Does Staphylococcus Aureus Bacteremia Early Dual Therapy Improve Outcomes?

Official title

Does Staphylococcus Aureus Bacteremia Early Dual Therapy Improve Outcomes? (SABEDTIO) Clinical Trial

Overview

The goal of this open-label, pragmatic, randomized controlled clinical trial is to learn if patients with Staphylococcus aureus bacteremia (SAB) given the intervention of early dual intravenous (IV) antibiotic therapy will decrease duration of bacteremia (\< 6 days) and improve outcomes compared to single IV antibiotic therapy. The main questions this study aims to answer are: * To decrease SAB duration and improve outcomes by using early dual vs. single agent IV antibiotic therapy * To accelerate practice transformation of earlier IV to oral (PO) antibiotic transition by switching to PO antibiotic therapy once blood cultures are negative at 72 hours Participants will be asked to agree to be randomized (like flipping a coin) to receive two or one IV antibiotic(s). Once the infection has cleared, the treatment will be changed to PO antibiotics. As part of usual care, participants will have weekly lab tests for monitoring while on antibiotics, receive a telephone call to see how the participants are doing, and follow up in person or by telephone or video in Infectious Diseases (ID) Clinic. Participant participation will last 12 weeks after the participant is discharged from the hospital.

Interventions

• Drug Early Dual IV Antibiotic Therapy - MRSA
  Participant given IV daptomycin plus ceftaroline dosing per standard of care. Oral rifampin may be added for participants with prosthetic material.
• Drug Early Dual IV Antibiotic Therapy - MSSA
  Participant given IV cefazolin plus ertapenem dosing per standard of care. Oral rifampin may be added for participants with prosthetic material.
• Drug Single Agent IV Antibiotic Therapy - MRSA
  Participant given one of the following IV therapies: daptomycin, vancomycin, or ceftaroline. Oral rifampin may be added for participants with prosthetic material.
• Drug Single Agent IV Antibiotic Therapy - MSSA
  Participant given one of the following IV therapies: cefazolin, oxacillin, or nafcillin. Oral rifampin may be added for participants with prosthetic material.

Primary outcome measures

• Percentage of participants with prolonged bacteremia (≥ 6 days) [Time frame: Up to 12 weeks post hospital discharge]
• Seeding of a New Site - Incidence [Time frame: Up to 12 weeks post hospital discharge]
• All-Cause Mortality [Time frame: Up to 12 weeks post hospital discharge]

Secondary outcome measures (8)

• Number of patients with cure/control [Time frame: Up to 12 weeks post hospital discharge]
• Time to Positivity (TTP) [Time frame: Up to 14 days post hospital admission]
• Sequential Time to Positivity (STTP) [Time frame: Up to 14 days post hospital admission]
• Length of Hospital Stay [Time frame: Up to 12 weeks post hospital discharge]
• Overall Hospital Readmission [Time frame: Up to 12 weeks post hospital discharge]
• Rate of Relapsed Bacteremia [Time frame: Up to 12 weeks post hospital discharge]
• Time to First Negative Blood Culture [Time frame: Up to 14 days post hospital admission]
• Incidence of Antibiotic-Associated Side Effects and Toxicity [Time frame: Up to 12 weeks post hospital discharge]

Eligibility criteria

Inclusion criteria

• The patient is hospitalized at J.W. Ruby Memorial Hospital, Berkeley Medical Center, Camden Clark Medical Center, Princeton Community Hospital, Thomas Hospital, United Hospital Center, or Wheeling Hospital
• The patient has been identified to have Staphylococcus aureus bacteremia
• The patient is able to participate in lab monitoring and in-person or telemedicine ID Clinic follow-up

Exclusion criteria

• The patient or an appointed medical decision maker is unable to give informed consent
• The patient is a prisoner, pregnant, and/or mentally handicapped
• The patient is determined unsafe for enrollment at the primary team's discretion

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• West Virginia University — Morgantown

Publications

• Kim M, Ranganath N, Chesdachai S, Stevens RW, Sohail MR, Abu Saleh OM. Which trial do we need? Combination therapy with daptomycin plus ceftaroline versus standard-of-care monotherapy in the treatment of methicillin-resistant Staphylococcus aureus bacteraemia. Clin Microbiol Infect. 2025 Jan;31(1):18-21. doi: 10.1016/j.cmi.2024.08.011. Epub 2024 Sep 7. No abstract available. PMID 39182576
• Juskowich JJ, Thompson JM, Bage SD, Palmateer KM, Guilfoose JA, Lastinger AM, Smith CL, Arcega VA, Stanley JE, Summerfield HM, Fisher-Duda C, Nepal M, Wen S, Sarwari AR. Using the Comparing Oral versus Parenteral Antimicrobial Therapy (COPAT) Clinical Trial to Influence Institutional Practice Transformation Towards Earlier Transition to Oral Antibiotics. Clin Infect Dis. 2026 Apr 30;82(4):e674-e68 PMID 41419216
• Juskowich JJ, Thompson JM, Guilfoose JG, et al. P-106. Preliminary Results of the Comparing Oral versus Parenteral Antimicrobial Therapy (COPAT) Clinical Trial. Open Forum Infect Dis 2025;12(1):S197-198.
• Juskowich JJ, Thompson JM, Sarwari AR. 333. How the COVID-19 Pandemic Accelerated Development of our Complex Outpatient Oral Antimicrobial Therapy (COpAT) Program. Open Forum Infect Dis 2023;10(2):S212.
• Juskowich JJ, Ward A, Spigelmyer AE, et al. 1002. Complex Outpatient Antimicrobial Therapy (COpAT) Program at a Rural Academic Medical Center: Evaluation of First 100 Patients. Open Forum Infect Dis 2022;9(2):S418-S419.
• Kaasch AJ, Lopez-Cortes LE, Rodriguez-Bano J, Cisneros JM, Dolores Navarro M, Fatkenheuer G, Jung N, Rieg S, Lepeule R, Coutte L, Bernard L, Lemaignen A, Kosters K, MacKenzie CR, Soriano A, Hagel S, Fantin B, Lafaurie M, Talarmin JP, Dinh A, Guimard T, Boutoille D, Welte T, Reuter S, Kluytmans J, Martin ML, Forestier E, Stocker H, Vitrat V, Tattevin P, Rommerskirchen A, Noret M, Adams A, Kern WV, PMID 38244557
• Kaasch AJ, Barlow G, Edgeworth JD, Fowler VG Jr, Hellmich M, Hopkins S, Kern WV, Llewelyn MJ, Rieg S, Rodriguez-Bano J, Scarborough M, Seifert H, Soriano A, Tilley R, Torok ME, Weiss V, Wilson AP, Thwaites GE; ISAC, INSTINCT, SABG, UKCIRG, and Colleagues. Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J Infect. 2014 Mar;68(3):242-51. doi: PMID 24247070
• Li HK, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, Lipsky BA, Hughes HC, Bose D, Kumin M, Scarborough C, Matthews PC, Brent AJ, Lomas J, Gundle R, Rogers M, Taylor A, Angus B, Byren I, Berendt AR, Warren S, Fitzgerald FE, Mack DJF, Hopkins S, Folb J, Reynolds HE, Moore E, Marshall J, Jenkins N, Moran CE, Woodhouse AF, Stafford S, Seaton RA, Vallance C, Hemsley CJ, Bisnauthsing K, San PMID 30699315

Identifiers

NCT: NCT07148960 · 2507187207

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗