Prolonged Infusion Cefepime and Nosocomial Infections

Study Overview
=================
Brief Summary
-----------------
It is advocated that prolonged infusion of beta-lactamic antibiotics provides better bactericidal effect. The aim of the present study is to randomize patients a to extended cefepime infusion regimen (lasting four hours) or to a usual infusion regimen (not lasting more than thirty minutes) and evaluate the clinical efficacy of this theoretical pharmacokinetic advantage.

Detailed Description
-----------------
Introduction: it has been proved that the main determinant for microbiological cure gram-negative infections treated with cefepime is the time above minimal inhibitory concentration (T>MIC). Although this particular pharmacokinetic property have never been proved in clinical trials utilizing cefepime, intervention studies with other betalactamic antibiotics, such as pipercillin-tazobactam, showed clinical benefit. Objective: to evaluate if prolonged infusion (lasting 4 hours) with cefepime translate into better clinical outcomes. Methods: the investigators aim to conduct an open-label, unique-centered, randomized controlled trial using cefepime in prolonged infusions in patients being treated for urinary or respiratory tract infections. Patients developing these infections after 72 hours of hospital admission, requiring the use of broader spectrum antibiotics after clinical failure or isolating gram-negative bacteria from adequate sample sensible to cefepime will be enrolled. The use of a second antibiotic such as clindamycin, vancomycin or metronidazole will be allowed. Interventions: the investigators aim to randomize 134 patients to two different treatment arms, the intervention arm who will receive the medication in a four hour lasting infusion, and the active control arm who will receive the medication in a 30 minutes lasting infusion. The randomization will be conducted in blocks of ten patients each, and it will be balance according to the patients age (older or younger than 65 years old) and presence of SIRS criteria.

Official Title
-----------------
Prolonged Infusion Cefepime and Nosocomial Infections

Conditions
-----------------
Urinary Tract Infection, Respiratory Tract Infection

Intervention / Treatment
-----------------
* Drug: Prolonged Cefepime Infusion
* Drug: Usual Cefepime Infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Urinary tract infection after 48-72 hours of hospital stay Respiratory tract infection after 48-72 hours of hospital stay Catheter related urinary tract infection after 48-72 hours of hospital stay Urinary or respiratory infections not responding to a narrower spectrum antibiotic Isolation of bacteria sensible to cefepime in blood, urine or sputum in a clinical context of infection Exclusion Criteria: Glomerular filtration rate lower than 30 ml.min/1,73m² ICU admission for at least 72 hours before randomization Neutrophil count lower than 1000 cels per mm³ Hematologic malignancy, bronchiectasis and cystic fibrosis Patients allergic to cefepime Concomitant treatment to another infectious disease Central nervous system, cutaneous or intrabdominal infections Solid organ transplantation HIV with a cluster differentiation 4 (CD4) lower than 100 cels per mm³

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged Cefepime Infusion<br>Cefepime infusions should last 4 hours at least | Drug: Prolonged Cefepime Infusion<br>* Cefepime infusion should last at least 4 hours with the aide of an infusion bomb<br>* Other names: Estended Cefepime Infusion;|
| Active Comparator: Usual Cefepime Infusion<br>Cefepime infusion should last no more than 30 minutes | Drug: Usual Cefepime Infusion<br>* Cefepime infusion occurs directly without the aide of an infusion bomb, lasting roughly thirty minutes<br>* Other names: Regular Cefepime Infusion;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Death in 30 days since randomization | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Death in 14 days since randomization | 14 days | 
| Duration of hospital stay | Duration of hospital stay | 30 days since randomization | 
| Intensive care unit (ICU) admission | Intensive care necessity for any reason | 30 days since randomization | 
| Duration of intensive care unit (ICU) stay | Number of days when intensive care was considered necessary | 30 days since randomization | 
| Treatment change | Treatment change required based com clinical or microbiological data | 3 days after randomization | 
| Treatment success | Patient reaching the completion until it end with infection resolution | 30 days since randomization | 
| Time to clinical stability | Time required for patient to reach the normalization of all following vital signs: that is, body temperature lower than 37,9 degrees celsius, a cardiac rate lower than 100 beats per minute and a respiratory rate lower than 25 respiratory movements per minute and peripheral oxygen saturation higher than 91% with low oxygen requirement (that is 4 liters per minute delivered by nasal canula) | 3 days |