Report

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

Authors: Scawn N, Saul D, Pathak D, Matata B, Kemp I, Stables R, Lane S, Haycox A, Houten R

Journal: Health Technology Assessment Volume: 16 Issue: 36

Publication date: October 2012

DOI: 10.3310/hta16360

Citation:

Scawn N, Saul D, Pathak D, Matata B, Kemp I, Stables R, et al.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. Health Technol Assess 2012;16(36)


Journal issues* can be purchased by completing the form.


The cost of reports varies according to number of pages and postage address. The minimum cost for a copy sent to a UK address is £30.00. We will contact you on receipt of your completed form to advise you of actual cost. If you have any queries, please contact nihredit@southampton.ac.uk.


*We regret that unfortunately we are unable to supply bound print copies of Health Technology Assessment published before issue 12:31. However, PDFs are available to print from the "Downloads" tab of the issue page.

Responses

No responses have been published. If you would like to submit a response to this publication, please do so using the form below.

Comments submitted to the NIHR Journals Library are electronic letters to the editor. They enable our readers to debate issues raised in research reports published in the Journals Library. We aim to post within 2 working days all responses that contribute substantially to the topic investigated, as determined by the Editors.

Your name and affiliations will be published with your comment.

Once published, you will not have the right to remove or edit your response. The Editors may add, remove, or edit comments at their absolute discretion.

Post your response

Surname

Forename

Middle Initial

Occupation / Job title

Affiliation / Employer

Email

Address

Other authors

For example, if you are responding as a team or group. Please ensure you include full names and separate these using commas

Statement of competing interests

We believe that readers should be aware of any competing interests (conflicts of interest).

The International Committee of Medical Journal Editors (ICMJE) define competing interests as including: financial relationships with industry (for example through employment, consultancies, stock, ownership, honoraria, and expert testimony), either directly or through immediate family; personal relationships; academic competition; and intellectual passion.

If yes, provide details below:

Enter response title

Enter response message

Enter CAPTCHA

Security key

Regenerate security key

By submitting your response, you are stating that you agree to the terms & conditions

  • Abstract

Abstract

Background

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.

Objective

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.

Design

A pilot, single-centre, open-label randomised trial.

Setting

This study was carried out in the ICU of a tertiary heart and chest hospital.

Participants

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.

Interventions

Broad-spectrum antibiotic treatment administered for 48 hours (experimental) compared with treatment for 7 days (control).

Main outcome measures

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.

Results

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 during the trial period received no additional antibiotics in excess of their trial allocation. There were no documented incidences of MRSA or C. difficile infection in either group. No significant differences in adverse events were observed between the groups. Key economic findings were mean antibiotic costs per patient of £168.97 for the 2-day group and £375.86 for the 7-day group. The potential per annum cost saving for the ICU of 2-day treatment was estimated to range from £108,140 to £126,060. Patient screening was considered the biggest barrier to recruitment. There was no crossover between the two randomised groups. Data verification ascertained > 98% accuracy in data collection. Baseline procalcitonin was found to be predictive of the composite outcome (death and needing further antibiotics) (odds ratio 1.79, 95% CI 1.20 to 2.67; p = 0.005). Analysis of baseline procalcitonin also indicated a trend towards it being a predictor of restarting antibiotics, with an odds ratio of 1.45 (95% CI 1.04 to 2.02; p = 0.01).

Conclusions

Data from this pilot study suggest that there could be significant benefits of reducing broad-spectrum antibiotic use in the ICU without it undermining patient safety, with a potential cost saving in our unit of over £100,000 per year. Evidence from this pilot trial is not definitive but warrants further investigation using a large randomised controlled trial.

Trial registration

Current Controlled Trials ISRCTN82694288.

Funding

This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 36. See the HTA programme website for further project information.

Publication updates

If you would like to receive information on publications and the latest news, click below to sign up.