Search Results (543)

Pomegranate is valued for its abundant polyphenolic content and its capacity to promote health. In this study, pomegranate juice or pericarp extracts from two Mediterranean regions (Montenegro and Italy) were systematically and comparatively evaluated for the first time with respect to their polyphenolic composition, antioxidant capacity, and antimicrobial activity. The extraction of juice extracts was accomplished by means of the Kutscher–Steudel liquid–liquid extraction technique, which was employed to selectively recover phenolics. In contrast, the extraction of pericarp extracts from the solid matrix was achieved via Soxhlet extraction. A thorough high-performance liquid chromatography (HPLC) analysis was conducted to identify and quantify the major phenolic compounds present in the sample. This analysis revealed the presence of ellagitannin punicalagin isomers, with concentrations reaching up to 254.75 mg/g of the sample, as well as ellagic acid and gallic acid. The antioxidant potential of the samples was assessed using the antioxidant activity index (AAI) from the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and by a ferric reducing antioxidant power (FRAP) assay. Juice extracts demonstrated a range of activity levels, with AAI values ranging from 0.17 to 2.12 and FRAP values ranging from 2.49 to 19.41 mmol Fe²⁺/g. In contrast, pericarp extracts exhibited notably higher activity, with AAI values ranging from 0.18 to 27.57 and FRAP values ranging from 2.99 to 372.17 mmol Fe²⁺/g. This study demonstrates the markedly higher functional potential of pericarp extracts compared to juice extracts by linking detailed phenolic profiles with bioactivity data. Antimicrobial testing, inclusive of the determination of minimum bactericidal concentration (MBC), demonstrated that certain pericarp extracts manifested bactericidal properties at low concentrations against selected clinically pertinent strains, including methicillin-resistant Staphylococcus aureus (0.109% p/v), methicillin-sensitive S. aureus (0.109% p/v), carbapenem-resistant Acinetobacter baumannii (0.109% p/v), and Escherichia coli (0.563% p/v). Candida albicans and Klebsiella pneumoniae strains exhibited minimal sensitivity to these extracts. The findings indicate that pomegranate pericarp is a valuable by-product, and they demonstrate the potential of both juice and pericarp extracts as functional ingredients. Full article

Antibiotic resistance is arguably one of the greatest threats to global health today. The worldwide emergence of multidrug-resistant and hypervirulent Klebsiella pneumoniae underscores the urgent need for alternative treatments. Bacteriophages (phages) are considered one of the most promising alternatives to address this crisis. In this review, we summarize current knowledge of phage–host interactions and highlight recent advances in phage therapy against K. pneumoniae, including phage cocktails, antibiotic combination therapy, and treatments based on phage-derived proteins. Despite their tremendous therapeutic potential, significant challenges remain. We therefore also discuss strategies to optimize phage research and recent innovations in the field. Full article

Background/Objectives: Healthcare-associated infections (HAIs), particularly those caused by multidrug-resistant (MDR) bacteria, remain a major challenge for Romanian hospitals. This study aimed to evaluate the epidemiological burden of MDR-related HAIs and to characterize the distribution of MDR bacterial isolates and their antimicrobial resistance patterns over four consecutive semesters in a Romanian tertiary care hospital. Methods: A retrospective study was conducted using data from the Electronic Registry of HAIs, clinical observation sheets, and microbiology laboratory records. An epidemiological analysis was performed on patients diagnosed with MDR-related HAIs, while a separate microbiological analysis included all MDR bacterial isolates identified during the study period. Descriptive and comparative statistical analyses were applied to assess temporal trends, pathogen distribution, and resistance profiles. Results: Of the 327 HAIs identified, 56 cases (17.13%) were caused by MDR bacteria. Most MDR-HAIs originated from the Intensive Care Unit (≈60%), with Acinetobacter baumannii and Klebsiella spp. as the predominant pathogens. Overall mortality among patients with MDR-HAIs was high (51.79%), particularly in infections caused by A. baumannii and K. pneumoniae. Microbiological analysis of MDR isolates (n = 406) revealed consistently high resistance rates to ciprofloxacin, cefepime, and ceftazidime, exceeding 95% in 2023–2024, while resistance to carbapenems surpassed 90% by the end of the study period. Temporal variability in MDR burden was observed across semesters, suggesting an influence of clinical and institutional factors. Conclusions: MDR-related HAIs represent a significant and persistent problem in Romanian acute-care hospitals, particularly in Intensive Care Units. The dominance of carbapenem-resistant A. baumannii and extended-spectrum beta-lactamase-producing and carbapenem-resistant Klebsiella spp. highlights the urgent need for strengthened antimicrobial stewardship, enhanced microbiological surveillance, and reinforced infection prevention strategies. Full article

Acinetobacter baumannii has been characterized by CDC, WHO and most National Healthcare Systems worldwide as a critical nosocomial pathogen, and classified as an ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogen. Mortality of invasive infections due to A. baumannii exceeds 40%. To highlight its impact on public health, ECDC has organized a special project on national lab co-ordination to accurately detect and report carbapenem-resistant strains, to identify epidemiological factors for infection (or colonization) with carbapenem-resistant A. baumanii at clonal and sub-genomic level. This review aims to describe the history, epidemiology, and evolution of resistance of A. baumannii, and stress the caveats associated with the management of systemic infections. Available active antimicrobials and drugs in the pipeline are listed, and available clinical evidence on their pharmacokinetics and efficacy in various types of infections are described. Clinician’s choice of treatment (drug, and monotherapy vs. combination treatment) depends on the patients’ profile, site of infection and antimicrobial resistance profile. Emphasis is laid on specific patient subpopulations, whose management is discussed. Full article

Background and Objectives: Secondary bacterial infection drives poor outcomes in older adults with COVID-19, but age-specific microbiology and its interaction with severity scores are not well defined. We characterized respiratory and pleural pathogens, resistance profiles, and their impact on day-5 SOFA/APACHE II in octogenarians versus younger adults. Methods: We performed a retrospective cohort study of adults with RT-PCR-confirmed coronavirus disease 2019 (COVID-19) at a tertiary infectious diseases center (≥80 years, n = 152; <65 years, n = 327). Respiratory and pleural samples were processed according to EUCAST standards. Identification employed matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Pathogen distributions, susceptibilities, and rates of superimposed pneumonia, empyema, and bacteremia were compared by age, and associations between secondary pneumonia, day-5 SOFA/APACHE II, and 28-day mortality were analyzed. Results: Sputum was obtained in 67.1% of older and 65.7% of younger adults, with numerically higher culture positivity in older patients (73.5% vs. 65.1%). Pathogen spectra were similar, dominated by Streptococcus pneumoniae (24.0% vs. 24.3%), methicillin-susceptible Staphylococcus aureus (MSSA) (18.7% vs. 20.7%), methicillin-resistant Staphylococcus aureus (MRSA) (9.3% vs. 6.4%), and Klebsiella pneumoniae, including extended-spectrum β-lactamase (ESBL)-producing strains. Empyema was more frequent in octogenarians (7.9% vs. 3.1%), and pleural cultures were usually positive. Meropenem retained 100% activity against ESBL-producing K. pneumoniae and Pseudomonas in both strata. In ≥80-year-olds, superimposed pneumonia was associated with higher day-5 SOFA (6.6 vs. 5.5) and APACHE II (24.3 vs. 21.0) scores and markedly increased 28-day mortality (37.5% vs. 9.8%). Conclusions: In octogenarians with COVID-19, secondary bacterial pneumonia and empyema are frequent, microbiologically similar to younger adults, and strongly amplify organ dysfunction and mortality even with largely preserved carbapenem susceptibility. Full article

Emerging antimicrobial resistance (AMR) in companion animals represents a global health concern as they serve as potential reservoirs for multidrug-resistant (MDR) bacteria, which can be transmitted to humans. Herein, we provide comprehensive surveillance data on resistance patterns in veterinary hospital settings, focusing on urinary tract infection. A total of 23 bacterial strains were isolated from urine specimens of hospitalized companion animals suspected of urinary tract infections (UTIs) between 2022 and 2024. 16S rRNA sequencing analysis revealed that Escherichia coli (47.8%), Klebsiella pneumoniae (21.7%), and Pseudomonas aeruginosa (8.7%) were predominant uropathogens. Minimum inhibitory concentration and minimum bactericidal concentration tests were employed to analyze AMR patterns across different classes of antibiotics. Moreover, antimicrobial susceptibility test exhibited 73.91% MDR according to the standard definition given by the Clinical and Laboratory Standards Institute (CLSI) M100 guidelines. Most Gram-negative bacteria have been shown to be resistant to beta-lactam antibiotics, especially carbapenems. Notably, an E. coli strain was confirmed to possess the bla_NDM-1 gene encoding the carbapenemase New Delhi metallo-β-lactamase. These findings support the implementation of targeted infection control measures and evidence-based treatment protocols to preserve antimicrobial efficacy in companion animal medicine to minimize potential public health risks through the One Health approach. Full article

Background/Objectives: Antimicrobial resistance (AMR) among Enterobacterales poses a major threat to public health in Southern Africa and has led to limited treatment options and increased mortality. Despite Africa bearing the brunt, there is limited data on the epidemiology and molecular epidemiology of the genetic determinants of β-lactam and/or carbapenem resistance. This narrative literature review summarizes the epidemiology and molecular characteristics of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE), carbapenem-resistant Enterobacterales (CRE), and carbapenemase-producing Enterobacterales (CPE) in Southern Africa, while identifying data gaps and surveillance challenges. Methods: A comprehensive literature review was conducted using peer-reviewed articles from ten Southern African countries, including South Africa, Lesotho, Eswatini, Botswana, Namibia, Angola, Zambia, Zimbabwe, Mozambique, and Malawi, reporting the epidemiology and/or molecular characterization of ESBL-PE, CRE, and CPE. Results: ESBL-PE, CRE, and CPE pose an increasing healthcare threat in Southern Africa, with prevalence varying widely by source. Klebsiella pneumoniae and E. coli are the predominant ESBL-PE, CRE, and CPE species. The most frequent resistance genes are bla_CTX-M among ESBLs and bla_NDM and bla_OXA among carbapenemases, reflecting global patterns. However, molecular characterization across the region remains limited, with countries such as Botswana, Lesotho, Eswatini, Zambia, and Zimbabwe lacking sufficient data on the prevalence and diversity of these resistance determinants. Conclusions: Despite the paucity of genomic and epidemiological data, Southern Africa faces an urgent AMR challenge. Strengthening laboratory infrastructure, genomic surveillance, and regional coordination is crucial to mitigate AMR and guide antibiotic stewardship policies. Full article

Background: In China, Carbapenem-resistant Klebsiella pneumoniae (CRKP) is dominated by sequence type 11 (ST11) harbouring KPC-2, with KL64 displacing KL47 and KL25 emerging. ST859 (ST11 variant) has caused outbreaks, but its epidemiology is unclear. Materials and Methods: A total of 99 non-duplicate CRKP isolates were collected from June to December 2024. Antimicrobial susceptibility was determined by broth microdilution. The genomic sequences of the strains were obtained using next-generation sequencing technology. Resistance genes, virulence loci, and plasmid replicons were identified with Kleborate, Abricate, and MOB-suite, respectively. Results: ST11 accounted for 63.64% and ST859 for 15.15%. All ST859 were KL19, while ST11 were mainly KL25 (60.32%) and KL64 (26.98%). 76.8% co-harbored carbapenemase and extended-spectrum beta-lactamase (ESBL) genes, with KPC-2 and CTX-M-65 being the predominant types. Susceptibility rates were 100% to tigecycline, and 78.79% to ceftazidime/avibactam. ST859 CRKP isolates exhibited higher phenotypic resistance to tetracycline and colistin than ST11 CRKP isolates (p < 0.05), and carrying LAP-2, QnrS1, QnrS10, and tet(A) more frequently. ST11-KL25 showed higher resistance to amikacin, gentamicin, and chloramphenicol, with increased prevalence of CTX-M-65, TEM-1, rmtB, catA2, and dfrA14 compared to ST11-KL64 (p < 0.05). IncF was the most prevalent replicon and both ST859 and ST11 CRKP carry conjugative resistance plasmids, and the host range is predominantly Enterobacterales. Conclusions: ST859-KL19 ranks second to ST11 with higher resistance to tetracyclines and colistin. ST11-KL25 may have already displaced ST11-KL64 as the predominant capsular type in Shanghai, with distinct resistance profiles between KL variants. Long-term, multicenter surveillance is urgently needed to delineate the evolutionary trajectory and clinical impact of these emerging clones. Full article

Eravacycline, a novel fluorocycline antimicrobial, was approved by China’s National Medical Products Administration (NMPA) in March 2023; however, clinical breakpoints and real-world data on its use in China remain limited. We conducted a retrospective, questionnaire-based analysis of eravacycline use across 21 provinces in China during the first year after NMPA approval (September 2023–September 2024). Data from 3369 patients who received eravacycline were collected. We analyzed the distribution of pathogens and specimens, reported in vitro susceptibility to eravacycline, imipenem, meropenem, tigecycline, and polymyxins and evaluated microbiological outcomes. Acinetobacter baumannii (52.0%, 1259/2419) and Klebsiella pneumoniae (26.1%, 631/2419) were the most commonly reported pathogens. High levels of carbapenem resistance were observed: 704 of 771 (91.3%) for A. baumannii and 323 of 392 (82.4%) for K. pneumoniae. In contrast, susceptibility to eravacycline was 95.5% (737/772) and 92.5% (297/321), respectively. Microbiological outcomes suggested potential activity against these resistant isolates, though post-treatment culture data were limited. This study demonstrates that eravacycline exhibited potent in vitro activity against prevalent carbapenem-resistant Gram-negative pathogens in real-world Chinese clinical practice during its first-year post-approval. Continuous monitoring of eravacycline resistance trends, together with prospective studies that correlate microbiological and clinical outcomes in specific infection types, will be crucial for defining its long-term therapeutic utility and the risk of resistance emergence. Full article

Carbapenem-resistant Enterobacterales (CREs) pose a critical threat to global public health, largely driven by the enzymatic activity of Klebsiella pneumoniae carbapenemase-2 (KPC-2), a class A serine β-lactamase that hydrolyzes most β-lactam antibiotics. While β-lactamase inhibitors like avibactam offer temporary relief, emerging KPC variants demand novel, sustainable inhibitory scaffolds. This study aimed to identify and characterize potential natural inhibitors of KPC-2 from Pongamia pinnata, leveraging a comprehensive in silico workflow. A curated library of 86 phytochemicals was docked against the active site of KPC-2 (PDB ID: 3DW0). The top-performing ligands were subjected to ADMET profiling (pkCSM), and 100 ns molecular dynamics simulations (GROMACS) to evaluate structural stability and interaction persistence, using avibactam as control. Ponganone V exhibited the most favorable binding energy (−9.0 kcal/mol), engaging Ser70 via a hydrogen bond and forming π–π interactions with Trp105. Glabrachromene II demonstrated a broader interaction network but reduced long-term stability. ADMET analysis confirmed high intestinal absorption, non-mutagenicity, and absence of hERG inhibition for both ligands. Molecular dynamics simulations revealed that Ponganone V maintained compact structure and stable hydrogen bonding throughout the 100 ns trajectory, closely mirroring the behavior of avibactam, whereas Glabrachromene II displayed increased fluctuation and loss of compactness beyond 80 ns. Principal Component Analysis (PCA) further supported these findings, with Ponganone V showing restricted conformational motion and a single deep free energy basin, while avibactam and Glabrachromene II exhibited broader conformational sampling and multiple energy minima. The integrated computational findings highlight Ponganone V as a potent and pharmacologically viable natural KPC-2 inhibitor, with strong binding affinity, sustained structural stability, and minimal toxicity. This study underscores the untapped potential of Pongamia pinnata phytochemicals as future anti-resistance therapeutics and provides a rational basis for their experimental validation. Full article

Urinary tract infections are among the most common bacterial infections worldwide, with increasing antimicrobial resistance posing a significant public health challenge. This study aimed to determine the demographic distribution, antimicrobial susceptibility patterns of uropathogens, and the clinical implications of UTIs in patients with renal comorbidities in the Al-Baha region of Saudi Arabia. A retrospective, cross-sectional study was conducted at King Fahad Hospital, Al-Baha, from January 2021 to September 2022. A total of 1126 culture-positive UTI cases were included. Patient demographics, uropathogen distribution, antimicrobial resistance profiles, and clinical characteristics were extracted from hospital records. Subgroup analysis was performed for 32 patients with renal comorbidities, including end-stage renal disease (ESRD), glomerulonephritis (GN), and kidney transplant recipients (KTs). Statistical analysis was performed using SPSS version 25. Most cases occurred in patients aged >70 years (43.2%) and females (68.29%). Escherichia coli (38.09%) and Klebsiella pneumoniae (14.02%) were the leading pathogens. High resistance to ampicillin (47–67%), cotrimoxazole (35–37%), and third-generation cephalosporins (34–47%) was observed, whereas carbapenems and aminoglycosides remained largely effective. Among the 32 patients with renal comorbidities, E. coli (43.8%), Staphylococcus aureus (25%), and Enterococcus spp. (18.8%) were the most common isolates. Dysuria (46.87%) and fever (31.25%) were the most frequent clinical presentations. Treatment regimens in this subgroup often required multidrug combinations, reflecting higher resistance burdens. Uropathogens in the Al-Baha region shows rising resistance to first-line antibiotics, with vulnerable populations such as patients with renal comorbidities experiencing distinct pathogen distributions and treatment challenges. Continuous surveillance, prudent antibiotic use, and targeted strategies for high-risk patients are essential to mitigate the impact of multidrug-resistant UTIs in Saudi Arabia. Full article

Klebsiella pneumoniae (Kp) is a leading cause of hospital-acquired infections representing a growing threat driven by emerging multidrug resistance (MDR) and hypervirulence. In this study, we aim to characterise the genomic and epidemiological landscape of Kp in a Portuguese regional hospital (Braga) lacking prior genomic data. We performed whole-genome sequencing of 115 Kp isolates collected from colonisation and infection cases. Phylogenetic, resistance, and virulence profiles were integrated with clinical and epidemiological data. Genomic analysis revealed high diversity, with 83.5% of isolates forming evolutionary clusters. Several novel sequence types (STs), as ST2623 and ST1562, were detected for the first time in Portugal to our knowledge. ST45, uncommonly associated with carbapenem resistance, emerged as dominant with multiple blaKPC-3-positive isolates. Results suggest active transmission of carbapenem resistance genes. One hypervirulent carbapenem-resistant ST13 warrants careful surveillance. Virulence-associated yersiniabactin was common (66.9%) but other hypervirulence loci were rare. Epidemiologically, MDR-Kp was associated with older hospitalised patients with prior antibiotic use and invasive procedures, while community-acquired infections were genetically diverse and affected younger patients with comorbidities. An unusually low number of respiratory infections was observed, likely reflecting strict COVID-19 mitigation measures. Although widespread dissemination of hypervirulent or MDR clones was not evident, the emergence of high-risk lineages and the detection of ongoing gene transmission episodes underscore the need for ongoing genomic surveillance. Immediate mitigation strategies could include reducing device use and hospital transfers, given the high prevalence of colonisation. Full article

Background: Rapid antimicrobial susceptibility testing (RAST) allows early detection of resistance directly from positive blood cultures, potentially improving outcomes in bloodstream infections (BSIs). We evaluated the performance of EUCAST RAST for Gram-negative ESKAPEEc pathogens and characterized carbapenemase genes in carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: A total of 354 positive blood cultures were screened, including 51 monomicrobial Gram-negative ESKAPEEc isolates. RAST results at 4, 6, 8, and 16–20 h were compared with standard antimicrobial susceptibility testing (AST) obtained using the BD Phoenix™ system. Categorical agreement (CA) and error frequency were calculated. Multiplex PCR and Sanger sequencing were performed on 15 CRKP isolates to identify carbapenemase genes and allelic variants. Results: 51 Gram-negative ESKAPEEc isolates met the inclusion criteria for RAST (15 E. coli, 19 K. pneumoniae, 11 A. baumannii, and 6 P. aeruginosa). Overall performance varied markedly by species and antibiotic. E. coli showed frequent unreadable or ATU zones at early timepoints and wide CA variability (50–100%), with high very major error (VME) rates for AMP, TZP, and CAZ, particularly at 6–8 h. K. pneumoniae displayed consistently high CA (mostly 100%) for carbapenems, CAZ, and TZP. A. baumannii demonstrated excellent agreement (100% for most agents), except for GEN at 6–8 h. P. aeruginosa could be evaluated only at 16–20 h, showing high CA for AMK, CAZ, and CIP; lower CA for MEM (83%); non-calculable CA for IMI due to universal ATU readings; and a CA value of 0% for TZP due to the predominance of the ATU results. VMEs ranged from 0% to 26.1% across species and reading times, but carbapenems did not generate VMEs. Molecular analysis revealed bla_KPC in 66.7%, bla_NDM in 46.7%, and bla_OXA-48 in 33.3% of isolates, with co-occurrence in several strains. Sequencing identified bla_KPC-2 and bla_NDM-1 as the predominant variants, with one isolate harboring bla_NDM-5. Conclusions: EUCAST RAST markedly accelerates susceptibility reporting from positive blood cultures, but its accuracy is species- and time-dependent. Performance was excellent for K. pneumoniae (including CRKP) and A. baumannii and acceptable for P. aeruginosa at 16–20 h. In contrast, E. coli showed frequent ATU results at early timepoints and high ME/VME rates, making readings before 8 h unreliable for clinical decisions. Overall, RAST can effectively support rapid antimicrobial stewardship when species-specific limitations are recognized, and early-timepoint results are interpreted with caution. Full article

Background/Objectives: Metallo-β-lactamase (MBL)-producing Gram-negative bacteria represent a growing global health threat due to their broad resistance to β-lactam antibiotics, including carbapenems, which severely limits treatment options. This study aimed to evaluate the in vitro synergistic activity of fosfomycin (FOS) in combination with selected older and newer antimicrobials against MBL-producing Klebsiella pneumoniae and Pseudomonas aeruginosa. Methods: Synergistic interactions were assessed using agar dilution checkerboard on 42 MBL-producing clinical isolates (22 K. pneumoniae, 20 P. aeruginosa) and confirmed using time-kill assays with selected isolates. FOS was tested in combination with colistin (COL), ceftazidime–avibactam (CAZ-AVI), meropenem (MER), amikacin (AMI), aztreonam (AZT), aztreonam–avibactam (AZT-AVI), or cefiderocol (FDC). Results: Most FOS combinations exhibited additive or synergistic effects against clinical isolates. Synergy rates reached 72.7% for the FOS+CAZ-AVI combination (K. pneumoniae) and 65.0% for the FOS+COL combination (P. aeruginosa). An asymmetric synergistic interaction was identified for FOS+CAZ-AVI, with FOS enhancing the activity of CAZ-AVI more markedly than vice versa, especially in K. pneumoniae. Time-kill assays on selected isolates confirmed synergistic and bactericidal activity of FOS+CAZ-AVI and FOS+COL, and showed that bacterial regrowth observed with FOS, CAZ-AVI, and COL alone was suppressed in combination therapy. Conclusions: FOS-based combinations, particularly with CAZ-AVI and COL, demonstrated potent synergistic activity against MBL-producing K. pneumoniae and P. aeruginosa, supporting their potential utility in rational combination therapies for infections due to MBL-producing bacteria. Full article

Urinary tract infections (UTIs) represent one of the most frequent bacterial infections worldwide, with Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) as the predominant uropathogens. The emergence of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales has severely limited treatment options, making regional surveillance crucial. This study aimed to determine the prevalence of uropathogens, assess antimicrobial resistance patterns, and evaluate the burden of ESBL-producing organisms among patients presenting with suspected UTIs in a tertiary care hospital in Riyadh. We conducted a retrospective analysis of 19,556 urine cultures from a tertiary care hospital in Riyadh, Saudi Arabia, between January and December 2024. Of these, 2629 (13.4%) cultures showed significant bacterial growth, predominantly in females (83.2%) and in the 16–30 year age group. E. coli accounted for 65.9% of isolates, followed by K. pneumoniae (16.8%). ESBL production was detected in 28.5% of E. coli and Klebsiella isolates. ESBL producers exhibited complete resistance to third-generation cephalosporins and β-lactam/β-lactamase inhibitor combinations, whereas carbapenems, aminoglycosides, and fosfomycin maintained high efficacy. Resistance to ciprofloxacin and co-trimoxazole was widespread in both ESBL and non-ESBL isolates. Additionally, vancomycin-resistant enterococci (7%), methicillin-resistant Staphylococcus aureus (2%), and carbapenem-resistant Enterobacterales (0.9%) were found. These findings highlight the escalating burden of ESBL-associated UTIs and underscore the urgent need for strengthened antimicrobial stewardship, continuous surveillance, and optimized empirical therapy to mitigate the impact of multidrug-resistant uropathogens in clinical practice. Full article