The growing threat of NDM-producing E. coli with penicillin-binding protein 3 mutations in the United States - is there a potential role for durlobactam?

We report identification of 5 patients with infections caused by NDM-5-producing E. coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane ß-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.

Sequential Treatment Failure With Aztreonam-Ceftazidime-Avibactam Followed by Cefiderocol Due to Preexisting and Acquired Mechanisms in a New Delhi Metallo-ß-lactamase-Producing Escherichia coli Causing Fatal Bloodstream Infection.

We report a fatal case of New Delhi metallo-ß-lactamase (NDM)-producing Escherichia coli in a bacteremic patient with sequential failure of aztreonam plus ceftazidime-avibactam followed by cefiderocol. Acquired resistance was documented phenotypically and mediated through preexisting and acquired mutations. This case highlights the need to rethink optimal treatment for NDM-producing organisms.

Successful treatment of sino-pulmonary infection & skull base osteomyelitis caused by New Delhi metallo-ß-lactamase-producing Pseudomonas aeruginosa in a renal transplant recipient by using an investigational antibiotic cefepime/zidebactam (WCK 5222).

A case of sino-pulmonary infection with skull base osteomyelitis due to XDR-Pseudomonas aeruginosa in renal transplant recipient was successfully treated with investigational antibiotic, cefepime/zidebactam (WCK 5222). This case highlights challenges in managing XDR-pseudomonal infection where source control was infeasible, antibiotic options were extremely limited and individualized dose adjustments were needed.

Ceftazidime-avibactam alone or in combination with Aztreonam versus Polymyxins in the management of carbapenem-Resistant Klebsiella pneumoniae nosocomial Infections (CAPRI study): a retrospective cohort study from South India.

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/- aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production. METHODS: We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later. RESULTS: Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime-avibactam +/- aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime-avibactam +/- aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03-3.9). CONCLUSION: Ceftazidime-avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP.

Genomic characterization of New Delhi metallo-beta-lactamase-producing species of Morganellaceae, Yersiniaceae, and Enterobacteriaceae (other than Klebsiella) from Brazil over 2013-2022.

Over the last decade, New Delhi metallo-beta-lactamase (NDM) carbapenemase has silently spread in Brazil. In this study, we analyzed a large collection of Enterobacterales other than Klebsiella spp. received in our reference laboratory between 2013 and 2022. A total of 32 clinical isolates displaying different pulsed-field gel electrophoresis profiles, and represented by 11 species in the families Enterobacteriaceae (Citrobacter freundii, Citrobacter portucalensis, Enterobacter hormaechei, and Escherichia coli), Morganellaceae (Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Raoultella ornithinolytica), and Yersiniaceae (Serratia marcescens) had their whole genomes sequenced and further analyzed. Antimicrobial susceptibility was determined by disk diffusion, except for polymyxin B, assessed by broth microdilution. The blaNDM-1 allele was predominant (n = 29), but blaNDM-5 was identified in an E. coli specimen with a novel ST, and the blaNDM-7 allele was found in E. hormaechei ST45 and E. coli ST1049. Polymyxin was active against all but one Enterobacteriaceae isolate: an mcr-1-producing E. coli presenting minimal inhibitory concentration (4 mg/L). Isolates producing extended-spectrum ß-lactamases were common: cefotaximase from Munich (CTX-M)-15 (n = 10), CTX-M-2 (n = 4), and CTX-M-8 (n = 3) were detected, and the mcr-1-producing E. coli was found to co-produce both CTX-M-8 and CTX-M-55 ß-lactamases. The mcr-9 gene was found in 5/8 E. hormaechei isolates, distributed in four different sequence types, all of them presenting susceptibility to polymyxin. This study showed that NDM-producing Enterobacterales other than Klebsiella are already spread in Brazil, in diversified species, and cocarrying important resistance genes. Prompt detection and effective implementation of measures to prevent further spread are mandatory for mitigating the dissemination of NDM carbapenemase in hospital settings and preserving the already limited antimicrobial therapy options.

Novel partially reversible NDM-1 inhibitors based on the naturally occurring houttuynin.

Discovering novel NDM-1 inhibitors is an urgent task for treatment of 'superbug' infectious diseases. In this study, we found that naturally occurring houttuynin and its sulfonate derivatives might be effective NDM-1 inhibitors with novel mechanism, i.e. the attribute of partially covalent inhibition of sulfonate derivatives of houttuynin against NDM-1. Primary structure-activity relationship study showed that both the long aliphatic side chain and the warhead of aldehyde group are vital for the efficiency against NDM-1. The homologs with longer chains (SNH-2 to SNH-5) displayed stronger inhibitory activities with IC50 range of 1.1-1.5 µM, while the shorter chain the weaker inhibition. Further synergistic experiments in cell level confirmed that all these 4 compounds (at 32 µg/mL) recovered the antibacterial activity of meropenem (MER) against E. coli BL21/pET15b-blaNDM-1.

Aerosol-PM2.5 Dynamics: In-situ and satellite observations under the influence of regional crop residue burning in post-monsoon over Delhi-NCR, India.

The increasing air pollution in the urban atmosphere is adversely impacts the environment, climate and human health. The alarming degradation of air quality, atmospheric conditions, economy and human life due to air pollution needs significant in-depth studies to ascertain causes, contributions and impacts for developing and implementing an effective policy to combat these issues. This work lies in its multifaceted approach towards comprehensive understanding and mitigating severe pollution episodes in Delhi and its surrounding areas. We investigated the aerosol dynamics in the post-monsoon season (PMS) from 2019 to 2022 under the influence of both crop residue burning and meteorological conditions. The study involves a broad spectrum of factors, including PM2.5 concentrations, active fire events, and meteorological parameters, shedding light on previously unexplored studies. The average AOD550 (0.79) and PM2.5 concentration (140.12 µg/m³) were the highest in 2019. PM2.5 was higher from mid-October to mid-November each year, exceeding the WHO guideline of 15 µg/m³ (24 h) by 27-34 times, signifying a public health emergency. A moderate to strong correlation between PM2.5 and AOD was found (r = 0.65) in 2021. The hotspot region accounts for almost 50% (2019), 47.51% (2020), 57.91% (2021) and 36.61% (2022) of the total fire events. A statistically significant negative non-linear correlation (r) was observed between wind speed (WS) and both AOD and PM2.5 concentration, influencing air quality over the region. HYSPLIT model and Windrose result show the movement of air masses predominated from the North and North-West direction during PMS. This study suggest to promotes strategies such as alternative waste management, encouraging modern agricultural practices in hot-spot regions, and enforcing strict emission norms for industries and vehicles to reducing air pollution and its detrimental effects on public health in the region and also highlights the need for future possibilities of research to attract the global attention.

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Transcontinental Dissemination of Enterobacterales Harboring blaNDM-1 in Retail Frozen Shrimp.

The global food trade provides a means of disseminating antimicrobial resistant (AMR) bacteria and genes. Using selective media, carbapenem-resistant species of Enterobacterales (Providencia sp. and Citrobacter sp.), were detected in a single package of imported frozen shrimp purchased from a grocery store in Ohio, USA. Polymerase chain reaction confirmed that both isolates harbored blaNDM-1 genes. Following PacBio long read sequencing, the sequences were annotated using the NCBI Prokaryotic Genome Annotation Pipeline. The blaNDM-1 genes were found in IncC plasmids, each with different antimicrobial resistance island configuration. We found that the blaNDM-1 AMR islands had close relationships with previously reported environmental, food, and clinical isolates detected in Asia and the United States, highlighting the importance of the food chain in the global dissemination of antimicrobial resistance.

The warming city: the increasing risk of summer fires in Delhi.

Rising temperatures are mainly associated with wildfires, but the incidence of fire may also increase in the urban context. Yet, fire in Delhi, India, as elsewhere in the towns and cities of the Global South, remains largely invisible, despite the nearly 11 million people each year who are burnt severely enough to require medical attention. This paper focuses on whether summer temperatures in Delhi are rising and whether higher temperatures and lower humidity contribute to a greater number of fires in urban areas. The data strongly suggest a relationship between the warming city, a growing number of summer fires, and mounting temperatures around the world. Delhi, however, is only one example of an urban reality that is common to much of the Global South. Similar questions about the incidence of fire and whether the number is increasing need to be asked of other towns and cities that share the same vulnerabilities.

AI-based prediction of the improvement in air quality induced by emergency measures.

Several cities in the developing world, of which the capital city of India, New Delhi, is an example, often experience air quality in which pollutant levels go way above the levels considered hazardous for human health. To bring down the air quality to within permissible limits quickly, the measures typically taken involve shutting down certain high-polluting activities for some time to enable the air quality to recover temporarily. This paper presents a first-ever model based on artificial neural networks to forecast the extent of reduction in air quality parameters that can be achieved and the time period within which a change can be experienced when the source of the emissions is cut off temporarily. The model is based on the extensive data on the extent of reduction in air quality parameters that occurred during the lockdown that was imposed during the COVID-19 pandemic. The non-linear autoregressive exogenous network-based model chosen for the purpose employs the hour since stopping of emissions, relative humidity, wind speed, wind direction, and ambient temperature as input parameters to predict the rate of change of PM2.5 with respect to the concentration at the start of the stopping of the emissions. Air quality data from a key monitoring station in New Delhi was used to develop the model. The model predicted the rate of drop in PM2.5 with an R and MSE of 0.0044 and 0.9736, respectively, while training and 0.0095 and 0.9583 while testing. The model was then tested with data from 19 other stations in New Delhi, and accuracy of the model was found to be exceptionally accurate, with the correlation between the measured and the predicted PM2.5 levels ranging from 0.74 to 0.94 and the MSE ranging from 0.0110 to 1.0746. Thus, the model can be employed to determine the number of hours of temporary stoppage of emissions required for the PM2.5 concentration to reach safe levels. The methodology of development of the model can be extrapolated to construct models tailored for use in other parts of the world as well.

Composition of heavy metals in sediment, water, and fish of the Ganga and Yamuna Rivers in two major cities of India.

The rapid industrial development in the Indian capital region has led to significant waste generation, which, despite undergoing treatment prior to disposal, contributes substantially to water body contamination. Given the diverse nature of these wastes and their potential repercussions across the food chain, a study was conducted to evaluate heavy metal contamination levels in the Ganga and Yamuna Rivers of two major cities. Six heavy metals (Pb, Cd, Hg, Cu, Cr, and Zn) were analyzed in fish, water, and sediment samples by utilizing flame atomic absorption spectrophotometry (Avanta Σ) from March 2019 to February 2020. Results revealed distinct heavy metal distribution patterns, with Cr > Zn > Pb > Cu > Cd > Hg in the Ganga River and Zn > Cr > Pb > Cu > Cd > Hg in the Yamuna River for fish samples. Additionally, levels of Hg in Cyprinus carpio and Sperata oar from the Ganga River, and Pb, Cd, Hg, and Cr in Salmophasia bacaila and Mystus cavasius from the Yamuna River exceeded WHO/FAO permissible limits. In water samples, the predominant heavy metal sequences were Pb > Cu > Zn > Cr > Cd > Hg for the Ganga River and Cr > Zn > Pb > Cu > Cd > Hg for the Yamuna River, with Pb, Cr, Zn, and Cd surpassing WHO standards. Sediment analysis revealed varying heavy metal compositions, with Zn > Cr > Pb > Cu > Cd > Hg in the Ganga River and Cr > Zn > Pb > Cu > Cd > Hg in the Yamuna River. While drinking water and fish from the Ganga River were deemed safe for consumption, those from the Yamuna River were not. Given the toxic nature of heavy metals and their detrimental health impacts, regular monitoring and effective management strategies are imperative.

Chemical characteristics, morphology and source apportionment of PM10 over National Capital Region (NCR) of India.

The present study frames the physico-chemical characteristics and the source apportionment of PM10 over National Capital Region (NCR) of India using the receptor model's Positive Matrix Factorization (PMF) and Principal Momponent Mnalysis/Absolute Principal Component Score-Multilinear Regression (PCA/APCS-MLR). The annual average mass concentration of PM10 over the urban site of Faridabad, IGDTUW-Delhi and CSIR-NPL of NCR-Delhi were observed to be 195 ± 121, 275 ± 141 and 209 ± 81 µg m-3, respectively. Carbonaceous species (organic carbon (OC), elemental carbon (EC) and water-soluble organic carbon (WSOC)), elemental constituents (Al, Ti, Na, Mg, Cr, Mn, Fe, Cu, Zn, Br, Ba, Mo Pb) and water-soluble ionic components (F-, Cl-, SO42-, NO3-, NH4+, Na+, K+, Mg2+, Ca2+) of PM10 were entrenched to the receptor models to comprehend the possible sources of PM10. The PMF assorted sources over Faridabad were soil dust (SD 15%), industrial emission (IE 14%), vehicular emission (VE 19%), secondary aerosol (SA 23%) and sodium magnesium salt (SMS 17%). For IGDTUW-Delhi, the sources were SD (16%), VE (19%), SMS (18%), IE (11%), SA (27%) and VE + IE (9%). Emission sources like SD (24%), IE (8%), SMS (20%), VE + IE (12%), VE (15%) and SA + BB (21%) were extracted over CSIR-NPL, New Delhi, which are quite obvious towards the sites. PCA/APCS-MLR quantified the similar sources with varied percentage contribution. Additionally, catalogue the Conditional Bivariate Probability Function (CBPF) for directionality of the local source regions and morphology as spherical, flocculent and irregular were imaged using a Field Emission-Scanning Electron Microscope (FE-SEM).

BREATH-Net: a novel deep learning framework for NO2 prediction using bi-directional encoder with transformer.

Air pollution poses a significant challenge in numerous urban regions, negatively affecting human well-being. Nitrogen dioxide (NO2) is a prevalent atmospheric pollutant that can potentially exacerbate respiratory ailments and cardiovascular disorders and contribute to cancer development. The present study introduces a novel approach for monitoring and predicting Delhi's nitrogen dioxide concentrations by leveraging satellite data and ground data from the Sentinel 5P satellite and monitoring stations. The research gathers satellite and monitoring data over 3 years for evaluation. Exploratory data analysis (EDA) methods are employed to comprehensively understand the data and discern any discernible patterns and trends in nitrogen dioxide levels. The data subsequently undergoes pre-processing and scaling utilizing appropriate techniques, such as MinMaxScaler, to optimize the model's performance. The proposed forecasting model uses a hybrid architecture of the Transformer and BiLSTM models called BREATH-Net. BiLSTM models exhibit a strong aptitude for effectively managing sequential data by adeptly capturing dependencies in both the forward and backward directions. Conversely, transformers excel in capturing extensive relationships over extended distances in temporal data. The results of this study will illustrate the proposed model's efficacy in predicting the levels of NO2 in Delhi. If effectively executed, this model can significantly enhance strategies for controlling urban air quality. The findings of this research show a significant improvement of RMSE = 9.06 compared to other state-of-the-art models. This study's primary objective is to contribute to mitigating respiratory health issues resulting from air pollution through satellite data and deep learning methodologies.

Air pollution and its effects on lung health in never-smoker youth of Delhi NCR versus Pauri Garhwal: a comparative cross-sectional study.

Background: Ambient air pollution is a major factor that can affect lung growth and reduce lung capacity. This study aims at drawing parallel between respiratory discomfort and lung function between youth of Delhi-National Capital Region (NCR) where air pollution level is poor and hazardous as compared to that of Pauri Garhwal (Uttarakhand) where air pollution level is low via a comparative cross-sectional study. Methods: A community-based cross-sectional study conducted among 354 never-smoker subjects (177 from NCR and 177 from Pauri) between the ages of 15 and 29 years. Pulmonary Function Test coupled with COPD Assessment Test (CAT)-based questionnaire for respiratory problems helped elicit information regarding lung health of subjects. Results: Mean forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1), forced expiratory flow 25-75%, FEV1/FVC ratio, and peak expiratory flow rate were lower by 12.9%, 17%, 5%, 7.8%, and 7.3%, respectively, in NCR participants as compared to that of Pauri. Upon spirometry, restrictive pattern was present in 40 (22.6%), and obstructive pattern was present in 9 (5.1%) of NCR participants. Out of these, nine (5.1%) having obstructive pattern, five (55.6%) had 50% ≤ FEV1<80%, and four (44.4%) had 30% ≤ FEV1<50% of predicted value. Neither restrictive nor obstructive pattern was found evident in subjects from Pauri. The mean CAT score in subjects from NCR was 5.2 ± 4.9 and .46 ± 1.1 in subjects from Pauri. Conclusion: Subjects belonging to NCR performed poorly in spirometry and reported higher respiratory complaints in comparison to participants from Pauri Garhwal.

Diversity and phylogeography of begomoviruses and DNA satellites associated with the leaf curl and mosaic disease complex of eggplant.

Eggplant is one of the important vegetable crops grown across the world, and its production is threatened by both biotic and abiotic stresses. Diseases caused by viruses are becoming major limiting factors for its successful cultivation. A survey for begomovirus-like symptoms in 72 eggplant fields located in six different Indian states revealed a prevalence of disease ranging from 5.2 to 40.2%, and the symptoms recorded were mosaic, mottling, petiole bending, yellowing, and upward curling, vein thickening, and enation of the leaves, and stunting of plants. The causal agent associated with these plants was transmitted from infected leaf samples to healthy eggplant seedlings via grafting and whiteflies (Bemisia tabaci). The presence of begomovirus was confirmed in 72 infected eggplant samples collected from the surveyed fields exhibiting leaf curl and mosaic disease by PCR using begomovirus specifc primers (DNA-A componet), which resulted in an expected amplicon of 1.2 kb. The partial genome sequence obtained from amplified 1.2 kb from all samples indicated that they are closely related begomovirus species, tomato leaf Karnataka virus (ToLCKV, two samples), tomato leaf curl Palampur virus (ToLCPalV, fifty eggplant samples), and chilli leaf curl virus (ChLCuV, twenty samples). Based on the partial genome sequence analysis, fourteen representative samples were selected for full viral genome amplification by the rolling circle DNA amplification (RCA) technique. Analyses of fourteen eggplant isolates genome sequences using the Sequence Demarcation Tool (SDT) indicated that one isolate had the maximum nucleotide (nt) identity with ToLCKV and eight isolates with ToLCPalV. Whereas, four isolates four isolates (BLC1-CH, BLC2-CH, BLC3-CH, BLC4-CH) are showing nucleotide identity of less than 91% with chilli infecting viruses begomoviruses with chilli infecting begomoviruses and as per the guidelines given by the ICTV study group for the classification of begomoviruses these isolates are considered as one novel begomovirus species, for which name, Eggplant leaf curl Chhattisgarh virus (EgLCuChV) is proposed. For DNA-B component, seven eggplant isolates had the highest nt identity with ToLCPalV infecting other crops. Further, DNA satellites sequence analysis indicated that four betasatellites identified shared maximum nucleotide identity with the tomato leaf curl betasatellite and five alphasatellites shared maximum nucleotide identity with the ageratum enation alphasatellite. Recombination and GC plot analyses indicated that the bulk of begomovirus genome and associated satellites presumably originated from of previously known mono and bipartite begomoviruses and DNA satellites. To the best of our knowledge, this is India's first report of ToLCKV and a noval virus, eggplant leaf curl Chhattisgarh virus associated with eggplant leaf curl disease.

Three separate acquisitions of blaNDM-1 in three different bacterial species from a single patient.

To investigate the acquisition and relatedness of New Delhi Metallo-beta-lactamase among multiple separate species from one patient. Five isolates from three species (Pseudomonas aeruginosa; Pa, Acinetobacter baumannii; Ab and Proteus mirabilis; Pm) suspected of harbouring a carbapenemase were investigated by phenotype (antimicrobial susceptibilities) and whole genome sequencing. Epidemiological data was collected on this patient. Three different carbapenemase genes were detected; blaVIM-1 (Pa; ST773), blaOXA-23 (Ab, ST499) and blaNDM-1 identified in all isolates. NDM regions were found chromosomally integrated in all isolates. Data showed no evidence of NDM-1 transfer within this patient suggesting the enzyme was acquired in three separate events.

Epidemiological characteristics of New Delhi Metallo-ß-Lactamase-producing Enterobacteriaceae in the Fourth hospital of Hebei Medical University.

The epidemiological characteristics of New Delhi Metallo-ß-Lactamase-Producing (NDM) Enterobacteriaceae were analyzed to provide theoretical support for clarifying the distribution characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in the hospital environment and early identification of susceptible patients. From January 2017 to December 2021,42 strains of NDM-producing Enterobacteriaceae were gathered from the Fourth Hospital of Hebei Medical University, primarily Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. The micro broth dilution method combined with the Kirby-Bauer method was used to determine the minimal inhibitory concentrations (MICs) of antibiotics. The carbapenem phenotype was detected by the modified carbapenem inactivation method (mCIM) and EDTA carbapenem inactivation method (eCIM). Carbapenem genotypes were detected by colloidal gold immunochromatography and real-time fluorescence PCR. The results of antimicrobial susceptibility testing showed that all NDM-producing Enterobacteriaceae were multiple antibiotic resistant, but the sensitivity rate to amikacin was high. Invasive surgery prior to culture, the use of excessive amounts of different antibiotics, the use of glucocorticoids, and ICU hospitalization were clinical characteristics of NDM-producing Enterobacteriaceae infection. Molecular typing of NDM-producing Escherichia coli and Klebsiella pneumoniae was carried out by Multilocus Sequence Typing (MLST), and the phylogenetic trees were constructed. Eight sequence types (STs) and two NDM variants were detected in 11 strains of Klebsiella pneumoniae, primarily ST17, and NDM-1. A total of 8 STs and 4 NDM variants were detected in 16 strains of Escherichia coli, mainly ST410, ST167, and NDM-5. For high-risk patients who have CRE infection, CRE screening should be done as soon as feasible to adopt prompt and efficient intervention measures to prevent outbreaks in the hospital.

Compassionate use of a novel ß-lactam enhancer-based investigational antibiotic cefepime/zidebactam (WCK 5222) for the treatment of extensively-drug-resistant NDM-expressing Pseudomonas aeruginosa infection in an intra-abdominal infection-induced sepsis patient: a case report.

Infections in critically-ill patients caused by extensively-drug-resistant (XDR)-Pseudomonas aeruginosa are challenging to manage due to paucity of effective treatment options. Cefepime/zidebactam, which is currently in global Phase 3 clinical development (Clinical Trials Identifier: NCT04979806, registered on July 28, 2021) is a novel mechanism of action based ß-lactam/ ß-lactam-enhancer combination with a promising activity against a broad-range of Gram-negative pathogens including XDR P. aeruginosa. We present a case report of an intra-abdominal infection-induced sepsis patient infected with XDR P. aeruginosa and successfully treated with cefepime/zidebactam under compassionate use. The 50 year old female patient with past-history of bariatric surgery and recent elective abdominoplasty and liposuction developed secondary pneumonia and failed a prolonged course of polymyxins. The organism repeatedly isolated from the patient was a New-Delhi metallo ß-lactamase-producing XDR P. aeruginosa resistant to ceftazidime/avibactam, imipenem/relebactam and ceftolozane/tazobactam, susceptible only to cefepime/zidebactam. As polymyxins failed to rescue the patient, cefepime/zidebactam was administered under compassionate grounds leading to discharge of patient in stable condition. The present case highlights the prevailing precarious scenario of antimicrobial resistance and the need for novel antibiotics to tackle infections caused by XDR phenotype pathogens.

First report of New Delhi metallo-ß-lactamase-1-producing Acinetobacter soli in Japan.

New Delhi metallo-ß-lactamase (NDM)-producing gram-negative rods, including Acinetobacter species, are a global problem but have rarely been isolated in Japan. To our knowledge, this is the first study to isolate an NDM-1-producing Acinetobacter soli strain, KUH106, in Japan. We analyzed this strain using next-generation sequencing to examine the plasmid carrying NDM-1. This plasmid, named pKUH106_NDM1, is 41,135 bp in length and contains genetic contexts with the structure ISAba14-aph(3')-VI-ISAba125-blaNDM-1ble-MBL. Comparative analysis of the plasmid revealed that it resembled the plasmids of Acinetobacter detected in various countries, such as the A. soli isolate from Taiwan and the Acinetobacter baumannii isolate from a healthcare facility in Osaka Prefecture, Japan. These results suggest that blaNDM-1 may spread via this plasmid in Acinetobacter species. This phenomenon needs to be confirmed through the genetic analysis of A. baumannii and other carbapenem-resistant Acinetobacter species. In particular, blaNDM-1 and other resistance genes must be investigated, and the spread of these genes in the community must be cautioned.