 October 2017.