Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection

This study has been completed.
The Physicians' Services Incorporated Foundation
Information provided by:
Canadian Critical Care Trials Group
ClinicalTrials.gov Identifier:
First received: February 17, 2007
Last updated: February 21, 2007
Last verified: February 2007

Infection developing in the intensive care unit is a common complication of critical illness, but notoriously difficult to diagnose. A definite diagnosis based on the most reliable tests usually is not possible for at least two days. It is unclear what the optimal management approach should be while awaiting the results of diagnostic tests. In some circumstances, broad spectrum antibiotics are started with a plan to adjust them once the results of cultures are available. Observational studies show that this results in greater antibiotic use, and the risk of superinfection and resistance. In other circumstances, antibiotics may be withheld pending the results of cultures, a strategy that leads to a delay in therapy when cultures are positive, and that may be associated with a worse clinical outcome.

We undertook a randomized pilot study to address the question: "In a critically ill patient for whom clinicians are uncertain whether infection may be present, and in whom potential sites of infection have been managed by removing or changing invasive devices, can a policy of delaying antibiotic treatment until cultures are available reduce the risks of excessive antibiotic use, without increasing the risks associated with delayed therapy?"

Recognizing that the question has not been formally addressed before, and that approaches to clinical management are both widely divergent and passionately held, our pilot study tested the feasibility and acceptability of undertaking a larger trial with sufficient power to determine equivalence.

Condition Intervention Phase
Nosocomial Infection
Systemic Inflammatory Response Syndrome
Critical Illness
Drug: Site-specific empiric regimens included: Meropenem
Drug: Piperacillin/tazobactam
Drug: Ciprofloxacin and cefazolin +/- metronidazole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Appropriate Antimicrobial Therapy in Critical Care: A Pilot Randomized Controlled Trial

Resource links provided by NLM:

Further study details as provided by Canadian Critical Care Trials Group:

Primary Outcome Measures:
  • Feasibility: = % of eligible patients who were consented and randomized
  • Acceptability: = % of patients in each study arm who were switched to open label therapy prior to culture results

Secondary Outcome Measures:
  • Mortality (14, 30, 90 day)
  • Microbial resistance patterns
  • ICU-free days
  • Antibiotic-free days
  • Change in organ dysfunction (MOD scores)

Estimated Enrollment: 80
Study Start Date: February 2003
Estimated Study Completion Date: March 2005
Detailed Description:

We randomized critically ill patients who had been in hospital for at least 72 hours, and in the ICU for at least 24 hours, and who manifested either a temperature >38.5 degrees, or a temperature>38.0 degrees and a white cell count >12,000, and in whom clinicians entertained the possibility of infection as a diagnosis, to either site-specific broad spectrum empiric antibiotics or the corresponding placebo. All patients underwent a comprehensive series of investigations to identify an infectious focus, and all patients had full source control, including changes of central lines and urinary catheters, and change of nasogastric to orogastric tubes.

Patients were maintained in assigned study arm for seven days, or until culture data were available, at which time they were switched to culture-guided narrow spectrum therapy


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • In hospital > 72 hrs and in ICU > 24hrs, and
  • Core temperature ≥38.5°C, or temperature ≥ 38.0°C with a WBC>12,000/mm3, or temperature ≤ 36.0°C with a WBC > 12,000/mm3
  • Suspicion of infection

Exclusion Criteria:

  • Age < 18 years
  • Imminent death (within 24 hrs) or withdrawal of aggressive therapy
  • Prosthetic heart valve or vascular graft
  • Neutropenia (Absolute neutrophil count < 1000/mm3)
  • Received > 16 hours of a broad spectrum antibiotic in the last 24 hours (3rd gen cephalosporin, fluoroquinolone, carbapenem, anti-pseudomonal penicillin) or any combination therapy
  • History of allergic reaction to both study medications
  • New physical findings consistent with infection:

    • Meningeal signs
    • Peritonitis + free air on Abdo x-ray
    • Soft tissue infection / cellulitis
    • Murmur & suspicion of endocarditis
  • Newly available (within past 24 hours) culture results consistent with infection
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00438269

Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
Canadian Critical Care Trials Group
The Physicians' Services Incorporated Foundation
Principal Investigator: Mary-Anne W Aarts, MD MSc University of Toronto
Principal Investigator: John C Marshall, MD University of Toronto
  More Information

ClinicalTrials.gov Identifier: NCT00438269     History of Changes
Other Study ID Numbers: AATICC Pilot Study 
Study First Received: February 17, 2007
Last Updated: February 21, 2007
Health Authority: Canada: Health Canada

Keywords provided by Canadian Critical Care Trials Group:

Additional relevant MeSH terms:
Critical Illness
Cross Infection
Systemic Inflammatory Response Syndrome
Disease Attributes
Iatrogenic Disease
Pathologic Processes
Penicillanic Acid
Piperacillin, tazobactam drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Beta-Lactamase Inhibitors
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on May 26, 2016