Efficacy and Safety of Colistin Based Antibiotic Therapy

Efficacy and Safety of Colistin Based Antibiotic Therapy for Multidrug Resistant Gram Negative Infections in Pediatric Intensive Care Unit

To evaluate the efficacy and safety of antibiotic combinations containing Colistin in the treatment of children with multidrug-resistant gram negative infections admitted in the pediatric surgery intensive care unit.

The main outcome measure is clinical and microbiological responses to therapy.

The secondary outcome is the occurrence of adverse events during Colistin combination treatment.

Study Overview

• Status: Unknown
• Conditions: Bacterial Infections; Septicemia
• Intervention / Treatment: Drug: Tienam 500; Device: Infusion

Detailed Description

Patients and Methods

Design of the study:

- Prospective, Randomized, interventional study.

Setting:

- The study will be conducted in the pediatric surgery intensive care unit in Children's Hospitals, Ain Shams University, Cairo, Egypt.

Subjects:

- Pediatric patients admitted in pediatric surgery intensive care unit.

Inclusion criteria:

All children with culture-proven nosocomial infections due to multidrug resistance gram-negative organisms

Exclusion criteria:

1. Patients who started on Colistin treatment outside the pediatric surgery intensive care unit and transferred to the unit afterward will be excluded.
2. Patients who will receive <6 doses of intravenous Colistin will be excluded.
3. Patients received Imipenem or Colistin-Imipenem compination as empirical antibiotic.

Methodology:

- Sixty pediatric patients admitted to the pediatric surgery intensive care unit will be enrolled in the study and will be randomly assigned to either Group I or Group II

Group I: Thirty patients will receive IV Colistin in dosages of 50,000-75,000 IU/kg/day in three divided doses, infused IV in 10mL normal saline over 30 minutes with IV Imipenem in doses of 15 to 25 mg/kg every 6 hours¬.21,22,24 Colistin formulation consists of 2 million IU per vial. Group II: Thirty patients will receive IV Imipenem in doses of 15 to 25 mg/kg every 6 hours¬. 22,24

For all patients the following data will be collected:

1. Demographic data (age, gender, weight).
2. The risk factors for nosocomial infections.
3. Pediatric surgery intensive care unit stay.
4. Type of surgeries performed.
5. Site of isolation of organisms.
6. The dose and duration of therapy.
7. Serum creatinine levels will be assessed at baseline, once weekly and at the end of Colistin combination therapy.
8. Nephrotoxic co-medication monitoring.
9. Clinical (resolution of signs and symptoms of infection) and
10. microbiological (bacteriologic responses) outcomes will be evaluated during treatment and at the end of the treatment.

According to the inclusion and exclusion criteria, the demographic data for the intended ICU patients was collected, then the sample was withdrawn from the infected site to be cultured on specific culture media (such as blood agar, MacConkey agar, Chocolate agar), and identification of the isolated microorganism was detected by biochemical tests and Vitek-2 compact system whenever required. Antimicrobial sensitivity to Colistin was tested using the micro broth dilution method, in order to be evaluated in Colistin therapy. After culture-proven, the drug was given, either IV Colistin-Imipenem/Cilastatin as a combination or Imipenem/Cilastatin as a monotherapy. Throughout this step, the hemodynamic parameters were measured during the process of treatment, without neglecting the serum creatinine level to detect any nephrotoxicity.

We assure the right drug handling, dosing, dispensing, and monitoring. At the end of the treatment, the duration and length of PICU stay were recorded.

The decision and/or conclusion of treatment failure and/ or success was based upon the worsening and/or improvement of the patients' parameters and their situation including the results of the microbiological examination before and after the intervention

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ain Shams Univesity Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All children with culture proven nosocomial infections due to multidrug resistance gram-negative organisms

Exclusion Criteria:

• 1. Patients who started on Colistin treatment outside the pediatric surgery intensive care unit and transferred to the unit afterward will be excluded.

  2. Patients who will receive <6 doses of intravenous Colistin will be excluded.

  3. Patients received Imipenem or Colistin-Imipenem compination as empirical antibiotic.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Montherapy; Thirty patients will receive IV Imipenem in doses of 15 to 25 mg/kg every 6 hours	Drug: Tienam 500; Imipenem and cilastatin sodium; Other Names: Meronem; Device: Infusion; Health caregivers give the drug to the patients and monitoring the infusion rate
Other: Combination; Thirty patients will receive IV Colistin in dosages of 50,000-75,000 IU/kg/day in three divided doses, infused IV in 10mL normal saline over 30 minutes with IV Imipenem in doses of 15 to 25 mg/kg every 6 hours¬.21,22,24 Colistin formulation consists of 2 million IU per vial.	Drug: Tienam 500; Imipenem and cilastatin sodium; Other Names: Meronem; Device: Infusion; Health caregivers give the drug to the patients and monitoring the infusion rate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic Parameters Measurement ,heart beating rate.	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the heart beating rate.	2 year
Hemodynamic Parameters Measurement ,body temperature	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the body temperature	2 year
Hemodynamic Parameters Measurement ,respiratory rate.	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the respiratory rate.	2 year
Hemodynamic Parameters Measurement ,blood pressure	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the blood pressure	2 year
Hemodynamic Parameters Measurement ,partial oxygen saturation pressure	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the partial oxygen saturation pressure	2 year
Hemodynamic Parameters Measurement and Septic Markers, serum lactate	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the serum lactate	2 year
Hemodynamic Parameters Measurement ,serum creatinine	the efficacy and safety of antibiotic combination containing Colistin. We will monitor the serum creatinine	2 year

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: AHMED S ATTIA, Heliopolis University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): September 1, 2019
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Infections; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; Cilastatin, Imipenem Drug Combination
• Other Study ID Numbers: 210

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