Comparison of the Clinical Efficacy of Ampicillin/Sulbactam and Cefoperazone/Sulbactam Against Multidrug Resistant Acinetobacter Baumannii Infections in Critically Ill Patients

NCT ID: NCT07118384

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2026-01-31

Brief Summary

To compare the clinical effectiveness of two different sulbactam-based regimens (ampicillin-sulbactam versus cefoperazone-sulbactam) in the treatment of Acinetobacter baumannii infections in critically ill patients.

Detailed Description

Among Acinetobacter species, Acinetobacter baumannii is the most important member and is commonly implicated in nosocomial infections. Acinetobacter baumannii is a gram-negative coccobacillus that has emerged from an organism of questionable pathogenicity to an infectious agent of importance to hospitals worldwide. In the intensive care unit ICU setting, Acinetobacter baumannii has been implicated in severe and occasionally life-threatening infections such as ventilator-associated pneumonia and bloodstream infections. Acinetobacter baumannii can produce biofilms in environments exposed to antibiotics; thus, it can survive for long periods and easily develop multidrug (MD), extremely or extensively drug (XD), and even pan-drug resistances (R) to various types of antibiotics, resulting in high patient mortality.

The underlying mechanisms can be divided into three categories. First, A. baumannii produces decomposition enzymes that deactivate antibiotics. Second, it can reduce or hinder the entry of antibiotics. For example, A. baumannii prevents the entry of antibiotics by controlling efflux pumps, or it can remove the antibiotics that have entered the cells. Third, point mutations alter the targets or functions of bacteria and reduce their affinity for antibiotics. Owing to its strong infectivity and drug resistance, A. baumannii has been added to the list of the World Health Organization's antibiotic-resistance priority pathogens.

Sulbactam, a beta-lactamase inhibitor, is commercially available mainly in combination with β-lactam antibiotics (as in ampicillin-sulbactam or cefoperazone-sulbactam), is a drug containing a beta-lactam ring derived from 6-aminopenicllanic acid. It can bind to the active sites of b-lactamase antibiotics to protect against antibiotic hydrolysis and restore antibiotic activity.

The antimicrobial property distinguishing sulbactam from other beta-lactamase inhibitors is its activity against Acinetobacter spp. Therefore, sulbactam is an alternative treatment option due to the worldwide spread of multidrug resistance Acinetobacter baumannii, for which only a few effective antimicrobial agents are currently available. The Infectious Diseases Society of America Antimicrobial-Resistant Treatment Guidance suggests that high-dose ampicillin-sulbactam (total daily dose of 6-9 grams of the sulbactam component) be included in the combination therapy regimen. If ampicillin-sulbactam non-susceptibility is shown, high-dose ampicillin-sulbactam can still be a helpful therapy choice. Acinetobacter baumannii isolates in China were more susceptible to cefoperazone-sulbactam than to ampicillin-sulbactam (resistance rates 48.8% vs 59.1%). The literature's limited data indicated that patients with Acinetobacter baumannii may expect moderate clinical benefits with Cefoperazone -Sulbactam. Salvation therapy may be attempted with combination treatment, particularly with polymyxins. There are no randomized controlled studies investigating the effectiveness of cefoperazone-sulbactam in the presence or absence of polymyxins for Acinetobacter baumannii infections.

Conditions

Acinetobacter Baumannii Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ampicillin- sulbactam

Intravenous ampicillin-sulbactam (2:1)

Group Type: ACTIVE_COMPARATOR

Ampicillin - Sulbactam Injection

Intervention Type: DRUG

Two grams of Ampicillin/sulbactam IV are administered every 8 hours, and each dose is administered as an extended infusion over 4 hours. The solution is diluted with a compatible solution (normal saline 0.9%) with a final concentration not exceeding 45mg/ml.

Cefoperazone-sulbactam

intravenous cefoperazone-sulbactam (1:1)

Group Type: EXPERIMENTAL

Cefoperazone-sulbactam injection

Intervention Type: DRUG

Two grams of Cefoperazone/sulbactam IV are administered every 8 hours, and each dose is administered as an extended infusion over 4 hours. The solution is diluted with a compatible solution (normal saline 0.9%) with a maximum final concentration of 250 mg/ml

Interventions

Cefoperazone-sulbactam injection

Two grams of Cefoperazone/sulbactam IV are administered every 8 hours, and each dose is administered as an extended infusion over 4 hours. The solution is diluted with a compatible solution (normal saline 0.9%) with a maximum final concentration of 250 mg/ml

Intervention Type: DRUG

Ampicillin - Sulbactam Injection

Two grams of Ampicillin/sulbactam IV are administered every 8 hours, and each dose is administered as an extended infusion over 4 hours. The solution is diluted with a compatible solution (normal saline 0.9%) with a final concentration not exceeding 45mg/ml.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥21 years old.

2. Patient with signs and symptoms of sepsis.

3. positive culture Carbapenem-resistant Acinetobacter baumannii (CRAB).

Exclusion Criteria

1. Empirical sulbactam-based therapy against Gram-negative bacteria

2. History of hypersensitivity reactions to ampicillin-sulbactam/cefoperazone-sulbactam

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Ayah Mohammed Khalil Ibrahem

Senior Clinical pharmacist -Trauma and surgical ICU ER185 at Kasr alainy hospital, MSc , BCPS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed M Mukhtar, Professor Anesthesia and ICU

Role: STUDY_DIRECTOR

Cairo Univesrsity hospitals Kasr Alainy

Locations

Cairo university hospitals kasr alainy

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Ayah M Khalil Ibrahem, MSc in clinical pharmacy

Role: CONTACT

dr.ayaaa@yahoo.com

+20 1094748214

Other Identifiers

N-138-2025

Identifier Type: -

Identifier Source: org_study_id