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Carbapenem-resistant Enterobacteriaceae （CRE） is an increasingly serious threat to human health worldwide. CRE usually carries multiple drug resistance genes, which limit the selection of therapeutic drugs, prolong treatment time, require higher treatment costs and greater treatment risks. The epidemiology, resistance mechanisms, current resistance status of CRE and the latest therapeutic drugs for CRE were summarized in this papoer, which provide a basis for the rational use of antibiotics in clinical prevention and treatment of drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients, detect their related resistance genes, and provide reference for the clinical treatment of carbapenem resistant Enterobacteria (CRE) infections and the rational use of antibiotics. Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected. The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method. The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR. Results Among the 400 strains, 51 strains were identified as CRE, accounting for 12.75%. Among these, 49 strains produced carbapenemases, with 41 strains (80.39%) being CR Klebsiella pneumoniae and 10 strains (19.61%) being CR Escherichia coli. Among the CRE strains, 34 strains (66.67%) carried blaKPC, 13 strains (25.49%) carried blaNDM, and 2 strains (3.92%) carried blaOXA-48. Conclusion Compared with other commonly used antibiotics, colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli. In addition, there was good concordance between drug resistance phenotype testing and genotyping. Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions. [ABSTRACT FROM AUTHOR]

Introduction: Carbapenem-resistant Gram-negative Bacilli (CRGNB) cause many serious infections, resulting in increased treatment costs, prolonged hospitalisation, and a high mortality rate among infected patients. The survival of carbapenemaseproducing Gram-negative organisms is enhanced by mechanisms such as the presence of carbapenemases, reduced expression, and porin mutations. Accurate tests for rapid detection of bacterial antibiotic resistance are crucial for tracking, preventing, and containing the spread of resistant genes within hospitals and communities, as well as for guiding therapy. Aim: To evaluate the performance of the 'Carba M test' compared to phenotypic Carba NP tests, Carbapenem Inactivation Method (mCIM/eCIM) tests, and genotypic Carba R tests for the phenotypic detection and characterisation of various types of carbapenemase-producing GNB. Materials and Methods: A cross-sectional study was conducted in the Department of Microbiology at PSG Hospitals, Coimbatore, Tamil Nadu, India which has 1400 beds. The study was carried out over a period of 15 months (from June 2022 to August 2023). A total of 250 CR-GNB were included as the study population. A comparative evaluation of the Carba M test, Carba NP test, Carbapenem Inactivation Method (mCIM/eCIM), and Carba R test for the rapid detection of carbapenemase-producing GNB using standard methods was done. The data were analysed, and odds ratios and p-values were calculated for statistical significance at a 95% Confidence Interval (CI). Results: A total of 250 CR-GNB were isolated during the study period, of which 83 (33.2%) were from the Medical Intensive Care Unit (MICU), followed by the Medicine department with 24 (9.6%). Enterobacteriaceae accounted for the majority of the isolates, with 229 (91.6%), followed by Pseudomonas aeruginosa with 17 (6.8%) and Acinetobacter species with 4 (1.6%). Klebsiella pneumoniae was the most common isolate among Enterobacteriaceae, accounting for 216 (86.4%). Out of the 250 CR isolates tested by the Carba R test, 100 (40%) were positive for the Oxacillinase (OXA)-48 enzyme, 35 (14%) for the New Delhi Metallobetalactamase (NDM) enzyme, 4 (1.6%) for Verona Integron-encoded Metallobetalactamase (VIM), and all were negative for Imipenemase (IMP), and Oxacillinase (OXA), and Klebsiella pneumoniae Carbapenemase (KPC) genotypes. The sensitivity of mCIM/eCIM observed in the study was 67.12%, and specificity was 85.71% when compared to the molecular genotype (GeneXpert® Carba R test). The modified Carba NP test detected carbapenemases in 229 isolates, yielding an overall sensitivity of 95.07% and a specificity of 74.07%. The overall sensitivity and specificity of the Carba M test for detecting carbapenemase-producing GNB were 97.31% and 70.37%, respectively. The isolates producing Class A/D (OXA-48-like) enzymes were identified with sensitivities of 98% and specificities of 73.68%, while those producing Class B (NDM, VIM) enzymes showed sensitivities of 94.87% and specificities of 87.5%. Conclusion: The Carba M test is a cost-effective, feasible, and rapid phenotypic test for detecting and differentiating Class B from Class A/D carbapenemases. The Carba M test could serve as a supplemental test alongside the Carba R, Carba NP test, or mCIM/eCIM for diagnosing carbapenemase production in GNB. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs. [ABSTRACT FROM AUTHOR]

Xiaolan Guo,1 Dansen Wu,1 Xiaoping Chen,2 Jing Lin,1 Jialong Chen,1 Liming Wang,1 Songjing Shi,1 Huobao Yang,1 Ziyi Liu,3 Donghuang Hong1,4 1Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 2Computer Science and Mathematics, Fujian University of Technology, Fuzhou, Fujian, People’s Republic of China; 3Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Ziyi Liu, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai, 200127, People’s Republic of China, Email liu-ziyi@sjtu.edu.cn Donghuang Hong, Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134, Dongjie Street, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email hongdh2003@fjmu.edu.cnPurpose: The objective of this study was to identify the risk factors associated with Carbapenem-resistant Enterobacteriaceae (CRE) colonization in intensive care unit (ICU) patients and to develop a predictive risk model for CRE colonization.Patients and Methods: In this study, 121 ICU patients from Fujian Provincial Hospital were enrolled between January 2021 and July 2022. Based on bacterial culture results from rectal and throat swabs, patients were categorized into two groups: CRE-colonized (n = 18) and non-CRE-colonized (n = 103). To address class imbalance, Synthetic Minority Over-sampling Technique (SMOTE) was applied. Statistical analyses including T-tests, Chi-square tests, and Mann–Whitney U-tests were employed to compare differences between the groups. Feature selection was performed using Lasso regression and Random Forest algorithms. A Logistic regression model was then developed to predict CRE colonization risk, and the results were presented in a nomogram.Results: After applying SMOTE, the dataset included 198 CRE-colonized patients and 180 non-CRE-colonized patients, ensuring balanced groups. The two groups were comparable in most clinical characteristics except for diabetes, previous emergency department admission, and abdominal infection. Eight independent risk factors for CRE colonization were identified through Random Forest, Lasso regression, and Logistic regression, including Acute Physiology and Chronic Health Evaluation (APACHE) II score > 16, length of hospital stay > 31 days, female gender, previous carbapenem antibiotic exposure, skin infection, multi-site infection, immunosuppressant exposure, and tracheal intubation. The risk prediction model for CRE colonization demonstrated high accuracy (87.83%), recall rate (89.9%), precision (85.6%), and an AUC value of 0.877. Patients were categorized into low-risk (0– 90 points), medium-risk (91– 160 points), and high-risk (161– 381 points) groups, with corresponding CRE colonization rates of 1.82%, 7.14%, and 58.33%, respectively.Conclusion: This study identified independent risk factors for CRE colonization and developed a predictive model for assessing the risk of CRE colonization.Keywords: carbapenem-resistant Enterobacteriaceae, intensive care unit, colonization, risk factors, risk prediction model

Introduction: Carbapenem-resistant Gram-negative Bacilli (CR-GNB) cause many serious infections, resulting in increased treatment costs, prolonged hospitalisation, and a high mortality rate among infected patients. The survival of carbapenemase-producing Gram-negative organisms is enhanced by mechanisms such as the presence of carbapenemases, reduced expression, and porin mutations. Accurate tests for rapid detection of bacterial antibiotic resistance are crucial for tracking, preventing, and containing the spread of resistant genes within hospitals and communities, as well as for guiding therapy. Aim: To evaluate the performance of the ‘Carba M test’ compared to phenotypic Carba NP tests, Carbapenem Inactivation Method (mCIM/eCIM) tests, and genotypic Carba R tests for the phenotypic detection and characterisation of various types of carbapenemase-producing GNB. Materials and Methods: A cross-sectional study was conducted in the Department of Microbiology at PSG Hospitals, Coimbatore, Tamil Nadu, India which has 1400 beds. The study was carried out over a period of 15 months (from June 2022 to August 2023). A total of 250 CR-GNB were included as the study population. A comparative evaluation of the Carba M test, Carba NP test, Carbapenem Inactivation Method (mCIM/eCIM), and Carba R test for the rapid detection of carbapenemase-producing GNB using standard methods was done. The data were analysed, and odds ratios and p-values were calculated for statistical significance at a 95% Confidence Interval (CI). Results: A total of 250 CR-GNB were isolated during the study period, of which 83 (33.2%) were from the Medical Intensive Care Unit (MICU), followed by the Medicine department with 24 (9.6%). Enterobacteriaceae accounted for the majority of the isolates, with 229 (91.6%), followed by Pseudomonas aeruginosa with 17 (6.8%) and Acinetobacter species with 4 (1.6%). Klebsiella pneumoniae was the most common isolate among Enterobacteriaceae, accounting for 216 (86.4%). Out of the 250 CR isolates tested by the Carba R test, 100 (40%) were positive for the Oxacillinase (OXA)-48 enzyme, 35 (14%) for the New Delhi Metallobetalactamase (NDM) enzyme, 4 (1.6%) for Verona Integron-encoded Metallobetalactamase (VIM), and all were negative for Imipenemase (IMP), and Oxacillinase (OXA), and Klebsiella pneumoniae Carbapenemase (KPC) genotypes. The sensitivity of mCIM/eCIM observed in the study was 67.12%, and specificity was 85.71% when compared to the molecular genotype (GeneXpert® Carba R test). The modified Carba NP test detected carbapenemases in 229 isolates, yielding an overall sensitivity of 95.07% and a specificity of 74.07%. The overall sensitivity and specificity of the Carba M test for detecting carbapenemase-producing GNB were 97.31% and 70.37%, respectively. The isolates producing Class A/D (OXA-48-like) enzymes were identified with sensitivities of 98% and specificities of 73.68%, while those producing Class B (NDM, VIM) enzymes showed sensitivities of 94.87% and specificities of 87.5%. Conclusion: The Carba M test is a cost-effective, feasible, and rapid phenotypic test for detecting and differentiating Class B from Class A/D carbapenemases. The Carba M test could serve as a supplemental test alongside the Carba R, Carba NP test, or mCIM/eCIM for diagnosing carbapenemase production in GNB.

Background: In this study, Escherichia coli, Klebsiella oxytoca, and Citrobacter amalonaticus carrying blaNDM-5 were isolated from a single patient. Methods: The antibiotic susceptibility of the isolates was evaluated by using E-test and agar dilution methods, and blaNDM-5 was identified in genomic and plasmid DNA by using polymerase chain reaction and sequencing. Whole genome sequencing and de novo assembly were used for species characterization, resistance gene identification, and plasmid analysis. Results: All three species had identical plasmids, which were similar to pEC463-NDM5, a plasmid harboring blaNDM-5. Transconjugation experiments confirmed the horizontal gene transfer of blaNDM-5, highlighting the need for a close monitoring of Enterobacteriaceae species harboring this gene. Conclusions: This study conclusively demonstrates the propensity for horizontal gene transfer of blaNDM-5 among Enterobacteriaceae species, underlining the importance of vigilant monitoring to combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime–avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection's fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA's potential as a primary treatment option against OXA-48-producing infections. [ABSTRACT FROM AUTHOR]

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/ or infectious diseases. Treatment options for infections caused by multidrugresistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is made up of a diverse range of bacteria, especially gram-negative bacteria, and is crucial for human health and illness. There is a great deal of interest in the dynamic interactions between gram-negative bacteria and their host environment, especially considering antibiotic resistance. This work aims to isolate gram-negative bacteria that exist in the gut, identify their species, and use resistance-associated gene analysis to define their resistance mechanisms. Methods: Samples were collected from all patients who had a stool culture at a tertiary care center in Lebanon. Each type of bacteria that was identified from the stool samples was subjected to critical evaluations, and all discovered strains underwent antimicrobial susceptibility testing. Polymerase chain reaction was used to profile the genes for Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum beta-lactamase (ESBL), and that of Pseudomonas aeruginosa strains. Results: Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa turned out to be the predominant microbiota members. Escherichia coli strains had a high frequency of extended-spectrum beta-lactamase genes, with the most discovered gene being bla CTX-M. Additionally, a considerable percentage of isolates had carbapenemase-resistant Enterobacteriaceae genes, suggesting the rise of multidrug-resistant strains. Multidrug resistance genes, such as bla mexR, bla mexB, and bla mexA, were found in strains of Pseudomonas aeruginosa, highlighting the possible difficulties in treating infections brought on by these bacteria. Conclusion: The findings highlight the critical importance of effective surveillance and response measures to maintain the effectiveness of antibiotics considering the introduction of multidrug resistance genes in Pseudomonas aeruginosa and ESBL and CRE genes in Escherichia coli.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) infections pose a significant threat to global health due to limited treatment options and high mortality rates. Colistin-based regimens have emerged as a primary treatment approach, but the effectiveness and mortality outcomes of colistin monotherapy versus colistin-fosfomycin combination therapy remain uncertain. This study aims to compare the effectiveness and mortality of colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. Notably, our study is the first to undertake a comprehensive examination of the effectiveness and mortality outcomes between colistin monotherapy and colistin-fosfomycin combination therapy in the context of CRE infections. Methods: A retrospective cohort study was conducted using data from patients diagnosed with carbapenem-resistant Enterobacteriaceae (CRE) infections at Nakornping Hospital during 2015 to 2022. Inverse probability weighting (IPW) was employed to create balanced cohorts of patients receiving either colistin monotherapy or colistin-fosfomycin combination therapy. The primary outcome measure was treatment effectiveness, assessed by 30-day mortality. Secondary outcome measures included clinical response, mortality at the end of treatment, and microbiologic response. Univariate and multivariate logistic regression analysis were employed after applying propensity score weighting using inverse probability of weighting (IPW). Results: A total of 220 patients were included in the analysis, with 67 receiving colistin monotherapy and 153 receiving colistin-fosfomycin combination therapy. Propensity score weighting using IPW balanced the baseline characteristics between the two groups. The effectiveness of treatment, as measured by 30-day mortality, was not significantly different between the colistin monotherapy group and the colistin-fosfomycin combination therapy group (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: 0.60–3.78, p = 0.383). Similarly, no significant difference was observed in the mortality at the end of treatment between the two groups (aOR = 1.26, 95% CI: 0.55–2.90, p = 0.576). The clinical response (aOR = 1.48, 95% CI: 0.61–3.59, p = 0.383) and microbiologic response (aOR = 0.66, 95% CI: 0.18–2.38, p = 0.527) were similar between the colistin monotherapy and colistin-fosfomycin combination therapy groups. Conclusion: The propensity score analysis among 220 matched patients showed comparable treatment effectiveness and mortality between colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. These results suggest that colistin monotherapy may be as effective as combination therapy. More prospective randomized controlled trials are needed to confirm these findings and establish optimal CRE treatment strategies.

ABSTRACTCarbapenem-resistant Enterobacteriaceae (CRE) pose a global health threat; however, there is still limited understanding of the risk factors and underlying mechanisms of CRE colonization in the gut microbiome. We conducted a matched case-control study involving 282 intensive care unit patients to analyze influencing covariates on CRE colonization. Subsequently, their effects on the gut microbiome were analyzed in a subset of 98 patients (47 CRE carriers and 51 non-CRE carriers) using whole metagenome sequences. The concomitant use of proton pump inhibitors (PPIs) and antibiotics was a significant risk factor for CRE colonization. The gut microbiome differed according to PPI administration, even within the CRE and non-CRE groups. Moreover, the transfer of mobile genetic elements (MGEs) harboring carbapenem resistance genes (CRGs) between bacteria was higher in the PPI-treated group than in the PPI-not-treated group among CRE carriers. The concomitant use of PPIs and antibiotics significantly alters the gut microbiome and increases the risk of CRE colonization by facilitating the transfer of CRGs among bacteria of the gut microbiome. Based on these findings, improved stewardship of PPIs as well as antibiotics can provide strategies to reduce the risk of CRE colonization, thereby potentially improving patient prognosis.

Carbapenem-resistant Enterobacteriaceae (CRE) infections pose a significant threat to global health due to limited treatment options and high mortality rates. Colistin-based regimens have emerged as a primary treatment approach, but the effectiveness and mortality outcomes of colistin monotherapy versus colistin-fosfomycin combination therapy remain uncertain. This study aims to compare the effectiveness and mortality of colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. Notably, our study is the first to undertake a comprehensive examination of the effectiveness and mortality outcomes between colistin monotherapy and colistin-fosfomycin combination therapy in the context of CRE infections. A retrospective cohort study was conducted using data from patients diagnosed with carbapenem-resistant Enterobacteriaceae (CRE) infections at Nakornping Hospital during 2015 to 2022. Inverse probability weighting (IPW) was employed to create balanced cohorts of patients receiving either colistin monotherapy or colistin-fosfomycin combination therapy. The primary outcome measure was treatment effectiveness, assessed by 30-day mortality. Secondary outcome measures included clinical response, mortality at the end of treatment, and microbiologic response. Univariate and multivariate logistic regression analysis were employed after applying propensity score weighting using inverse probability of weighting (IPW). A total of 220 patients were included in the analysis, with 67 receiving colistin monotherapy and 153 receiving colistin-fosfomycin combination therapy. Propensity score weighting using IPW balanced the baseline characteristics between the two groups. The effectiveness of treatment, as measured by 30-day mortality, was not significantly different between the colistin monotherapy group and the colistin-fosfomycin combination therapy group (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: 0.60–3.78, p = 0.383). Similarly, no significant difference was observed in the mortality at the end of treatment between the two groups (aOR = 1.26, 95% CI: 0.55–2.90, p = 0.576). The clinical response (aOR = 1.48, 95% CI: 0.61–3.59, p = 0.383) and microbiologic response (aOR = 0.66, 95% CI: 0.18–2.38, p = 0.527) were similar between the colistin monotherapy and colistin-fosfomycin combination therapy groups. The propensity score analysis among 220 matched patients showed comparable treatment effectiveness and mortality between colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. These results suggest that colistin monotherapy may be as effective as combination therapy. More prospective randomized controlled trials are needed to confirm these findings and establish optimal CRE treatment strategies. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacteriaceae (CRE) is a major pathogen that poses a serious threat to human health. Unfortunately, currently, there are no effective measures to curb its rapid development. To address this, an in-depth study on the surface-enhanced Raman spectroscopy (SERS) of 22 strains of 7 categories of CRE using a gold silver composite SERS substrate was conducted. The residual networks with an attention mechanism to classify the SERS spectrum from three perspectives (pathogenic bacteria type, enzyme-producing subtype, and sensitive antibiotic type) were performed. The results show that the SERS spectrum measured by the composite SERS substrate was repeatable and consistent. The SERS spectrum of CRE showed varying degrees of species differences, and the strain difference in the SERS spectrum of CRE was closely related to the type of enzyme-producing subtype. The introduced attention mechanism improved the classification accuracy of the residual network (ResNet) model. The accuracy of CRE classification for different strains and enzyme-producing subtypes reached 94.0% and 96.13%, respectively. The accuracy of CRE classification by pathogen sensitive antibiotic combination reached 93.9%. This study is significant for guiding antibiotic use in CRE infection, as the sensitive antibiotic used in treatment can be predicted directly by measuring CRE spectra. Our study demonstrates the potential of combining SERS with deep learning algorithms to identify CRE without culture labels and classify its sensitive antibiotics. This approach provides a new idea for rapid and accurate clinical detection of CRE and has important significance for alleviating the rapid development of resistance to CRE. [ABSTRACT FROM AUTHOR]

Introduction: There has been a shift in the care of older patients from hospital settings to home healthcare. Older patients are more susceptible to infections, and infections associated with home healthcare are often understudied. This study aimed to investigate the changing trends in carbapenem resistance in these infections over time. Materials and Method: Microbiological data of home healthcare patients between 2018 and 2023 were analyzed using hospital records. Results: The rate of carbapenem resistance increased significantly from 4.17% to 19.53% between 2018 and 2023, particularly in Klebsiella spp. and Pseudomonas spp. Additionally, an increase in the number of respiratory and wound tissue samples was observed. Conclusion: Carbapenem resistance is a growing problem not only in hospitals but also in home healthcare settings. Effective infection prevention and control measures should be implemented, given the complexities of managing these infections, especially in geriatric populations. [ABSTRACT FROM AUTHOR]

Introduction: Resistance to carbapenems in Enterobacteriaceae is a challenge for public health. Carbapenemase production is the leading mechanism. This work aims to evaluate four phenotypic methods for carbapenemase detection in comparison with a molecular method. Materials and Methods: Thirty-seven nonrepeating Enterobacteriaceae strains with decreased susceptibility to ertapenem were included. Imipenem MIC, Modified Hodge Test (MHT), Neo-Rapid Carb Kit® and KPC, MBL, and OXA-48 Confirm Kit® were performed. Isolates were tested for blaOXA-48, blaNDM, and blaVIM genes by end-point polymerase chain reaction. The results of the molecular study were used as a reference test to determine the performances of the phenotypic tests. Results: Imipenem resistance does not seem to be a good marker for carbapenemase production with a sensitivity of 54% (95% CI: 38–71). MHT showed 82% sensitivity (95% CI: 65–91). Overall, the enzymatic test showed the best performances for carbapenemase detection with 100% sensitivity (95% CI: 89–100) and the best turnaround time. The characterization of carbapenemases classes by the combined discs test demonstrated 88% overall sensitivity (95% CI: 72–95). Conclusion: The results of this study support the combination of the enzymatic and the combined disc tests for carbapenemase detection in Enterobacteria. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial resistance is a major threat to public health worldwide. To gain an understanding of the clinical infection distribution, drug resistance information, and genotype of CRE in Dongguan, China, as well as the resistance of relevant genotypes to CAZ-AVI, this research aims to improve drug resistance monitoring information in Dongguan and provide a reliable basis for the clinical control and treatment of CRE infection. Methods: VITEK-2 Compact automatic analyzer was utilized to identify 516 strains of CRE collected from January 2017 to June 2023. To determine drug sensitivity, the K-B method, E-test, and MIC methods were used. From June 2022 to June 2023, 80 CRE strains were selected, and GeneXpert Carba-R was used to detect and identify the genotype of the carbapenemase present in the collected CRE strains. An in-depth analysis was conducted on the CAZ-AVI in vitro drug sensitivity activity of various genotypes of CRE, and the results were statistically evaluated using SPSS 23.0 and WHONET 5.6 software. Results: This study identified 516 CRE strains, with the majority (70.16%) being K.pneumoniae, followed by E.coli (18.99%). Respiratory specimens had highest detection rate with 53.77% identified, whereas urine specimens had the second highest detection rate with 17.99%. From June 2022 to June 2023, 95% of the strains tested using the CRE GeneXpert Carba-R assay possessed carbapenemase genes, of which 32.5% were blaNDM strains and 61.25% blaKPC strains. The results showed that CRE strains containing blaKPC had a significantly higher rate of resistance to amikacin, cefepime, and aztreonam than those harboring blaNDM. Conclusions: The CRE strains isolated from Dongguan region demonstrated a high resistance rate to various antibiotics used in clinical practice but a low resistance rate to tigecycline. These strains produce Class A serine carbapenemases and Class B metals β-lactamases, with the majority of them carrying blaNDM and blaKPC. Notably, CRE strains with blaKPC and blaNDM had significantly lower resistance rates to tigecycline. CAZ-AVI showed a good sensitivity rate with no resistance to CRE strains carrying blaKPC. Therefore, CAZ-AVI and tigecycline should be used as a guide for rational use of antibiotics in clinical practice to effectively treat CRE. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH fourvaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gramnegative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 studywith the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period. [ABSTRACT FROM AUTHOR]

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/or infectious diseases. Treatment options for infections caused by multidrug-resistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms.

Background: Pyogenic infection is a significant cause of morbidity. Infection with multidrug-resistant strains poses a major difficulty in the treatment. The study was conducted to know the bacteriological profile of pyogenic infections and their antibiotic susceptibility. Methods: A cross-sectional study was conducted in a tertiary care hospital from October 2021 to March 2022. Isolates from pus specimens were subjected to an antibiotic sensitivity test using the Kirby-Bauer method as per CLSI 2021. Results: Out of 752 samples, etiology could be revealed in 510 (68.4%) specimens. Enterobacterales dominated the profile, with K pneumoniae isolated in the maximum number of specimens. Staphylococcus aureus was the culprit in 14% of the cases. Non-fermenters were isolated in 17% of the cases. Methicillin resistance in S aureus was 67%. Gram-positive cocci showed high sensitivity to linezolid. For both Piptaz and carbapenem, Enterobacterales and non-fermenters showed around 50% and 60% susceptibility, respectively. Conclusion: Continuous surveillance of the aetiologic agents of pyogenic infections and their antibiotic sensitivity pattern needs to be done to design and implement the antibiotic policy for the infection in our set-up.

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.

Introduction: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) pose a significant threat, leading to severe morbidity and mortality among newborns. Methods: This study, conducted at Franceville hospital's maternity and neonatology wards from February 22nd to June 20th, 2022, investigated the prevalence of CPE in 197 parturients and 203 newborns. Rectal swabs were taken from parturients before delivery and from newborns 30 minutes after birth. Blood culture samples were collected if signs of infection were observed in newborns during a 28-day follow-up. A total of 152 environmental samples were obtained, comprising 18 from sinks, 14 from incubators, 27 from cradles, 39 from maternal beds, 14 from tables and desks, four from the two baby scales and 36 from bedside furniture. Results: None of the 203 newborns were found to be CPE carriers 30 minutes after delivery. CPE carriage was found in 4.6% of mothers. When comparing colonized and uncolonized parturients, well-established risk factors for CPE carriage, such as recent hospitalization and antibiotic therapy, were more frequently observed among CPE carriers (33.3 vs 10.6% for hospitalization in the past 15 days; 55.5 vs 30.3% for hospitalization during pregnancy, and 55.5 vs 35.1% for antibiotic therapy during pregnancy). Notably, the prevalence of treatment with amoxicillin and clavulanic acid was 44.4% in CPE carriers compared to 17.0% in non-carriers. The incidence density of CPE-associated bloodstream infection was 0.49 per 100 newborns, accounting for a fatal case of CPE-associated bacteremia identified in one of the 203 newborns. Seven environmental samples returned positive for CPE (5 sinks and two pieces of furniture). Whole genome sequencing, performed on the 25 CPE isolates, revealed isolates carrying blaNDM-7 (n=10), blaNDM-5 (n=3), blaOXA181 (n=10), blaOXA48 (n=2) or blaOXA244 (n=1), along with genetic traits associated with the ability to cause severe and difficult-to-treat infections in newborns. Core genome comparison revealed nine CPE belonging to three international high-risk clones: E. coli ST410 (four mothers and a sink), two E. coli ST167 (a mother and a piece of furniture), and K. pneumoniae ST307 (a sink and a piece of furniture), with highly similar genetic backgrounds shared by maternal and environmental isolates, suggesting maternal contamination originating from the environment. Discussion: Our study reveals key findings may guide the implementation of infection control measures to prevent nosocomial infections in newborns: the prevalence of CPE carriage in one out of 20 parturients, an infection occurring in one out of 400 newborns, substantial contamination of the care environment, clinical and environmental CPE isolates possessing genetic traits associated with the ability to cause severe and challenging infections, and clonal relationships between clinical and environmental isolates suggesting CPE spread within the wards, likely contributing to the acquisition and colonization of CPE by parturients during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant threat to human health and have emerged as a major public health concern. We aimed to compare the efficacy and the safety of ceftazidime–avibactam (CAZ–AVI) and polymyxin in the treatment of CRE infections. Methods: A systematic review and meta-analysis was performed by searching the databases of EMBASE, PubMed, and the Cochrane Library. Published studies on the use of CAZ–AVI and polymyxin in the treatment of CRE infections were collected from the inception of the database until March 2023. Two investigators independently screened the literature according to the inclusion and exclusion criteria, evaluated the methodological quality of the included studies and extracted the data. The meta-analysis was performed using RevMan 5.4 software. Results: Ten articles with 833 patients were included (CAZ–AVI 325 patients vs Polymyxin 508 patients). Compared with the patients who received polymyxin-based therapy, the patients who received CAZ–AVI therapy had significantly lower 30-days mortality (RR = 0.49; 95% CI 0.01–2.34; I2 = 22%; P < 0.00001), higher clinical cure rate (RR = 2.70; 95% CI 1.67–4.38; I2 = 40%; P < 0.00001), and higher microbial clearance rate (RR = 2.70; 95% CI 2.09–3.49; I2 = 0%; P < 0.00001). However, there was no statistically difference in the incidence of acute kidney injury between patients who received CAZ–AVI and polymyxin therapy (RR = 1.38; 95% CI 0.69–2.77; I2 = 22%; P = 0.36). In addition, among patients with CRE bloodstream infection, those who received CAZ–AVI therapy had significantly lower mortality than those who received polymyxin therapy (RR = 0.44; 95% CI 0.27–0.69, I2 = 26%, P < 0.00004). Conclusions: Compared to polymyxin, CAZ–AVI demonstrated superior clinical efficacy in the treatment of CRE infections, suggesting that CAZ–AVI may be a superior option for CRE infections. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a pressing topic, which also affects β -lactam antibiotic molecules. Until a few years ago, it was considered no more than an interesting species from an academic point of view, Acinetobacter baumanii is today one of the most serious threats to public health, so much so that it has been declared one of the species for which the search for new antibiotics, or new ways to avoid its resistance, is an absolute priority according to WHO. Although there are several molecular mechanisms that are responsible for the extreme resistance of A. baumanii to antibiotics, a class D β -lactamase is the main cause for the clinical concern of this bacterial species. In this work, we analyzed the A. baumanii OXA-23 protein via molecular dynamics. The results obtained show that this protein is able to assume different conformations, especially in some regions around the active site. Part of the OXA-23 protein has considerable conformational motility, while the rest is less mobile. The importance of these observations for understanding the functioning mechanism of the enzyme as well as for designing new effective molecules for the treatment of A. baumanii is discussed. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant enterobacteriaceae (CRE) is associated with high mortality in critically ill patients, with limited treatment options. This study aims to compare clinical response, microbiological response, and mortality in patients treated with ceftazidime--avibactam with or without aztreonam (CAZ-AVI + AZT) and colistin or polymyxin B (polymyxins) in CRE infections. Materials and methods: This single-center prospective observational study included adult patients with CRE infections treated with CAZ-AVI+AZT or polymyxins between January 2022 and December 2022 at a Tertiary Care Medical Center in India. The clinical response, microbiological response, and mortality were compared between the two groups using a Cox multivariate regression model adjusted for the baseline SOFA score and comorbidities. Results: A total of 89 patients were enrolled, with 59 (66%) patients receiving CAZ-AVI + AZT and 30 receiving polymyxins. Baseline demographics and clinical characteristics were similar between the two groups. The Cox multivariate regression analysis showed a statistically significant difference in clinical failure on day 14 with the CAZ-AVI + AZT group vs polymyxins (HR = 0.78, 95% CI 0.63-0.95, p = 0.018). There was no difference in microbiological failure (HR = 1.08, 95% CI 0.66-1.77, p = 0.76), microbiological relapse (HR = 0.75, 95% CI 0.36-3.02, p = 0.62), and hospital mortality (HR = 1.04, 95% CI 0.75-1.43, p = 0.796) between the two groups. Conclusion: Treatment with ceftazidime--avibactam with or without aztreonam for CRE infections associated with a better clinical response compared with polymyxins monotherapy but without any difference in microbiological response or mortality. [ABSTRACT FROM AUTHOR]

Objective To analyze the distribution of plasmid-mediated quinolone resistance gene (PMQR) in carbapenem-resistant enterobacteriaceae (CRE),and to explore the mechanism of quinolone resistance.Methods A total of 43 non-repetitive CRE strains isolated from the hospital from July 2021 to September 2022 were collected.The automatic microbial analysis system was used for strain identification and drug sensitivity test.The PMQR,carbapenemase and β-lactamase resistance genes were detected by polymerase chain reaction (PCR),and the quinolone resistance mechanism of CRE strains was analyzed.Results The drug resistant rates of 31 strains of carbapenem-resistant escherichia coli to quinolones were 93.55%-96.77%.The drug resistant rates of 12 strains of carbapenem-resistant Klebsiella pneumoniae to quinolones were 66.67%-83.33%.The drug resistant rates of 43 CRE strains to β-lactamase blockers were 79.07%-100.00%.It was 100.00% sensitive to polycolistin and tigacycline.The drug resistant rates of amikacin and tobramycin to polymyxin and tigecycline and aminoglycosides were low.Among the 43 CRE strains, 88.37% carried one or two PMQRs, of which the detection rate of acc (6′) Ib-cr was 83.72%,the detection rate of qnrS was 69.77%,the detection rate of qnrB was 2.33%,and qnrA and qepA were not detected.Carbapenemase resistance genes were mainly NDM (88.97%) and KPC (32.56%）.β-lactamase resistance genes were mainly SHV (83.23%) and CTX-M15 (67.57%）.Conclusion The detection rate of PMQR in CRE strains is high, which is related to the quinolone resistance mechanism of CRE,and may lead to multidrug resistance with the combined action of NDM,KPC and CTX-M15. [ABSTRACT FROM AUTHOR]

Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and assessed probiotics' preventive role. In this single-center, retrospective study, 9099 ICU patients were tested for stool CRE culture from March 2017 to April 2022. We excluded 136 patients with CRE colonization within one week post-admission and 26 who received probiotics before CRE colonization. Ultimately, 8937 CRE-negative patients were selected. Logistic analysis identified CRE colonization risk factors and evaluated probiotics' influence, including Saccharomyces boulardii or Lactobacillus rhamnosus, used by 474 patients (5.3%) in the ICU. Compared with data on initial admission, 157 patients (1.7%) had newly discovered CRE colonization before discharge. In a multivariate analysis, coronavirus disease 2019, the ICU, tube feeding, antibiotics such as aminoglycoside, extended-spectrum penicillin, stool vancomycin-resistance enterococci colonization, and chronic kidney disease were significantly associated with de novo CRE infection. However, probiotic use was negatively correlated with CRE infection. Managing risk factors and administering probiotics in the ICU may help prevent CRE colonization; large randomized prospective studies are needed. [ABSTRACT FROM AUTHOR]

ABSTRACTGram-negative metallo-β-lactamase-producing bacteria can be extremely problematic, especially when found to be extensively drug-resistant (XDR). Cefiderocol is a novel antimicrobial that has been shown to overcome most carbapenemases, with very rare resistance reported to date. Within our institution, two multidrug-resistant and one XDR strains were isolated from a patient who recently emigrated from India. Each isolate underwent whole-genome sequencing to resolve plasmids and determine phylogenetics, strain typing, and mechanisms of resistance. The XDR E. coli was ST167, harbored NDM-5, cirA and PBP3 mutations, consistent with cefiderocol resistance. Our study suggests that the NDM region is required in conjunction with cirA and PBP3 mutations. It is not clear why; however, our study did determine a potential novel iron-transport region unique to the cefiderocol-resistant isolate. This is the first characterized cefiderocol-resistant E.coli reported from Canada. Health centers should be on alert for this clone.IMPORTANCEThe development of cefiderocol, a novel siderophore cephalosporin, has provided additional options to the treatment of extensively drug-resistant (XDR) Gram-negative bacteria. Resistance to cefiderocol is poorly understood and only recently described. Here, we describe a case of a patient with recent travel to India harboring three Escherichia coli isolates, one resistant and two susceptible to cefiderocol. Two isolates are highly similar genetically, allowing the mechanism of resistance to be described more closely. The importance of this manuscript contributes both globally to the understanding of cefiderocol resistance in E. coli as well as nationally as this is the first resistant case reported in Canada. This is especially concerning as cefiderocol is not currently approved in Canada. The implications of reporting emerging resistance to new antimicrobials for XDR Gram negatives are impactful to infectious disease specialists, clinical microbiologists, physicians, and public health.

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gram-negative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 study with the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period.

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.MethodsIn this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete.FindingsBetween June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2-6] vs 2 [0-4] vs 2 [0-4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2-5] vs 1 [0-3] vs 1 [0-2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42-65) for China versus South America, 50% (41-61) for the USA versus China, and 53% (41-66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8-16; 29 of 246) than in the USA (23%, 16-30; 30 of 130) and South America (28%, 20-37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22-10·50) and the USA (aOR 3·34, 1·50-7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70-2·96).InterpretationGlobal CRKP epidemics have important regional differences in patients' baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions.FundingThe National Institutes of Health.

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) present substantial challenges to clinical intervention, necessitating the formulation of novel antimicrobial strategies to counteract them. Nanomaterials offer a distinctive avenue for eradicating bacteria by employing mechanisms divergent from traditional antibiotic resistance pathways and exhibiting reduced susceptibility to drug resistance development. Non-caloric artificial sweeteners, commonly utilized in the food sector, such as saccharin, sucralose, acesulfame, and aspartame, possess structures amenable to nanomaterial formation. In this investigation, we synthesized gold nanoparticles decorated with non-caloric artificial sweeteners and evaluated their antimicrobial efficacy against clinical CRE strains. Results Among these, gold nanoparticles decorated with aspartame (ASP_Au NPs) exhibited the most potent antimicrobial effect, displaying minimum inhibitory concentrations ranging from 4 to 16 µg/mL. As a result, ASP_Au NPs were chosen for further experimentation. Elucidation of the antimicrobial mechanism unveiled that ASP_Au NPs substantially elevated bacterial reactive oxygen species (ROS) levels, which dissipated upon ROS scavenger treatment, indicating ROS accumulation within bacteria as the fundamental antimicrobial modality. Furthermore, findings from membrane permeability assessments suggested that ASP_Au NPs may represent a secondary antimicrobial modality via enhancing inner membrane permeability. In addition, experiments involving crystal violet and confocal live/dead staining demonstrated effective suppression of bacterial biofilm formation by ASP_Au NPs. Moreover, ASP_Au NPs demonstrated notable efficacy in the treatment of Galleria mellonella bacterial infection and acute abdominal infection in mice, concurrently mitigating the organism's inflammatory response. Crucially, evaluation of in vivo safety and biocompatibility established that ASP_Au NPs exhibited negligible toxicity at bactericidal concentrations. Conclusions Our results demonstrated that ASP_Au NPs exhibit promise as innovative antimicrobial agents against clinical CRE. Graphical Abstract

Jia Xu,1,&ast; Chengjia Luo,1,&ast; Liang Huang,2 Xi Xiao,3 Ling Liu,1 Zhiling Yang1 1Department of Clinical Pharmacy, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, 410016, People’s Republic of China; 2Department of Rehabilitation, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, 410016, People’s Republic of China; 3Department of Clinical Laboratory, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, 410016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiling Yang, Tel +86 0737-84762738, Email pharma8888@sina.comBackground: Ceftazidime-avibactam (CAZ-AVI) is a new cephalosporin/β-lactamase inhibitor combination that received clinical approval in China in 2019. This study aims to investigate the efficacy and safety of CAZ-AVI in the treatment of Klebsiella pneumoniae (KP) infection in a hospital, and differences in efficacy among various infection sites and between monotherapy and combination therapy, providing valuable insights for its further application.Methods: Patients who used CAZ-AVI between January 2019 and April 2023 were identified through the hospital information system. Demographic information, details of the infection site, KP strain’s drug sensitivity report, treatment duration, combination therapies, adverse drug reactions (ADR), and 28-day survival were recorded. Clinical and microbiological efficacies were analyzed using SPSS 23.0 software to compare different infection sites and combination therapies.Results: The overall effective clinical response (CR) rate of CAZ-AVI against KP infection was 62.13%, with a favorable microbial response (MR) rate was 65.68% and a 28-day survival rate was 63.91%. No significant difference occurred in effective CR and 28-day survival rate among different infection sites (P = 0.709 and 0.862, respectively). The favorable MR rate for abdominal infections was slightly lower than that for other sites of infection (P = 0.021). No significant differences in effective CR, favorable MR, and 28-day survival between monotherapy and combination therapy were present (P values were 0.649, 0.123, and 0.280, respectively). The incidence of ADR was 1.78%, including increased creatinine, elevated transaminase, hematuria, and thrombocytopenia.Conclusion: CAZ-AVI demonstrates good clinical efficacy and safety in the treatment of KP infections. The clinical efficacy of CAZ-AVI was similar across different infection sites, and combination therapy did not show an advantage over monotherapy. Further studies are warranted. It should be noted that CAZ-AVI may induce thrombocytopenia and hematuria.Keywords: ceftazidime-avibactam, Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, urethral hemorrhage, thrombocytopenia, combination therapy

Jinzhu Huang,&ast; Jinxin Zhao,&ast; Miao Yi, Yaling Yuan, Peiwen Xia, Bingxue Yang, Jiajia Liao, Zijun Dang, Yun Xia&ast; Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Xia, Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13668043942, Fax +86-23-89012513, Email xiayun12cn@aliyun.comPurpose: This research aims to profile ten novel strains of carbapenem-resistant Enterobacteriaceae (CRE) co-carrying blaKPC and blaNDM.Methods: Clinical CRE strains, along with corresponding medical records, were gathered. To ascertain the susceptibility of the strains to antibiotics, antimicrobial susceptibility tests were conducted. To validate the transferability and cost of fitness of plasmids, conjugation experiments and growth curves were employed. For determining the similarity between different strains, ERIC-PCR was utilised. Meanwhile, whole genome sequencing (WGS) was performed to characterise the features of plasmids and their evolutionary characteristics.Results: During the course of this research, ten clinical CRE strains co-carrying blaKPC and blaNDM were gathered. It was discovered that five out of these ten strains exhibited resistance to tigecycline. A closer examination of the mechanisms underlying tigecycline resistance revealed that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 existed concurrently within a single Citrobacter freundii strain (CF10). This strain, with a minimum inhibitory concentration (MIC) of 32 mg/L to tigecycline, was obtained from a sepsis patient. Furthermore, an investigation of genome evolution implied that CF10 belonged to a novel ST type 696, which lacked analogous strains. Aligning plasmids exposed that similar plasmids all had less than 70% coverage when compared to pCF10-tmexCD1, pCF10-KPC, and pCF10-NDM. It was also found that tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 were transferred by Tn 5393, IS 5, and Tn 6296, respectively.Conclusion: This research presents the first report of coexistence of tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1 in a carbapenem and tigecycline-resistant C. freundii strain, CF10.Importance: Tigecycline is considered a “last resort” antibiotic for treating CRE infections. The ongoing evolution of resistance mechanisms to both carbapenem and tigecycline presents an alarming situation. Moreover, the repeated reporting of both these resistance mechanisms within a single strain poses a significant risk to public health. The research revealed that the genes tmexCD 1-toprJ 1, blaKPC-2, and blaNDM-1, which cause carbapenem and tigecycline-resistance in the same strain, were located on mobile elements, suggesting a potential for horizontal transmission to other Gram-negative bacteria. The emergence of such a multi-resistant strain within hospitals should raise significant concern due to the scarcity of effective antimicrobial treatments for these “superbugs”.Keywords: blaKPC, blaNDM, carbapenem-resistantEnterobacteriaceae, tigecycline-resistance, tmexCD 1-toprJ 1

ABSTRACT: Objectives: Carbapenems are among the few effective antibiotics against multidrug-resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae (CRE) recovered from 2016 to 2019 from hospitalized patients in Lebanon. Methods: Plasmid typing and whole-genome sequencing were used to study the genomic characteristics of 65 clinical CREs including 27 Escherichia coli, 24 Klebsiella pneumoniae, one Klebsiella quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens. Results: blaOXA-48 (33.8%; n = 22) and blaOXA-48-like genes were among the detected resistance determinants, with two isolates co-harbouring blaNDM-5. Various blaNDM variants, blaNDM-1 (16.9%; n = 11), blaNDM-5 (9.2%; n = 6), blaNDM-7 (9.2%; n = 6), and blaNDM-19 (4.6%; n = 3), different ESBLs, and AmpC β-lactamases were detected. Carbapenem resistance determinants were linked to a variety of incompatibility groups with IncFIB(K) (43.1%; n = 28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), and IncFIIK (29.2%). Conclusions: We analysed the clonality and resistance determinants of 65 multidrug-resistant (MDR) Enterobacteriaceae recovered in the period from 2016 to 2019 from a large tertiary hospital in Lebanon. NDM variants, OXA-48, and OXA-181 were the most prevalent detected carbapenemases and were mostly linked to the dissemination of IncL, IncX3, and IncF. This study reinforces the need to track the spread and dominance of clinically relevant carbapenemase-encoding plasmids in healthcare settings.

Background: Pyogenic infection is a significant cause of morbidity. Infection with multidrug-resistant strains poses a major difficulty in the treatment. The study was conducted to know the bacteriological profile of pyogenic infections and their antibiotic susceptibility. Methods: A cross-sectional study was conducted in a tertiary care hospital from October 2021 to March 2022. Isolates from pus specimens were subjected to an antibiotic sensitivity test using the Kirby-Bauer method as per CLSI 2021. Results: Out of 752 samples, etiology could be revealed in 510 (68.4%) specimens. Enterobacterales dominated the profile, with K pneumoniae isolated in the maximum number of specimens. Staphylococcus aureus was the culprit in 14% of the cases. Non-fermenters were isolated in 17% of the cases. Methicillin resistance in S aureus was 67%. Grampositive cocci showed high sensitivity to linezolid. For both Piptaz and carbapenem, Enterobacterales and nonfermenters showed around 50% and 60% susceptibility, respectively. Conclusion: Continuous surveillance of the aetiologic agents of pyogenic infections and their antibiotic sensitivity pattern needs to be done to design and implement the antibiotic policy for the infection in our set-up. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime–avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection’s fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA’s potential as a primary treatment option against OXA-48-producing infections.

Abstract Background Rectal colonisation with carbapenem-resistant Gram-negative bacilli (CR-GNB) may cause CR-GNB infection in children with haematological malignancies (HMs) haematological. To date, information on its epidemiology is limited. This study aimed to assess the the risk factors for rectal colonisation with CR-GNB in children with HMs. Methods A case–control study in a tertiary children’s hospital in Hangzhou City, was conducted between July 2019, and September 2021. Based on the hospitalisation date, children in the CR-GNB colonisation group and control groups were matched at a ratio of 1:2. Conditional logistic regression models were used to compute the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of the risk factors for CR-GNB rectal colonisation in children with HMs. Results A total of 85 non-duplicated CR-GNB isolates were collected from rectal swab samples of 69 children with HMs. The 30-day mortality rates were 5.8% in the CR-GNB colonisation group and 0% in the control group (P = 0.020).colonisation In the conditional logistic regression model, the aORs were 6.84 (95% CI 1.86–25.20) for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), 4.16 (95% CI 1.17–14.84) for prior concomitant infections within the last 1 month, 2.33 (95% CI 1.16–4.69) for prior carbapenems usage within the last 1 month and 7.46 (95% CI 1.81–30.67) for prior hematopoietic stem-cell transplantation (HSCT). Conclusion AML/ALL, prior concomitant infections within the last 1 month, prior carbapenems usage within the last 1 month, and prior HSCT are associated with an increased risk of rectal colonisation with CR-GNB in children with HMs.

Objective To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). Results Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P

Abstract Introduction Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. Methods The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. Results Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p

IntroductionInfections caused by carbapenemase-producing Enterobacteriaceae (CPE) pose a significant threat, leading to severe morbidity and mortality among newborns.MethodsThis study, conducted at Franceville hospital's maternity and neonatology wards from February 22nd to June 20th, 2022, investigated the prevalence of CPE in 197 parturients and 203 newborns. Rectal swabs were taken from parturients before delivery and from newborns 30 minutes after birth. Blood culture samples were collected if signs of infection were observed in newborns during a 28-day follow-up. A total of 152 environmental samples were obtained, comprising 18 from sinks, 14 from incubators, 27 from cradles, 39 from maternal beds, 14 from tables and desks, four from the two baby scales and 36 from bedside furniture.ResultsNone of the 203 newborns were found to be CPE carriers 30 minutes after delivery. CPE carriage was found in 4.6% of mothers. When comparing colonized and uncolonized parturients, well-established risk factors for CPE carriage, such as recent hospitalization and antibiotic therapy, were more frequently observed among CPE carriers (33.3 vs 10.6% for hospitalization in the past 15 days; 55.5 vs 30.3% for hospitalization during pregnancy, and 55.5 vs 35.1% for antibiotic therapy during pregnancy). Notably, the prevalence of treatment with amoxicillin and clavulanic acid was 44.4% in CPE carriers compared to 17.0% in non-carriers. The incidence density of CPE-associated bloodstream infection was 0.49 per 100 newborns, accounting for a fatal case of CPE-associated bacteremia identified in one of the 203 newborns. Seven environmental samples returned positive for CPE (5 sinks and two pieces of furniture). Whole genome sequencing, performed on the 25 CPE isolates, revealed isolates carrying blaNDM-7 (n=10), blaNDM-5 (n=3), blaOXA181 (n=10), blaOXA48 (n=2) or blaOXA244 (n=1), along with genetic traits associated with the ability to cause severe and difficult-to-treat infections in newborns. Core genome comparison revealed nine CPE belonging to three international high-risk clones: E. coli ST410 (four mothers and a sink), two E. coli ST167 (a mother and a piece of furniture), and K. pneumoniae ST307 (a sink and a piece of furniture), with highly similar genetic backgrounds shared by maternal and environmental isolates, suggesting maternal contamination originating from the environment.DiscussionOur study reveals key findings may guide the implementation of infection control measures to prevent nosocomial infections in newborns: the prevalence of CPE carriage in one out of 20 parturients, an infection occurring in one out of 400 newborns, substantial contamination of the care environment, clinical and environmental CPE isolates possessing genetic traits associated with the ability to cause severe and challenging infections, and clonal relationships between clinical and environmental isolates suggesting CPE spread within the wards, likely contributing to the acquisition and colonization of CPE by parturients during pregnancy.

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) are a substantial health burden. Existing management guidelines are primarily based on clonal evidence. Therefore, epidemiological data are required. We evaluated the risk factors for CRE colonization and described the molecular and clinical characteristics of CRE colonization in pediatric inpatients in Guangzhou, China. Pediatric inpatients from three hospitals in Guangzhou, China, between July 2019 and January 2021 were included. Fecal samples were collected and screened for CRE. Microbiological cultures were grown on MacConkey agar plates, and bacteria were identified with a mass spectrometry microbial identification system. Antimicrobial susceptibility was tested with a VITEK2 system, and carbapenemase genes were amplified. A case-control study was conducted to evaluate the risk factors for fecal CRE colonization in pediatric inpatients. Of 4,033 patients screened, 158 (3.92%) were positive for CRE, including Escherichia coli (51.27%), Klebsiella pneumoniae (37.97%), and Enterobacter cloacae (6.96%). The most common carbapenemase genes were blaNDM-5 (51.89%), blaNDM-1 (15.19%), and blaIMP-4 (7.60%) and blaKPC-2 (3.80%). Hematological malignancies, respiratory diseases, otolaryngological diseases, nervous system diseases, oral administration of third-generation cephalosporins, and the combined use of two or more antibiotics were independently associated with CRE colonization. The most prevalent carbapenem-resistant K. pneumoniae sequence types (STs) were ST11 (8.06%), ST37 (8.06%), and ST76 (8.06%), and the most prevalent carbapenem-resistant E. coli STs were ST10 (9.88%), ST48 (13.58%), and ST58 (8.64%). Pediatric inpatients were colonized by a diversity of CRE strains. Infection control and prevention measures should be implemented to reduce CRE colonization. IMPORTANCE This study assessed the clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae in pediatric inpatients at three hospitals in South China by means of screening stool samples for carbapenem-resistant genes and a nested case-control study to determine risk factors for carriage of carbapenem-resistant Enterobacteriaceae. Of 4,033 fecal samples screened, 158 (3.92%) were positive for CRE, including Escherichia coli (51.27 %), Klebsiella pneumoniae (37.97%), and Enterobacter cloacae (6.96%). The most common carbapenemase genes harbored by gastrointestinal CRE strains were blaNDM-5, blaNDM-1, and blaIMP-4. Hematological malignancies, respiratory diseases, otolaryngological diseases, nervous system diseases, oral administration of third-generation cephalosporins, and the combined use of two or more antibiotics were independently associated with CRE colonization.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) present substantial challenges to clinical intervention, necessitating the formulation of novel antimicrobial strategies to counteract them. Nanomaterials offer a distinctive avenue for eradicating bacteria by employing mechanisms divergent from traditional antibiotic resistance pathways and exhibiting reduced susceptibility to drug resistance development. Non-caloric artificial sweeteners, commonly utilized in the food sector, such as saccharin, sucralose, acesulfame, and aspartame, possess structures amenable to nanomaterial formation. In this investigation, we synthesized gold nanoparticles decorated with non-caloric artificial sweeteners and evaluated their antimicrobial efficacy against clinical CRE strains. Results: Among these, gold nanoparticles decorated with aspartame (ASP_Au NPs) exhibited the most potent antimicrobial effect, displaying minimum inhibitory concentrations ranging from 4 to 16 µg/mL. As a result, ASP_Au NPs were chosen for further experimentation. Elucidation of the antimicrobial mechanism unveiled that ASP_Au NPs substantially elevated bacterial reactive oxygen species (ROS) levels, which dissipated upon ROS scavenger treatment, indicating ROS accumulation within bacteria as the fundamental antimicrobial modality. Furthermore, findings from membrane permeability assessments suggested that ASP_Au NPs may represent a secondary antimicrobial modality via enhancing inner membrane permeability. In addition, experiments involving crystal violet and confocal live/dead staining demonstrated effective suppression of bacterial biofilm formation by ASP_Au NPs. Moreover, ASP_Au NPs demonstrated notable efficacy in the treatment of Galleria mellonella bacterial infection and acute abdominal infection in mice, concurrently mitigating the organism's inflammatory response. Crucially, evaluation of in vivo safety and biocompatibility established that ASP_Au NPs exhibited negligible toxicity at bactericidal concentrations. Conclusions: Our results demonstrated that ASP_Au NPs exhibit promise as innovative antimicrobial agents against clinical CRE. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify the colonization rate of carbapenem-resistant Enterobacteriaceae (CRE), the characteristics of CRE isolates, and risk factors for CRE colonization in patients transferred to the general wards of a small/medium-sized hospital. Methods: This retrospective study was conducted on patients who underwent CRE culture tests within 24 hours of admission among patients transferred to a small/medium-sized hospital. Forty-seven patients confirmed as positive for CRE were classified as belonging to the patient group. For the control group, 235 patients (five times the number of the patient group) were matched by sex, age, and diagnosis, and then selected at random. Data were analyzed using descriptive analysis and multiple logistic regression analysis. Results: The CRE colonization rate was 5% (47 out of 933 patients), and Klebsiella pneumoniae (68.0%) was the most common isolate of CRE. The positivity rate of carbapenemase-producing Enterobacteriaceae was 61.7%. The risk factors for CRE colonization included renal disease (odds ratio [OR]=4.93; 95% confidence interval [CI], 1.49-16.31), heart disease (OR=3.86; 95% CI, 1.35-11.01), indwelling urinary catheters (OR=4.43; 95% CI, 1.59-12.36), and cephalosporin antibiotic use (OR=8.57; 95% CI, 1.23-59.60). Conclusion: Having a comorbid renal or cardiac disease, an indwelling urinary catheter, or a history of exposure to cephalosporin antibiotics could be classified as risk factors for CRE colonization in patients transferred to small and medium-size hospitals. It is necessary to perform active infection control through proactive CRE culture testing of patients with risk factors. [ABSTRACT FROM AUTHOR]

Background: Intensive care units (ICUs) in developing countries constitute a high risk for patients acquiring infection by multidrug-resistant organisms (MDROs). The rise in antimicrobial resistance (AMR) threatens the effective prevention and treatment of an increasing range of infections. The present study analyzed the local trends of AMR in Gram-negative isolates of ICU patients from a tertiary care facility in North India. Methods: This retrospective study was conducted over 5 years (January 2018–December 2022). All bacterial isolates from patients admitted to ICU during the study period were included in the study, and their AMR pattern was analyzed. In addition, sensitivity trends of different antimicrobials against the common Gram-negative bacteria were analyzed, and AMR trends were analyzed over the study period. Results: Klebsiella spp. was the most common isolate in samples received from ICU. A rise of carbapenem-resistant microorganisms was observed over the study period. Escherichia coli and Klebsiella spp. showed around 10% and a 17% decrease in susceptibility to carbapenems, respectively. In contrast, a marked 29% decrease in sensitivity to carbapenems was observed in Acinetobacter spp. Conclusion: The inception of integrated stewardship measures has shown a rising trend in susceptibility and is the need of the hour to prevent the spread of MDROs. Surveillance studies help us understand the impact of AMR in hospitals and help plan prevention programs. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a significant global health challenge, with Klebsiella pneumoniae being one of the most common antibiotic-resistant pathogens. This study provides an in-depth analysis of the prevalence and resistance patterns of antibiotic-resistant Klebsiella pneumoniae in the General Hospital of Corfu, Greece, between 2019 and 2022, with the aim of understanding the potential impact of the COVID-19 pandemic on the epidemiology of this bacterium. Utilizing a retrospective epidemiological approach, this study analyzed 212 isolates obtained from the hospital's Microbiology Department. These isolates were subjected to genotypic and phenotypic identification, with resistance genes (bla-KPC, bla-NDM, bla-VIM, bla-OXA-48, and mcr-1) and antibiotic resistance patterns as the primary focus. The results revealed a significant shift in resistance gene prevalence, with a notable increase in bla-KPC from 16.67% in 2021 to 58.46% in 2022, and a decrease in bla-NDM from 81.48% in 2021 to 38.46% in 2022. In terms of antibiotic resistance patterns, there was a consistent increase in resistance to amikacin and a significant decrease in resistance to ceftazidime/avibactam. These findings underscore the dynamic nature of carbapenem-resistant Klebsiella pneumoniae (CRKP) resistance and highlight the need for ongoing surveillance and adaptive therapeutic strategies in the face of evolving resistance patterns. [ABSTRACT FROM AUTHOR]

Introduction and background: Rapid molecular diagnostics to predict carbapenem resistance well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of Carbapenem-resistant Enterobacteriaceae (CRE). Materials and methods: A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on gram-negative bacteria (GNB) flagged blood culture samples, in an Indian intensive care unit between January 2015 and November 2018. We analyzed the performance of Xpert Carba-R in comparison with routine DST. Results: A total of 164 GNBs were isolated from 160 patients. Klebsiella pneumoniae and Escherichia coli were the predominant isolates. Carba-R was positive in 35.36% of samples and 45.34% were carbapenem-resistant (CR) on routine DST. The distribution of the CR gene was: Oxacillinase (OXA) (50%), NDM (32.7%) followed by OXA and NDM co-expression (15.51%). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of Carba-R were 90.74, 93.15, 13.25, 0.10, 83.58 and 96.31% for Enterobacteriaceae. The median time to obtain the Carba-R report was 30 hours 34 minutes vs 74 hours and 20 minutes for routine DST. Based on the Carba-R report, 9.72% of patients had escalation and 27.08% had de-escalation of antibiotics. Conclusion: Xpert Carba-R serves as a rapid diagnostic tool for predicting carbapenem resistance in intensive care unit patients with bacteremia caused by Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is due to presence of the blaNDM-1 gene that expresses the NDM-1 enzyme. As antibiotic resistance is a threat to public health, it is important to determine the prevalence of CRKP isolated from patients at a teaching hospital in the east coast of Peninsular Malaysia and understand the demographical trend of the bacteria in patients to keep infection at bay. Methods: A total of 213 Klebsiella pneumoniae isolates from the year 2017 to 2019, of non-repetitive clinical specimens of patients were tested for sensitivity against carbapenems using the disc-diffusion method. Phenotypic detection of carbapenemase was performed using the modified Hodge test and polymerase chain reaction was used to detect the presence of blaNDM-1 from bacterial DNA. Results: Isolates with blaNDM-1 gene was present in 93.4% (n=199) of 213 samples, with the highest number in blood (20.7%, n=44) and urine samples (20.7%, n=44). CRKP isolates producing NDM-1 enzyme were found to be the highest in male patients (56.8%, n=113) and in those aged between 61 and 80 years (49.7%, n=99), although it was not significantly associated. Conclusion: This study identified the presence of blaNDM-1 in a large proportion of CRKP isolates obtained from samples at the teaching hospital. This may require the formulation of protocols to screen for CRKP and reduce the risk of infection, especially among elderly males. The Ministry of Health may need to implement screening protocols to reduce infection risk. [ABSTRACT FROM AUTHOR]

Background and Objectives: Health care-associated infections (HAI) are one of the most common adverse events in health-care delivery and an endemic burden as major health-care problem. Carbapenems have broad-spectrum antibacterial activity and thus known as Extended-spectrum ß-lactamases. Therefore, the emergence of carbapenem-resistant bacteria poses great significance in HAI. Methods: The study was undertaken to see the prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant enterobacteriaceae (CRE) in patient samples and surrounding environment. During the study, all the patients' clinical samples sent to the microbiology department for culture sensitivity were considered. All isolates were processed according to standard microbiological protocols and reported according to the Clinical and Laboratory Standards Institute guidelines. Environmental swabs were taken from HI-touch areas from all intensive care unit (ICU)-admitted patients' rooms. Results: Around 290 isolates were reported during the study from concerned ICUs. Out of which 80 samples were carbapenemase producers. Environmental samples were collected from ICUs from Hi-Touch areas showed growth in 23 samples out of a total of 270. Carbapenem-resistant isolates identified in the study belonged equally to Enterobacteriaceae (most common-Klebsiella pneumoniae and Escherichia coli) and nonfermenters classes (CRAB and Pseudomonas aeruginosa), were of similar concern and also difficult to treat, and further compounds the morbidity and mortality of associated infections. The majority of carbapenem-resistant pathogens in this study were resistant to extended-spectrum cephalosporins, fluoroquinolones, and piperacillin-tazobactam (multidrug-resistant [MDR]). Interpretation and Conclusions: In a setting where CRE and CRAB persist, environmental contamination is common. Screening of patients, ensuring strict contact precautions, and strictly following decontamination guidelines in ICUs can be a powerful tool in discerning HAI caused due to CRE and CRAB. [ABSTRACT FROM AUTHOR]

Raoultella planticola harboring genes that confer resistance to antimicrobials, such as carbapenems, have been associated with severe infections in immunocompromised patients. In this study, we reported the first whole genome sequence of a Brazilian isolate of R. planticola and the genomic context of antibiotic resistance markers. By whole-genome sequencing (WGS) of a carbapenem-resistant R. planticola isolate, RpHUM1, we found 23 resistance-encoding genes belonging to 9 classes of antibiotics (aminoglycosides, β-lactams, fluoroquinolones, fosfomycin, macrolides, phenicols, sulfonamides, tetracycline, and diaminopyrimidine derivatives) and 3 plasmids (RpHUM1pEaer-4382s, RpHUM1_pFDAARGOS_440, and RpHUM1pRSF1010). This isolate coharbored the genes blaKPC-2, which is carried by the plasmid RpHUM1pEaer-4382s, and blaNDM-1 and blaCTX-M-15 all located in the accessory genome. In addition, these genes were associated with, at least, one mobile genetic element. This comprehensive knowledge is of great importance for implementation of control measures to prevent the rapid dissemination of this neglected microorganism and their genetic resistance background. [ABSTRACT FROM AUTHOR]