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Prolonged Infusion Cefepime and Nosocomial Infections

Phase 3
Conditions
Urinary Tract Infection
Respiratory Tract Infection
Interventions
Registration Number
NCT02568800
Lead Sponsor
Hospital de Clinicas de Porto Alegre
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
134
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Prolonged Cefepime InfusionProlonged Cefepime InfusionCefepime infusions should last 4 hours at least
Usual Cefepime InfusionUsual Cefepime InfusionCefepime infusion should last no more than 30 minutes
Primary Outcome Measures
NameTimeMethod
Death30 days

Death in 30 days since randomization

Secondary Outcome Measures
NameTimeMethod
Duration of hospital stay30 days since randomization

Duration of hospital stay

Time to clinical stability3 days

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)

Death14 days

Death in 14 days since randomization

Intensive care unit (ICU) admission30 days since randomization

Intensive care necessity for any reason

Duration of intensive care unit (ICU) stay30 days since randomization

Number of days when intensive care was considered necessary

Treatment change3 days after randomization

Treatment change required based com clinical or microbiological data

Treatment success30 days since randomization

Patient reaching the completion until it end with infection resolution

Trial Locations

Locations (1)

Hospital de Clínicas de Porto Alegre

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Porto Alegre, Rio Grande do Sul, Brazil

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