Early Targeted Antibiotic Therapy in Patients With Sepsis

Study Overview
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Brief Summary
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The aim of this study is to assess the efficacy of early targeted antibiotic therapy in patients with sepsis and septic shock using the new biomarker Sirtuin 1 and PCR for bacterial resistance detection. The primary outcome is change in SOFA score (ΔSOFA) which will be calculated by subtracting the final SOFA score and sirtuin 1 level at 5 days from the corresponding initial value at enrollment. Secondary outcomes included mortality rates, ventilator free days and length of icu stay.

Detailed Description
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A prospective, single-center, open labeled, randomized interventional study Patients will be recruited from a private hospital in Alexandria Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University Fourty eight critically ill patients, with sepsis and septic shock according to the 2016 third international consensus definitions, will be included Patients with risk for Carbapenemase producing organisms: Use of broad spectrum cephalosporins and/or carbapenems within the past three months Polytrauma Diabetes Malignancy Organ transplantation Mechanical ventilation Indwelling urinary or venous catheters Overall poor functional status or severe illness Residence in a long-term care facility(18-28). The baseline characteristics of the patients will be collected at the time of enrollment. The collected data included age, sex, ratio of septic shock to sepsis, ratio of ventilated to non-ventilated patients, source of infection, vital signs, laboratory data, arterial blood gas (ABG), APACHE II score, Glasgow Coma Scale score, and SOFA scores. The level of Procalcitonin (PCT) and Sirtuin-1 will also be measured at this time(29). Patients will be randomly allocated to antibiotic regimen guided by conventional culture technique (n=24) or targeted antibiotics therapy guided by resistance genotyping (n=24) (29, 30). Levels of Sirtuin1 will be detected using ELISA kits as prescribed by manufacturer. Traditional diagnostic microbiology techniques relying on the growth of organisms on appropriate culture media (Control group). Qualitative Multiplex pcr test will be used for rapid detection of carbapenemases genes (Intervention group) Statistical tests appropriate to the study will be conducted to evaluate significance of results Results, conclusion, discussion and recommendations will be given.

Official Title
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Efficacy of Early Targeted Antibiotic Therapy in Patients With Sepsis and Septic Shock

Conditions
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Sepsis

Intervention / Treatment
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* Other: targeted antibiotics therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 years or older A definite diagnosis of sepsis or septic shock according to the definition of the 2016 SCCM/ESICM task force. Patients at risk for carbapenemase producing organisms Exclusion Criteria: Pregnant and lactating women hematological disorders (e.g., leukemia, myelodysplastic syndrome, neoplastic metastases to bone marrow), life-threatening diseases (e.g., malignant solid tumors), acquired immunodeficiency syndrome. Lethal traumatic injury Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score ≥34 (due to high predicted mortality of 80%) Primary fungal or viral infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

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
Interventional Model Description: Patients will be randomly allocated to antibiotic regimen guided by conventional culture technique (n=24) or targeted antibiotics therapy guided by resistance genotyping (n=24)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group A<br>antibiotic regimen guided by conventional culture technique (n=24) | |
| Experimental: Group B<br>targeted antibiotics therapy guided by resistance genotyping (n=24) | Other: targeted antibiotics therapy<br>* targeted antibiotics therapy guided by resistance genotyping (n=24)<br>* Other names: genotyping;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sirtuin1 (ng/ml) | Levels of Sirtuin1 will be detected using ELISA kits as prescribed by manufacturer. | 5 days | 
| SOFA (score) | SOFA score (ΔSOFA) which will be calculated by subtracting the final SOFA score at 5 days from the corresponding initial value at enrollment. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality rates (%) | number of dead patients. | 5 days | 
| ventilator free days (days) | count of days free from ventilator, | 5 days | 
| length of icu stay (Days) | count of days in ICU | 5 days |