Sepsis is a severe and potentially fatal clinical condition requiring prompt initiation of empirical antimicrobial therapy. In the pre- and post-COVID-19 periods, the use of broad-spectrum antimicrobials, particularly third- and fourth-generation cephalosporins has increased, intensifying concerns about bacterial resistance. The objective of this study was to describe the introduction of the amoxicillin/sulbactam combination into the institutional sepsis protocol of an emergency hospital, focusing on infections of probable community origin – such as pneumonia, skin and soft-tissue infections, and secondary infections – and to discuss its relevance within the context of antimicrobial stewardship.

A narrative literature review was conducted in PubMed, SciELO, and LILACS databases, focusing on studies published between 2012 and 2024, using the descriptors “amoxicillin/sulbactam,” “sepsis,” “community-acquired infections,” “antimicrobial stewardship,” and “cephalosporin sparing.” Institutional microbiological sensitivity data from January 2015 to June 2018 and from 2018 to 2024 (pre- and post-pandemic periods) were also analyzed.

The literature demonstrates that amoxicillin/sulbactam has an adequate therapeutic profile for common community-acquired infections, with good activity against pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and methicillin-susceptible Staphylococcus aureus. Incorporation of this antibiotic into the sepsis protocol proved feasible and well-accepted by the medical teams. There was an improvement trend in cephalosporin susceptibility rates for hospital-acquired infections: for Pseudomonas aeruginosa, ceftazidime sensitivity increased from 32% to 45% (p = 0.017); for Acinetobacter spp., sensitivity improved by 6% (p = 0.20), without evidence of increased therapeutic failure.

The use of amoxicillin/sulbactam as initial empirical therapy for sepsis of probable community origin represents a viable and safe alternative in emergency hospital settings. In addition to maintaining clinical efficacy, this strategy contributes to the rational use of broad-spectrum antimicrobials, aligns with stewardship practices, and supports the preservation of higher-generation cephalosporins for complex clinical scenarios or settings with high resistance rates.