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

Canadian Critical Care Trials Group

Status and phase

Completed

Phase 2

Conditions

Nosocomial Infection

Pyrexia

Critical Illness

Systemic Inflammatory Response Syndrome

Pneumonia

Treatments

Drug: Site-specific empiric regimens included: Meropenem

Drug: Ciprofloxacin and cefazolin +/- metronidazole

Drug: Piperacillin/tazobactam

Study type

Interventional

Funder types

Other

Identifiers

NCT00438269

AATICC Pilot Study

Details and patient eligibility

About

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.

Full 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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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