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NCT Number: NCT00438269

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

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.

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Key information

Conditions

Nosocomial Infection Body Temperature Changes Critical Illness Cross Infection Disease Attributes Fever Hematologic Diseases Hemic and Lymphatic Diseases Iatrogenic Disease Infections Inflammation Leukocyte Disorders Leukocytosis Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pyrexia Respiratory Tract Diseases Respiratory Tract Infections Shock Signs and Symptoms Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Site-specific empiric regimens included: Meropenem

Drug

Piperacillin/tazobactam

Drug

Ciprofloxacin and cefazolin +/- metronidazole

Drug

Primary outcomes

  1. Feasibility: = % of eligible patients who were consented and randomized

  2. Acceptability: = % of patients in each study arm who were switched to open label therapy prior to culture results

Secondary outcomes

  1. Mortality (14, 30, 90 day)

  2. Microbial resistance patterns

  3. ICU-free days

  4. Antibiotic-free days

  5. Change in organ dysfunction (MOD scores)

Sponsors and collaborators

Lead sponsor

Canadian Critical Care Trials Group

Other

Collaborators

  • The Physicians' Services Incorporated Foundation

Registry information

Official study title

Appropriate Antimicrobial Therapy in Critical Care: A Pilot Randomized Controlled Trial

Important dates

Study start
2003
Study completion
2005
First posted
Feb 22, 2007
Registry last updated
Feb 22, 2007

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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