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

This study has been completed.
Sponsor:
Collaborator:
The Physicians' Services Incorporated Foundation
Information provided by:
Canadian Critical Care Trials Group
ClinicalTrials.gov Identifier:
NCT00438269
First received: February 17, 2007
Last updated: February 21, 2007
Last verified: February 2007
  Purpose

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
Pneumonia
Systemic Inflammatory Response Syndrome
Critical Illness
Pyrexia
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

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438269

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

No publications provided

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:
Infection
Empiric
Antibiotics
Nosocomial
Pyrexia
Leukocytosis
Resistance

Additional relevant MeSH terms:
Critical Illness
Fever
Pneumonia
Cross Infection
Systemic Inflammatory Response Syndrome
Disease Attributes
Pathologic Processes
Body Temperature Changes
Signs and Symptoms
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Infection
Inflammation
Shock
Anti-Bacterial Agents
Cefazolin
Piperacillin
Meropenem
Piperacillin-tazobactam combination product
Penicillanic Acid
Antibiotics, Antitubercular
Ciprofloxacin
Metronidazole
Tazobactam
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014