Multidrug-resistant Superbugs Research Articles

Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.

Naturally Derived Malabaricone B as a Promising Bactericidal Candidate Targeting Multidrug-Resistant Staphylococcus aureus also Possess Synergistic Interactions with Clinical Antibiotics.

The emergence of multidrug-resistant (MDR) superbugs underlines the urgent need for innovative treatment options to tackle resistant bacterial infections. The clinical efficacy of natural products directed our efforts towards developing new antibacterial leads from naturally abundant known chemical structures. The present study aimed to explore an unusual class of phenylacylphenols (malabaricones) from Myristicamalabarica as antibacterial agents. In vitro antibacterial activity was determined via broth microdilution, cell viability, time-kill kinetics, biofilm eradication, intracellular killing, and checkerboard assays. The efficacy was evaluated in vivo in murine neutropenic thigh and skin infection models. Confocal and SEM analyses were used for mechanistic studies. Among the tested isolates, malabaricone B (NS-7) demonstrated the best activity against S. aureus with a favorable selectivity index and concentration-dependent, rapid bactericidal killing kinetics. It displayed equal efficacy against MDR clinical isolates of S. aureus and Enterococci, efficiently clearing S. aureus in intracellular and biofilm tests, with no detectable resistance. In addition, NS-7 synergized with daptomycin and gentamicin. In vivo, NS-7 exhibited significant efficacy against S. aureus infection. Mechanistically, NS-7 damaged S. aureus membrane integrity, resulting in the release of extracellular ATP. The results indicated that NS-7 can act as a naturally derived bactericidal drug lead for anti-staphylococcal therapy.

Engineered exosome hybrid copper nanoscale antibiotics facilitate simultaneous self-assembly imaging and elimination of intracellular multidrug-resistant superbugs

Engineered exosome hybrid copper nanoscale antibiotics facilitate simultaneous self-assembly imaging and elimination of intracellular multidrug-resistant superbugs

Potential Broad-Spectrum Antimicrobial, Wound Healing, and Disinfectant Cationic Peptide Crafted from Snake Venom.

Antimicrobial cationic peptides are intriguing and propitious antibiotics for the future, even against multidrug-resistant superbugs. Venoms serve as a source of cutting-edge therapeutics and innovative, unexplored medicines. In this study, a novel cationic peptide library consisting of seven sequences was designed and synthesized from the snake venom cathelicidin, batroxicidin (BatxC), with the inclusion of the FLPII motif at the N-terminus. SP1V3_1 demonstrated exceptional antibacterial effectiveness against Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae and destroyed the bacteria by depolarizing, rupturing, and permeabilizing their membranes, as evident from fluorescence assays, atomic force microscopy, and scanning electron microscopy. SP1V3_1 was observed to modulate the immune response in LPS-elicited U937 cells and exhibited good antibiofilm activity against MRSA and K. pneumoniae. The peptide promoted wound healing and disinfection in the murine model. The study demonstrated that SP1V3_1 is an exciting peptide lead and may be explored further for the development of better therapeutic peptides.

WO3 Nanowire-Attached Reduced Graphene Oxide-Based 1D-2D Heterostructures for Near-Infrared Light-Driven Synergistic Photocatalytic and Photothermal Inactivation of Multidrug-Resistant Superbugs.

The rapid emergence of superbugs which are resistant to existing antibiotics is becoming a huge global threat to public health, which demands the discovery of next-generation antibacterial agents for combating superbugs. Herein, we report the design of a two-dimensional (2D) reduced graphene oxide (r-GO) and one-dimensional (1D) WO3 nanowire-based photothermal-photocatalytic heterostructure for combating multiantibiotic-resistant Salmonella DT104, carbapenem-resistant Enterobacteriaceae Escherichia coli, and methicillin-resistant Staphylococcus aureus superbugs. In the presence of near-infrared (NIR) light, due to the generation of electrons and holes, the WO3-based heterostructure generates reactive oxygen species by photocatalytic reaction from water and oxygen, which kills superbugs. To enhance the photocatalytic superbug killing efficiency, r-GO has been used for suppressing the recombination of the photoinduced electron-hole pairs. Reported data show that NIR light-driven synergistic photocatalytic-photothermal processes can be used for 100% degradation of methylene blue using a heterostructure-based catalyst, and the photodegradation rate for the heterostructure is much better than the literature data for different types of WO3/GO-based nanocomposites. Experimentally, time-dependent antibacterial efficiency data reveals that the heterostructure can destroy 100% superbugs within 30 min of light exposure via a synergistic photothermal and photocatalytic mechanism, whereas the WO3 nanowire can kill around 35% superbugs only via photocatalytic action only and r-GO can kill 25% superbugs via photothermal action even after 30 min of exposure to light. Systematic time-dependent microscopy and spectroscopy studies reveal that the excellent antisuperbug activities for heterostructures are due to membrane damage, ATP, and DNA/RNA breakage. For possible real-life applications, sun light-based superbug inactivation shows 100% inactivation possible within 250 min of light exposure using 12 mg/mL heterostructures. The reported sun light-driven killing of superbugs provides a simple and versatile platform to combat drug-resistant superbugs.

Association of antibiotics and heavy metal arsenic to horizontal gene transfer from multidrug-resistant clinical strains to antibiotic-sensitive environmental strains.

The emergence of multidrug-resistant bacteria is currently posing a significant threat to global public health. By testing for resistance to different antibiotic classes, we discovered that the majority of clinical bacteria are multidrug-resistant. These clinical multidrug-resistant species have antibiotic resistance genes on their plasmids that can be horizontally transferred to various antibiotic susceptible environmental bacterial species, resulting in antibiotic-resistant transconjugates. Furthermore, we discovered that the presence of an optimal concentration of antibiotics or heavy metal (arsenic) facilitates horizontal gene transfer through the formation of transconjugants. Notably, the addition of a conjugation inhibitor (2-hexadecynoic acid, a synthetic fatty acid) completely blocked the formation of antibiotic or arsenic-induced transconjugants. We discovered a high level of arsenic in water from the Shukratal region, Uttarakhand, India, which corresponded to a high serum level of arsenic in clinically infected individuals from the Shukratal region compared to other locations in Uttarakhand. Importantly, bacterial strains isolated from infected people who drink water from the Shukratal region with high arsenic levels were found to be more antibiotic-resistant than strains isolated from other sites. We discovered that bacterial strains isolated from individuals with high serum arsenic levels are significantly more resistant to antibiotics than individuals with low serum arsenic levels within the Shurkratal. This research sheds light on imminent threats to global health in which improper clinical, industrial, and other waste disposal, increased antibiotic concentrations in the environment, and increased human interference can easily transform commensal and pathogenic bacteria found in environmental niches into life-threatening multidrug-resistant superbugs.

Precise digital bacteria enumeration and antibiotic susceptibility testing via a portable vibrating capillary-based droplet platform

Antibiotic resistance can lead to multidrug-resistant superbugs and threaten global health, putting forward a high demand for accurate and fast antibiotic susceptibility testing (AST). Conventional AST methods are labor-intensive and time-consuming, far from meeting the requirement for rapid clinical decision-making. Here, we develop a portable vibrating capillary-based droplet platform for precise digital bacteria enumeration and rapid AST. Multi-volume droplets encapsulating bacteria with or without antibiotics are generated on demand, and the elevated fluorescence from resazurin reduction is measured, which corresponds to the growing bacteria. Automated data analysis is achieved by a self-developed image processing program. Multi-volume droplet digital counting allows precise bacteria enumeration over a wide dynamic range spanning more than 4 orders of magnitude. Droplet digital AST of ampicillin against E. coli demonstrates that it is feasible for accurately assessing the minimum inhibitory concentration and investigating the inoculum effect, with the assay time reduced to 5 h. In sum, this method is easy to operate, cost-effective, with high accuracy and short time-to-result, which is highly promising for rapid and precise assessment of antimicrobial susceptibility in resource-limited settings.

Membrane Vesicles Derived from Gut Microbiota and Probiotics: Cutting-Edge Therapeutic Approaches for Multidrug-Resistant Superbugs Linked to Neurological Anomalies.

Multidrug-resistant (MDR) superbugs can breach the blood-brain barrier (BBB), leading to a continuous barrage of pro-inflammatory modulators and induction of severe infection-related pathologies, including meningitis and brain abscess. Both broad-spectrum or species-specific antibiotics (β-lactamase inhibitors, polymyxins, vancomycin, meropenem, plazomicin, and sarecycline) and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been used to treat these infections. However, new therapeutic platforms with a broad impact that do not exert off-target deleterious effects are needed. Membrane vesicles or extracellular vesicles (EVs) are lipid bilayer-enclosed particles with therapeutic potential owing to their ability to circumvent BBB constraints. Bacteria-derived EVs (bEVs) from gut microbiota are efficient transporters that can penetrate the central nervous system. In fact, bEVs can be remodeled via surface modification and CRISPR/Cas editing and, thus, represent a novel platform for conferring protection against infections breaching the BBB. Here, we discuss the latest scientific research related to gut microbiota- and probiotic-derived bEVs, and their therapeutic modifications, in terms of regulating neurotransmitters and inhibiting quorum sensing, for the treatment of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases. We also emphasize the benefits of probiotic-derived bEVs to human health and propose a novel direction for the development of innovative heterologous expression systems to combat BBB-crossing pathogens.

Kribbellichelins A and B, Two New Antibiotics from Kribbella sp. CA-293567 with Activity against Several Human Pathogens.

Current needs in finding new antibiotics against emerging multidrug-resistant superbugs are pushing the scientific community into coming back to Nature for the discovery of novel active structures. Recently, a survey of halophilic actinomyectes from saline substrates of El Saladar del Margen, in the Cúllar-Baza depression (Granada, Spain), led us to the isolation and identification of 108 strains from the rhizosphere of the endemic plant Limonium majus. Evaluation of the potential of these strains to produce new anti-infective agents against superbug pathogens was performed through fermentation in 10 different culture media using an OSMAC approach and assessment of the antibacterial and antifungal properties of their acetone extracts. The study allowed the isolation of two novel antibiotic compounds, kribbellichelin A (1) and B (2), along with the known metabolites sandramycin (3), coproporphyrin III (4), and kribelloside C (5) from a bioassay-guided fractionation of scaled-up active extracts of the Kribbella sp. CA-293567 strain. The structures of the new molecules were elucidated by ESI-qTOF-MS/MS, 1D and 2D NMR, and Marfey’s analysis for the determination of the absolute configuration of their amino acid residues. Compounds 1–3 and 5 were assayed against a panel of relevant antibiotic-resistant pathogenic strains and evaluated for cytotoxicity versus the human hepatoma cell line HepG2 (ATCC HB-8065). Kribbellichelins A (1) and B (2) showed antimicrobial activity versus Candida albicans ATCC-64124, weak potency against Acinetobacter baumannii MB-5973 and Pseudomonas aeruginosa MB-5919, and an atypical dose-dependent concentration profile against Aspergillus fumigatus ATCC-46645. Sandramycin (3) confirmed previously reported excellent growth inhibition activity against MRSA MB-5393 but also presented clear antifungal activity against C. albicans ATCC-64124 and A. fumigatus ATCC-46645 associated with lower cytotoxicity observed in HepG2, whereas Kribelloside C (5) displayed high antifungal activity only against A. fumigatus ATCC-46645. Herein, we describe the processes followed for the isolation, structure elucidation, and potency evaluation of these two new active compounds against a panel of human pathogens as well as, for the first time, the characterization of the antifungal activities of sandramycin (3).

Genome Informatics and Machine Learning-Based Identification of Antimicrobial Resistance-Encoding Features and Virulence Attributes in Escherichia coli Genomes Representing Globally Prevalent Lineages, Including High-Risk Clonal Complexes.

ABSTRACTEscherichia coli, a ubiquitous commensal/pathogenic member from the Enterobacteriaceae family, accounts for high infection burden, morbidity, and mortality throughout the world. With emerging multidrug resistance (MDR) on a massive scale, E. coli has been listed as one of the Global Antimicrobial Resistance and Use Surveillance System (GLASS) priority pathogens. Understanding the resistance mechanisms and underlying genomic features appears to be of utmost importance to tackle further spread of these multidrug-resistant superbugs. While a few of the globally prevalent sequence types (STs) of E. coli, such as ST131, ST69, ST405, and ST648, have been previously reported to be highly virulent and harboring MDR, there is no clarity if certain ST lineages have a greater propensity to acquire MDR. In this study, large-scale comparative genomics of a total of 5,653 E. coli genomes from 19 ST lineages revealed ST-wide prevalence patterns of genomic features, such as antimicrobial resistance (AMR)-encoding genes/mutations, virulence genes, integrons, and transposons. Interpretation of the importance of these features using a Random Forest Classifier trained with 11,988 genomic features from whole-genome sequence data identified ST-specific or phylogroup-specific signature proteins mostly belonging to different protein superfamilies, including the toxin-antitoxin systems. Our study provides a comprehensive understanding of a myriad of genomic features, ST-specific proteins, and resistance mechanisms entailing different lineages of E. coli at the level of genomes; this could be of significant downstream importance in understanding the mechanisms of AMR, in clinical discovery, in epidemiology, and in devising control strategies.

Mcr Genes Conferring Colistin Resistance in Enterobacterales; a Five Year Overview.

The present review aims to study and detect the global emergence of mcr genes in E. coli, K. pneumoniae and Salmonella spp., isolates from human specimens over the last six years. Nowadays the rise of multidrug-resistant superbugs has made essential the return of drugs that were previously abandoned. A clear example is colistin, which acts against multidrug - resistant gram - negative pathogens, including Enterobacterales. Colistin resistance is an unfortunate fact, with the emergence of mcr genes conferring resistance to colistin in Enterobacterales posing the most recent threat. Literature about mcr genes and their spread in E. coli, K. pneumoniae and Salmonella spp. is cited, focusing on the emergence of mcr genes in human specimens since 2015. The data were taken from the PubMed and Scopus databases. It seems that the mcr-1 gene continues to be the protagonist among the three species. E. coli is the dominant species harbouring mcr genes. Moreover, plasmid - mediated colistin resistance is also conferred upon other species that carry different genes resistant to antibiotics. There are only scarse reports on human Salmonella spp isolates harbouring mcr genes. Finally, the emergence of the mcr-9 gene in all of them is quite remarkable. CONCLUSION: Plasmid - mediated colistin resistance in Enterobacterales is a global issue and has been worsening over the years. The continuous mutations of mcr gene subtypes underline the need for better surveillance, constant investigation and wise use of colistin, especially in countries with high levels of antibiotic resistance.

Physiological properties of indigenous lytic bacteriophages as monophage suspension and cocktail against poultry-adapted typhoidal Salmonella variants.

The emergence and spread of multidrug resistance among pathogens of the agro-food sector is increasing at an alarming rate, which has directed attention to the search for alternative to antibiotic therapy. The present work studied the physiological and population dynamics of lytic bacteriophages against avian-adapted Salmonella. Out of 28 positive samples, four bacteriophage isolates (SalØ-ABF37, SalØ-RCMPF12, SalØ-MCOH26, SalØ-DNLS42) were selected based on their ability to clearly lyse bacterial test strains. The isolates propagated were active against closely related D1 serotypes, i.e., S. Enteritidis and S. Typhimurium, with no heterologous activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 23235. Each of the monophage suspension and cocktail efficiently suppressed the bacterial count from exponential increase in comparison to the untreated bacterial control. The bacterial turbidity was recorded as 0.244 at λ600 during 400 min of co-incubation, in contrast to bacterial control showing λ600 = 0.669. The latent period was recorded to be 25, 35, 25 and 30 for SalØ-ABF37, SalØ-RCMPF12, SalØ-MCOH26 and SalØ-DNLS42, with 73.00, 97.00, 132 and 75.00 PFU cell-1, respectively. The highest lytic activity was seen at 37.00 ˚C - 42.00 ˚C, with phage particle count being fairly stable at pH 3.00 - 9.00. Each of the isolates possessed dsDNA by being resistant to RNase A. The current study concludes that lytic phages are promising alternative to combat multidrug resistant superbugs. The physiological characterization and bacterial growth inhibition are important parameters in standardization of phage therapy.

Macromolecular Nanotherapeutics and Antibiotic Adjuvants to Tackle Bacterial and Fungal Infections.

The escalating rise in the population of multidrug-resistant (MDR) pathogens coupled with their biofilm forming ability has struck the global health as nightmare. Alongwith the threat of aforementioned menace, the sluggish development of new antibiotics and the continuous deterioration of the antibiotic pipeline has stimulated the scientific community toward the search of smart and innovative alternatives. In near future, membrane targeting antimicrobial polymers, inspired from antimicrobial peptides, can stand out significantly to combat against the MDR superbugs. Many of these amphiphilic polymers can form nanoaggregates through self-assembly with superior and selective antimicrobial efficacy. Additionally, these macromolecular nanoaggregrates can be utilized to engineer smart antibiotic-delivery system for on-demand drug-release, exploiting the infection site's micoenvironment. This strategy substantially increases the local concentration of antibiotics and reduces the associated off-target toxicity. Furthermore, amphiphilc macromolecules can be utilized to rejuvinate obsolete antibiotics to tackle the drug-resistant infections. This review article highlights the recent developments in macromolecular architecture to design numerous nanostructures with broad-spectrum antimicrobial activity, their application in fabricating smart drug delivery systems and their efficacy as antibiotic adjuvants to circumvent antimicrobial resistance. Finally, the current challenges and future prospects are briefly discussed for further exploration and their practical application in clinical settings.

A nematode-derived, mitochondrial stress signaling-regulated peptide exhibits broad antibacterial activity.

ABSTRACTA dramatic rise of infections with antibiotic-resistant bacterial pathogens continues to challenge the healthcare field due to the lack of effective treatment regimes. As such, there is an urgent need to develop new antimicrobial agents that can combat these multidrug-resistant superbugs. Mitochondria are central regulators of metabolism and other cellular functions, including the regulation of innate immunity pathways involved in the defense against infection. The mitochondrial unfolded protein response (UPRmt) is a stress-activated pathway that mitigates mitochondrial dysfunction through the regulation of genes that promote recovery of the organelle. In the model organism Caenorhabditis elegans, the UPRmt also mediates an antibacterial defense program that combats pathogen infection, which promotes host survival. We sought to identify and characterize antimicrobial effectors that are regulated during the UPRmt. From our search, we discovered that the antimicrobial peptide CNC-4 is upregulated during this stress response. CNC-4 belongs to the caenacin family of antimicrobial peptides, which are predominantly found in nematodes and are known to have anti-fungal properties. Here, we find that CNC-4 also possesses potent antimicrobial activity against a spectrum of bacterial species and report on its characterization.

Multidrug resistant superbugs in pyogenic infections: a study from Western Rajasthan, India.

Introductionthe crude mortality rate due to infectious diseases in India is approximately 417 per one lakh persons and pyogenic infections are one of the significant contributor. Poor antimicrobial stewardship in India has led to an increase in multidrug resistant superbugs in both community as well as hospital settings. The aim of this study was to identify the bacterial etiology of pyogenic infections and to evaluate their antimicrobial resistance profile.Methodsthis is a retrospective observational study from January, 2018 to December, 2018. A total 1851 samples, collected as a part of patient care were included in this study. Specimens were subjected to culture on Blood agar and MacConkey agar and incubated at 37°C for 48 hours. Species identification was done as per standard laboratory protocol. Antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion according to Clinical and Laboratory Standards Institute guidelines.Resultsof total 1851 samples, culture was positive in 61.54%. A total 70.59%, Gram negative organisms were isolated followed by Gram positive cocci in 45.48%, yeast in 1.05%, coryneform bacteria in 0.79% and in one case, non-tubercular mycobacteria was isolated. Staphylococcus aureus (30.9%) was the predominant organism isolated. Most common multi drug resistant isolates were Klebsiella spp. (74.79%) and Acinetobacter spp. (74.32%).Conclusionthis study gives an insight about the prevalence and common etiology of pyogenic infections along with their antimicrobial resistance profile in north western region of India. This study will contribute in formulating antibiotic stewardship program by selecting the antibiograms of pyogenic isolates.

Development of Human Host Defense Antimicrobial Peptide-Conjugated Biochar Nanocomposites for Combating Broad-Spectrum Superbugs.

Infectious diseases by multidrug-resistant superbugs, which cannot be cured using commercially available antibiotics, are the biggest threat for our society. Due to the lack of discovery of effective antibiotics in the last two decades, there is an urgent need for the design of new broad-spectrum antisuperbug biomaterials. Herein, we report the development of antisuperbug nanocomposites using human host defense antimicrobial peptide-conjugated biochar. To develop an economically viable technology, biochar, a carbon-rich material from naturally abundant resource, has been used. For combating broad-spectrum superbugs, a nanocomposite has been designed by combining biochar with α-defensin human neutrophil peptide-1 (HNP-1), human β-defensin-1 (hBD-1), and human cathelicidin LL-37 antimicrobial peptide. The designed three-dimensional (3D) nanocomposites with pore size between 200 and 400 nm have been used as channels for water passage and captured superbugs. The reported data demonstrated that antimicrobial nanocomposite can be used for efficient capture and eradication of Gram-negative carbapenem-resistant Enterobacteriaceae (CRE) Escherichia coli (E. coli) and Klebsiella pneumoniae (KPN) superbugs, as well as Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) superbugs. Possible mechanisms for broad-spectrum antisuperbug activities using hydrogel have been discussed.

Antibacterial activity of graphene oxide nanosheet against multidrug resistant superbugs isolated from infected patients.

Graphene oxide (GO) is a derivative of graphene nanosheet which is the most promising material of the decade in biomedical research. In particular, it has been known as an antimicrobial nanomaterial with good biocompatibility. In this study, we have synthesized and characterize GO and checked its antimicrobial property against different Gram-negative and Gram-positive multidrug drug resistant (MDR) hospital superbugs grown in solid agar-based nutrient plates with and without human serum through the utilization of agar well diffusion method, live/dead fluorescent staining and genotoxicity analysis. No significant changes in antibacterial activity were found in these two different conditions. We also compare the bactericidal capability of GO with some commonly administered antibiotics and in all cases the degree of inhibition is found to be higher. The data presented here are novel and show that GO is an effective bactericidal agent against different superbugs and can be used as a future antibacterial agent.

Detection of New Delhi metallo-beta-lactamase enzyme gene bla NDM-1 associated with the Int-1 gene in Gram-negative bacteria collected from the effluent treatment plant of a tuberculosis care hospital in Delhi, India.

Background Organisms possessing the bla NDM-1 gene (responsible for carbapenem resistance) with a class-1 integron can acquire many other antibiotic resistance genes from the community sewage pool and become multidrug-resistant superbugs. In this regard, hospital sewage, which contains a large quantity of residual antibiotics, metals and disinfectants, is being recognized as a significant cause of antimicrobial resistance (AMR) origination and spread across the major centres of the world and is thus routinely investigated as a marker for tracing the origin of drug resistance. Therefore, in this study, an attempt has been made to identify and characterize the carbapenem-resistant microbes associated with integron genes amongst the organisms isolated from the effluent treatment plant (ETP) installed in a tertiary respiratory care hospital in Delhi, India.Methods One hundred and thirty-eight organisms belonging to Escherichia , Klebsiella , Pseudomonas and Acinetobacter spp. were collected from the incoming and outgoing sewage lines of the ETP. Carbapenem sensitivity and characterization was performed by the imipenem and imipenem-EDTA disc diffusion method. Later DNA extraction and PCR steps were performed for the Int-1 and bla NDM-1 genes.Results Of the 138 organisms, 86 (62.3 %) were imipenem-resistant (P<0.05). One hundred and twenty-four (89.9 %) organisms had one or both of the genes. Overall, the bla NDM-1 gene (genotypic resistance) was present in 71 % (98/138) of organisms. 53.6 % (74/138) organisms were double gene-positive (bla NDM-1 + Int-1), of which 40 were producing the metallo-beta-lactamase enzyme, making up almost 28.9 % (40/138) of the collected organisms.Conclusion The current study strengthens the hypothesis that Carbapenem resistant organisms are in a high-circulation burden through the human gut and hospital ETPs are providing an environment for resistance origination and amplification.

Unusual accumulation of a wide array of antimicrobial resistance mechanisms in a patient with cytomegalovirus-associated hemophagocytic lymphohistiocytosis: a case report

BackgroundInfections with multidrug-resistant organisms (MDRO) pose a serious threat to patients with dysregulated immunity such as in hemophagocytic lymphohistiocytosis (HLH), but such infections have rarely been comprehensively characterized. Here, we present a fatal case of HLH secondary to cytomegalovirus (CMV) infection complicated by both anti-viral drug resistance and sepsis from multiple MDROs including pandrug-resistant superbug bacteria.Case presentationA previously healthy, six-year-old boy presented with a 45-day history of fever prior to a diagnosis of hemophagocytic lymphohistiocytosis and hemorrhagic colitis, both associated with CMV. On hospital admission, the patient was found to be colonized with multiple, multidrug-resistant (MDR) bacteria including vancomycin-resistant enterococci (VRE) and carbapenamase-producing organisms (CPO). He eventually developed respiratory, urine and bloodstream infections with highly drug-resistant, including pandrug-resistant bacteria, which could not be controlled by antibiotic treatment. Antiviral therapy also failed to contain his CMV infection and the patient succumbed to overwhelming bacterial and viral infection. Whole genome sequencing (WGS) of the MDR bacteria and metagenomic analysis of his blood sample revealed an unusual accumulation of a wide range of antimicrobial resistance mechanisms in a single patient, including antiviral resistance to ganciclovir, and resistance mechanisms to all currently available antibiotics.ConclusionsThe case highlights both the risk of acquiring MDR superbugs and the severity of these infections in HLH patients.

One-step Synthesis of Silver Nanoparticles Using Saudi Arabian Desert Seasonal Plant Sisymbrium irio and Antibacterial Activity Against Multidrug-Resistant Bacterial Strains.

Globally, antimicrobial resistance has grown at an alarming rate. To combat the multidrug-resistant (MDR) superbugs, silver nanoparticles (Ag NPs) were synthesized using an aqueous leaf extract of seasonal desert plant Sisymbrium irio obtained from the central region of Saudi Arabia by a simple one-step procedure. The physical and chemical properties of the Ag NPs were investigated through ultraviolet visisble analysis (UV-vis), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) analysis. The UV-vis spectrum showed an absorption band at 426 nm. The XRD results showed a highly crystalline face-centered cubic structure. The surface morphology analyzed using SEM and TEM analyses showed the particle size to be in the range 24 nm to 50 nm. Various concentrations of Ag NPs were tested against MDR Pseudomonas aeruginosa and Acinetobacter baumanii that cause ventilator-associated pneumonia (VAP). American Type Culture Collection (ATCC) Escherichia coli-25922 was used as the reference control strain. The Ag NPs effectively inhibited tested pathogens, even at the lowest concentration (6.25 µg) used. The bacterial inhibitory zone ranged from 11–21 mm. In conclusion, the newly synthesized Ag NPs could be a potential alternative candidate in biomedical applications in controlling the spread of MDR pathogens.