Early Targeted Antibiotic Therapy in Patients With Sepsis

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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Other: targeted antibiotics therapy

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Elbehairah
    • Damanhūr, Elbehairah, Egypt, 31527
      • Rehab Hussein Werida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female patients 18 years or older
2. A definite diagnosis of sepsis or septic shock according to the definition of the 2016 SCCM/ESICM task force.
3. Patients at risk for carbapenemase producing organisms

Exclusion Criteria:

1. Pregnant and lactating women
2. hematological disorders (e.g., leukemia, myelodysplastic syndrome, neoplastic metastases to bone marrow),
3. life-threatening diseases (e.g., malignant solid tumors), acquired immunodeficiency syndrome.
4. Lethal traumatic injury
5. Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score ≥34 (due to high predicted mortality of 80%)
6. Primary fungal or viral infections

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group A; antibiotic regimen guided by conventional culture technique (n=24)
Experimental: Group B; targeted antibiotics therapy guided by resistance genotyping (n=24)	Other: targeted antibiotics therapy; targeted antibiotics therapy guided by resistance genotyping (n=24); Other Names: genotyping

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rehab Werida
• Investigators: Study Director: Rehab H Werida, Ass. Prof., Damanhour University; Principal Investigator: Noha Elbassiony, Damanhour University; Principal Investigator: Eman Momtaz, Damanhour University

Publications and helpful links

General Publications

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Martinez ML, Plata-Menchaca EP, Ruiz-Rodriguez JC, Ferrer R. An approach to antibiotic treatment in patients with sepsis. J Thorac Dis. 2020 Mar;12(3):1007-1021. doi: 10.21037/jtd.2020.01.47.
• Bhattacharyya RP, Bandyopadhyay N, Ma P, Son SS, Liu J, He LL, Wu L, Khafizov R, Boykin R, Cerqueira GC, Pironti A, Rudy RF, Patel MM, Yang R, Skerry J, Nazarian E, Musser KA, Taylor J, Pierce VM, Earl AM, Cosimi LA, Shoresh N, Beechem J, Livny J, Hung DT. Simultaneous detection of genotype and phenotype enables rapid and accurate antibiotic susceptibility determination. Nat Med. 2019 Dec;25(12):1858-1864. doi: 10.1038/s41591-019-0650-9. Epub 2019 Nov 25.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): August 30, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: Early Antibiotic in Sepsis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No