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

Critical Illness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00438269
• Other study ID #: AATICC Pilot Study
• Status: Completed
• Phase: Phase 2
• First received: February 17, 2007
• Last updated: February 21, 2007
• Start date: February 2003
• Est. completion date: March 2005

Study information

• Verified date: February 2007
• Source: Canadian Critical Care Trials Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Cross Infection
• Infection
• Nosocomial Infection
• Pneumonia
• Pyrexia
• Systemic Inflammatory Response Syndrome

Intervention

Drug:
• Site-specific empiric regimens included: Meropenem

• Piperacillin/tazobactam

• Ciprofloxacin and cefazolin +/- metronidazole

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Canadian Critical Care Trials Group	The Physicians' Services Incorporated Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility: = % of eligible patients who were consented and randomized
Primary	Acceptability: = % of patients in each study arm who were switched to open label therapy prior to culture results
Secondary	Mortality (14, 30, 90 day)
Secondary	Microbial resistance patterns
Secondary	ICU-free days
Secondary	Antibiotic-free days
Secondary	Change in organ dysfunction (MOD scores)