Norwegian guidelines for empirical antibiotic therapy in suspected community acquired sepsis recommend the combination of narrow spectrum betalactam and aminoglycoside as the first choice, but broad spectrum betalactams are considered equally appropriate, effective, and safe. However, fear of renal complications due to gentamicin and concern for lacking evidence for efficiency commonly leads to the use of broad spectrum betalactam therapy, a larger driver of antibiotic resistance. In patients with suspected community acquired sepsis, the investigators hypothesize that empirical combination therapy with narrow spectrum betalactams and aminoglycosides is safe and non-inferior to empirical therapy with broad spectrum betalactams. More specifically, the investigators hypothesize that the proportion of patients with acute kidney injury or death will be similar between these two treatment groups. Furthermore, the investigators hypothesize that the aminoglycoside-based regimen has lesser impact on the gut microbiome. Antimicrobial resistance is one of the most urgent health threats of our time, and Norwegian hospitals were required but failed to reduce the use of broad-spectrum antibiotics with 30% by the end of 2020. In this context, novel initiatives aiming at reducing use of antibiotics are direly needed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,900
Empirical therapy for suspected community-acquired sepsis with gentamicin + narrow spectrum betalactam (either one of penicillin, ampicillin, or cloxacillin)
Empirical therapy for suspected community-acquired sepsis with cefotaxime
Empirical therapy for suspected community-acquired sepsis with piperacillin-tazobactam
Akershus University Hospital
Lørenskog, Norway
Oslo University Hospital Ullevål
Oslo, Norway
30-day mortality
All-cause mortality up to 30 days after randomization
Time frame: Up to 30 days after randomization
30-day acute kidney injury
Any acute kidney injury up to 30 days after randomization
Time frame: Up to 30 days after randomization
In-hospital mortality
All-cause mortality during index hospitalization
Time frame: During index hospitalization (commonly up to 30 days)
Duration of hospital stay
Duration of index hospitalization (days)
Time frame: During index hospitalization (commonly up to 30 days)
Duration of intensive care stay
Duration of stay in intensive care unit (days)
Time frame: During index hospitalization (commonly up to 30 days)
Duration of ventilator therapy
Duration of therapy with invasive mechanical ventilation (days)
Time frame: During index hospitalization (commonly up to 30 days)
Duration of vasopressor therapy
Duration of therapy with vasoactive (vasopressor) (days)
Time frame: During index hospitalization (commonly up to 30 days)
Hospital readmissions
Readmission after discharge from index hospitalization
Time frame: Up to 30 days after discharge from index hospitalization
Post-discharge mortality
All-cause mortality after discharge from index hospitalization
Time frame: Up to 30 days after discharge from index hospitalization
Duration of antibiotic treatment
Duration of antibiotic therapy during index hospitalization (days of therapy, DOT)
Time frame: During index hospitalization (commonly up to 30 days)
Gut microbiome composition
Impact on the gut microbiome
Time frame: During index hospitalization (commonly up to 30 days)
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