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The investigators plan an open label randomized controlled trial to compare short-course antibiotic therapy (<=7 days) versus longer treatment (>7 days). The investigators will include hospitalized patients with gram-negative bacteremia. The investigators primary objective is to investigate the safety and efficacy of short-course antibiotics.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| short-course | Experimental | antibiotic treatment stopped on day 7 if the patient has been afebrile for 48 hours and clinically stable. Continued hospitalization will be left to the discretion of the treating physician. Antibiotics will be restarted if fever recurs in at least 2 consecutive measurements above 38 or in cases of clinically or microbiologically documented infections. |
|
| accepted prolonged antibiotic treatment | Active Comparator | antibiotic treatment continued for 14 days according to accepted hospital local guidelines. Duration of hospital stay will also be left to the discretion of the treating physician. Type of empiric antibiotic treatment and later, specific antibiotic treatment, will be chosen by the treating physicians in consultation with the infectious diseases unit. The decision on timing of switch to oral antibiotic therapy will also be left to the discretion of the treating physician. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| short-course antibiotic treatment | Drug | On day 7 of appropriate intravenous or oral antibiotic treatment for the bacteremic episode (day 1 is the first day of appropriate antibiotic therapy), patients will be randomized to:
|
| Measure | Description | Time Frame |
|---|---|---|
| composite of the following | The primary outcome is a composite of the following outcome measures | Until day 90 after randomization |
| All -cause mortality | All- cause mortality | Until day 90 after randomization |
| Treatment Failure | Failure including any of the following:
| Until day 90 after randomization |
| Hospital re-admissions or extended hospitalization | We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome. We will define re-admission as a new hospitalization for any cause occurring more than14 days from start of appropriate antibiotic treatment. Patients hospitalized after day 14 (were never discharged or 7-day regimen who were readmitted between days 7-14) will be counted as failures for this outcome. | Until day 90 after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Clostridium difficile associated diarrhea | Clostridium difficile associated diarrhea | Until day 30 after randomization |
| Development of Antibiotic resistance | Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the bacteremia episode. Surveillance sampling will not be conducted. |
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Inclusion Criteria:
We will include the following sources of bacteremia:
Exclusion Criteria:
Gram-negative bacteremia due to specific infections as detailed here:
Polymicrobial growth in blood cultures involving gram-positive or anaerobes in addition to gram-negatives (defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode (< 48 h) and with clinical or microbiological evidence of the same source).
Specific pathogens including:
Immunosuppression, including:
Clinical instability during the 48 hours before randomization, defined as mean blood pressure<60 mmHg despite adequate fluid resuscitation or vasopressors support.
Repeated positive blood cultures for the same organism separated by at least 24 hours, regardless of antibiotic treatment. Patients with repeated isolates on the first 24 hours will be included.
Uncontrolled focus of infection: e.g. an abscess that was not drained sufficiently; non-drained moderate to severe hydronephrosis in a patient with bacteremia of urinary source; deep seated intra-abdominal infections that were not drained properly.
Fever > 38.0C measured at least twice in the 48 h prior to recruitment; or > 38.5C once during the 48 h; or hypothermia <35.5C measured once during the 48 h.
Previous enrollment in this trial
Concurrent participation in another clinical trial
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| Name | Affiliation | Role |
|---|---|---|
| Dafna Yahav, MD | Rabin Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rambam Health Care Center | Haifa | Israel | ||||
| Rabin medical center, Beilinson Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30535100 | Derived | Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054. |
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|
| accepted prolonged antibiotic treatment | Drug |
|
| Until day 30 after randomization |
| Carriage of carbapenem resistant Klebsiella pneumonia. | Carriage of carbapenem resistant Klebsiella pneumonia (screened routinely) | Until day 30 after randomization |
| Total in hospital days | Total in hospital days within 30 and 90 days | Until day 90 after randomization. |
| Total antibiotic days | Total antibiotic days | Until day 30 after randomization |
| Adverse events |
| Until day 30 after randomization |
| Infection caused by other than gram-negative bacteremia | Development of either clinically or microbiologically documented infection other than gram-negative bacteremia. We will use the 2008 CDC/NHSN surveillance definitions of health-care associated infections for bacterial infections | Until day 90 after randomization |
| Number of hospital re-admissions | Number of hospital re-admissions until day 90 | Until day 90 after randomization |
| Functional capacity and time to return to baseline activity | Functional capacity and time to return to baseline activity | Until day 30 after randomization |
| Petah Tikvah |
| Israel |
| Policlinico di Modena, Italy | Modena | Emilia-Romagna | Italy |