Duration of Antibiotics for the Treatment of Gram-negative Bacilli Bacteremia

NCT ID: NCT01737320

Last Updated: 2019-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 604 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2018-03-04

Brief Summary

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.

Conditions

Gram Negative Bacteremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

short-course

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.

Group Type: EXPERIMENTAL

short-course antibiotic treatment

Intervention Type: 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:

1. Intervention group - antibiotic treatment stopped on day 7

2. Control group - antibiotic treatment continued for 14 days according to accepted hospital local guidelines.

accepted prolonged antibiotic treatment

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.

Group Type: ACTIVE_COMPARATOR

accepted prolonged antibiotic treatment

Intervention Type: DRUG

Interventions

short-course antibiotic treatment

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:

1. Intervention group - antibiotic treatment stopped on day 7

2. Control group - antibiotic treatment continued for 14 days according to accepted hospital local guidelines.

Intervention Type: DRUG

accepted prolonged antibiotic treatment

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• patients with gram-negative aerobic bacilli bacteremia, defined as growth of a single gram-negative microorganism in one or more blood cultures, associated with evidence of infection (hyper- or hypothermia, a localized infection, sepsis or septic shock).
• We will include patients receiving appropriate antibiotic treatment for 7 days and are afebrile / not hypothermic for the last 48 hours. Both community and hospital acquired gram-negative bacteremias will be included, regardless of antibiotic susceptibility patterns. We will allow the inclusion of patients receiving less than 7 days if clinically stable and discharge from hospital is considered. We will then recruit the patient before discharge, if stable at least for 48 hours before randomization.

We will include the following sources of bacteremia:

1. Primary bacteremia / unknown source

2. Urinary tract

3. Abdominal

4. Respiratory tract

5. Central venous catheter(CVC), when the catheter was removed before randomization

6. Skin and soft tissue, including surgical site infection

Exclusion Criteria

1. Gram-negative bacteremia due to specific infections as detailed here:

1. Endocarditis / endovascular infections

2. Necrotizing fasciitis

3. Osteomyelitis

4. Abdominal abscesses and other unresolved abdominal sources requiring surgical intervention (e.g., cholecystitis)

5. Central nervous system infections

6. Empyema

7. CVC- related or CVC-associated bloodstream infections when the catheter is retained. We will permit the inclusion of patients with retained CVCs in whom the source of the bacteremia is not the CVC.

2. 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).

3. Specific pathogens including:

1. Salmonella spp.

2. Brucella spp.

4. Immunosuppression, including:

1. HIV infection

2. Hematopoietic stem-cell transplantation

3. Neutropenia on day of randomization or in the 48 hours prior to randomization. Patients with neutropenic fever at presentation that are afebrile and non-neutropenic in the 48 hours before randomization will be included.

5. Clinical instability during the 48 hours before randomization, defined as mean blood pressure<60 mmHg despite adequate fluid resuscitation or vasopressors support.

6. 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.

7. 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.

8. 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.

9. Previous enrollment in this trial

10. Concurrent participation in another clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rabin Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dafna yahav

MD, a specialist in internal medicine and a specialist in the infectious disease unit, Principal investigator.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dafna Yahav, MD

Role: PRINCIPAL_INVESTIGATOR

Rabin Medical Center

Locations

Rambam Health Care Center

Haifa, , Israel

Rabin medical center, Beilinson Hospital

Petah Tikvah, , Israel

Policlinico di Modena, Italy

Modena, Emilia-Romagna, Italy

Countries

Israel; Italy

References

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.

Reference Type: DERIVED

PMID: 30535100 (View on PubMed)

Other Identifiers

0258-12-RMC

Identifier Type: -

Identifier Source: org_study_id