Bacteraemia Caused by Gram-Negative Bacteria Clinical Trial
Official title:
The PIRATE PROJECT: a Point-of-care, Informatics-based Randomized Controlled Trial for Decreasing Over-utilization of Antibiotic ThErapy in Gram-negative Bacteremia
Gram-negative bacteremia (GNB) is a frequent hospital & community-acquired infection, yet there is as yet no evidence from randomized studies on the optimal duration of antibiotic therapy. This point-of-care, multicenter randomized controlled non-inferiority trial will randomize 500 patients with GNB on day 5 of appropriate antibiotic therapy to either (1) a total of 7 days of antibiotic therapy, (2) a total of 14 days of antibiotic therapy, or (3) an individualized duration of antibiotic therapy (guided by the patient's clinical course & C-reactive protein levels). The primary outcome is the incidence of clinical failure at day 30.
Antibiotic resistance continues to grow and is now considered to be one of the most serious
global threats of the 21st century. The key driver of resistance is antibiotic overuse; long
antibiotic courses select for resistance among the trillions of bacteria hosted by the human
body. There is as yet no evidence from randomized studies on its optimal duration of
antibiotic therapy. Traditionally, guidelines have somewhat arbitrarily recommended long
courses of two weeks, even though patients with no structural complications may recover after
only five days of therapy. Evidence is mounting that longer courses leave patients with
multi-resistant organisms. Indeed, given rising concerns over resistance, many physicians
have reduced antibiotic durations for GNB to 7 days with no apparent untoward consequences.
This point-of-care, multicenter randomized controlled non-inferiority trial will randomize
500 patients with GNB on day 5 of appropriate antibiotic therapy to either (1) a total of 7
days of antibiotic therapy, (2) a total of 14 days of antibiotic therapy, or (3) an
individualized duration of antibiotic therapy (guided by the patient's clinical course &
C-reactive protein levels). The primary outcome is the incidence of clinical failure at day
30. Patients will be followed through day 90; secondary outcomes will include the incidence
of clinical failure on days 60 and 90, the total number of antibiotic days, the incidence of
antibiotic-related adverse events (including Clostridium difficile infection), the emergence
of bacterial resistance, length of hospital stay. Cost-effectiveness/health-economic analyses
will also be performed.
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