Impact of prehospital antibiotic therapy differs depending on septic shock origin

International guidelines recommend early a bundle of care to reduce sepsis mortality. Among bundle of care, antibiotic therapy is all the additionally effective when early initiated, especially for the sicker patients, i.e., those with septic shock, for whom it should be started within the first hour. This study aims to examine the impact of prehospital antibiotics administration on 30-day mortality in patients with septic shock, as defined by Sepsis-2, cared for by a prehospital mobile intensive care unit (MICU).

We performed a nationwide observational cohort study in France using data from May 2016 to December 2021 including septic shock patients admitted to ICU after receiving prehospital care from a MICU. An emulate retrospective randomized controlled trial using a weighted Cox proportional hazards model was conducted to compare the efficacy of prehospital antibiotic administration versus no prehospital antibiotic administration on 30-day mortality. A secondary analysis assessed the association between prehospital antibiotic administration and 30-day mortality according to presumed septic shock origin.

Among the 530 patients analyzed, 341 (64%) were males and the mean age was 70 ± 15 years. The 30-day mortality was 31%. The presumed origins of sepsis in the prehospital setting were primarily pulmonary, digestive, and urinary, with respective percentages of 43%, 25%, and 17%, respectively. One-hundred and thirty-two patients (25%) received prehospital antibiotic therapy, a 3rd generation cephalosporin for 98 patients (18%). The inverse probability of treatment weighting analysis emulating the target trial revealed that prehospital antibiotic administration was associated with a lower risk of 30-day mortality compared with no prehospital antibiotic administration: RR = 0.64, 95%CI [0.41-0.97]. The weighted logistic regression model showed a significant association between 30-day mortality and prehospital antibiotic administration for pulmonary origin: RRa = 0.80 [0.86-0.93], urinary origin: RRa = 0.89 [0.80-0.98], and unknown origin: RRa = 0.94 [0.86-0.99].

The prehospital antibiotics administration is associated with a reduced risk of 30-day mortality among patients suffering from septic shock cared for by a prehospital MICU. The prehospital antibiotic treatment effect differs according to septic shock origin. However, prospective studies are necessary to validate these preliminary findings and to assess the supplementary effects of the bundle of care components.