Single-center blood-culture analysis maps antibiotic resistance and dosing challenges in sepsis

A retrospective analysis of 760 blood cultures collected from patients with sepsis at the Clinic of Internal Diseases, UMBALSM “N. I. Pirogov,” in Sofia, found microbiological growth in 196 cultures, or 25.8%. The single-center study covered 24 months, from 12 March 2023 through 28 February 2025, and was designed to characterize pathogens, resistance patterns, and pharmacological challenges in antibiotic treatment.

Sepsis was identified using Sepsis-3 criteria based on the Sequential Organ Failure Assessment score and quick SOFA criteria. The clinical analysis was descriptive rather than interventional, so the reported associations do not establish that any antibiotic regimen, patient characteristic, or dosing strategy caused an improvement or deterioration in outcomes.

Among the 196 positive cultures, the average hospital stay was 22 days. For patients who required intubation and transfer to the intensive care unit, the average stay rose to 41 days. Mortality was higher among patients aged 65 or older in both sexes. It was 8 of 37 men younger than 65, compared with 24 of 69 men aged 65 or older; among women, it was 4 of 44 younger patients and 8 of 46 aged 65 or older. Men had higher observed mortality in each age group, although the analysis did not demonstrate that age or sex caused the differences.

Cardiovascular disease was the most frequently recorded concomitant condition, reported in 38% of the study population, and diabetes mellitus was second at 24%. These findings describe the clinical profile of the analyzed group. As a single-center retrospective series based on blood cultures, the study did not include an untreated or non-sepsis comparison group and could not determine whether the observed lengths of stay, mortality, or resistance patterns were representative of other hospitals or populations.

The isolates included a broad range of bacteria, with Staphylococcus species predominating. The investigators also identified enterobacteria such as Klebsiella and Escherichia coli producing extended-spectrum beta-lactamases, along with Acinetobacter baumannii, Providencia stuartii, Citrobacter freundii, and Klebsiella oxytoca. The presence of ESBL-producing enterobacteria and A. baumannii complicated treatment choices in the study population, while the rare isolates demonstrated the etiological diversity among the sampled patients.

Resistance patterns differed among the organisms examined. Among the Gram-positive isolates, Staphylococcus haemolyticus showed 37% resistance to erythromycin and approximately 28% resistance to levofloxacin, while Enterococcus faecalis showed high resistance to ciprofloxacin and erythromycin. The authors associated the macrolide and fluoroquinolone resistance with the widespread use of these drug classes over preceding years. S. aureus had very low measured resistance in this sample, and no Gram-positive isolate was resistant to vancomycin, teicoplanin, or linezolid.

Among the Gram-negative organisms, ESBL-producing K. pneumoniae had the highest resistance to most tested penicillins and cephalosporins, and the pattern for A. baumannii was not substantially different. By comparison, K. oxytoca and Proteus mirabilis were susceptible to most antibiotics tested. These results identify resistance in the sampled blood-culture isolates; they do not determine which drugs were administered, whether prescribed therapy was appropriate for each isolate, or whether resistance was associated with an individual patient’s outcome.

The review also describes how sepsis-related physiological changes can alter antibiotic exposure. Capillary leak and fluid movement into interstitial spaces expand the distribution volume of hydrophilic drugs such as aminoglycosides, beta-lactams, glycopeptides, and lipopeptides, which can increase loading-dose requirements. Augmented renal clearance, commonly operationalized as creatinine clearance of at least 130 mL/min/1.73 m², may further accelerate elimination and has been associated with antibiotic underdosing. Hypoalbuminemia may increase the free fraction and clearance of highly protein-bound drugs such as ceftriaxone, potentially reducing drug exposure near the end of a dosing interval.

Within those pharmacological constraints, the authors discuss pharmacokinetic and pharmacodynamic dosing strategies. Prolonged or continuous beta-lactam infusions are intended to maintain concentrations above the pathogen’s minimum inhibitory concentration, while high loading doses and subsequent adjustments are described for vancomycin. High-dose, extended-interval regimens are presented for concentration-dependent drugs such as aminoglycosides and fluoroquinolones, with therapeutic drug monitoring particularly important for aminoglycosides. The study concludes that collaboration between physicians and clinical pharmacists is important for individualized antibiotic dosing, but the retrospective blood-culture data do not directly test these strategies or establish their clinical effectiveness in the included patients.

Subject of Research: Antibiotic resistance, pathogen distribution, and pharmacokinetic challenges in patients with sepsis

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

Article References: Kobakova, Y. A., Kirkova-Bogdanova, A. G., Vakrilova Becheva, M. S., Semerdzhieva, N. E., Ivanova, S. A., Chaneva, M. S., Atanasova, V. P., Bashov, I. E., Yonchev, Y. T., Todorov, R. F., Bashev, N. Z., Teneva, D. N., Danov, K. V., Moneva-Sakelarieva, M. G., Atliev, K. T., Kyosev, V. S., Pavlova, S. M., & Atanasov, P. Y. (2026). Antibiotic treatment in sepsis–etiological structure, antibiotic resistance, and pharmacological challenges: A retrospective analysis. Pharmacia, 73, Article e212551. https://doi.org/10.3897/pharmacia.73.e212551

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e212551

Keywords: sepsis, blood cultures, antibiotic resistance, pathogen distribution, pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, antimicrobial stewardship, retrospective study, Antibiotic, treatment, etiological