Antibiotic treatment in sepsis–etiological structure, antibiotic resistance, and pharmacological challenges: A retrospective analysis

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This retrospective study evaluates the etiological spectrum, antimicrobial resistance patterns, and pharmacokinetic/pharmacodynamic (PK/PD) challenges in patients with sepsis treated at the Clinic of Internal Diseases, UMBALSM “N. I. Pirogov,” Sofia. A total of 760 blood cultures collected over a 24-month period (12 March 2023–28 February 2025) were analyzed. Sepsis was diagnosed according to Sepsis-3 criteria, including SOFA ≥2 and qSOFA parameters. Positive microbiological growth was identified in 196 samples (25.8%). Patients with positive blood cultures had an average hospital stay of 22 days, while critically ill individuals requiring intubation and ICU transfer stayed for 41 days. Mortality increased sharply in patients aged ≥65 years, with men demonstrating a consistently higher risk across all age groups. The etiological profile was dominated by Staphylococcus spp., followed by Escherichia coli , Klebsiella pneumoniae (including ESBL-producing strains), and Acinetobacter baumannii , highlighting the high prevalence of multidrug-resistant Gram-negative pathogens. Rare isolates such as Providencia stuartii and Citrobacter freundii further demonstrated substantial etiological diversity. Gram-positive isolates exhibited high resistance to macrolides and fluoroquinolones, while susceptibility to vancomycin, teicoplanin, and linezolid remained preserved. Gram-negative organisms–particularly ESBL-producing K. pneumoniae and A. baumannii –showed extensive resistance to beta-lactams and standard cephalosporins. Pharmacokinetic/pharmacodynamic considerations: Sepsis induced significant PK/PD alterations, including an increased volume of distribution for hydrophilic antibiotics; frequent augmented renal clearance (ARC), leading to subtherapeutic exposure; and hypoalbuminemia, which accelerates the clearance of highly protein-bound drugs. These factors necessitate individualized dosing strategies, such as prolonged or continuous beta-lactam infusions, and emphasize the critical role of clinical pharmacists in therapeutic drug monitoring (TDM). Sepsis remains a condition associated with high mortality and substantial therapeutic complexity, intensified by antimicrobial resistance and dynamic PK/PD variability. Optimal management requires early empiric broad-spectrum therapy, followed by precise, individualized dosing tailored to the physiological changes in critically ill patients. Multidisciplinary collaboration between physicians and clinical pharmacists is essential for improving clinical outcomes.

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