Sepsis
Conditions
Keywords
sepsis, antibiotics, aminoglycosides, cephalosporins
Brief summary
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.
Interventions
DRUGGentamicin + narrow spectrum betalactam
Empirical therapy for suspected community-acquired sepsis with gentamicin + narrow spectrum betalactam (either one of penicillin, ampicillin, or cloxacillin)
DRUGCefotaxime
Empirical therapy for suspected community-acquired sepsis with cefotaxime
Empirical therapy for suspected community-acquired sepsis with piperacillin-tazobactam
Sponsors
University Hospital, Akershus
Ullevaal University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized * Adults 18 year or older * Clinical suspicion of community acquired sepsis with indication for empirical antibiotic therapy * National Early Warning Score 2 (NEWS2) ≥ 5 * Signed informed consent must be obtained and documented according to ICH GCP, and national/local regulations
Exclusion criteria
* Established chronic kidney failure (eGFR \< 30 ml/min/1.73m2) * Presentation with septic shock with multiorgan failure * Suspicion of condition necessitating specific antimicrobial therapy (e.g. atypical pneumonia, fungal infection, parasitic infection, mycobacterial infection) * Current or recent use of nephrotoxic drugs (e.g cisplatin within previous 2 months) * Suspected or confirmed carrier of extended spectrum betalactamase (ESBL) producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), or other drug-resistant microbes necessitating specific antimicrobial therapy * Multiple myeloma * Renal transplantation * Renal replacement therapy * Myasthenia gravis * Known hypersensitivity to any of the study drugs * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30-day mortality | Up to 30 days after randomization | All-cause mortality up to 30 days after randomization |
| 30-day acute kidney injury | Up to 30 days after randomization | Any acute kidney injury up to 30 days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital mortality | During index hospitalization (commonly up to 30 days) | All-cause mortality during index hospitalization |
| Duration of hospital stay | During index hospitalization (commonly up to 30 days) | Duration of index hospitalization (days) |
| Duration of intensive care stay | During index hospitalization (commonly up to 30 days) | Duration of stay in intensive care unit (days) |
| Duration of ventilator therapy | During index hospitalization (commonly up to 30 days) | Duration of therapy with invasive mechanical ventilation (days) |
| Duration of vasopressor therapy | During index hospitalization (commonly up to 30 days) | Duration of therapy with vasoactive (vasopressor) (days) |
| Hospital readmissions | Up to 30 days after discharge from index hospitalization | Readmission after discharge from index hospitalization |
| Post-discharge mortality | Up to 30 days after discharge from index hospitalization | All-cause mortality after discharge from index hospitalization |
| Duration of antibiotic treatment | During index hospitalization (commonly up to 30 days) | Duration of antibiotic therapy during index hospitalization (days of therapy, DOT) |
Countries
Norway
Contacts
CONTACTMagnus N Lyngbakken, MD PhD
CONTACTKristian Tonby, MD PhD
Outcome results
None listed