Search Results (332)

Background and Objectives: Antimicrobial resistance (AMR) is a major challenge, particularly in intensive care units, where broad-spectrum therapy is often initiated before microbiological confirmation. Artificial intelligence (AI) may improve AMR prediction, but its clinical value depends on integration with bioengineering-enabled digital microbiology. This narrative review examines how AI, bioengineering platforms and digital microbiology can support AMR prediction, clinical decision support and antimicrobial stewardship across the sample-to-decision pipeline. Materials and Methods: A targeted narrative review was conducted using PubMed/MEDLINE and Google Scholar. Publications from 2020 onward were prioritized, while earlier seminal studies, methodological frameworks and regulatory documents were included when relevant. Evidence was synthesized across AI-based resistance prediction, antimicrobial stewardship, digital microbiology and bioengineering technologies. Results: AI and machine-learning approaches showed promising performance in patient-level resistance prediction, pathogen-level susceptibility prediction and antimicrobial stewardship. For example, model discrimination reached an AUROC of 0.936 for carbapenem-resistant Klebsiella pneumoniae prediction, while model-guided empirical therapy in Enterobacterales bloodstream infections could have increased active beta-lactam therapy from 70% to 79%. However, most evidence remains retrospective and single-centre, with limited external or prospective validation. Conclusions: AI has considerable potential to support AMR prediction and antimicrobial stewardship, but current evidence primarily demonstrates technical feasibility rather than established clinical effectiveness. Broader implementation will require rigorous validation, integration into clinical workflows, continuous monitoring and demonstration of clinical benefit. Full article

Background/Objectives: Surveillance of local antibiotic resistance plays a critical role in guiding empirical antibiotic therapies in emergency departments (EDs). This study aimed to collect and analyze a five-year period of prevalence and AMR rates among “ESKAPE” pathogens in a tertiary-care ED setting. Methods: This retrospective observational study included a complete census of microbiological specimens collected from patients presenting to the emergency department between 1 January 2019 and 31 December 2023. Data was retrieved from the MedBakter laboratory information system. Non relevant isolated and duplications were excluded. Only the first isolates per patient per phenotype were included in the final dataset. Results: The final dataset contained 6510 isolates. The most frequent isolates were E. coli (2717, 41.7%), K. pneumoniae (715, 11.0%), and P. mirabilis (696, 10.7%) followed by E. faecalis (662, 10.2%). Prevalence of multi-drug resistance (MDR) was 23.26% among “ESKAPE” pathogens, with highest prevalence in M. morganii (79.6%), P. stuartii (78.5%) and S. marcescens (77.1%). Difficult-to-treat resistance (DTR) was found in 32 isolates, while extensive drug resistance (XDR) was found in 5 isolates. The prevalence of other high-priority MDR bacteria was 12.4% for MRSA and 4.7% for VRE, while among Gram-negative bacteria the prevalence of carbapenem-resistant Enterobacterales was 0.52%. The prevalence of cephalosporin-resistant Enterobacterales varied greatly between 0 and 33%. Conclusions: Despite these important AMR trends, the cumulative antibiogram, according to the World Health Organization (WHO)-issued Access, Watch and Reserve (AWaRe) classification, revealed room for empirical antibiotic choices that spare Watch and Reserve agents. The results will aid the revision of the local antibiotic guidelines. Full article

Carbapenem-resistant Enterobacterales (CRE) are a major public health concern, yet genomic data from Bulgaria remain limited. We investigated the genomic epidemiology and genomic characteristics of clinically significant CRE recovered at University Hospital “Lozenetz”, Sofia, between 2022 and 2025. Antimicrobial susceptibility testing, phenotypic carbapenemase characterization, and PCR were combined with whole-genome sequencing of 23 purposively selected isolates chosen to capture temporal, species, carbapenemase, specimen, ward, and resistance-phenotype diversity. The proportion of CRE among all Enterobacterales remained broadly stable over the study period, and Klebsiella pneumoniae was the predominant species throughout. NDM-type carbapenemases were the most frequent overall, although VIM-, KPC-, and OXA-48-like enzymes were also detected. Among the sequenced isolates K. pneumoniae ST6260 (n = 16) was predominant. The remaining isolates included single K. pneumoniae isolates belonging to ST11, ST101, and ST258; two Enterobacter hormaechei ST114; one Proteus mirabilis ST93; and one Providencia stuartii ST46. All ST6260 isolates carried chromosomal blaNDM-5 within a conserved multidrug-resistance module with variable downstream regions, whereas blaOXA-232 was situated on a small ColKP3 plasmid within a defined subcluster. Overall, the data indicate that ST6260 is an emerging hospital-associated multidrug-resistant lineage. Full article

Background/Objectives: The rise of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales has led to an increased carbapenem use, raising concerns regarding selection pressure for carbapenem-resistant organisms. Ceftolozane–tazobactam (C/T) is a potential effective carbapenem-sparing alternative. This single-centre retrospective study evaluated the clinical effectiveness and mortality predictors of ceftolozane–tazobactam versus meropenem as definitive targeted therapy for ESBL-producing Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center retrospective analysis of adult hospitalized patients between January 2022 and February 2024 who presented with BSIs caused by ESBL-producing Enterobacterales. Patients (N = 185) were included if they received either C/T (n = 73) or optimized high-dose meropenem (n = 112) for at least 48 h. The primary clinical endpoint was all-cause 30-day mortality. Secondary endpoints included clinical success (cure), in-hospital mortality, treatment duration, microbiological eradication, and infection recurrence rates. A multivariable logistic regression model was executed to determine independent predictors of 30-day mortality. Results: Escherichia coli (54.1%) and Klebsiella pneumoniae (35.1%) were the primary pathogens. The raw clinical success rate was higher with C/T than meropenem (83.6% vs. 71.6%, p = 0.078). Unadjusted 30-day mortality was 12.3% for C/T and 19.6% for meropenem (p = 0.342). Zero recurrences occurred with C/T compared to an 8.0% recurrence rate with meropenem (0/73 [0.0%] in C/T vs. 9/112 [8.0%] in meropenem, p = 0.015). In the multivariable logistic regression analysis, definitive targeted treatment with C/T was independently associated with lower odds of all-cause 30-day mortality (Adjusted Odds Ratio [aOR] 0.60; 95% Confidence Interval [CI] 0.33–0.92; p = 0.022). Conversely, independent clinical mortality risks included male gender (p = 0.027), baseline SOFA score (p = 0.001), septic shock (p = 0.001), and an unknown primary infection source (p = 0.001). Conclusions: In this single-center retrospective observational cohort, definitive targeted therapy with ceftolozane–tazobactam was associated with favorable clinical success and lower adjusted 30-day mortality compared to meropenem in patients with ESBL Enterobacterales BSIs. These observational data support further prospective evaluation of C/T as a potential carbapenem-sparing option. Prospective randomized controlled trials are required to confirm these findings before clinical practice algorithms are modified. Full article

Carbapenem-resistant Enterobacterales (CRE) represent one of the most important antimicrobial resistance threats in Europe, particularly in healthcare settings. Their increasing epidemiological significance is driven by the dissemination of carbapenem-resistant Klebsiella pneumoniae, the emergence of high-risk clones, horizontal transfer of mobile genetic elements, and the convergence of antimicrobial resistance and hypervirulence. Despite the growing epidemiological importance of CRE, surveillance and preparedness remain heterogeneous across European countries, creating a need for a continent-wide assessment of existing surveillance systems, implementation gaps, and emerging challenges. This narrative review summarizes the current epidemiology of CRE in Europe and critically discusses the role of European and global surveillance systems in monitoring their spread. Particular attention is given to the European Antimicrobial Resistance Surveillance Network (EARS-Net), European Antimicrobial Resistance Genes Surveillance Network (EURGen-Net), Healthcare-Associated Infections Surveillance Network (HAI-Net), European Surveillance of Antimicrobial Consumption Network (ESAC-Net), Point Prevalence Survey (PPS), EpiPulse/TESSy, the Central Asian and European Surveillance of Antimicrobial Resistance (CAESAR) programme, and the World Health Organization Global Antimicrobial Resistance and Use Surveillance System (WHO GLASS). Although Europe has well-established surveillance infrastructures, substantial heterogeneity persists among countries with respect to microbiological and genomic diagnostic capacity, reporting practices, infection prevention and control (IPC), antimicrobial stewardship, healthcare infrastructure, and implementation of national policies. These differences limit data comparability and may delay the detection of colonization, outbreaks, and cross-border transmission. The available evidence indicates that effective CRE control requires integrated surveillance combining microbiological, genomic, epidemiological, and antimicrobial consumption data within a coordinated One Health framework. Further expansion of genomic surveillance, harmonization of surveillance indicators, strengthening of healthcare system preparedness, and wider implementation of antimicrobial stewardship programmes are identified as priority areas for improve CRE prevention and control across Europe. By integrating evidence across surveillance, diagnostics, infection prevention and control, and antimicrobial stewardship, this review highlights key gaps in current European approaches and provides a framework for prioritizing future surveillance and preparedness efforts. Full article

Background/Objectives: The epidemiology of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) in Europe is evolving towards an increasing contribution of metallo-β-lactamases (MBLs). In particular, co-production of New Delhi metallo-β-lactamase (NDM) and OXA-48-like carbapenemases represents a major concern due to limited therapeutic options and epidemic potential. We aimed to describe temporal trends and genomic characteristics of NDM and OXA-48-like co-producing K. pneumoniae within a regional surveillance programme targeting ceftazidime-avibactam (CZA)-resistant carbapenem-resistant Enterobacterales (CRE) in the Latium Region, Italy. Methods: Between January 2019 and December 2025, CZA-resistant CRE isolates were collected through a regional surveillance network. Antimicrobial susceptibility testing and carbapenemase detection were performed, and NDM-producing K. pneumoniae (NDM-Kpn) was analysed by whole-genome sequencing (WGS). Genomic analyses included multi-locus sequence typing, assessment of clonal relatedness, and resistome/virulome profiling. Results: A total of 2752 non-repetitive CZA-resistant CRE were collected. The analysis of CZA-resistant K. pneumoniae isolates submitted to the regional surveillance network showed that the proportion of NDM producers increased markedly from 2023 onwards. In particular, NDM in association with OXA-48-like reached 26.0% in 2024 and 43.6% in 2025, becoming the predominant carbapenemase profile within this selected surveillance population. WGS of 437 NDM-Kpn revealed a structured population dominated by Sequence Type (ST)147 (63.2%), widely disseminated across 24 hospitals and characterised by a predominant NDM-1 variant and OXA-48-like co-producing profile associated with KL10/wzi420 capsular type. A subset of isolates, mainly within the ST147-KL64 subgroup, showed higher virulence scores, indicating a possible convergence of resistance and virulence. Conclusions: Our findings indicate a rapid shift towards NDM-mediated resistance among CZA-resistant K. pneumoniae submitted to the regional surveillance network, with the emergence of NDM and OXA-48-like co-producing isolates associated with a dominant ST147 clone detected across multiple hospitals. These results highlight the urgent need for coordinated genomic surveillance and infection prevention strategies. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a high-priority healthcare-associated pathogen. This study aimed to estimate rectal CRKP carriage and characterize same-patient clinical-site CRKP detection. Methods: We conducted a single-center retrospective microbiological surveillance study in a Romanian tertiary-care hospital between 1 January 2025 and 1 April 2026. Patient-level prevalence used all 3123 screened patients, with each patient counted once. CRKP recovery from rectal screening specimens was classified as gastrointestinal carriage; non-rectal recovery was reported as clinical-site detection and not as confirmed infection because clinical adjudication was not systematic. Results: Among 3123 screened patients, 712 (22.8%) had a positive rectal screen, 294 (9.4%) had resistant rectal K. pneumoniae carriage, and 168 (5.4%) had rectal CRKP carriage. Of these 168 carriers, 83 (49.4%) also had a retained non-rectal CRKP isolate; rectal recovery occurred first in 45, non-rectal recovery first in 36, and collection timestamps were identical in 2. Healthcare exposures, prior carbapenem-resistant Enterobacterales carriage, and admission-relative timing were analyzed descriptively using the full 168-patient denominator, with unavailable values retained as unknown. Invasive-device, intensive-care, recent hospitalization or readmission, and recent antimicrobial exposures were frequently documented. Admission-relative timing identified early detections, probable within-admission screen conversions, hospital-onset detections without a preceding negative screen, and indeterminate cases. Conclusions: Rectal CRKP carriage was frequent and commonly associated with same-patient CRKP detection at non-rectal clinical sites, indicating a substantial hospital-associated burden. In critically ill patients with sepsis or septic shock, known CRKP carriage should inform the choice of empirical CRKP-active therapy, with prompt de-escalation once microbiological findings and clinical response allow. Full article

Understanding the functional potential of the gut microbiota for carbapenem-resistant Enterobacterales (CRE) decolonisation is essential for developing novel non-antibiotic strategies to promote their clearance. In a previous study, we identified distinct taxonomic signatures associated with spontaneous CRE decolonisation (DeCol). Here, we aimed to determine whether these taxonomic differences were accompanied by differences in the predicted functional potential of the gut microbiota. Patients were identified from a database of individuals colonised with CRE. We performed Illumina shotgun metagenomic sequencing on 14 persistent CRE carriage (Col) and 23 DeCol patients with OXA-48-producing isolates. Bioinformatic analysis was performed using SqueezeMeta and differential abundance of functional and metabolic genes was assessed using DESeq2. Several antimicrobial resistance genes, including blaOXA-48, were underrepresented in DeCol patients. In contrast, DeCol patients showed an overrepresentation of genes associated with motility, regulated adhesion, short-chain fatty acid (SCFA)-related pathways and alternative carbohydrate metabolism. These orthologue enrichment patterns are consistent with functions previously linked to intestinal homeostasis in the literature. Conversely, Col patients exhibited an overrepresentation of genes associated with redox defence, biofilm formation and amino acid metabolism, suggesting distinct predicted functional profiles between persistent carriage and spontaneous decolonisation. Spontaneous CRE decolonisation was associated with distinct KEGG-based functional signatures and a lower abundance of antimicrobial resistance determinants. These functional profiles were consistent with the taxonomic differences previously identified in the same cohort and generate hypotheses regarding microbiome functions that may contribute to colonisation clearance. Because these findings are based on gene-content analysis, they reflect predicted functional potential rather than direct evidence of metabolic activity. Further multi-omics and experimental studies are required to validate these observations. Full article

Objectives: The intent of this study was to report reference in vitro antimicrobial susceptibility testing results for funobactam (formerly XNW4107) in combination with imipenem against recent, worldwide clinical isolates of Gram-negative bacilli. Methods: MICs for imipenem in combination with a fixed concentration of funobactam (8 mg/L), and seven comparator agents, were determined using the reference CLSI M07 broth microdilution method for 4003 clinical isolates of Gram-negative bacilli (2008 Enterobacterales, 999 Acinetobacter baumannii, and 996 Pseudomonas aeruginosa) collected from 211 unique clinical laboratory sites in 54 countries as part of industry-sponsored antimicrobial surveillance studies in 2021 and 2022. MICs were interpreted by 2026 CLSI M100 breakpoints. Most isolates with imipenem-funobactam MICs of ≥4 mg/L (95.4%) underwent whole genome sequencing to identify acquired β-lactamase gene carriage. Results: MIC₉₀ values for imipenem-funobactam were 2 mg/L for all 2008 isolates of Enterobacterales, and 1, 0.5, and 0.5 mg/L, respectively, for metallo-β-lactamase (MBL)-negative Enterobacterales (n = 1969), non-Morganellaceae Enterobacterales (NME) (n = 1752), and MBL-negative NME (n = 1718) isolate subsets. MIC₉₀ values for imipenem-funobactam and imipenem alone were identical or within one doubling dilution for all 14 species of Enterobacterales tested except Klebsiella pneumoniae, Citrobacter freundii, and Enterobacter bugandensis which showed differences of 32-fold (imipenem-funobactam MIC₉₀, 0.5 mg/L; imipenem MIC₉₀, 16 mg/L), 8-fold (0.25 mg/L; 2 mg/L), and 4-fold (0.25 mg/L; 1 mg/L), respectively. Both for all A. baumannii isolates (n = 999) and for MBL-negative isolates (n = 962), the imipenem-funobactam MIC₉₀ value (4 mg/L) was 32-fold lower than for imipenem alone (128 mg/L). Both for all P. aeruginosa (n = 996) isolates and MBL-negative isolates (n = 962), we observed a 4-fold difference in potency between imipenem-funobactam (MIC₉₀, 4 mg/L) and imipenem alone (MIC₉₀, 16 mg/L). Isolates carrying MBL demonstrated the highest MICs for imipenem-funobactam. Conclusions: Imipenem-funobactam demonstrated potent in vitro activity against most carbapenem-resistant isolates of A. baumannii, K. pneumoniae, NME and many isolates of carbapenem-resistant P. aeruginosa. Continued development of imipenem-funobactam is warranted. Full article

Background: Carbapenem-resistant Enterobacterales (CRE) are a major therapeutic challenge, particularly in settings where metallo-β-lactamases are prevalent. Aztreonam–avibactam (AZA) may provide activity against metallo-β-lactamase-producing isolates, whereas ceftazidime–avibactam (CZA) has limited activity against the isolates that harbor these enzymes. This study aimed to evaluate the in vitro activity of aztreonam–avibactam and ceftazidime–avibactam against invasive carbapenem-resistant Enterobacterales isolates and to characterize the distribution of carbapenemase genes in a tertiary-care center in Türkiye. Methods: A total of 100 non-duplicate CRE isolates recovered from blood cultures and sterile body fluids between January 2024 and January 2026 were included. Species identification and routine antimicrobial susceptibility testing were performed using MALDI-TOF MS and an automated system. CZA and AZA MICs were determined by gradient diffusion testing, whereas CZA–aztreonam synergy was assessed separately using a disk/gradient diffusion-based method. Carbapenemase genes were detected by real-time PCR. Whole-genome sequencing was performed for the two AZA-resistant Escherichia coli isolates. Results: The isolate collection was dominated by Klebsiella pneumoniae (87.0%), and most isolates were recovered from blood cultures (80.0%). CZA susceptibility was observed in 31.0% of isolates, with MIC_50/90 values of 256/256 mg/L. In contrast, AZA showed high in vitro activity, with 98.0% of isolates categorized as susceptible and MIC_50/90 values of 0.25/0.50 mg/L. CZA–aztreonam synergy was detected in 98.0% of isolates. Qualitative CZA–aztreonam synergy testing did not fully concord with direct AZA MIC-based susceptibility categorization: one AZA-resistant isolate showed a positive synergy result, whereas one synergy-negative isolate remained AZA-susceptible. Carbapenemase genes were detected in 99.0% of isolates; bla_NDM was the most frequent gene (81.0%), followed by bla_OXA-48 (72.0%), bla_KPC (14.0%), and bla_VIM (4.0%). The most common carbapenemase profile was bla_NDM + bla_OXA-48 (62.0%). bla_NDM carriage was strongly associated with CZA resistance, and CZA MICs were significantly higher among bla_NDM-positive isolates. The two AZA-resistant E. coli isolates belonged to ST500 and ST410, and both carried a YRIK insertion in PBP3; one of them additionally showed ompF disruption associated with a 4 bp insertion. Conclusions: AZA demonstrated potent in vitro activity against invasive CRE isolates in this setting, whereas CZA activity was substantially limited, likely reflecting the high prevalence of bla_NDM and frequent carbapenemase co-carriage. These findings support the potential value of AZA in regions with emerging metallo-β-lactamase predominance and highlight the importance of local molecular surveillance to guide antimicrobial strategies. Full article

Background: Colonization with multidrug-resistant (MDR) Gram-negative bacteria is common in critically ill patients, yet the meaning of a positive surveillance culture is not always clear at the bedside. For some patients, colonization remains asymptomatic; for others, it may represent the first step toward an invasive infection that can develop rapidly. Objectives: This review examines the transition from colonization to infection in intensive care unit (ICU) patients carrying MDR Pseudomonas aeruginosa, carbapenem-resistant or extended-spectrum β-lactamase-producing Enterobacterales, and carbapenem-resistant Acinetobacter baumannii (CRAB). Discussion: Across these pathogens, colonization should not be viewed as an isolated microbiological finding. Its clinical relevance depends on the organism involved, site and persistence of carriage, extent of colonization, prior antibiotic exposure, severity of illness, invasive devices, impaired host defences, and the epidemiological pressure within the ICU. Intestinal carriage of resistant Enterobacterales is particularly relevant because it may act as an endogenous reservoir for subsequent invasive infection. In patients colonized with CRAB, respiratory and multisite carriage appear to identify those at greatest risk of pneumonia and poor outcomes. For Pseudomonas aeruginosa, the relationship is less uniform but becomes more relevant in the presence of respiratory vulnerability, ICU exposure, and previous broad-spectrum antibiotic use. Conclusions: Colonization results should therefore support risk stratification, infection-prevention measures, and informed empirical treatment when infection is suspected, rather than automatically leading to antibiotic therapy. Full article

Background/Objectives: Diabetic foot infections (DFI) drive most non-traumatic lower-limb amputations, and empirical regimens must track local microbiology, which is itself evolving under broad-spectrum antibiotic pressure. Methods: We retrospectively analysed all consecutive bacterial cultures from clinically infected diabetic foot lesions at a single Polish outpatient centre over 2021–2025. Isolates were identified by MALDI-TOF mass spectrometry and susceptibility was interpreted under contemporaneous EUCAST breakpoints (v12.0–v15.0). Results: A total of 274 cultures yielded 443 isolates (polymicrobial index 1.62). Staphylococcus aureus remained the most common pathogen but fell from 55.0% to 38.9% of cultures, while Enterobacterales rose from 36.1% to 47.7% of all isolates. Proteus mirabilis and Streptococcus agalactiae emerged as major contributors, and Enterobacter hormaechei showed an apparent increase (the apparent rise in E. hormaechei reflects, at least in part, improved species-level identification rather than a true increase in incidence). Methicillin-resistant S. aureus was first documented in 2025 (6/38; 15.8%). P. mirabilis showed deteriorating activity against trimethoprim–sulfamethoxazole and ciprofloxacin, the first meropenem-resistant isolate appeared in 2025, and two carbapenem-non-susceptible Enterobacterales were also detected (2/18 carbapenem-tested isolates in 2025; 11%). Conclusions: The DFI profile has shifted from an S. aureus-dominated Gram-positive ecology toward a polymicrobial, increasingly Gram-negative one, with the first documentation of MRSA (on reintroduction of routine oxacillin testing) and of carbapenem-non-susceptible Enterobacterales. Empirical policy for moderate-to-severe DFI should reliably cover Enterobacterales and methicillin-resistant Gram-positives while preserving carbapenems and glycopeptides through active stewardship. Full article

Background/Objectives: Urinary tract infections (UTIs) are common infectious complications in kidney transplant recipients (KTRs) and non-transplant nephrology patients. However, direct culture-based comparisons of urinary isolate distribution and antimicrobial resistance profiles between KTRs and non-transplant nephrology (NTN) patients remain limited. This study compared urinary isolates recovered from urine cultures with significant growth and their in vitro antimicrobial resistance profiles in hospitalized KTRs and NTN patients. Methods: In this retrospective culture-based study, urine culture results from patients hospitalized in the nephrology and kidney transplantation units between 1 January 2024 and 31 December 2025 were reviewed. Urinary isolate distribution, in vitro antimicrobial resistance profiles, and extended-spectrum β-lactamase (ESBL) production were compared between the two. Results: A total of 397 patients with at least one urine culture showing significant growth were included, comprising 220 KTRs and 177 NTN patients. Enterobacterales were significantly more frequent among KTRs than among NTN patients (77.2% vs. 41.1%, p < 0.001). Escherichia coli was the predominant urinary isolate in both groups. In contrast, Candida spp. (26.8% vs. 3.2%, p < 0.001), Enterococcus spp. (15.8% vs. 7.7%, p < 0.001), and non-fermenting Gram-negative bacteria (9.4% vs. 3.4%, p = 0.001) were more frequently recovered from NTN patients. Among E. coli isolates, resistance to gentamicin (p = 0.006) and ertapenem (p = 0.001) was significantly higher in the NTN group. Likewise, Klebsiella pneumoniae isolates from NTN patients showed significantly higher resistance to third-generation cephalosporins, aminoglycosides, and carbapenems (p < 0.05). ESBL production was also more frequent in NTN patients than in KTRs (55.7% vs. 41.9%, p = 0.013). Conclusions: Hospitalized KTRs and NTN patients exhibited distinct urinary isolate distributions and in vitro antimicrobial resistance profiles. These findings should be interpreted as culture-based epidemiological data rather than as differences in clinically confirmed UTI burden. Stratified local surveillance may help contextualize urinary isolate and susceptibility patterns across hospitalized nephrology populations. Full article

Longitudinal data on carbapenem-resistant Enterobacterales (CRE) from Saudi secondary healthcare settings remain limited. This study evaluated eight-year antimicrobial resistance trends among CRE isolates to provide locally relevant evidence for antimicrobial stewardship and empiric therapy. This retrospective surveillance study analyzed Enterobacterales isolates recovered from clinical specimens between 2017 and 2024 from a Saudi healthcare setting. Isolates were deduplicated by including only the first isolate per patient per year. CRE were defined as Enterobacterales demonstrating non-susceptibility to imipenem or meropenem. Demographic data, specimen sources, species distribution, and antimicrobial resistance profiles were summarized descriptively. Temporal trends in CRE prevalence and antimicrobial non-susceptibility were evaluated using logistic regression. Factors associated with CRE were assessed using multivariable logistic regression analyses. A total of 2378 Enterobacterales isolates were identified, of which 684 (28.8%) were CRE. CRE prevalence increased significantly over the study period, rising from 9.5% in 2017 to a peak of 40.1% in 2021 before declining to 27.1% in 2024. Multivariable logistic regression demonstrated that collection year (adjusted OR 1.12, 95% CI 1.08–1.17; p < 0.0001), male sex, and specimen source were independently associated with CRE. Klebsiella pneumoniae was the predominant species. High non-susceptibility rates were observed for cephalosporins and fluoroquinolones, while aminoglycosides and tigecycline demonstrated comparatively lower resistance. Significant temporal trends in non-susceptibility were observed for cefepime, ceftazidime, ciprofloxacin, and tigecycline. CRE represented a substantial proportion of Enterobacterales isolates and demonstrated extensive antimicrobial resistance. These findings highlight the importance of continuous local surveillance to inform empirical antimicrobial therapy, support antimicrobial stewardship, and monitor evolving resistance patterns. Full article

Introduction: Cefazolin is a first-generation cephalosporin with a moderate antimicrobial spectrum and the ability to induce the production of beta-lactamases by bacterial hosts. We investigated the effect of prophylactic cefazolin administration on the gut microbiome in patients undergoing orthopedic surgery. Methods: A total of 42 patients were included in this study, and fecal samples were collected before cefazolin administration, within 3 days after administration, and 1 month after surgery. Shotgun whole-metagenome sequencing was performed with DNA extracted from fecal samples to assess the taxonomic composition and antimicrobial resistance genes (ARGs). Results: Within 3 days after perioperative prophylactic cefazolin administration, both the diversity indices and the Gut Microbiome Health Index were significantly decreased. Furthermore, a decrease in two beneficial anaerobic Gram-positive taxa, Ruminococcus and Fusicatenibacter, and an increase in Enterobacterales was observed. The relative abundances of ARGs related to fluoroquinolone and beta-lactam antimicrobials including penicillin, cephalosporin, carbapenem, and monobactam, were also significantly increased. The changes in the taxonomic composition and resistome related to perioperative cefazolin administration partially reverted after one month. Conclusions: Our findings suggest that even perioperative administration of a single-class antimicrobial agent could be related to the decrease of the gut microbiome diversity with potentially unfavorable taxonomic changes and lead to an increase in ARGs. Full article