Search Results (799)

Background/Objectives: Atypical skull base osteomyelitis (ASBO) is a rare disease, typically involving the basisphenoid and basiocciput. Diagnosis consists of clinical examination, imaging methods such as PET-CT scans and MRI, microbiological testing, and possibly native tissue samples. Long-term intravenous antibiotic therapy is the treatment of choice. Methods/Case Report: We present a case of ASBO of the clivus initially suspected to be a malignant lesion due to malignant melanoma in the patient’s history. Several tissue biopsies were taken, and microbiological testing of native tissue biopsies in combination with PET-CT and MRI imaging led to the diagnosis of ASBO. The patient received long-term antibiotic therapy with meropenem and drastically improved in his overall health. Discussion and Conclusions: This case highlights the challenges encountered in the diagnosis and management of ASBO, especially with relevant possible differential diagnoses. Full article

Carbapenem-resistant Gram-negative infections have become one of the most formidable challenges in intensive care units (ICUs). Critically ill patients—often exposed to invasive procedures, prolonged hospitalization, and broad-spectrum antibiotics—are highly susceptible to infections by carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB). These pathogens are associated with mortality exceeding 40%, prolonged ICU stays, and increased healthcare costs. Therapeutic advances have reshaped management in recent years. New β-lactam/β-lactamase inhibitor combinations—ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, and sulbactam–durlobactam—along with cefiderocol, have provided safer and more effective alternatives to previously used regimens. Yet, none are universally effective, particularly against carbapenemase-producing organisms, especially metallo-β-lactamase (MBL) producers, and resistance may still emerge during treatment. Rapid molecular and phenotypic diagnostics, when integrated into antimicrobial stewardship, have improved early therapy alignment and reduced unnecessary broad-spectrum use. Beyond antibiotics, colonization surveillance and infection control remain pivotal, as colonization often precedes invasive infection. Biofilm formation on devices such as endotracheal tubes and catheters further promotes persistence and relapse. Strategies targeting biofilm disruption, improved dosing guided by pharmacokinetic/pharmacodynamic optimization, and therapeutic drug monitoring are crucial in ICU practice. The future of managing these infections will depend on integrating precision tools—rapid diagnostics, mechanism-based therapy, and stewardship-guided decisions—with emerging treatments and adjunctive options such as immunomodulators, bacteriophages, and AI-driven decision support. Continued research in ICU-specific populations, especially regarding pharmacokinetics in patients on ECMO or CRRT, is urgently needed. In summary, while the therapeutic landscape for carbapenem-resistant Gram-negative infections has evolved substantially, sustained success will rely on a multifaceted strategy combining innovation, precision, and prevention to improve outcomes for the most vulnerable patients. Full article

Objectives: The primary objective was to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa causing infection in elderly (≥65 years old) patients hospitalized in intensive care units (ICUs) of United States medical centers. Susceptibility results from isolates of elderly patients in ICUs were compared to isolates from elderly patients not in ICUs (elderly non-ICU) and adult ICU patients (18 to 64 years old; adult ICU). Methods: P. aeruginosa isolates were consecutively collected from 74 US medical centers in 2021–2025 and susceptibility tested by reference broth microdilution in the monitoring laboratory (Element Iowa City [JMI Laboratories]). The organism collection included 999 isolates from elderly ICU, 2027 isolates from elderly non-ICU, and 1022 isolates from adult ICU patients. Results: The most active agents against P. aeruginosa from all three patient groups were ceftazidime-avibactam (95.8% to 97.3% susceptible), ceftolozane-tazobactam (96.0% to 98.3% susceptible), imipenem-relebactam (97.6% to 98.7% susceptible), and tobramycin (91.4% to 94.7% susceptible). Susceptibility to piperacillin-tazobactam, ceftazidime, cefepime, meropenem, and imipenem were markedly lower among isolates from elderly and adult ICU patients compared to elderly non-ICU patients. Susceptibility to levofloxacin and tobramycin were lower among isolates from adult ICU patients compared to elderly ICU and non-ICU patients. Moreover, the frequency of multidrug-resistant (MDR) isolates was markedly higher among elderly (18.4%) and adult (22.4%) ICU patients compared to elderly non-ICU (11.0%) patients. An annual analysis of susceptibility to selected β-lactams showed a slight variation in susceptibility rates without a clear trend. Conclusions: Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam were highly active and exhibited similar coverage against a large contemporary collection of P. aeruginosa isolates from ICU elderly, non-ICU elderly, and ICU adult patients. Cross-resistance among these β-lactamase inhibitor combinations (BLICs) varied markedly, indicating that all three should be tested in the clinical laboratory and available for clinical use. Full article

Background: Acinetobacter baumannii is a major global health threat due to its rapid acquisition of multidrug resistance, particularly to carbapenems. Combination antibiotic therapy has been proposed to enhance antimicrobial activity and suppress resistance; however, evidence from randomized trials remains inconclusive. Methods: A systematic review of randomized controlled trials (RCTs) was conducted following PRISMA guidelines to evaluate the efficacy and safety of antibiotic combination therapy versus monotherapy for drug-resistant A. baumannii infections. Searches across MEDLINE, Embase, Global Health, and Cochrane Central (January 2010–June 2025) identified eligible RCTs reporting clinical outcomes. Data on clinical cure, mortality, microbiological eradication, adverse events, and resistance emergence are described narratively. Results: Eight RCTs enrolling 324 participants were included. Most trials investigated colistin-based combinations (e.g., colistin plus rifampicin, meropenem, fosfomycin, or sitafloxacin); one assessed tigecycline plus cefoperazone–sulbactam. No regimen demonstrated a significant mortality or clinical cure benefit over monotherapy, despite some combinations showing earlier or higher microbiological clearance, most notably colistin–fosfomycin and colistin–rifampicin, without corresponding improvement in clinical outcomes. Adverse events, predominantly nephrotoxicity, were common but comparable across groups. Heterogeneity in trial size, infection severity, and resistance mechanisms limited cross-study comparability. Conclusions: Current RCT evidence does not support routine use of combination therapy over monotherapy for drug-resistant A. baumannii infections, particularly in septic ICU populations where host factors dominate outcomes. Future trials should focus on early-stage or non-sepsis infections, incorporate molecular resistance profiling, and evaluate emerging agents such as sulbactam–durlobactam to guide precision therapy. Full article

Background: Hospital wastewater (HWW) is a critical reservoir for carbapenem-resistant Gram-negative bacteria. Methods: Between November 2024 and August 2025, sixty 24 h composite wastewater samples were collected from five tertiary hospitals. Of the 244 carbapenem-resistant isolates recovered, 34 bla_NDM-1-positive Acinetobacter isolates were subjected to phenotypic, genotypic, and plasmid analyses. Results: Eleven species were identified among the 34 carbapenem-resistant Acinetobacter isolates, predominantly non-baumannii Acinetobacter (NBA). All isolates were carbapenem-resistant (34/34, 100%) with high-level MICs (meropenem MIC_50/90, 32/64 mg/L; imipenem MIC_50/90, >128/>128 mg/L); 21% (7/34) of isolates were resistant to colistin, and resistance to ceftazidime, cefepime, and trimethoprim-sulfamethoxazole was 100%, 94%, and 76%, respectively. Core-genome SNP analysis revealed highly similar isolates across hospitals within the same season (1-2 SNPs) or within the same hospital across seasons (19 SNPs). Genomic analysis showed that bla_NDM-1 was present in all isolates (34/34, 100%), with plasmid carriage in 85.3% (29/34); bla_OXA-58 co-occurred in 62.1% (18/29), mainly on Rep_3 plasmids (19/29), especially R3-T28 (15/29) that frequently carried bla_OXA-58 (10/15). Two unclassified plasmids co-harboring bla_NDM-1 and bla_OXA-23 were detected in Acinetobacter tandoii isolates. The bla_NDM-1 gene was embedded in a conserved Tn125-like structures with variable flanks. Conclusions: Overall, carbapenem-resistant Acinetobacter from hospital wastewater frequently carried Rep_3 plasmid-borne bla_NDM-1, especially R3-T28 and often co-occurring with bla_OXA-58, within a conserved Tn125-like core structures. These findings highlight HWW as a potential hotspot for dissemination of carbapenem resistance and support routine genomic surveillance under a One Health framework. Full article

Background/Objectives: Carbapenem-resistant Acinetobacter spp. represent an emerging concern in human medicine; however, their epidemiology and genetic backgrounds in companion animals in Japan remain unclear. This study aimed to determine the prevalence of carbapenem resistance among Acinetobacter spp. isolated from diseased dogs and cats and elucidate the underlying genetic mechanisms. Methods: In this surveillance study conducted as part of the Japanese Veterinary Antimicrobial Resistance Monitoring (JVARM) program, 139 isolates were collected from diseased companion animals across Japan (84 from dogs and 55 from cats) during 2020, 2021 and 2023. Antimicrobial susceptibility testing was performed for seven antimicrobials and carbapenem-resistant isolates (meropenem MIC ≥ 8 μg/mL) underwent whole-genome sequencing to identify resistance genes, genomic contexts, and associated mobile genetic elements. Results: Resistance rates to all tested antimicrobials were below 20%. Meropenem resistance was detected in three isolates: one from a dog and two from cats. These resistant strains were identified as A. radioresistens, A. proteolyticus, and A. johnsonii, all harboring carbapenemase genes. The A. radioresistens isolate carried chromosomal bla_OXA-23, the A. proteolyticus isolate carried bla_OXA-58, and the A. johnsonii isolate possessed a plasmid containing bla_NDM-1 and bla_OXA-58. This represents the first report of bla_NDM-1-harboring Acinetobacter isolate from companion animals in Japan. Conclusions: Carbapenem-resistant Acinetobacter spp. remain rare in companion animals in Japan; however, insertion sequence mobility may promote resistance gene dissemination. As carbapenems are not approved for veterinary use in Japan, strict antimicrobial stewardship and appropriate hygiene management are essential. Full article

Background/Objectives: In the area of pharmacology and clinical research, it is necessary to use versatile technologies able to quantify last-line antibiotic molecules with high specificity and sensitivity. This article describes the development of two types of immunosensors based on amperometric and surface plasmon resonance (SPR) measurements and their applicability in the measurement/assessment of therapeutic drug monitoring (TDM) of four last-line antibiotics such as vancomycin, colistin, daptomycin and meropenem in human plasma. In this study, ligand immobilization by preconcentration assays, sensor surface regeneration, determination of sensitivity and correlation of plasma sample quantification results by HPLC were considered. Results: In the case of the electrochemical biosensor the IC50 values obtained were 3.49 μg/L for vancomycin (VAN), 5.44 μg/L for colistin (COL), 0.82 μg/L for meropenem (MER) and 5.10 μg/L for daptomycin (DAP). For the SPRi biosensor the LODs achieved were 19 ng/mL for VAN, 9 μg/L for COL, 12 μg/L for MER and 12.3 μg/L for DAP. Finally, both electrochemical biosensor and the SPRi optical biosensor showed that for the four antibiotics the standard deviations were less than 10% with respect to the HPLC results, with ranges for VAN between ~5–6 µg/mL, for COL ~0.2–0.7 µg/mL, for MER ~4.5–5.5 µg/mL and for DAP ~0.09–0.65 µg/mL. Conclusions: These kinds of biosensors provide a precise and sensitive strategy, together with real-time determination, to quantify last-line antibiotics, with working ranges like those shown by robust techniques such as HPLC and great potential for the clinic. Full article

Background: Maintaining therapeutic meropenem plasma concentrations requires prolonged infusion, but stability concerns exist between preparation and administration. This study compared the stability and operability of ready-to-use powder–liquid double-chamber bag (DCB) infusions versus traditional powder-for-injection (PFI) meropenem under clinical conditions. Methods: Infusions at clinically relevant concentrations were stored at 2–8 °C, 25 ± 5 °C, and 40 ± 2 °C for 12 h. Stability assessments included appearance, pH, osmolality, insoluble particle count, meropenem content (HPLC), and impurity A level. Results: DCBs demonstrated superior content uniformity, significantly fewer insoluble particles (p < 0.05), and greater operational simplicity compared to PFI. Refrigeration maintained meropenem content > 95% and effectively suppressed impurity formation for up to 12 h. However, at both room temperature and elevated temperature, impurity A exceeded pharmacopoeial limits within 2 h, particularly at higher concentrations. An innovative bedside solvent volume adjustment method enabled DCBs to deliver high-concentration infusions, facilitating individualized critical care dosing. Conclusions: Compared with traditional powder injection formulations, the Meropenem powder–liquid dual-chamber bag offers more convenient operation under routine preparation conditions and poses a lower risk of contamination during the preparation process. Its stability is more sensitive to storage temperature, requiring strict adherence to refrigeration conditions. When stored under standardized conditions, the dual-chamber bag can better ensure drug efficacy stability and medication safety, making it particularly suitable for clinical emergency use and standardized workflow management. Full article

Background/Objectives: Carbapenem-resistant Acinetobacter baumannii poses a critical threat due to its ability to acquire multiple resistance mechanisms and persist under antibiotic pressure. This study aimed to elucidate the molecular basis of imipenem resistance in clinical A. baumannii isolates by integrating phenotypic, molecular, transcriptional, and clonal analyses. Methods: Eleven A. baumannii isolates identified by MALDI-TOF MS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were investigated. Antimicrobial susceptibility to imipenem and meropenem was assessed, followed by polymerase chain reaction (PCR) detection of Ade efflux pump, outer membrane porin, and OXA-type carbapenemase genes. Transcriptional responses to sub-inhibitory imipenem exposure were evaluated using quantitative real-time PCR, and clonal relatedness was assessed by arbitrarily primed PCR. Results: All isolates were carbapenem-resistant, with bla_OXA-23 detected in all isolates and bla_OXA-24 absent in one isolate. Transcriptional analysis revealed isolate-specific responses to imipenem exposure. Among Ade efflux pump components, only adeR exhibited expression changes, displaying either downregulation or upregulation depending on the isolate, whereas adeA, adeB, adeC, and adeS transcripts were not detected under the tested conditions. Outer membrane porin genes showed heterogeneous regulation, with ompA and carO downregulated, while some isolates showed increased expression. Expression of oprD varied among isolates, and omp33–36 transcripts were detected in a single isolate and were reduced after exposure. Clonal analysis identified nine distinct genotypes, indicating genetic diversity and the absence of clonal dominance. Conclusions: These findings highlight the multifactorial and heterogeneous nature of carbapenem resistance in A. baumannii, emphasizing the interplay between regulatory efflux mechanisms, porin modulation, and carbapenemase carriage. Full article

Listeria innocua is a bacterium frequently detected in food and food production plants (FPPs). Understanding the heterogeneity of L. innocua food isolates is essential for predicting potential food safety threats and developing preventive and control measures. This study aimed to characterize L. innocua isolated from raw drinking milk by investigating the genomic features related to virulence, antimicrobial resistance, and persistence using whole-genome sequencing (WGS), along with phenotypic antimicrobial susceptibility testing using the disk diffusion method. All ten isolates analyzed in this study belonged to sequence type (ST) 492 and were distantly related to the reference strain. A total of 80 virulence-associated genes were identified, including the complete Listeria Pathogenicity Islands-3 (LIPI-3) and LIPI-4 clusters typically found in virulent L. monocytogenes clones, as well as 66 additional genes involved in adhesion, invasion, motility, post-translational modification, regulation, immune modulation, and stress survival. Stress survival islet 2 (SSI-2) and genes encoding the Clp protease complex (clpC, clpE, clpP), which support both persistence and virulence, were also detected, whereas LIPI-1 and internalin genes were not detected. The antimicrobial resistance determinants included fosX, lin, norB, sul, and three multidrug efflux pumps (lde, mdrL and mdrM). Mobile genetic elements (plasmids, prophages, or transposons) were not detected. All isolates were phenotypically susceptible to benzylpenicillin, ampicillin, meropenem, erythromycin, and trimethoprim–sulfamethoxazole. These findings underscore the importance of ongoing genomic surveillance of L. innocua in food environments and highlight the need to assess the potential risk posed by specific lineages, such as ST492, to food safety. Full article

(1) Background: Chronic rhinosinusitis (CRS) with recurrent symptoms despite therapy raises concern for underlying antimicrobial resistance. While inflammation is central to disease pathophysiology, increasing evidence suggests that resistant bacterial populations within the sinonasal niche may contribute to treatment failure. This study aimed to characterize the molecular resistance profiles of bacterial isolates from refractory CRS patients and evaluate genotype–phenotype concordance and clinical resistance burden. (2) Methods: Our observational study includes 99 bacterial isolates obtained by endoscopically guided nasal swabs from adult CRS patients with recurrent disease. Species identification and antimicrobial susceptibility testing were performed using the VITEK^®2 system. Resistance genes were detected using multiplex-PCR. Statistical analyses included Mann–Whitney U tests for genotype–phenotype associations, Kruskal–Wallis testing across MDR categories, Spearman correlation between gene burden and clinical risk, and concordance metrics. (3) Results: Recognized sinonasal pathogens accounted for 46.5% of isolates, predominantly Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. β-lactamase genes (tem 25.3%, shv 9.1%, ctxM 8.1%) and macrolide resistance markers (ermB 20.2%) were most prevalent, while carbapenemase genes remained infrequent. Significant phenotype–genotype correlations were observed for mecA–oxacillin, sul1–TMP-SMX, KPC–meropenem, and tem–β-lactams (p < 0.01). Gene burden increased progressively across clinical risk categories (p < 0.001), with MDR/XDR isolates concentrated in patients with repeated antibiotic exposure. Molecular and phenotypic analyses demonstrated high concordance for selected gene–antibiotic pairs, supporting targeted molecular screening as an adjunct to culture-based diagnostics in refractory CRS. Full article

Background/Objectives: In the broad and current context of antimicrobial resistance, antibiotic management and therapeutic surveillance are essential in hospitals. The present study (five-year retrospective, 2020–2024) aimed to analyze antibiotic consumption in relation to pathogens identified in a multidisciplinary hospital. Results: In terms of antibiotic consumption (overall 2020–2024), although initially Watch antibiotics were predominantly used, a decrease was observed in favor of Access class antibiotics (sharply increase from 2022 to 2023 and maximum in 2024). For Reserve antibiotics, only slight annual fluctuations were observed, but there was an important reduction in colistin consumption. The most used were cephalosporins (cefazolin, cefuroxime and ceftriaxone), carbapenems (meropenem and ertapenem), vancomycin and linezolid. Regarding pathogens, the most notable were: Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus spp., Pseudomonas aeruginosa. Among the ESKAPE bacteria, Acinetobacter baumannii was the least frequent in our samples. ESKAPE bacteria predominantly colonized specimens from the respiratory tract, digestive tract, skin and soft tissue. Resistant strains were observed, mainly Methicillin-resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) Klebsiella spp., but no alarming increases in number were recorded in the analyzed period. Methods: The analysis was carried out using tools recommended by the World Health Organisation (Access Watch Reserve antibiotics classification (AWaRe); Bacterial Priority Pathogen List (BBPL); Defined Daily Dose (DDD)), Average Annual Percent Change (AAPC) calculation and ESKAPE classification (bacteria group: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). Conclusions: Relatively stable trends in bacterial isolates and resistant strains over five years (2020–2024) are consistent with effective antimicrobial stewardship practices. Full article

Background: The goal of this study was to characterize the microbial etiology, antimicrobial susceptibility, and temporal resistance trends of early-onset neonatal sepsis (EOS) pathogens in a tertiary neonatal intensive care unit over 10 years (2014–2023), assessing empirical therapy adequacy and mortality associations. Methods: Retrospective analysis was performed on the positive blood cultures of neonates with confirmed EOS, born between 1 January 2014 and 31 December 2023. Blood was aseptically collected into PEDS Plus/BC bottles, incubated using the BACTEC system, with pathogen identification by biochemical assays or MALDI-TOF MS. Susceptibility testing followed EUCAST disk-diffusion standards, with additional resistance assays. Results: Among 6631 NICU admissions, 39 neonates met EOS criteria (31 preterm, 8 term). In preterm infants, Gram-negative Enterobacterales—mainly E. coli (n = 20)—predominated, while GBS was most common in term infants. All GBS isolates (n = 7) were susceptible to benzylpenicillin and vancomycin. Although 90% of E. coli were ampicillin-resistant, 90–95% remained susceptible to third-generation cephalosporins, piperacillin–tazobactam, and aminoglycosides. Two E. coli isolates produced ESBL but remained susceptible to aminoglycosides and carbapenems. Mortality was higher in E. coli EOS (50%) than in GBS (0%) or other pathogens (25%), with borderline significance (p = 0.0547; adjusted RR 1.55, 95% CI 0.54–4.41). Ampicillin resistance was not associated with increased mortality. No annual resistance trends were observed. Conclusions: In this 10-year NICU cohort, the etiology of EOS differed markedly between preterm and term neonates. Recommended empirical ampicillin–aminoglycoside therapy demonstrated in vitro efficacy against most neonatal bloodstream isolates pending pathogen identification. However, the widespread ampicillin resistance, particularly among E. coli strains, supports consideration of cephalosporin–aminoglycoside combinations or meropenem monotherapy when rapid beta-lactam bactericidal activity is clinically essential. Mortality was higher in E. coli EOS, though not statistically significant, and unrelated to ampicillin resistance. Full article

Carbapenems are essential for the treatment of severe infections caused by Gram-negative bacteria, particularly in critically ill and immunocompromised patients. However, the global rise of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii has significantly eroded their effectiveness, and the phenomenon is now recognized as a major public health threat. Resistance is driven by the complex and evolving interplay of enzymatic and non-enzymatic mechanisms, occurring within highly successful clonal lineages and mobile genetic platforms. This review summarizes advances since 2020 in the molecular basis of carbapenem resistance, integrating enzymatic mechanisms across Ambler classes A, B, C, and D with emerging non-enzymatic contributors, including porin remodeling, efflux pump upregulation, target-site alterations, and outer-membrane adaptations. Particular attention is given to adaptive genome dynamics, such as IS26-mediated gene amplification, plasmid multimerization, and heteroresistance, that generate unstable resistance phenotypes and complicate routine susceptibility testing. Newly introduced β-lactam/β-lactamase inhibitor combinations exert distinct selective pressures: ceftazidime–avibactam favors KPC Ω-loop variants and permeability defects, often restoring carbapenem susceptibility, whereas meropenem–vaborbactam and imipenem–relebactam resistance is driven mainly by porin loss and β-lactamase gene amplification. Cefiderocol resistance is multifactorial, frequently involving impaired siderophore uptake and heteroresistance, while sulbactam–durlobactam remains active against OXA-producing A. baumannii but is compromised by metallo-β-lactamases and PBP3 alterations. Carbapenem resistance is increasingly characterized by convergent, multi-layered adaptations that undermine both established and novel therapies. While high-level randomized evidence remains limited for some resistance mechanisms, emerging mechanistic, microbiological, and clinical data support the need for mechanism-aware diagnostics, repeated susceptibility assessment during therapy, and stewardship strategies informed by resistance biology. Integrating molecular context into routine practice will be critical to preserving emerging treatment options and limiting the global impact of carbapenem resistance. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global public health threat, particularly in hospitals. Antimicrobial Stewardship Programs (ASPs) aim to optimize prescribing, reduce unnecessary exposure to broad-spectrum agents, and mitigate resistance. This study evaluated the clinical, ecological, and economic impact of an ASP implemented in January 2021 in a high-complexity hospital in Brazil, focusing on antimicrobial consumption, temporal trends in bacterial susceptibility, and direct antimicrobial-related costs. Methods: A quasi-experimental pre–post study using an interrupted time-series design was conducted in the adult intensive care unit from January 2019 to December 2023. Antimicrobial consumption was measured as Defined Daily Doses per 1000 patient-days (DDD/1000-PD) for ceftriaxone, meropenem, piperacillin–tazobactam, vancomycin, and polymyxin B. Temporal trends were assessed using Joinpoint regression, and pre- and post-intervention periods were compared using Student’s or Mann–Whitney tests. Susceptibility data were interpreted according to BrCAST standards. Results: Significant and sustained reductions were observed for all agents except polymyxin B. Susceptibility improved or stabilized among key Gram-negative pathogens, with a significant increase in aggregated Gram-negative susceptibility after 2021, while intrinsically resistant organisms showed limited change. Annual antimicrobial costs decreased by approximately USD 174,000. Conclusions: The ASP was associated with reduced broad-spectrum antimicrobial use, favorable ecological trends, and substantial cost savings. Full article