Comparing Tigecycline Vs. Colistimethate in CNS Infections

Comparative Study of the Efficacy and Safety of Tigecycline Based Regimen Versus Colistimethate Sodium-based Regimen in Patients with Central Nervous System Bacterial Infections

This observational study compares the efficacy and safety of tigecycline, an alternative antibiotic with broad-spectrum activity, versus the standard colistimethate sodium-based regimen in managing these infections in pediatric patients.

Inclusion Criteria:

Pediatric patients aged 1 month to 18 years. Presence of CNS infection symptoms such as fever, altered mental status, and positive cerebrospinal fluid (CSF) findings.

EVD placement for managing CNS infections.

Exclusion Criteria:

Known allergy to tigecycline or colistimethate sodium. Patients with concurrent severe comorbid conditions that may confound study results.

Neonates (less than 1 month old), pregnant, or breastfeeding patients.

Outcome Measures:

Primary Outcomes: Clinical cure (resolution of infection symptoms) and microbiological cure (sterilization of CSF cultures).

Secondary Outcomes: Mortality rates and adverse drug events, such as nephrotoxicity, hepatotoxicity, chemical meningitis, or seizures.

Study Overview

• Status: Not yet recruiting
• Conditions: Central Nervous System Infections
• Intervention / Treatment: Drug: Tigecycline (Tygacil); Drug: Colistimethate sodium (CMS)

Detailed Description

Background:

Central nervous system (CNS) bacterial infections, such as meningitis and ventriculitis, are severe conditions in pediatric patients, often resulting from healthcare-associated complications, invasive procedures, or the spread of infection from other body sites. Multi-drug-resistant (MDR) pathogens, particularly carbapenem-resistant Acinetobacter baumannii, pose significant challenges in treating these infections. Standard treatment options, like colistimethate sodium, are associated with limited penetration into the CNS and potential toxicity. This study compares the efficacy and safety of tigecycline, an alternative antibiotic with broad-spectrum activity, versus the standard colistimethate sodium-based regimen in managing these infections in pediatric patients.

Data Collection and Analysis:

Patient data, including demographics, clinical presentations, treatment regimens, laboratory findings (CSF analysis, cultures), and adverse effects, will be systematically collected and analyzed. The study will employ appropriate statistical tests to determine the significance of differences between the two groups.

Ethical Considerations:

Ethical approval will be obtained from the Research Ethics Committees of Ain Shams University and Cairo University. Informed consent will be obtained from the guardians of all pediatric patients. The study will ensure strict adherence to ethical guidelines, including patient confidentiality and data protection.

Expected Impact:

This study aims to provide crucial data on the effectiveness and safety of alternative antibiotic regimens for pediatric CNS infections, potentially guiding clinical practice and improving outcomes for children affected by these severe infections in Egypt and globally.

Study Design:

A prospective observational clinical trial conducted on Pediatrics at Cairo University Hospitals, Egypt.

Study Population:

A total of 70 pediatric patients, aged 1 month to 18 years, admitted with confirmed or suspected CNS infections and with an external ventricular drain (EVD) in place.

Patient Groups:

Intervention Group (n = 35): Pediatric patients receiving a tigecycline-based regimen administered both intravenously (IV) and intraventricularly (IVT) for 14-21 days.

Control Group (n = 35): Pediatric patients receiving a colistimethate sodium-based regimen (standard therapy for MDR infections) administered both IV and IVT for 14-21 days.

Data Collection and Analysis:

Patient data, including demographics, clinical presentations, treatment regimens, laboratory findings (CSF analysis, cultures), and adverse effects, will be systematically collected and analyzed. The study will employ appropriate statistical tests to determine the significance of differences between the two groups.

Ethical Considerations:

Ethical approval will be obtained from the Research Ethics Committees of Ain Shams University and Cairo University. Informed consent will be obtained from the guardians of all pediatric patients. The study will ensure strict adherence to ethical guidelines, including patient confidentiality and data protection.

Expected Impact:

This study aims to provide crucial data on the effectiveness and safety of alternative antibiotic regimens for pediatric CNS infections, potentially guiding clinical practice and improving outcomes for children affected by these severe infections in Egypt and globally.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Abdelwahab, MSc; Phone Number: +20-1224959630; Email: Nouran_elsherazy@yahoo.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

A total of 70 pediatric patients, aged 1 month to 18 years, admitted with confirmed or suspected CNS infections and with an external ventricular drain (EVD) in place.

Description

Inclusion Criteria:

• Pediatric patients aged 1 month to 18 years.
• Presence of CNS infection symptoms such as fever, altered mental status, and positive cerebrospinal fluid (CSF) findings.
• EVD placement for managing CNS infections.

Exclusion Criteria:

• Known allergy to tigecycline or colistimethate sodium. Patients with concurrent severe comorbid conditions that may confound study results.

Neonates (less than 1 month old).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatrics patients having EVD and suffering from meningitis caused by MDR bacteria	Drug: Tigecycline (Tygacil); tigecycline-based regimen administered both intravenously (IV) and intraventricularly (IVT) for 14-21 days; Drug: Colistimethate sodium (CMS); Colistimethate sodium-based regimen (standard therapy for MDR infections) administered both IV and IVT for 14-21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological eradication	CSF Culture: Conducted at diagnosis and follow up for it till the end of the treatment course to monitor microbiological clearance. Two consecutive negative cultures are required to consider positive microbiological eradication.	follow up of the patients from time of enrollment to end of treatment is for 14-21 days
Clinical Cure rate	Resolution of infection symptoms like fever, seizures, fatigue and neck stiffness.	follow up of the patients from time of enrollment to end of treatment is for 14-21 days

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Estimated): November 25, 2024

Study Record Updates

• Last Update Posted (Estimated): November 25, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Central nervous system infections; MDR bacteria
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Central Nervous System Infections; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Synthesis Inhibitors; Tigecycline
• Other Study ID Numbers: ACUC-FP-ASU#265

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes