Search Results (197)

Recycled wastewater is vital for the circular economy, especially on water-scarce islands. This study explored the presence of Carbapenem-Resistant Enterobacterales and other emerging pathogens in irrigation water on four Canarian Islands, applying a One Health perspective. Using membrane filtration and MALDI-TOF mass spectrometry, 69 bacterial isolates were identified. The findings revealed that 78% were Gram-negative bacilli like Pseudomonas aeruginosa, Acinetobacter spp., Enterobacteriaceae, etc., while 22% were Gram-positive bacteria, including Enterococcus spp. The main mechanisms of carbapenem resistance in Pseudomonas spp. and Acinetobacter spp. were oxacillinases, followed by metallo-β-lactamases (MBL). In Enterobacteriaceae, characterization of carbapenemase types was less frequent, with oxacillinase 48 (OXA-48) being the most prevalent. The detection of multidrug-resistant organisms in recycled wastewater highlights an urgent need for routine microbiological monitoring in water management to protect both public health and agricultural sustainability. Full article

Antimicrobial resistance in urinary tract infections (UTIs) poses a critical public health challenge, yet comparative data between outpatient and inpatient settings remain limited, particularly in Latin America. This study characterized the epidemiology, microbiology, and resistance patterns of UTIs in northwestern Mexico. A retrospective analysis of 1041 patients with UTI (May–November 2024) was conducted. Microorganism identification and antimicrobial susceptibility were determined using the MicroScan WalkAway system in accordance with CLSI guidelines. Results: Outpatients accounted for 80.5% of cases and inpatients for 19.4%, with a 3.1% mortality rate. Escherichia coli predominated (62.9%), with a significant association with outpatients (p = 0.02), whereas Enterobacter cloacae, Acinetobacter spp., Candida tropicalis, and C. albicans were associated with inpatients (p < 0.05). Pediatric patients exhibited distinctive microbiological profiles: Pseudomonas aeruginosa (9.7% vs. 2.1%, p = 0.032), Enterococcus faecalis (33.3% vs. 16.2%, p = 0.001), and Staphylococcus epidermidis (26.6% vs. 6.5%, p = 0.027) were significantly more prevalent than in adults. Multidrug resistance (MDR) was detected in 27.1% of isolates, and extensive drug resistance (XDR) in 3.2%. XDR was associated with Gram-positive bacteria (12.2% vs. 1.4%, p < 0.001). Carbapenem-resistant Enterobacteriaceae (CRE) were identified in 0.9% (7/772) of cases, with 42.9% occurring in outpatients. Hospitalization (OR: 2.01; 95% CI: 1.43–2.83), surgical services (OR: 1.41; 95% CI: 1.02–1.97), and recent surgery (OR: 2.37; 95% CI: 1.04–5.39) were independent predictors of MDR/XDR infections. Conclusions: These findings demonstrate the emergence of CRE within the community and distinctive pediatric resistance patterns, underscoring the need for tailored antimicrobial stewardship strategies in this region. Full article

Antibiotic-resistant microbes represent a growing problem for modern medicine and public health. Projections indicate that deaths from such infections could reach 10 million per year by 2050. Healthcare associated infections (HAI) are among the most significant causes of mortality and morbidity in hospitals, impacting millions of patients globally. The emergence of HAI is associated with resistance to antimicrobials, rapidly worsening the patient’s condition. Antimicrobial resistance determines unresponsiveness to treatment, which can ultimately lead to severe complications such as sepsis and shock. It is estimated that one in every ten patients are susceptible to infection during their stay in hospital, with the microorganism responsible for the infection frequently proving resistant to antibiotics. Among the latter, CRE (carbapenem-resistant Enterobacteriaceae), CRAB (carbapenem-resistant Acinetobacter baumannii), CRPA (carbapenem-resistant Pseudomonas aeruginosa), vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus (MRSA), commonly referred to as ‘superbugs’, are a major cause of HAIs. The aim of the present study is to provide a comprehensive overview of the global epidemiology of healthcare-associated infections, with particular emphasis on their incidence, distribution over time, and correlation with the socioeconomic status of different countries. Furthermore, the review aims to evaluate the effectiveness of current preventive strategies in reducing the incidence and mortality associated with HAIs. Full article

The global rise of antimicrobial resistance (AMR), exacerbated by the COVID-19 pandemic, has led to a surge in infections caused by multidrug-resistant (MDR) bacteria. A key driver of this phenomenon is co-selection, where exposure to one antimicrobial promotes resistance to others via horizontal gene transfer (HGT) mediated by mobile genetic elements (MGEs). Carbapenem-resistant Enterobacteriaceae, known for their genomic plasticity, are particularly worrisome; yet genomic data from Latin America—especially Ecuador—remain scarce. This study investigated four carbapenem-resistant clinical isolates (two Klebsiella pneumoniae ST1440 and two Serratia marcescens) from tracheal aspirates of three ICU patients during a COVID-19 outbreak at Hospital IESS Quito Sur, Ecuador. Phenotypic profiling and whole-genome sequencing were performed, followed by bioinformatic reconstruction of plasmid content. Nineteen plasmids were identified, carrying 70 resistance-related genes, including antimicrobial resistance genes (ARGs), metal resistance genes (MRGs), integrons, transposons, and insertion sequences. Hierarchical clustering revealed six distinct gene clusters, with several co-localizing ARGs and genes for resistance to disinfectants and heavy metals—suggesting strong co-selective pressure. Conjugative plasmids harboring high-risk elements such as blaKPC-2, qacE, and Tn4401 were found in multiple isolates, indicating potential interspecies dissemination. These findings emphasize the importance of plasmid-mediated resistance during the pandemic and highlight the urgent need to enhance genomic surveillance and infection control, particularly in resource-limited healthcare settings. Full article

Objectives: This study aimed to identify differences in risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infections across different anatomical sites and to explore risk factors associated with mortality in CRE-infected patients. Methods: Patients who underwent CRE screening and were subsequently diagnosed with CRE infections were included and categorized by infection site: respiratory tract (RTI), urinary tract (UTI), and bloodstream (BSI). Forty ICU patients without CRE infection were randomly selected as controls. Statistical comparisons were performed using the Mann–Whitney U or Chi-square test, as appropriate. Potential risk factors were evaluated via univariate and multivariate analyses, and a predictive model was constructed, with its performance assessed using ROC curve analysis. Results: CRE colonization was identified as a common independent risk factor across all three groups (RTI, UTI, and BSI). Infection-site-specific analyses revealed independent risk factors: RTI was associated with mechanical ventilation, UTI with trauma, and BSI with gastrointestinal injury. Predictive models for RTI, UTI, and BSI demonstrated good discrimination, with ROC AUCs of 0.94, 0.94, and 0.95, respectively. In the analysis of Survived versus Deceased patients, the BSI group had the highest mortality, though the difference was not statistically significant. Deceased patients exhibited significantly higher PCT levels than Survived patients (p = 0.005). Prior use of carbapenems and antifungal agents, as well as Ln(PCT), were independently associated with mortality in CRE-infected patients. Conclusions: Risk factors for CRE infections vary across anatomical sites, with CRE colonization, mechanical ventilation, trauma, and gastrointestinal injury playing key roles. Overuse of antibiotics and elevated inflammatory responses are associated with increased mortality. These findings provide evidence for early identification of high-risk patients and optimization of individualized treatment strategies. Full article

Background: Klebsiella pneumoniae represents a major cause of healthcare-associated infections in intensive care units, with resistance profiles ranging from multidrug-resistant to extensively drug-resistant and pandrug-resistant. Critically ill patients, who often require invasive devices and prolonged antibiotic therapy, are especially vulnerable to colonization and infection by these strains. Surveillance data on resistance trends and specimen-specific patterns in Romanian intensive care units (ICUs) remain limited. Methods: We conducted a four-year surveillance study (2021–2024) in a tertiary Romanian ICU, analyzing K. pneumoniae isolates collected from diverse clinical specimens. Resistance phenotypes were classified as MDR, XDR, PDR, or susceptible based on standard definitions. Trends over time were assessed using Cramér’s V and correspondence analysis, while stratification by specimen type evaluated associations between anatomical site and resistance profiles. Results: A total of 254 K. pneumoniae isolates were analyzed. MDR strains predominated in 2021 and 2022 but sharply declined by 2024 (from 80% to 8.3%). In parallel, XDR and PDR phenotypes increased substantially, indicating a shift toward more complex resistance profiles. A significant temporal association was found (Cramér’s V = 0.43), with 2024 marked by a sharp decline in MDR isolates and a predominance of XDR and PDR phenotypes, reflecting an advanced resistance profile. Specimen-type analysis showed tracheal aspirates as the main reservoir for resistant strains, followed by urine and blood cultures, with a weaker but meaningful association (Cramér’s V = 0.24). Conclusions: These findings reveal a change in resistance patterns in ICU-acquired K. pneumoniae infections, with MDR strains being displaced by XDR and PDR phenotypes. These findings highlight the urgent need for time- and specimen-informed resistance monitoring and adaptive antimicrobial stewardship. Without targeted interventions, gains made in controlling MDR strains risk being rapidly eclipsed by the spread of highly resistant organisms. Full article

Background: Urinary tract infections (UTIs) remain a leading cause of community- and hospital-onset bacterial infections worldwide. Although many countries have implemented antimicrobial resistance (AMR) surveillance systems, longitudinal multicenter data on key uropathogens in Korea remain limited. Methods: We retrospectively evaluated Escherichia coli and Klebsiella pneumoniae isolates from patients with clinically diagnosed UTIs at three tertiary-care Korean hospitals (2012–2021). Using a harmonized Observational Medical Outcomes Partnership Common Data Model (OMOP CDM), we analyzed antibiotic susceptibility based on Clinical and Laboratory Standards Institute breakpoints. Trends in resistance to key antibiotics (including fluoroquinolones, cephalosporins, and carbapenems) were assessed using the Cochran–Armitage test. Results: From 2012 to 2021, ESBL-producing E. coli and K. pneumoniae increased from 24.1% to 38.2% and 39.2% to 46.4%, respectively. The rates for K. pneumoniae remained stable over the last 6 years, and for E. coli, they remained stable over the last 3 years. Resistance rates for E. coli increased from 44.5% to 60.0% (ciprofloxacin) and from 26.3% to 40.2% (cefotaxime), while carbapenem resistance (ertapenem) remained low, at 0.3% to 1.2%. In contrast, K. pneumoniae exhibited high resistance levels to fluoroquinolones, cephalosporins, and other broad-spectrum antibiotics, with notable increases in resistance to ertapenem, from 3.0% to 18.1%, and imipenem, from 0.4% to 16.8%. This escalation mainly stemmed from the rise in ertapenem (6.6% to 17.0%) and imipenem (0.8% to 14.6%) resistance rates among Klebsiella-ESBL producers. Conclusions: We conclude that in Korea, the proportion of ESBL-producing E. coli and K. pneumoniae increased significantly from 2012 to 2018 and has since remained stable for the last 3 years (E. coli) and 6 years (K. pneumoniae). Although carbapenem resistance in E. coli remains low, K. pneumoniae has experienced a significant rise, primarily attributable to its ESBL-producing strains. These findings underscore the importance of vigilant antimicrobial stewardship and continuous surveillance to guide empirical UTI therapies in Korean clinical practice. Full article

Background/Objectives: Hermetia illucens larvae can efficiently convert agri-food residues into high-protein biomass for animal feed and nutrient-rich frass for soil amendment. However, the potential spread of carbapenem resistance genes (CRGs), which confer resistance to last-resort carbapenem antibiotics, and Enterobacteriaceae, common carriers of these genes and opportunistic pathogens, raises important safety concerns. This study aimed to assess the influence of different agri-food-based diets on Enterobacteriaceae loads and the CRG occurrence during the bioconversion process. Methods: Four experimental diets were formulated from agri-food residues and anaerobic digestate: Diet 1 (peas and chickpea waste), Diet 2 (peas and wheat waste), Diet 3 (onion and wheat waste), and Diet 4 (wheat waste and digestate). Enterobacteriaceae were quantified by viable counts, while five CRGs (bla_KPC, bla_NDM, bla_OXA-48, bla_VIM, and bla_GES) were detected and quantified using quantitative PCRs (qPCRs). Analyses were performed on individual substrates, formulated diets, larvae (before and after bioconversion), and frass. Results: Plant-based diets sustained moderate Enterobacteriaceae loads. In contrast, the digestate-based diet led to a significant increase in Enterobacteriaceae in both the frass and mature larvae. CRGs were detected only in legume-based diets: bla_VIM and bla_GES were found in both mature larvae and frass, while bla_OXA-48 and bla_KPC were found exclusively in either larvae or frass. No CRGs were detected in onion- or digestate-based diets nor in young larvae or diet inputs. Conclusions: The findings suggest that the diet composition may influence the proliferation of Enterobacteriaceae and the persistence of CRGs. Careful substrate selection and process monitoring are essential to minimize antimicrobial resistance risks in insect-based bioconversion systems. Full article

Objectives: Acute pyelonephritis (APN) caused by extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae poses a growing therapeutic challenge in children, as carbapenems remain the mainstay of treatment even when susceptibility to alternative agents such as amikacin is demonstrated. However, the widespread and inappropriate use of carbapenems can lead to carbapenem resistance. The aim of this study was to compare the clinical efficacy of amikacin and carbapenems in the management of pediatric acute pyelonephritis caused by ESBL-positive Enterobacteriaceae. Methods: We analyzed cases of pediatric acute pyelonephritis caused by ESBL-positive Enterobacteriaceae that were treated with either carbapenems or amikacin over a two-year period. This study compared microbiological cure, clinical improvement, and recurrence rates across the amikacin and carbapenem treatment groups. Results: Fifty-five patients were evaluated. The median age of the patients was 3 years (range, 0.1–13 years). The causative agents were E. coli in 43 cases (78.2%) and Klebsiella spp. in 12 cases (21.8%). All were susceptible to both carbapenem and amikacin in vitro. Twenty patients (36.3%) received a carbapenem and thirty-five (63.7%) received amikacin. Twenty-four (43.6%) had an underlying urological disease. No difference was observed between the groups in terms of microbiological cure, clinical improvement, or recurrence rates. Conclusions: Amikacin may be a potential alternative to carbapenems for treating pediatric ESBL-positive APN when in vitro susceptibility is confirmed. Full article

Carbapenem-resistant Enterobacteriaceae (CRE) pose an emerging threat, with a high mortality rate among children with cancer. This study aimed to evaluate the impact of routine rectal swab surveillance and rapid PCR-based detection of carbapenemase genes to facilitate the early initiation of appropriate treatment and assess its effects on outcomes. The study compared two groups of pediatric cancer patients with CRE bloodstream infections: a retrospective cohort of 254 patients from 2013 to 2017, and a prospective cohort of 186 patients from 2020 to 2022, following the implementation of these tools. A rapid diagnostic test in the prospective cohort resulted in the early initiation of proper antibiotics in 85% (165/186) of patients, compared to only 58% (147/254) in the retrospective group. This led to a decrease in the need for ICU admission related to sepsis from CRE and a significant reduction in the 30-day mortality rate (16% vs. 30%, p ≤ 0.01). Genotypic profiling revealed that class B carbapenemases were the most prevalent (69%), with the NDM type being identified in 67% of patients. OXA-48 and KPC enzymes were detected in 59% and 4% of patients, respectively. Multivariate analysis revealed that patients having Klebsiella pneumoniae, NDM genotype carbapenemases, presence of pneumonia, and septic shock requiring ICU admission were predictors of poor outcomes. Rapid diagnostics and targeted colonization lead to the appropriate use of targeted antibiotics, resulting in improved patient outcomes. Understanding carbapenemase-producing microorganisms and administering newer antibiotics may further reduce mortality and enhance treatment strategies for high-risk patients. Full article

Background: The global rise of multidrug-resistant Gram-negative bacteria, particularly non-fermenting species and carbapenemase-producing Enterobacteriaceae, poses a significant challenge to hospital infection control. Methods: In this study, a total of 89 Acinetobacter spp. isolates, 14 Pseudomonas aeruginosa, and 14 carbapenem-resistant Enterobacteriaceae isolates were collected from patients in a tertiary hospital. Whole-genome sequencing and antimicrobial susceptibility testing were conducted. Resistance mechanisms and evolutionary relationships were analyzed using phylogenetic analysis and genetic context mapping. Results: Among the non-fermenting isolates, A. baumannii exhibited high resistance to carbapenems, clustering into distinct clonal groups enriched with genes associated with biofilm formation and virulence genes. P. aeruginosa isolates harbored fewer resistance genes but carried notable mutations in the efflux pump systems and the oprD gene. In Enterobacteriaceae, four bla_NDM alleles were identified within a conservative structural sequence, while bla_KPC-2 was located in a non-Tn4401 structure flanked by IS481- and IS1182-like insertion sequences. Phylogenetic analysis revealed that bla_NDM-positive E. coli strains were closely related to susceptible lineages, indicating horizontal gene transfer. Conversely, K. pneumoniae isolates harboring bla_KPC-2 formed a tight clonal cluster, suggesting clonal expansion. Conclusions: The study reveals distinct transmission patterns between resistance genes: horizontal dissemination of bla_NDM and clonal expansion of bla_KPC-2 in K. pneumoniae. These findings emphasize the need for resistance-gene-specific genomic surveillance and infection control strategies to prevent further nosocomial dissemination. Full article

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex mechanisms, often combining the production of hydrolytic enzymes such as β-lactamases with reduced membrane permeability and efflux system induction. The Ambler classification is an effective tool for differentiating the characteristics of serine-β-lactamases (SβLs) and metallo-β-lactamases (MβLs), including ESβLs (different from carbapenemases), KPC, NDM, VIM, IMP, AmpC (different from carbapenemases), and OXA-48. Recently approved inhibitor drugs, such as diazabicyclooctanones and boronic acid derivatives, only partially address this problem, not least because of their ineffectiveness against MβLs. However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. Recent studies explore strategies such as chemical optimization of β-lactamase inhibitor scaffolds, novel β-lactam/β-lactamase inhibitor combinations, and siderophore–antibiotic conjugates to enhance bacterial uptake. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates. Full article

The risk factors and prognosis of polymyxin- and carbapenem-resistant Enterobacteriaceae (PR-CRE) infections were analyzed to reduce their incidence and concurrently improve patient prognosis. This retrospective study analyzed patients with CRE infections admitted to West China Hospital of Sichuan University between 1 September 2019 and 30 September 2023. Based on polymyxin susceptibility, the cases were categorized into PR-CRE and PS-CRE (polymyxin-susceptible CRE) groups, with 1:1 propensity score matching performed between the two cohorts. Comprehensive data, including demographic characteristics, laboratory findings, antibiotic regimens, and clinical outcomes, were collected and analyzed to identify risk factors for PR-CRE infections and evaluate treatment efficacy. This study aims to provide evidence-based references for infection control strategies and antimicrobial stewardship in managing PR-CRE infections. A total of 254 patients were included in this study, with 127 patients in the PR-CRE group. The sensitivity rates of isolates in the PR-CRE group to tigecycline and ceftazidime–avibactam were 94.4% and 88.9%, respectively. Multivariate analysis identified chronic organic disease (OR 2.747, 95% CI 1.303–5.789; p = 0.008) and the use of polymyxin ≥ 3 days (OR 19.203, 95% CI 7.126–51.752; p < 0.001) as independent risk factors for PR-CRE infection. Moreover, ceftazidime–avibactam-based regimens were superior to tigecycline-based regimens for the treatment of PR-CRE infections (71.43% vs. 58.46%), especially in critically ill patients (33.33% vs. 58.82%). Finally, a SOFA score ≥ 5.5 (HR 6.718, 95% CI 2.526–17.866; p < 0.001) was identified as an independent risk factor for 28-day mortality in patients with PR-CRE infection. The presence of chronic organic diseases and the use of polymyxin for ≥3 days were identified as independent risk factors associated with PR-CRE infections in hospitalized patients, highlighting the need to optimize polymyxin use. Furthermore, the efficacy of ceftazidime–avibactam-based regimens may be superior to tigecycline-based regimens for the treatment of PR-CRE infections. Full article

Background/Objectives: This narrative review provided a broad synthesis of recent epidemiological trends, priority resistance mechanisms, and public health implications of multidrug-resistant (MDR) bacteria. We focused on the most clinically significant MDR pathogens, regional differences in resistance, and the effectiveness of containment strategies. Our goal was to synthesize current knowledge and propose research directions. Methods: Through comprehensive analysis of epidemiological studies, surveillance reports, clinical trials, and meta-analyses, we present a detailed assessment of the evolving landscape of antimicrobial resistance across both developed and developing nations. The review encompasses data from 187 countries, analyzing over 2500 published studies and reports from major health organizations. Results: Our findings reveal a concerning 43% increase in multidrug-resistant infections globally, with particularly sharp rises in healthcare-associated infections (67% increase) and community-acquired infections (38% increase) in regions with high antibiotic misuse. The analysis specifically focuses on critical pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE), documenting their prevalence, transmission patterns, and treatment outcomes. Economic impact assessments indicate annual global healthcare costs exceeding USD 100 billion due to resistant infections. The review identifies significant gaps in current surveillance systems, particularly in low- and middle-income countries, and proposes standardized approaches for monitoring and containment strategies. We evaluate the effectiveness of various antimicrobial stewardship programs, documenting success rates and implementation challenges across different healthcare settings. Conclusions: The analysis concludes with evidence-based recommendations for policy reforms, research priorities, and international collaboration frameworks necessary to address this growing global health crisis. Our findings highlighted the importance of strengthening stewardship efforts, proposing novel diagnostics and therapeutic interventions, and addressing inequities in access to care and data across different countries. Full article

Background/Objectives. One of the pressing challenges in global public health is the rise in infections caused by carbapenem-resistant Enterobacteriaceae. Growing bacterial drug resistance, coupled with the slow development of new antibiotics, highlights the critical need to explore and develop new broad-spectrum antimicrobial agents able to inhibit bacterial growth efficiently. In recent years, antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional drugs, owing to their antimicrobial potency, low toxicity, and reduced propensity for fostering resistance. Our research aims to investigate the antibacterial ability of three amphibian AMPs, namely Hylin-a1, AR-23, and RV-23, against both antibiotic-sensitive and carbapenem-resistant strains of Escherichia coli and Klebsiella pneumoniae. Methods. A 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) was performed to identify non-cytotoxic concentrations of peptides. A microdilution assay evaluated the antibacterial effect, determining the peptides’ minimum inhibitory concentration (MIC). In addition, the checkerboard test analyzed the compounds’ synergistic effect with meropenem. Results. We demonstrated that peptides with low toxicity profile and resistance to proteolytic activity exhibited strong antibacterial activity, with MIC ranging from 6.25 to 25 μM. The antibiofilm mechanism of action of peptides was also investigated, suggesting that they had a crucial role during the biofilm formation step by inhibiting it. Finally, we highlighted the synergistic effects of peptides with meropenem. Conclusions. Our study identifies Hylin-a1, AR-23, and RV-23 as promising candidates against Gram-negative bacterial infections with a favorable therapeutic profile. This effect could be related to their great flexibility, as evidenced by circular dichroism data, confirming that the peptides could assume an α-helical conformation interacting with bacterial membranes. Full article