The Resistance Constellation Across the Sepsis–Uropathogen Continuum: A Thirteen-Year Atlas of Epidemiological Expansion, Resistance Kinetics, and Progressive Therapeutic Attrition

Background: Conventional antibiograms compress antimicrobial resistance (AMR) into static percentages, obscuring whether therapeutic space is being lost gradually in high-burden pathogens or rapidly in less prevalent but increasingly resistant organisms. We developed a multidimensional longitudinal framework to map the evolving “resistance architecture” of bloodstream and urinary pathogens by integrating pathogen burden, demographic redistribution, specimen compartment, resistance velocity, and remaining antimicrobial-class activity. Methods: This retrospective, multicentre laboratory-surveillance study analysed 39,057 culture records collected through a multi-regional network from 2013 to 2025, comprising 4800 bloodstream and 34,257 urinary records. Three surveillance periods were compared: 2013–2017, 2018–2020, and 2021–2025. Analyses included temporal pathogen composition, demographic gravity, geographic surveillance concentration, compartment enrichment, descriptive Resistance Velocity, and Therapeutic Compression. Therapeutic Compression quantified the proportion of clinically relevant antimicrobial classes with susceptibility below a prespecified 80% threshold; sensitivity analyses were repeated at 70% and 90%. This measure represents microbiologically inferred treatment-space contraction, not patient-level therapeutic failure. Projections to 2030 were treated as exploratory scenarios. The urinary component derives substantially from 2013 to 2025 institutional surveillance resource previously used for a narrower urine-only analysis; overlap, counting units, and analytical distinctions are explicitly disclosed in the Methods. Results: Geographic surveillance contribution broadened over time, with the Herfindahl–Hirschman Index decreasing from 1.000 to 0.529 for bloodstream records and from 1.000 to 0.651 for urine. Bloodstream pathogen composition underwent greater temporal reorganization than the urinary compartment (Jensen–Shannon divergence: 0.0266 versus 0.0024). Between the earliest and latest periods, bloodstream Escherichia coli showed the greatest proportional expansion (odds ratio [OR] 4.05, 95% confidence interval [CI] 2.29–7.14), followed by Klebsiella spp. (OR 2.65, 95% CI 1.38–5.11) and Salmonella spp. (OR 1.26, 95% CI 1.04–1.53). Urine remained dominated by E. coli, although the proportional contributions of Klebsiella spp. and Pseudomonas aeruginosa increased. Age redistribution exceeded sex redistribution, particularly among urinary isolates. Distinct pathways of therapeutic-space contraction emerged: S. Typhi showed sequential loss of established treatment classes; E. coli remained an entrenched, high-volume urinary resistance reservoir; Klebsiella carbapenem resistance increased from approximately 8% to 40%; and P. aeruginosa carbapenem resistance increased from approximately 10% to 30%. Increasing vancomycin resistance among enterococci and expansion of urinary Candida added Gram-positive and fungal dimensions. At the primary 80% threshold, Therapeutic Compression was highest for Proteus spp. (0.750), S. Typhi (0.714), and Candida auris (0.667). Rankings were relatively concordant between the 70% and 80% thresholds (Spearman’s ρ = 0.789) but changed at 90%, where Klebsiella spp. and P. aeruginosa reached the highest compression scores (0.857). Exploratory 2030 scenarios indicated continued pressure on carbapenems and other reserve agents if the observed trajectories persist. Conclusions: AMR within this surveillance network did not follow a universal upward curve; it evolved through pathogen-specific architectures of burden, acceleration, redistribution, and therapeutic-space contraction. Integrating these dimensions distinguished entrenched high-volume reservoirs from rapidly deteriorating invasive or lower-frequency threats that cumulative antibiograms may overlook. This network-based framework offers a potential early-warning approach for identifying pathogen–drug trajectories requiring intensified laboratory surveillance, antimicrobial stewardship, and infection-prevention attention, while avoiding inference of national prevalence, causality, or individual treatment failure.