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

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.

Study Overview

• Status: Recruiting
• Conditions: Acinetobacter Baumannii Infection
• Intervention / Treatment: Drug: Ampicillin - Sulbactam Injection; Drug: Cefoperazone-sulbactam injection

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ayah M Khalil Ibrahem, MSc in clinical pharmacy; Phone Number: +20 1094748214; Email: dr.ayaaa@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt, 11562
    • Recruiting
    • Cairo university hospitals kasr alainy

Participation Criteria

Eligibility Criteria

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

Description

Inclusion 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:

• Exclusion criteria:

  1. Empirical sulbactam-based therapy against Gram-negative bacteria
  2. History of hypersensitivity reactions to ampicillin-sulbactam/cefoperazone-sulbactam

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ampicillin- sulbactam; Intravenous ampicillin-sulbactam (2:1)	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.
Experimental: Cefoperazone-sulbactam; intravenous cefoperazone-sulbactam (1:1)	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment effectiveness Based on Clinical improvement	Clinical response will be assessed by ICU physicians based on physical examination findings and daily clinical records on Day 5 of treatment. Patients will be classified into one of the following categories: Cure: Complete resolution of signs and symptoms related to the infection; Failure: No improvement, persistence of symptoms beyond 72 hours, or deterioration requiring antibiotic escalation Unit of Measure: % of patients with clinical cure or failure Clinical evaluation performed daily by ICU physicians using physical examination and patient records, in accordance with standardized definitions of clinical response outlined by the CDC (Centers for Disease Control and Prevention) and IDSA (Infectious Diseases Society of America) 2024-2025 guidelines including primary blood stream infection-skin and soft tissue and surgical site infection-intra abdominal infection- lower respiratory infection- urinary tract infection- catheter related infection and bone and joint infection.	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteriological Response Assessed by Culture and Sensitivity Testing	Microbiological eradication will be assessed using microbiological cultures collected on Day 5 from appropriate clinical specimens (e.g., sputum, blood, wound, urine, central line ). Categories of response include: Eradication: No growth of Acinetobacter baumannii; Persistence: Continued growth of A. baumannii; Superinfection: Growth of a new microorganism Unit of Measure: % of patients with eradication, persistence, or superinfection Antimicrobial susceptibility of the isolated bacteria was determined by the Kirby-Bauer disc diffusion method based on the Clinical and Laboratory Standard Institute (CLSI) guideline. The isolates resistant to 2 or more drug classes simultaneously were considered to be multidrug resistant (MDR) (hospital microbiology laboratory).	5 days

Collaborators and Investigators

• Sponsor: Cairo University
• Collaborators: Cairo University Hospitals
• Investigators: Study Director: Ahmed M Mukhtar, Professor Anesthesia and ICU, Cairo Univesrsity hospitals Kasr Alainy

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: June 20, 2025
• First Submitted That Met QC Criteria: August 8, 2025
• First Posted (Actual): August 12, 2025

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Acinetobacter baumannii; ampicillin-sulbactam; cefoperazone- sulbactam
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Infective Agents, Urinary; beta-Lactamase Inhibitors; Ampicillin; Sulbactam; Cefoperazone; Sulperazone
• Other Study ID Numbers: N-138-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No