Use of Inflammatory Biomarkers to Guide Antibiotic Therapy in Patients With Severe Infections

Federal University of Minas Gerais

Status: Completed

Conditions: Severe Sepsis; Septic Shock

Treatments: Other: Procalcitonin guided antibiotic therapy; Other: C-reactive protein guided antibiotic therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00934011

PRO_Protocol01

Details and patient eligibility

About

In this study the investigators aim to test if C-reactive protein (CRP)or procalcitonin(PCT) - guided strategy allows to reduce the antibiotic use in patients wiht severe sepsis and septic shock. Therefore, the safety of this intervention will be carefully measured.

Full description

Methods

• Patients and settings: Prospective controlled randomized open interventional study of antibiotic therapy in adult with severe sepsis or septic shock, admitted to the intensive care unit.

The study will be conducted in the intensive care unit (ICU) of the University Hospital Risoleta Tolentino Neves of the Federal University of Minas Gerais, Brazil. This is a 30-bed ICU with medical and surgical patients. All patients with suspected severe sepsis or septic shock admitted to the ICU will be assessed for eligibility. Patients developing severe sepsis or septic shock during their ICU stay will be also considered for enrollment.

Cultures of urine, blood, bronchoalveolar lavage fluid, and tracheal aspirates will be performed on admission and during ICU stay as clinically indicated. Blood gases and imaging exams will also be performed as clinically indicated, similarly in both groups.

• Interventions:

All adult (> 17 years old) patients with diagnosis of severe sepsis or septic shock will receive initial antibiotic therapy based on local guidelines and susceptibility patterns, according to the decision of the treating physician. They will have circulating PCT and CRP levels measured at baseline and daily until day 4 in both groups.

Eligible patients will be reassessed on day 4 and randomized at 1:1 basis to one of the two groups since any exclusion criteria (see below) is present at that time:

Group 1 - CRP group: the duration of antibiotic therapy will be based on circulating CRP levels.

Group 2 - PCT group: the duration of antibiotic therapy will be based on circulating PCT levels.

Patients enrolled in the study will undergo daily measurements of plasma CRP (Dry Chemistry - Johnsons & Johnsons) and PCT (BRAHMS PCT VIDAS) levels up to stopping antibiotic therapy, every 48hr for two measurements in patients remaining in the ICU, and then, every 5 days.Patients will be followed up 28 days, or until death or hospital transference, which comes first. PCT and CRP results will be released in sealed envelopes. During the study period, only the results corresponding to the patient randomization group will be open; i.e., CRP for CRP group patients and PCT for PCT group patients.

• Criteria for antibiotic interruption:

The investigators will propose the interruption of antibiotics if:

1. The patients is clinically stable, without signs of active infection
2. CRP group: a relative reduction of 50% in baseline CRP levels, or a value lower than 25mg/dl is reached.
3. PCT group: a relative reduction of 90% in baseline PCT levels, or if a absolute value lower than 0.1 ng/ml is reached.

The final decision regarding antibiotic therapy will be always let to the discretion of the treating physician.

Enrollment: 94 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age > 17 years
• patients in intensive care unit
• signed informed consent
• suspected or confirmed severe sepsis or septic shock

Exclusion criteria

• Infections caused by Listeria spp, Legionella pneumophilia, Mycobacterium tuberculosis
• Bacteremia due S. aureus
• Infections requiring prolonged therapies, such as endocarditis, cerebral abscess, chronic osteomyelitis
• Suspected or confirmed infection caused by virus, parasites
• Infections caused by P. aeruginosa ou A. baumannii
• Severe immunosuppression (ex: AIDS, post bone-marrow transplant,cystic fibrosis)
• Traumatism latest five days
• Surgery latest 5 days
• Carcinoid tumor, lung cancer, medullary thyroid cancer

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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94 participants in 2 patient groups

Group 1 - C-reactive protein (CRP) guided ab therapy

Experimental group

Description:

Intervention on antibiotic therapy will be based on circulating CRP levels

Treatment:

Other: C-reactive protein guided antibiotic therapy

Group 2 - procalcitonin (PCT) guided ab therapy

Active Comparator group

Description:

Intervention on antibiotic therapy will be based on circulating PCT levels

Treatment:

Other: Procalcitonin guided antibiotic therapy