Comparing Efficacy and Safety of (Meropenem + Colistin) Versus (Imipenem/Cilastatin + Tigecycline) on Eradication of Multi-Drug Resistance Bacteria

Обзор

This study aims to compare the efficacy and safety of two antibiotic combinations (Colistin + Meropenem) vs (Imipenem/cilastatin+ Tigecycline) in the treatment of adults with MDR gram-negative infections.

Подробное описание

Antimicrobial resistance is rapidly becoming a global focus of attention, especially with the rising number of microorganisms resistant to available antimicrobials. It encompasses both the gram-positive and gram-negative bacteria, with global prevalence rates of 60% or more.

Multidrug-resistance is described as acquired non-sensitivity to one or more agents in at least three groups of antimicrobials. This kind of resistance essentially predominates in hospitals , as The Centers for Disease Control and Prevention (CDC) declared that worldwide increasing infection rates with resistant pathogens strikingly endanger our healthcare systems creating both negative universal economic effects and a therapeutic challenge for clinicians hence delaying proper antibiotic therapy and increasing mortality rates.

A retrospective study on the prevalence and antimicrobial susceptibility profile of multidrug-resistant bacteria among intensive care units' patients at Ain Shams University Hospitals in Egypt showed that the majority of pathogens were isolated from blood cultures, with higher prevalence of gram-negative isolates, and Klebsiella sp. being the most common pathogen isolated followed by E. coli.

For complicated infections or hemodynamically unstable patients, it's recommended to administer polymyxins plus another agent to which organism has demonstrated susceptible MIC (like tigecycline, aminoglycosides, IV fosfomycin) or high dose carbapenems if MIC \< 16, Ceftazidime-avibactam alone if in-vitro susceptibility has been demonstrated or in combination with aztreonam if synergy test is demonstrating zone of inhibition., Tigecycline is approved for intra-abdominal infection and skin -soft tissue infection- but not highly recommended for blood stream infection or pneumonia as a standalone agent. Colistin is preferred over polymyxin B for UTI as a single agent for uncomplicated infections.

All the suggested treatments are provided as combinations not as a single agent because of the failure of single antibiotic regimens in many trials. and there are also many studies which were based on combination therapy with a few antibiotics showed certain activity against MDR bacteria including colistin, Imipenem/cilastatin , Meropenem, rifampicin, sulbactam and tigecycline.

Вмешательства

• Препарат "Imipenem/cilastatin" and "Tigecycline"
  Imipenem/cilastatinis 500mg or 1gm every 6 to 8 hrs , Tigecycline 200 mg loading dose once followed by 100mg BID
• Препарат "colistin" and "meropenem"
  meropenem IV 2g TID , colistin IV 9M loading then 5M BID

Первичные конечные точки

• Efficacy of Treatment (Laboratory Investigation): Complete blood picture (CBC) [Срок оценки: on day 1 , 3 , 5 , 7 , 9 , 11 ,13 ,15 , 17 , 19 , 21 , 23 , 25 , 27 , 29]
• Efficacy of treatment, (Laboratory Investigation): CRP [Срок оценки: on day 3 , 6 , 9 , 12 , 15 , 18 , 21 , 24 , 27 , 30]
• Efficacy of treatment, Bacteriology test (culture) [Срок оценки: on day 4 , 11 , 18 , 25]
• Efficacy parameters, Symptoms [Срок оценки: on day 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]
• Emergent adverse event by BUN (mg/dl) , Sr.Cr (mg/dl) and uric acid (mg/dl) [Срок оценки: on day 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29]
• Efficacy of treatment, (Laboratory Investigation): PCT [Срок оценки: on day 3 , 7 , 11 , 15 , 19 , 23 , 27]
• Emergent adverse event by ALT and AST [Срок оценки: on day 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29]

Критерии участия

Критерии включения

• Adult and elderly patients (aged 18-85 years)
• With Clinical and microbiological evidence of infection due to positive or negative multi-drug resistant bacterial culture whatever the cause of patient hospital admission from the beginning.
• Immunocompromised patient With Clinical and microbiological evidence of infection due to positive or negative multi-drug resistant bacterial culture

Критерии исключения

• • History of prior hypersensitivity to the study drugs.

• Recent fits or CNS events like seizures.
• Pregnancy and lactation.
• Bacterial MDR culture but sensitive to one of the antibiotics used in the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• El-Demerdash hospital — Cairo

Идентификаторы

NCT: NCT07524920 · CompCombABMDR REC 49

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗