A pilot randomised controlled trial in intensive care patients comparing 7 days' treatment with empirical antibiotics with 2 days' treatment for hospital-acquired infection of unknown origin

• Published in: Health technology assessment (Winchester, England) England), 2012-09, Vol.16 (36), p.i-xiii
• Main Authors: Scawn, N, Saul, D, Pathak, D, Matata, B, Kemp, I, Stables, R, Lane, S, Haycox, A, Houten, R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - therapeutic use; antibiotics; Biomarkers; Chi-Square Distribution; Critical Illness; Cross Infection - drug therapy; Female; hospital-acquired infection; Humans; Iatrogenic Disease - prevention & control; intensive care unit; Intensive Care Units; Male; Middle Aged; Pilot Projects; randomised controlled trial; Risk Factors; sepsis; systematic inflammatory response syndrome; Time Factors
• ISSN: 1366-5278; 2046-4924
• DOI: 10.3310/hta16360

Management of cardiac intensive care unit (ICU) sepsis is complicated by the high incidence of systemic inflammatory response syndrome, which mimics sepsis but without an infective cause. This pilot randomised trial investigated whether or not, in the ICU, 48 hours of broad-spectrum antibiotic treatment was adequate to safely treat suspected sepsis of unknown and unproven origin and also the predictive power of newer biomarkers of sepsis. The main objective of this pilot study was to provide preliminary data on the likely safety and efficacy of a reduced course of antibiotics for the treatment of ICU infections of unknown origin. A pilot, single-centre, open-label randomised trial. This study was carried out in the ICU of a tertiary heart and chest hospital. Patients being treated within the ICU were recruited into the trial if the intensivist was planning to commence antibiotics because of evidence of systemic inflammatory response syndrome and a strong suspicion of infection but there was no actual known source for that infection. Broad-spectrum antibiotic treatment administered for 48 hours (experimental) compared with treatment for 7 days (control). The primary outcome was a composite outcome of the rate of death or initiation of antibiotic therapy after the completion of the treatment schedule allocated at randomisation. Secondary outcomes included the duration of mechanical ventilation and ICU and hospital stay; the incidence of infection with Clostridium difficile (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008, or methicillin-resistant Staphylococcus aureus (MRSA) (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008; resource utilisation and costs associated with each of the two pilot arms; the ratio of patients screened to patients eligible to patients randomised; the incidence of crossover between groups; and the significance of newer biomarkers for sepsis for predicting patients' need for further antibiotics. A total of 46 patients were recruited into the trial, with 23 randomised to each group. There was no significant difference between the two groups in terms of the composite primary outcome measure. The risk difference was 0.12 [95% confidence interval (CI) 0.11 to 0.13; p = 0.3]. In the 2-day group, four patients (17.4%) required further antibiotics compared with three (13%) in the 7-day group. Four patients died within the trial period and the deaths were not trial related. Patients who died d