Which trial do we need? Optimal antibiotic duration for patients with sepsis

Randomized controlled trials (RCTs) are the reference standard for evidence-based medicine. However, conducting trials in the critically ill is often challenging because of small patient numbers, heterogeneity of populations and disease states, non-uniform ‘usual’ care, ethical concerns surrounding informed consent, and narrow windows for screening, enrolment, and intervention [ [1] Granholm A. Alhazzani W. Derde L.P.G. Angus D.C. Zampieri F.G. Hammond N.E. et al. Randomised clinical trials in critical care: past, present and future. Intens Care Med. 2022; 48: 164-178https://doi.org/10.1007/s00134-021-06587-9 Crossref PubMed Scopus (32) Google Scholar ]. Yet it is precisely in such high-stake settings that evidence to guide clinical decisions is paramount. In the field of infectious diseases, data from critically ill populations are largely limited to observational, retrospective studies at high risk of bias [ [2] Busch L.M. Kadri S.S. Antimicrobial treatment duration in sepsis and serious infections. J Infect Dis. 2020; 222: S142-S155https://doi.org/10.1093/infdis/jiaa247 Crossref PubMed Google Scholar ]. Without a strong evidence base to build upon, contemporary guidelines rarely address critical illness manifestations of common infectious syndromes (Table 1). Table 1Antibiotic treatment duration and consideration of critically ill populations in professional society guidance documents addressing common bacterial infectious diseases and syndromes (2010–2022) Infectious disease/syndrome Guidance document Duration of antibiotic course Consideration of critically ill populations Sepsis Surviving Sepsis Campaign 2021 ‘Shorter over longer’ Recommendation addresses sepsis and septic shock Community-acquired pneumonia (CAP) ATS/IDSA 2019 5 d; 7 d for methicillin-resistant S. aureus or P. aeruginosa Expert opinion: same durations apply for severe CAP Healthcare-associated ventriculitis and meningitis IDSA 2017 10–14 d; up to 21 d for gram-negative bacilli No Hospital-acquired or ventilator-associated pneumonia IDSA 2016 7 d Recommendation addresses mechanical ventilation Endocarditis AHA 2015 2–4 wk for Streptococci, 4–6 wk for Enterococci, 4–6 wk for HACEK organisms (Haemophilus spp, Aggregatibacter spp, C. hominis, E. corrodens, Kingella spp), 6 wk for S. aureus; longer if prosthetic material present No Vertebral osteomyelitis IDSA 2015 6 wk; 3 mo for Brucella No Skin and soft tissue infections IDSA 2015 24–48 h of adjunctive therapy for surgical site infections associated with systemic signs of infection; 5 d for cellulitis and erysipelas; necrotizing fasciitis treated until debridement no longer necessary; 2–3 wk for pyomyositis No Prosthetic joint infection IDSA 2013 24–48 h after amputation; 4–6 wk if infection remains after debridement Treatment durations for septic/bacteraemic patients ‘according to recommendations for these syndromes’ Diabetic foot infection IDSA 2012 2–5 d after debridement; ≥4 wk if infection remains after debridement No Cystitis IDSA/ESCMID 2011 Single-dose Fosfomycin, 3 d quinolone or trimethoprim-sulfamethoxazole, 3–5 d beta-lactam, 5–7 d nitrofurantoin No Pyelonephritis IDSA/ESCMID 2011 5–7 d quinolone, 10–14 d beta-lactam, 14 d trimethoprim-sulfamethoxazole No Catheter-associated urinary tract infection IDSA 2010 7 d; 10–14 d if delayed response No Intra-abdominal infection SIS/IDSA 2010 4–7 d No AHA = American Heart Association; ATS = American Thoracic Society; ESCMID = European Society of Clinical Microbiology and Infectious Diseases; IDSA = Infectious Diseases Society of America; SIS = Surgical Infection Society. Open table in a new tab AHA = American Heart Association; ATS = American Thoracic Society; ESCMID = European Society of Clinical Microbiology and Infectious Diseases; IDSA = Infectious Diseases Society of America; SIS = Surgical Infection Society.