Combination Antibiotic Therapy for Staphylococcus Aureus Bacteremia (COMBAT-SAB)

COMBAT-SAB: Combination Antibiotic Therapy for Staphylococcus Aureus Bacteremia

The purpose of this study is to see if, in selected patients with a serious bacterial infection of the bloodstream, treating the bacterial infection with a combination of antibiotics is more effective than treating the infection with a single antibiotic. Participants must have blood cultures which are positive for a certain type of bacteria.

Study Overview

• Status: Not yet recruiting
• Conditions: Staphylococcus Aureus Bacteremia
• Intervention / Treatment: Drug: Antibiotic Monotherapy (AM) for patients with methicillin-sensitive S. aureus bacteremia (MSSAB); Drug: Combination Antibiotic Therapy (CAT) for patients with methicillin-sensitive S. aureus bacteremia (MSSAB); Drug: Antibiotic Monotherapy (AM) for patients with methicillin-resistant S. aureus bacteremia (MRSAB); Drug: Combination Antibiotic Therapy (CAT) for patients with methicillin-resistant S. aureus bacteremia (MRSAB)

Detailed Description

Staphyloccocus aureus bacteremia (SAB) is a common infectious disease condition in hospitalized patients which is associated with significant morbidity, excessive costs, and high mortality, despite effective antibiotic therapy. This pragmatic study is designed to test the hypothesis that outcomes in adults hospitalized with SAB will be improved by using combination antibiotic therapy (CAT) as early, targeted therapy in a high-risk subgroup. A group of patients identified early in their course as meeting at least one high-risk criterion who have no contraindications will be treated with one of two antibiotic strategies commonly used within usual care, namely: 1) antibiotic monotherapy or 2) combination antibiotic therapy, depending on the random assignment for each hospital, each month. Low-risk patients will be treated per usual care. Data from all patients admitted to participating hospitals with SAB will be included in the analysis.

• Study Type: Interventional
• Enrollment (Estimated): 2096
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
• Study Contact Backup: Name: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org

Study Locations

• United States
  • Colorado
    • Brighton, Colorado, United States, 80601
      • Platte Valley Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Denver, Colorado, United States, 80218
      • Saint Joseph Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Regional Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Lafayette, Colorado, United States, 80026
      • Good Samaritan Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Wheat Ridge, Colorado, United States, 80401
      • Lutheran Medical Center
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
  • Montana
    • Billings, Montana, United States, 59101
      • St. Vincent Regional Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Butte, Montana, United States, 59701
      • St. James Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Miles City, Montana, United States, 59301
      • Holy Rosary Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
      • Principal Investigator: Brandon J Webb, MD
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Provo, Utah, United States, 84604
      • Utah Valley Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org
    • St. George, Utah, United States, 84790
      • St. George Regional Hospital
      • Contact: Brandon J Webb, MD; Phone Number: 801-507-7781; Email: Brandon.Webb@imail.org
      • Contact: Whitney R Buckel, PharmD; Phone Number: 801-284-1046; Email: Whitney.Buckel@imail.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Alive and admitted to an Intermountain Health (IH) hospital acute care unit at enrollment

• Initial positive blood culture with either methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-susceptible Staphylococcus aureus (MSSA), collected:

  1. on or during the index admission to an IH hospital, or
  2. in an ambulatory setting (laboratory, clinic or emergency department) within 48 hours of the index admission, or

  3. at a non-IH network hospital within 24 hours of subsequent transfer to an IH hospital

     Exclusion Criteria:

• Patient requests that patient health data not be included in the analysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with methicillin-sensitive S. aureus bacteremia (MSSAB); Patients with methicillin-sensitive S. aureus bacteremia (MSSAB) will be assigned to one of two different antibiotic treatment strategies appropriate for MSSA: 1) antibiotic monotherapy, or 2) combination antibiotic therapy	Drug: Antibiotic Monotherapy (AM) for patients with methicillin-sensitive S. aureus bacteremia (MSSAB); Intravenous anti-staphylococcal beta-lactam, either cefazolin or nafcillin, per the discretion of the treating physician.; Drug: Combination Antibiotic Therapy (CAT) for patients with methicillin-sensitive S. aureus bacteremia (MSSAB); Patients with methicillin-sensitive S. aureus bacteremia (MSSAB) and no contraindications will receive an anti-staphylococcal beta-lactam, either cefazolin or nafcillin, plus ertapenem
Experimental: Patients with methicillin-resistant S. aureus bacteremia (MRSAB); Patients with methicillin-resistant S. aureus bacteremia (MRSAB) will be assigned to one of two different antibiotic treatment strategies appropriate for MRSA: 1) antibiotic monotherapy, or 2) combination antibiotic therapy	Drug: Antibiotic Monotherapy (AM) for patients with methicillin-resistant S. aureus bacteremia (MRSAB); Vancomycin or daptomycin, per discretion of the treating physician; Drug: Combination Antibiotic Therapy (CAT) for patients with methicillin-resistant S. aureus bacteremia (MRSAB); Daptomycin plus ceftaroline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Desirability of Outcome Ranking (DOOR)	The DOOR ordinal scale includes four possible outcomes: treatment failure, infectious complications, antibiotic-associated adverse events and death. The ordinal scale comprises five levels: levels 1-4 are defined by survival at 30 days and the presence of either none, one, two or three of three possible outcomes; level 5 indicates death before 30 days. A DOOR analysis estimates the probability that overall outcomes in any given subject in one group are overall superior to those in a random subject from the other treatment group; probabilities >50% reject the null hypothesis.	From enrollment to 30 days post enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day hospital-free days alive	Number of days the patient is alive and out of the hospital	From enrollment to 90 days after enrollment
30-day all cause mortality	Number of deaths from any cause within 30 days after enrollment	From enrollment to 30 days after enrollment
90-day all-cause mortality	Number of deaths from any cause within 90 days after enrollment	From enrollment to 90 days after enrollment
30-day bacteremia-free days	Number of days without bacteremia within 30 days after enrollment	From enrollment to 30 days after enrollment
Length of stay	Number of days in the hospital following enrollment	Measured at the time of hospital discharge, up to 30 days after enrollment
Total hospital direct costs	Total financial charges incurred by a patient during their hospitalization	Measured at the time of hospital discharge, up to 30 days after enrollment
Total inpatient antibiotic cost	Total cost of all antibiotics received by a patient while hospitalized	Measured at the time of hospital discharge, up to 30 days after enrollment
Combination antibiotic days	Number of days a patient receives combination antibiotic therapy (CAT) as defined in protocol, instead of antibiotic monotherapy (AM)	Measured from the time of enrollment until study day 7, death, or hospital discharge
Antibiotic-associated adverse events	Number and type of patient adverse events definitively associated with the receipt of antibiotics while hospitalized	From enrollment to 30 days after enrollment
Clostridioides difficile infection	Presence of infection with Clostridioides difficile while hospitalized	From enrollment to 30 days after hospital discharge

Collaborators and Investigators

• Sponsor: Intermountain Health Care, Inc.
• Investigators: Principal Investigator: Brandon J Webb, MD, Intermountain Health Care, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 21, 2026
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Combination antibiotic therapy
• Other Study ID Numbers: 1053331

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In order to protect patient privacy and comply with relevant regulations, identified data will be unavailable. Requests for deidentified data from qualified researchers with appropriate ethics board approvals and relevant data use agreements will be processed by the Intermountain Office of Research, officeofresearch@imail.org
• IPD Sharing Time Frame: Data sharing will be available six months after anticipated enrollment completion, estimated August 2029, for a period to be determined by the Intermountain Office of Research and IRB
• IPD Sharing Access Criteria: Will be determined on an individual basis, upon request to the IH Office of Research.

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.: No