Antibiotic Therapy in the Acute Phase of Severe Burn Injury: A Critical Review of the Literature and Proposal of an Updated Decision-Making Algorithm (2009–2025)

Abstract: Background: Infections remain the leading cause of mortality in patients with severe burn injuries. Antibiotic therapy in this population is particularly challenging because of profound pathophysiological alterations, frequent need for invasive devices, and high exposure to broad-spectrum antimicrobials, all of which promote the emergence of multidrug-resistant (MDR) organisms. In 2009, the French Society for Burn Study and Treatment (SFETB) published foundational recommendations for antibiotic use in the acute phase of burn care; however, these guidelines predate major advances in pharmacokinetics/pharmacodynamics (PK/PD), therapeutic drug monitoring (TDM), biomarkers, and antimicrobial stewardship strategies. Objectives: To critically review the literature published between 2009 and 2025 regarding antibiotic therapy in severely burned patients, to compare historical recommendations with contemporary international guidelines, and to propose an updated decision-making algorithm integrating PK/PD optimization, microbiological data, biomarkers, and modern antimicrobial agents. Methods: A narrative review was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library. Randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international guidelines (IDSA, ESCMID, Surviving Sepsis Campaign, SFETB) focusing on adult burn patients were included. Particular attention was given to studies addressing antimicrobial resistance patterns, PK/PD optimization, TDM, duration of therapy, de-escalation strategies, and new antimicrobial agents active against MDR and extensively drug-resistant (XDR) pathogens. Results: Severely burned patients exhibit early and rapid colonization of wounds and invasive devices by Gram-negative bacilli and resistant Gram-positive cocci, with Pseudomonas aeruginosa, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) being predominant. Contemporary evidence supports early initiation of empiric broad-spectrum antibiotics in suspected severe infection, combined with systematic microbiological sampling and prompt source control. PK/PD-guided dosing, prolonged or continuous infusions of β-lactams, and routine TDM—particularly for aminoglycosides and glycopeptides—significantly improve target attainment. Shorter treatment durations (approximately 7 days) are non-inferior to longer courses in most bloodstream infections and pneumonias when adequate source control is achieved. Biomarkers such as procalcitonin facilitate safe de-escalation and early discontinuation. Since 2010, several novel agents (ceftazidime–avibactam, ceftolozane–tazobactam, imipenem–relebactam, cefiderocol, sulbactam–durlobactam) have expanded therapeutic options for MDR/XDR organisms. Conclusion: Antibiotic management in acute burn care should balance urgent empiric therapy with antimicrobial stewardship. An updated, biomarker-driven, PK/PD-optimized, and phenotype-oriented strategy is essential to improve outcomes and limit resistance. We propose an updated decision-making algorithm and practical tables to harmonize antibiotic use in severely burned patients.