Search Results (185)

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

The growing prevalence of antibiotic-resistant bacteria within the human microbiome has become a pressing global health crisis. While antibiotics have revolutionized medicine by significantly reducing mortality and enabling advanced medical interventions, their misuse and overuse have led to the emergence of resistant bacterial strains. Key resistance mechanisms include genetic mutations, horizontal gene transfer, and biofilm formation, with the human microbiota acting as a reservoir for antibiotic resistance genes (ARGs). Industrialization and environmental factors have exacerbated this issue, contributing to a rise in infections with multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. These resistant pathogens compromise the effectiveness of essential treatments like surgical prophylaxis and chemotherapy, increase healthcare costs, and prolong hospital stays. This crisis highlights the need for a global One-Health approach, particularly in regions with weak regulatory frameworks. Innovative strategies, including next-generation sequencing (NGS) technologies, offer promising avenues for mitigating resistance. Addressing this challenge requires coordinated efforts, encompassing research, policymaking, public education, and antibiotic stewardship, to safeguard current antibiotics and foster the development of new therapeutic solutions. An integrated, multidimensional strategy is essential to tackle this escalating problem and ensure the sustainability of effective antimicrobial treatments. Full article

Background/Objectives: Infections caused by multidrug-resistant (MDR)bacteria pose a significant public health threat by worsening patient outcomes, contributing to hospital outbreaks, and increasing health and economic burdens. Advanced genomic tools enhance the detection of resistance genes, virulence factors, and high-risk clones, thus improving the management of MDR infections. In the Autonomous Community of Aragon, the diversity and incidence of carbapenemase-producing Enterobacteriaceae (CPE) have increased during the last years. This study analyses CPE trends at a tertiary hospital in Spain from 2021 to 2023, aiming to optimize personalized medicine. Methods: CPE isolates were the first isolate per patient, year, species, and carbapenemase from January 2021 to December 2023. Additional metadata were collected from the laboratory’s information system. Antibiotic susceptibility testing was performed by broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina short reads. De novo assembly was used to generate draft genomes in order to determine their complete taxonomic classification, resistome, plasmidome, sequence type (ST), core–genome multilocus sequence typing (cgMLST), and phylogenetic relationships using a suite of bioinformatics tools and in-house scripts. Results: Between 2021 and 2023, 0.4% out of 38,145 Enterobacteriaceae isolates were CPE. The CPE rate tripled in 2022 and doubled again in 2023. The most common species was Klebsiella pneumoniae (51.8%) and the most common carbapenemase was bla_OXA-48. WGS revealed concordant species identification and the carbapenemase distribution in detail. Resistance rates to critical antibiotics, such as carbapenems, were variable, but in most cases were above 70%. Genetic diversity was observed in WGS and phylogenetic analyses, with plasmids often mediating carbapenemase dissemination. Conclusions: The increasing rate of CPE in healthcare settings highlights a critical public health challenge, with limited treatment options. Genomic characterization is essential to understanding resistance mechanisms, aiding therapy, limiting outbreaks, and improving precision medicine. Full article

Background: The rise in carbapenem-resistant Enterobacteriaceae (CRE) in Egypt, particularly in hospital settings, poses a significant public health challenge. This study aims to develop a combined epidemiological surveillance tool utilizing the Microreact online platform (version 269) and molecular microarray technology to track and analyze carbapenem-resistant Escherichia coli strains in Egypt. The objective is to integrate molecular diagnostics and real-time data visualization to better understand the spread and evolution of multidrug-resistant (MDR) bacteria. Methods: The study analyzed 43 E. coli isolates collected from Egyptian hospitals between 2020 and 2023. Nanopore sequencing and microarray analysis were used to identify carbapenemase genes and other resistance markers, whereas the VITEK2 system was employed for phenotypic antibiotic susceptibility testing. Microreact was used to visualize epidemiological data, mapping the geographic and temporal distribution of resistant strains. Results: We found that 72.09% of the isolates, predominantly from pediatric patients, carried the blaNDM-5 gene, while other carbapenemase genes, including blaOXA-48 and blaVIM, were also detected. The microarray method demonstrated 92.9% diagnostic sensitivity and 87.7% diagnostic specificity compared to whole-genome sequencing. Phenotypic resistance correlated strongly with next-generation sequencing (NGS) genotypic data, achieving 95.6% sensitivity and 95.2% specificity. Conclusions: This method establishes the utility of combining microarray technology, NGS and real-time data visualization for the surveillance of carbapenem-resistant Enterobacteriaceae, especially E. coli. The high concordance between genotypic and phenotypic data underscores the potential of DNA microarrays as a cost-effective alternative to whole-genome sequencing, especially in resource-limited settings. This integrated approach can enhance public health responses to MDR bacteria in Egypt. Full article

Background: Data on the health impact of carbapenem-resistant Enterobacteriaceae bloodstream infections (CRE-BSIs) in pediatric populations from Latin America and the Caribbean (LAC) are limited. This systematic review aims to examine the demographic, clinical, and microbiological aspects and resource utilization of this infection in children from this region. Methods: This systematic review investigates the impact of CRE-BSIs in pediatric populations across LAC. Following the Cochrane methodology and PRISMA/MOOSE guidelines, we conducted an extensive search of different databases, including MEDLINE/PubMed, LILACS (SciELO), CENTRAL, CINAHL, Embase (Ovid), the Cochrane Library, and the World Health Organization (WHO) database, and relevant websites for published articles between January 2012 and September 2024. The review included studies on hospitalized patients under 19 years of age with CRE-BSIs. Results: Fourteen studies involving 189 patients were analyzed. Most cases were reported from Brazil, Argentina, Colombia, and Paraguay. The median age of the patients was 35 months. Key risk factors included immunocompromised status, invasive procedures, carbapenem use, and colonization. The infections were predominantly hospital-acquired, with Klebsiella pneumoniae and Serratia spp. being the most common pathogens. KPC and NDM were the primary resistance mechanisms. Most patients received combination antimicrobial therapy for a median of 17 days. An alarmingly high mortality rate at 34% was found. Conclusions: Our findings highlight that CRE-BSIs pose a significant threat to children with underlying conditions in LAC, leading to substantial morbidity and mortality. Implementing robust antimicrobial stewardship programs and effective infection control measures are crucial to curbing the spread of CRE-BSIs in the region. This review underscores the need for targeted interventions and further research to address this critical public health concern in pediatric populations across LAC. Full article

Background: Bacterial infections constitute a large portion of infectious disorders. The location of culture-positive specimens and profiles of antibiotic resistance for common pathogens have been the focal points of subsequent investigations. Methodology: The diagnosis of microbiology was carried out using traditional culture techniques. In accordance with Clinical and Laboratory Standards Institute guidelines, the Kirby–Bauer disk diffusion method was employed for antimicrobial susceptibility analysis. The data were extracted from WHONET 2022 software version 22.5.5 and analyzed using SPSS software. Results: In total, 2489 pathogens were isolated from 2073 patients in three consecutive years. About 768 (34.9%) of the isolates were from the neonatal intensive care unit and the pediatric wards, and 63.2% isolates were from blood specimens. The ESKAPE pathogens were predominant (67%). About 100 Enterobacteriaceae family member bacteria were resistant to carbapenem drugs, and 320 isolates of this family were expected to be beta lactamase producers. A total of 120 methicillin-resistant S. aureus isolates were also identified. Conclusions: Among the isolates, ESKAPE pathogens accounted for the greatest proportion. Most isolates were from the neonatal intensive care unit. A significant number of multidrug-resistant, extreme drug-resistant, and pandrug-resistant isolates were identified in the present study. Full article

Background/Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) are types of bacteria that need urgent attention globally. Active surveillance programs at hospitals are essential for the early identification of CRE carriers and the timely adoption of infection control measures. We aimed to analyze the epidemiology of CRE identified by multiplex RT-PCR in rectal swabs of patients upon admission to high-risk wards and to compare data obtained from both molecular and culture CRE screening. Methods: A total of 2861 rectal swabs, prospectively collected within 12–24 h of admission, underwent molecular screening for identification of K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-mediated metallo-β-lactamase (VIM), imipenemase (IMP), and OXA-48 (Allplex^TM Entero-DR Assay). Only samples that tested positive or invalid underwent culture testing (Agar MacConkey and CHROMID^® CARBA plates, bioMérieux, Craponne, France). Results: A total of 118 out of 2861 (about 4%) were positive for at least one carbapenem-resistant gene by a molecular approach (MA), with KPC, NDM, and VIM having the highest prevalence. Culture testing confirmed the presence of carbapenemase in 89 samples (75.4%), showing a disagreement rate of about 25% between the two methods, which, unfortunately, rises up to 60% for VIM. The dominant bacterial species were K. pneumoniae and E. coli (MALDI-TOF mass spectrometry). Conclusions: Our data underlined the need for the molecular screening of CRE carriers in order to implement active surveillance protocol in critical care settings and to improve infection control measures. Full article

Lactic acid bacteria (LAB) are probiotic microorganisms widely used for their health benefits in the food industry. However, recent concerns regarding their safety have highlighted the need for comprehensive safety assessments. In this study, we aimed to evaluate the safety of L. bulgaricus IDCC 3601, isolated from homemade plain yogurt, via genomic, phenotypic, and toxicity-based analyses. L. bulgaricus IDCC 3601 possessed a single circular chromosome of 1,865,001 bp, with a GC content of 49.72%, and 1910 predicted coding sequences. No virulence or antibiotic resistance genes were detected. Although L. bulgaricus IDCC 3601 exhibited antibiotic resistance to gentamicin and kanamycin, this resistance is an intrinsic feature of this species. L. bulgaricus IDCC 3601 did not produce biogenic amines and did not exhibit hemolytic activity. Phenotypic analysis of enzyme activity and carbohydrate fermentation profiles revealed the metabolic features of L. bulgaricus IDCC 3601. Moreover, no deaths or abnormalities were observed in single-dose oral toxicity tests, suggesting that L. bulgaricus IDCC 3601 has no adverse effect on human health. Finally, L. bulgaricus IDCC 3601 inhibited the growth of potential carbapenem-resistant Enterobacteriaceae. Therefore, our results suggest that L. bulgaricus IDCC 3601 is a safe probiotic strain for human consumption. Full article