Early empirical antibiotherapy in patients attended for suspected sepsis in emergency departments: a systematic review

OBJECTIVE: Patients with suspected infections account for 15% to 35% of hospital emergency department (ED) caseloads in Spain and Latin America. The main objective of this systematic review was to compare evidence supporting the safety and efficacy of early (3 hours after triage) vs deferred ($ 3-6 hours) antibiotic therapy prescribed in EDs for adults with serious infections or sepsis. Efficacy and improved clinical course were defined by reduced progression to septic shock and short- and long-term mortality. METHODS: The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). PubMed, the Web of Sciencie, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase, and ClinicalTrials.gov were searched for the period from January 1, 2010, to December 31, 2023. No language restrictions were set. We used the following Medical English Subject Headings and strings: "Antibiotic OR Antibiotic Treatment OR Antibiotic Therapy OR Early Antibiotic Treatment OR Early Antibiotic Therapy," "Infection OR Bacterial Infection OR Sepsis," "Emergencies OR Emergency OR Emergency Department," "Timing," "Early," and "Adults." Observational cohort studies were included. To evaluate quality of research design and risk of bias, we applied the Newcastle-Ottawa Scale. Case-control studies, narrative reviews and other types of articles were excluded. We completed a narrative review of the findings and did not undertake meta-analysis. The review was registered in the PROSPERO database (CRD42024520687). RESULTS: The search yielded 1528 articles, of which 7 met the criteria for inclusion and analysis. The 7 studies comprised data for 118349 patients, 74141 of whom (62.6%) received early antibiotic treatment. Three studies were classified as high quality, 3 moderate, and 1 low. The 3 high-quality studies provided information on 2 aspects: 1) hospital and short-term mortality and 2) long-term mortality. One high-quality study showed a tendency for hospital and 30-day mortality to increase when antibiotics were administered more than 6 hours after triage vs within 1 hour of triage (hazard ratio, 2.25; 95% CI, 0.91-5.59; P = .08). Another reported an adjusted odds ratio of 1.09 (95% CI, 1.05-1.13; P = .024) for hospital mortality associated with each hour of therapeutic delay after triage. The third study reported that each additional hour of delay after triage was associated with a 10% increase (95% CI, 5%-14%; P .001) in the probability of 360-day mortality. Finally, the single low-quality study reported that each hour of delay in treatment was associated with an odds ratio of 1.08 (95% CI, 1.02-1.04; P .001) for increased risk of septic shock. CONCLUSIONS: Early initiation of antibiotic therapy, preferably within 3 hours of triage, can be recommended in cases of serious infection (sepsis or serious sepsis that do not meet the criteria for septic shock). In fact, based on a tendency for higher short- and long-term mortality associated with delay and a higher probability of developing septic shock with each hour of delay, therapy should start as soon as possible if infection is confirmed or suspected in the absence of an alternative diagnosis.

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