To Örebro University

Background: Combination therapy in the treatment of sepsis, especially the value of combining a beta-Lactam antibiotic with an aminoglycoside, has been discussed. This retrospective cohort study including patients with sepsis or septic shock aimed to investigate whether one single dose of gentamicin at admittance (SGA) added to beta-Lactam antibiotic could result in a lower risk of mortality than beta-Lactam monotherapy, without exposing the patient to the risk of nephrotoxicity.

Methods and findings: All patients with positive blood cultures were evaluated for participation (n = 1318). After retrospective medical chart review, a group of patients with community-acquired sepsis with positive blood cultures who received beta-Lactam antibiotic with or without the addition of SGA (n = 399) were included for the analysis. Mean age was 74.6 yrs. (range 19-98) with 216 (54%) males. Sequential Organ Failure Assessment score (SOFA score) median was 3 (interquartile range [IQR] 2-5) and the median Charlson Comorbidity Index for the whole group was 2 (IQR 1-3). Sixty-seven (67) patients (17%) had septic shock. The 28-day mortality in the combination therapy group was 10% (20 of 197) and in the monotherapy group 22% (45 of 202), adjusted HR 3.5 (95% CI (1.9-6.2),p= < 0.001. No significant difference in incidence of acute kidney injury (AKI) was detected.

Conclusion: This retrospective observational study including patients with community-acquired sepsis or septic shock and positive blood cultures, who meet Sepsis-3 criteria, shows that the addition of one single dose of gentamicin to beta-lactam treatment at admittance was associated with a decreased risk of mortality and was not associated with AKI. This antibiotic regime may be an alternative to broad-spectrum antibiotic treatment of community-acquired sepsis. Further prospective studies are warranted to confirm these results.