Staphylococcus Aureus Bacteremia
Conditions
Keywords
Combination antibiotic therapy
Brief summary
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.
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.
Interventions
DRUGAntibiotic 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.
DRUGAntibiotic Monotherapy (AM) for patients with methicillin-resistant S. aureus bacteremia (MRSAB)
Vancomycin or daptomycin, per discretion of the treating physician
DRUGCombination 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
DRUGCombination Antibiotic Therapy (CAT) for patients with methicillin-resistant S. aureus bacteremia (MRSAB)
Daptomycin plus ceftaroline
Sponsors
Intermountain Health Care, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Platform, embedded, pragmatic clinical trial using a multiple-crossover cluster-randomized design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Desirability of Outcome Ranking (DOOR) | From enrollment to 30 days post enrollment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 90-day hospital-free days alive | From enrollment to 90 days after enrollment | Number of days the patient is alive and out of the hospital |
| 30-day all cause mortality | From enrollment to 30 days after enrollment | Number of deaths from any cause within 30 days after enrollment |
| 90-day all-cause mortality | From enrollment to 90 days after enrollment | Number of deaths from any cause within 90 days after enrollment |
| 30-day bacteremia-free days | From enrollment to 30 days after enrollment | Number of days without bacteremia within 30 days after enrollment |
| Length of stay | Measured at the time of hospital discharge, up to 30 days after enrollment | Number of days in the hospital following enrollment |
| Total hospital direct costs | Measured at the time of hospital discharge, up to 30 days after enrollment | Total financial charges incurred by a patient during their hospitalization |
| Total inpatient antibiotic cost | Measured at the time of hospital discharge, up to 30 days after enrollment | Total cost of all antibiotics received by a patient while hospitalized |
| Combination antibiotic days | Measured from the time of enrollment until study day 7, death, or hospital discharge | Number of days a patient receives combination antibiotic therapy (CAT) as defined in protocol, instead of antibiotic monotherapy (AM) |
| Antibiotic-associated adverse events | From enrollment to 30 days after enrollment | Number and type of patient adverse events definitively associated with the receipt of antibiotics while hospitalized |
| Clostridioides difficile infection | From enrollment to 30 days after hospital discharge | Presence of infection with Clostridioides difficile while hospitalized |
Countries
United States
Contacts
CONTACTBrandon J Webb, MD
CONTACTWhitney R Buckel, PharmD
PRINCIPAL_INVESTIGATORBrandon J Webb, MD
Intermountain Health Care, Inc.
Outcome results
None listed