Clinical trial NCT06843668: Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections
Official title: Efficacy and Safety of Different Dosing Strategies of Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Critical Ill Patients
Multi Drug Resistant
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, single blind, randomized, comparative intervention study .
Primary purpose: TREATMENT

Brief summary: Nosocomial infections caused by multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative pathogens represent a major threat worldwide. The increasing trend of multi-drug resistance in Gram-negative bacteria (MDR-GNB) poses a particularly acute challenge to health systems especially in critically ill patients.

Patients in intensive care units (ICUs) have encountered an increasing emergence and spread of antibiotic-resistant pathogens. In Saudi Arabia mainly MDR-GNB such as Acinetobacter Baumannii, Pseudomonas Aeruginosa, Klebsiella Pnemoniae and Enterobacter are observed in ICUs.

Polymyxins are the last line therapy in the treatment of infection caused by these MDR-GNB. Colistin is the most widely used polymyxin antibiotic, it is administered as inactive prodrug colistimethate sodium (CMS) that is hydrolyzed to an active moiety of colistin base activity (CBA). It acts as cationic detergent and damages bacterial cytoplasmic membrane causing leaking of intracellular substances and then cell death.

During the first years of their use, polymyxin-associated neurotoxicity occurred in patients with an incidence as high as 27% following parenteral administration. However, other retrospective clinical trials have not exposed neurotoxicity to be a major concern. On the other hand, nephrotoxicity is by far the most common and dose-limiting side effect associated with parenteral polymyxins, with incidence rates in patients as high as 60%. Despite the high incidence of colistin induced nephrotoxicity, in 2012, the World Health Organization (WHO) reclassified polymyxins as critically important for the management of MDR-GNB infection, renewing the interest in these antibiotics.

To the best of our knowledge no study compared the efficacy and safety of both dosing strategies in critically ill patients. Moreover, there is still a lack of evidence on the efficacy and safety of both dosing strategies in obese patients. Therefore, this study aims at comparing the efficacy and toxicity of both strategies in colistin dosing (the fixed dose and the weight-based dosing) in obese patients and non- obese patients.


Eligibility criteria: Inclusion Criteria:

* Patients age ≥ 18 years old.
* Patients who will be treated with CMS for MR GNB infections.
* Patients who are admitted to the ICUs.

Exclusion Criteria:

* Known hypersensitivity to colistin.
* Pregnant and lactating women.
* Patients who are treated with colistin for \< 24 hours.
* Patients with myasthenia gravis or concomitant anesthetics or neuromuscular blocking drugs.

Primary outcomes:
measure: Clinical and microbiological success in eradication of infection reported as the number and percentage of patients with successful clinical improvement and microbiological clearance (Efficacy).
timeFrame: 14 days post colistin initiation.
Secondary outcomes:
measure: Nephrotoxicity (Safety)
timeFrame: 14 days
Other outcomes:
Locations:
city: Buraidah
country: Saudi Arabia
facility: King Fahad Specialist Hospital
Study officials:
affiliation: Mansoura University
name: Mohamed E Shams, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Paterson DL. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006 Sep;6(9):589-601. doi: 10.1016/S1473-3099(06)70580-1.
citation: Maraki S, Mantadakis E, Nioti E, Samonis G. Susceptibility of 2,252 Pseudomonas aeruginosa Clinical Isolates Over 4 Years to 9 Antimicrobials in a Tertiary Greek Hospital. Chemotherapy. 2014;60(5-6):334-41. doi: 10.1159/000437252. Epub 2015 Aug 18.