Neonatal Suspected Sepsis Treated With Cefazolin or Vancomycin

Study Overview
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Brief Summary
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The objective is to evaluate the effectiveness of empiric treatment with cefazolin versus to vancomycin in newborn infants with presumptive clinical signs of hospital acquired bacterial sepsis probably caused by Coagulase-negative staphylococcus. The investigators hypothesized that newborn infants with the presumptive diagnosis of nosocomial sepsis who received cefazolin as empiric treatment would have a clinical outcome not inferior to that of those treated with vancomycin.

Official Title
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Clinical Outcome of Newborn Infants With Suspected Nosocomial Coagulase-negative Staphylococcal Sepsis Treated With Cefazolin or Vancomycin. A Non-inferiority, Randomized, Controlled Trial

Conditions
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Nosocomial Neonatal Sepsis

Intervention / Treatment
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* Drug: Cefazolin
* Drug: Vancomycin
* Drug: Amikacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newborn infants older than three days of life with suspected bacterial sepsis and according to attending physicians, with an indication for initial treatment with vancomycin and at least one blood culture taken prior to receiving the antimicrobial treatment. Exclusion Criteria: previous treatment with vancomycin during the week before, infants referred from other hospitals and, upon admission, were being treated with antibiotics.

Ages Eligible for Study
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Minimum Age: 4 Days
Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cefazolin group<br>Initial empirical treatment with cefazolin and amikacin | Drug: Cefazolin<br> <br> Drug: Amikacin<br> <br> |
| Active Comparator: Vancomycin<br>Initial empirical treatment with vancomycin and amikacin | Drug: Vancomycin<br> <br> Drug: Amikacin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome of infants | Examination of each newborn infant by two of the investigators independently to establish whether the clinical outcome was adequate or inadequate. In order to achieve greater objectivity, the clinical examination was performed using the following criteria: Adequate: when the newborn infant had normal clinical parameters, a good general condition, appropriate tolerance to gastric feeding, normal temperature , negative blood and CSF cultures, and normalized results for the lab tests performed at the onset of the treatment. Inadequate: when one or more of the following were present: clinical course with persistence of any of the signs of sepsis, positive blood or CSF cultures after 72 hours from the onset of treatment, persistence of abnormal lab tests, and death by sepsis. | Seven to ten days after starting antibiotics | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of infants initially assigned to cefazolin group that were switched to vancomycin. | Patients with an inadequate 72 hour response to cefazolin were crossed over to receive vancomycin. The adjudication of response at 72 hours was delineated in a well-defined algorithm. To minimize bias, the final decision to switch treatments, initiated by the pediatrician in charge, required secondary review and agreement of another participating investigator as well as the attending NICU physician. | Within 72 hours of starting treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coagulase negative staphylococcus, nosocomial neonatal sepsis, cefazolin, vancomycin, newborn