Search

Priority 1: critical WHO pathogen Acinetobacter baumannii depends on ATP synthesis and ATP:ADP homeostasis and its bifunctional F1FO‐ATP synthase. While synthesizing ATP, it regulates ATP cleavage by its inhibitory ε subunit to prevent wasteful ATP consumption. We determined cryo‐electron microscopy structures of the ATPase active A. baumannii F1‐αßγεΔ134–139 mutant in four distinct conformational states, revealing four transition states and structural transformation of the ε's C‐terminal domain, forming the switch of an ATP hydrolysis off‐ and an ATP synthesis on‐state based. These alterations go in concert with altered motions and interactions in the catalytic‐ and rotary subunits of this engine. These A. baumannii interacting sites provide novel pathogen‐specific targets for inhibitors, with the aim of ATP depletion and/or ATP synthesis and growth inhibition. Furthermore, the presented diversity to other bacterial F‐ATP synthases extends the view of structural elements regulating such a catalyst. [ABSTRACT FROM AUTHOR]

Background/Objectives: Wastewater treatment plants (WWTPs) are hotspots for the spread of antimicrobial resistance into the environment. This study aimed to estimate the proportion of clinically relevant antimicrobial-resistant bacteria in two Spanish urban WWTPs, located in the region of La Rioja (Spain); Methods: Ninety-four samples (48 water/46 sludge) were collected and streaked on ten different selective media, in order to recover the culturable bacterial diversity with relevant resistance phenotypes: Extended-Spectrum β-Lactamase-producing Escherichia coli/Klebsiella pneumoniae (ESBL-Ec/Kp), Carbapenem-resistant Enterobacteriaceae (CR-E), Methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococcus faecium/faecalis (VR-E. faecium/faecalis). Isolates were identified by MALDI-TOF and were tested for antimicrobial susceptibility using the disk diffusion method. The confirmation of ESBL production was performed by the double-disk test; Results: A total of 914 isolates were recovered (31 genera and 90 species). Isolates with clinically relevant resistance phenotypes such as ESBL-Ec/Kp and CR-E were recovered in the effluent (0.4 × 100–4.8 × 101 CFU/mL) and organic amendment samples (1.0–101–6.0 × 102 CFU/mL), which are discharged to surface waters/agricultural fields. We reported the presence of VR-E. faecium in non-treated sludge and in the digested sludge samples (1.3 × 101–1 × 103 CFU/mL). MRSA was also recovered, but only in low abundance in the effluent (0.2 × 101 CFU/mL); Conclusions: This study highlights the need for improved wastewater technologies and stricter regulations on the use of amendment sludge in agriculture. In addition, regular monitoring and surveillance of WWTPs are critical for early detection and the mitigation of risks associated with the spread of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: Extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing Enterobacterales and Acinetobacter spp. pose significant challenges as nosocomial pathogens, demonstrating resistance against various antimicrobials. Their presence in food suggests that hospital kitchens could serve as antibiotic resistance reservoirs leading to patients' infection. Objectives: The aim of this study was to assess the prevalence and characteristics of β-lactam-resistant strains of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter spp. isolated from the kitchen environment and from the staff of two Greek hospitals. Methods: Strains were recovered after selective isolation with β-lactams and were identified with MALDI–TOF MS. Antimicrobial susceptibility and presence of common β-lactamase genes were evaluated. Protein profiles were examined to analyze potential relationships of the strain with those from hospital patients. E. coli strains were further categorized into phylogenetic groups. Results: The overall prevalence in the kitchen environment was 4.5%, 1.5%, and 15.0% for E. coli, K. pneumoniae, and Acinetobacter spp., respectively, whereas the prevalence of Acinetobacter spp. in human skin was 4.0%. Almost all strains were multidrug-resistant. All E. coli strains were ESBL producers and belonged to phylogroups A and B1. All K. pneumoniae and seven Acinetobacter strains were carbapenemase-producers. A protein profile analysis showed relatedness between chicken and kitchen environment strains, as well as between kitchen environment and patient strains originated either from the same or from different hospitals. Conclusions: The results suggest that hospital kitchens may act as important pathogen hotspots contributing to the circulation of resistant strains in the hospital environment. [ABSTRACT FROM AUTHOR]

Endophytic fungi (EF) are excellent sources of diverse and pharmacologically relevant molecules for drug development. The mangrove genus Rhizophora have been identified to contain fungal isolates. In this study, the EF Fusarium solani was isolated and characterized from R. apiculata. Disk diffusion assay of the crude ethyl acetate extract of F. solani on the ESKAPE clinical isolate pathogens showed inhibitory activities against Escherichia coli 5218S (ZOI 12.20 mm), methicillin-resistant Staphylococcus aureus 2729B (ZOI 8.90 mm), Klebsiella pneumoniae 4830WD (ZOI 12.58 mm), Acinetobacter baumannii 3975B (ZOI 12.85 mm), and Enterobacter cloacae 5276S (ZOI 15.53 mm). Bioassay guided isolation and spectroscopic analysis led to the identification of benzoic acid (1) and bis(3-methylhexyl) phthalate (2). Microtiter plate antimicrobial assay gave minimum inhibitory concentration (MIC) of 125 µg/mL for compound 1 and 250 µg/mL for compound 2. To the best of our knowledge, this is the first report on the isolation of F. solani from R. apiculata and the isolation of compounds 1 and 2 from the genus Fusarium. Hence, this study validated the importance of the EF as sources of bioactive molecules. [ABSTRACT FROM AUTHOR]

Background/Objectives: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. Methods: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e "Ruggi D'Aragona" Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. Results: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. Conclusions: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections. [ABSTRACT FROM AUTHOR]

This study aimed to determine the ESKAPE antimicrobial resistance patterns and associated factors with multi-drug resistance strains among hospitalized patients in a single tertiary care medical hospital in Palestine. Methods: A single-center retrospective cross-sectional study was conducted by reviewing patients' electronic medical records and laboratory results from November 1, 2021, to November 30, 2022, at the Palestine Medical Complex in Palestine. The study included patients aged > 18 years who had been infected with ESKAPE pathogens 48 hours after hospital admission. Results: This study included 231 patients, of whom 90.5% had MDR infections. In total, 331 clinical samples of ESKAPE pathogens were identified. A. baumannii was the most prevalent MDR pathogen (95.6%) with Carbapenem-resistant exceeding 95%, followed by K. pneumoniae (83.8%) with extended-spectrum cephalosporin resistance exceeding 90%, S. aureus (68.2) with 85% oxacillin-resistance, E. faecium (40%) with 20% vancomycin resistance, P. aeruginosa (22.6%) with 30% carbapenem resistance. Furthermore, emergent colistin resistance has been observed in A. baumannii, K. pneumoniae, and P. aerogenesis. Risk factors for MDR infection included age (p< 0.035), department (p< 0.001), and invasive procedures such as IUC (p< 0.001), CVC (p< 0.000), and MV (p< 0.008). Patients diagnosed with MDR bacteria had increased 30-day mortality (p< 0.001). Conclusion: The findings of this study show alarming MDR among hospitalized patients infected with ESKAPE pathogens, with resistance to first-line antimicrobial agents and emerging resistance to colistin, minimizing treatment options. Healthcare providers and the Ministry of Health must take steps, adopt policies to prevent antimicrobial resistance, adhere to infection control guidelines, implement antimicrobial stewardship programs to prevent and limit the growing health crisis, and support research to discover new treatment options. [ABSTRACT FROM AUTHOR]

The leading cause of hospital-acquired infections worldwide includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) infections. These bacteria are commonly isolated from clinical settings and linked to a number of potentially fatal diseases associated with hospitals. The objective of this study was to review the prevalence of ESKAPE pathogens in Africa. We gathered and systematically reviewed the literature concerning the prevalence of ESKAPE pathogens, published in the English language from January 2014 to February 2024, from three databases (PubMed, Web of Science and ScienceDirect). Our overall results revealed that S. aureus was the most prevalent species (79.5%), followed by A. baumannii (27.6%), K. pneumoniae (24.2%), Enterobacter spp. (20%), P. aeruginosa (9.0%), and E. faecium (5.1%). Moreover, stool samples had the highest Pooled Prevalence Estimates (PPEs) of 44.0%, followed by urine, nasal, and blood samples with 37.3%, 26.9%, and 22.9%, respectively. For the diagnostic method used to identify these ESKAPE pathogens, VITEK-MS had the highest PPE of 55.2%, followed by whole genome sequencing and PCR with 37.1% and 33.2%, respectively. The highest PPE of ESKAPE pathogens was recorded in West Africa with 77.3%, followed by Central/Middle Africa and East Africa with 43.5% and 25.1%, respectively. The overall PPE of ESKAPE pathogens from humans, animals, the environment (water, soil, and surfaces) and food sources was 35.8%, 37.3%, 47.7%, and 34.2%, respectively. Despite their prevalence in nosocomial settings, studies have shown that the ESKAPE pathogens may be isolated from a range of environmental reservoirs, including soil, dumping sites, beach sand, wastewater, food, and fish farms, among others. This wide source of ESKAPE pathogens substrates indicates the need for a multidisciplinary collaborative partnership for epidemiological studies and intervention efforts by the human, veterinary, and environmental health sectors in Africa. [ABSTRACT FROM AUTHOR]

Background: ESKAPE “(Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp.)” pathogens are commonly found in infections affecting the skin and underlying tissues. ESKAPE pathogens often exhibit widespread multidrug resistance in hospitals, contributing significantly to Hospital-acquired infections. ESKAPE pathogen prevalence can combat the vast challenge of Antibiotic Resistance (ABR). Materials and Methods: “The microbiological statistics of ESKAPE infections and sensitivity between January 2020 and October 2022 were extracted from the laboratory records and analysed for the bacterial profile and antibiotic sensitivity pattern”. Results: Out of the 2037 pathogens isolated from Skin and soft tissue infection, 1308 were ESKAPE pathogens accounting for a prevalence of 64.2%. Staphylococcus aureus (n=340/1308; 25.99%) was the predominant pathogen followed by Pseudomonas aeruginosa (n=332/1308; 25.38%). Among Gram-negative isolates, 29.43% exhibited multidrug resistance (MDR). Carbapenemase was found to be a frequent mechanism of resistance, highest among Acinetobacter species (n=99; 64.7%), followed by Klebsiella pneumoniae (n=109; 37.07%). Amp C production was seen most commonly in Enterobacter species (n=93; 61.2%), followed by Klebsiella pneumoniae (n=172; 58.5%) whereas ESBL production was seen in Enterobacter species (n=46; 30.03%). Conclusion: ESKAPE pathogens are critical etiologic agents of Skin and soft infections. Regular studies are vital for evaluating bacterial susceptibility and highlighting the importance of policies to reduce hospital infections and enhance antibiotic prescription oversight. Understanding virulence and resistance markers is critical for tailoring treatment strategies based on local antibiograms and managing related infections.

Public health is facing a worldwide challenge due to the emergence of multiple antibiotic resistance in ESKAPE (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli) infections. The natural antimicrobial nature of bee venoms makes them promising antimicrobial candidates against antibiotic-resistant pathogens. In this study, melittin and apamin bee venoms were investigated to generate novel antimicrobial agents effective against ESKAPE microorganisms. The antimicrobial and antibiofilm activities of melittin and apamin synthesized from endemic Apis mellifera L. bee venom were tested against ESKAPE microorganisms using minimal inhibition, minimal bactericidal inhibition and time-kill curve methods. The in-vitro cytotoxicity effect of melittin and apamin for L929 fibroblast cells was also examined. Synthesized melittin and apamin (0.78-600 μg/mL) were antimicrobial against ESKAPE pathogens. Time-kill curve studies confirmed the growth retardation effect and bactericidal activity of melittin and apamin. Antibiofilm studies also showed that melittin and apamin significantly (melittin 8%-82%, apamin 1.8%-78%) inhibited the biofilm formed by ESKAPE pathogens. Melittin and apamin were not cytotoxic to L929 fibroblast cells. We found that melittin and apamin have high antibacterial properties. These naturally synthesized bee venoms offer a promising powerful solution to fight various pathogens.

The escalating incidence of nosocomial infections stemming from ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) bacterial pathogens presents a formidable clinical challenge globally, affecting both the developed and developing nations. These pathogens, which are distinguished by their robust antibiotic resistance mechanisms, pose a significant threat to the public health. Their ability to evade traditional antimicrobial treatments underscores the urgent need for novel therapeutic stratifies or alternative approaches to mitigate their negative impact. Understanding the intricate mechanisms underpinning antibacterial resistance in ESKAPE bacteria is paramount for developing effective interventions. Enhanced insights into these mechanisms will facilitate the prediction of resistance patterns among the multidrug-resistant pathogens, thereby guiding the development of targeted therapies and preventive measures. Consequently, comprehensive efforts are needed aiming at unraveling the intricacies of antibacterial resistance in ESKAPE pathogens that are imperative to safeguarding the public health. The aim of the present review was to highlight the patho-mechanisms of ESKAPE bacteria towards the different antibiotics and genes involved in multi-drug resistance.

The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites. Twelve trials were used to screen for critical variables influencing productivity using the Placket-Burman Design method. S. baarensis MH-133 is significantly influenced by elicitation, yeast extract, inoculum size, and incubation period in terms of antibacterial activity. A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken design. The analyses revealed that the model was highly significant (p

Chronic wounds are becoming an increasing burden on healthcare services, as they have extended healing times and are susceptible to infection, with many failing to heal, which can lead ultimately to amputation. Due to the additional rise in antimicrobial resistance and emergence of difficult-to-treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. Many natural substances have been identified as having the potential to aid in both preventing infection and increasing the speed of wound closure processes. Manuka honey is already in some cases used as a topical treatment in the form of ointments, which in conjunction with dressings and fish skin grafts are an existing US Food and Drug Administration-approved treatment option. These existing treatment options indicate that fatty acids from fish oil and manuka honey are well tolerated by the body, and if the active components of the treatments were better understood, they could make valuable additions to topical treatment options. This review considers two prominent natural substances with established manufacturing and global distribution—marine based fatty acids (including their metabolites) and manuka honey—their function as antimicrobials and how they can aid in wound repair, two important aspects leading to resolution of chronic wounds. [ABSTRACT FROM AUTHOR]

Sodium hypochlorite (NaOCl) is widely recognized for its broad-spectrum antimicrobial efficacy in skin wound care. This study investigates the effectiveness of NaOCl against a range of bacterial and fungal isolates from pressure ulcer (PU) patients. We analyzed 20 bacterial isolates from PU patients, comprising carbapenemresistant Klebsiella pneumoniae (CRKP), multidrug-resistant Acinetobacter baumannii (MDRAB), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), along with 5 Candida albicans isolates. Antibiotic resistance profiles were determined using standard susceptibility testing. Whole-genome sequencing (WGS) was employed to identify antimicrobial resistance genes (ARGs) and disinfectant resistance genes (DRGs). Genetic determinants of biofilm formation were also assessed. The antimicrobial activity of NaOCl was evaluated by determining the minimum inhibitory concentration (MIC) and the minimal biofilm eradication concentration (MBEC) for both planktonic and biofilm-associated cells. CRKP and MDRAB showed resistance to fluoroquinolones and carbapenems, while MRSA exhibited resistance to ß-lactams and levofloxacin. MSSA displayed a comparatively lower resistance profile. WGS identified significant numbers of ARGs in CRKP and MDRAB, with fewer DRGs compared to MRSA and MSSA. All isolates possessed genes associated with fimbriae production and adhesion, correlating with pronounced biofilm biomass production. NaOCl demonstrated substantial antimicrobial activity against both planktonic cells and biofilms. The MIC90 for planktonic bacterial cells was 0.125 mg/mL, and the MBEC90 ranged from 0.225 to 0.5 mg/mL. For planktonic C. albicans, the MIC90 was 0.150 mg/mL, and the MBEC90 was 0.250 mg/mL. These results highlight the challenge in treating biofilm-associated infections and underscore the potential of NaOCl as a robust antimicrobial agent against difficult-to-treat biofilm infections at concentrations lower than those typically found in commercial disinfectants. [ABSTRACT FROM AUTHOR]

A series of 13 new 3-substituted 5-(5-nitro-2-furyl)-1,2,4-oxadiazoles was synthesized from different aminonitriles. All compounds were screened in the disc diffusion test at a 100 μg/mL concentration to determine the bacterial growth inhibition zone presence and diameter, and then the minimum inhibitory concentrations (MICs) were determined for the most active compounds by serial dilution. The compounds showed antibacterial activity against ESKAPE bacteria, predominantly suppressing the growth of 5 species out of the panel. Some compounds had similar or lower MICs against ESKAPE pathogens compared to ciprofloxacin, nitrofurantoin, and furazidin. In particular, 3-azetidin-3-yl-5-(5-nitro-2-furyl)-1,2,4-oxadiazole (2h) inhibited S. aureus at a concentration lower than all comparators. Compound 2e (5-(5-nitro-2-furyl)-3-[4-(pyrrolidin-3-yloxy)phenyl]-1,2,4-oxadiazole) was active against Gram-positive ESKAPE pathogens as well as M. tuberculosis. Differences in the molecular periphery led to high selectivity for the compounds. The induced-fit docking (IFD) modeling technique was applied to in silico research. Molecular docking results indicated the targeting of compounds against various nitrofuran-associated biological targets. [ABSTRACT FROM AUTHOR]

Acinetobacter pittii has increasingly been associated with several types of hospital-acquired severe infections. Genes implicated in carbapenem resistance, tigecycline resistance, or genes encoding extended spectrum cephalosporinases, such as blaADC, are commonly found in isolates implicated in these infections. A. pittii strains that are pandrug resistant have occasionally been identified. Food for human consumption, animals and plants are environmental sources of this pathogen. An alarming situation is that A. pitti has been identified as responsible for outbreaks in different regions worldwide. In this study, 384 genomes of A. pittii were analyzed, comprising sequences from clinical and non-clinical origins from 32 countries. The objective was to investigate if clinical strains possess genetic traits facilitating hospital adaptation. Results indicate significant genomic variability in terms of size and gene content among A. pittii isolates. The core genome represents a small portion (25-36%) of each isolate's genome, while genes associated with antibiotic resistance and virulence predominantly belong to the accessory genome. Notably, antibiotic resistance genes are encoded by a diverse array of plasmids. As the core genome between environmental and hospital isolates is the same, we can assume that hospital isolates acquired ARGs due to a high selective pressure in these settings. The strain's phylogeographic distribution indicates that there is no geographical bias in the isolate distribution; isolates from different geographic regions are dispersed throughout a core genome phylogenetic tree. A single clade may include isolates from extremely distant geographical areas. Furthermore, strains isolated from the environment or animal, or plant sources frequently share the same clade as hospital isolates. Our analysis showed that the clinical isolates do not already possess specific genes, other than antibiotic-resistant genes, to thrive in the hospital setting. [ABSTRACT FROM AUTHOR]

Public health is facing a worldwide challenge due to the emergence of multiple antibiotic resistance in ESKAPE (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli) infections. The natural antimicrobial nature of bee venoms makes them promising antimicrobial candidates against antibiotic-resistant pathogens. In this study, melittin and apamin bee venoms were investigated to generate novel antimicrobial agents effective against ESKAPE microorganisms. The antimicrobial and antibiofilm activities of melittin and apamin synthesized from endemic Apis mellifera L. bee venom were tested against ESKAPE microorganisms using minimal inhibition, minimal bactericidal inhibition and time-kill curve methods. The in-vitro cytotoxicity effect of melittin and apamin for L929 fibroblast cells was also examined. Synthesized melittin and apamin (0.78-600 μg/mL) were antimicrobial against ESKAPE pathogens. Time-kill curve studies confirmed the growth retardation effect and bactericidal activity of melittin and apamin. Antibiofilm studies also showed that melittin and apamin significantly (melittin 8%-82%, apamin 1.8%-78%) inhibited the biofilm formed by ESKAPE pathogens. Melittin and apamin were not cytotoxic to L929 fibroblast cells. We found that melittin and apamin have high antibacterial properties. These naturally synthesized bee venoms offer a promising powerful solution to fight various pathogens. [ABSTRACT FROM AUTHOR]

Despite the availability of various promising antibiotics, bacterial infections still impose a prominent issue of morbidity and mortality. Due to changing environment and widespread misuse of antibiotics, multiple drug- resistance (MDR) strains of bacteria evolved rapidly, intensifying the threat to humankind and environment. Excessive use and diminished potency of current antibiotics against these strains led the foundation; for development of new drug delivery and targeting approaches. Metallic nanoparticles (NPs) provide novel platform to fight against MDR strains. These nano beacons have an intrinsic antibacterial activity or may act as an innovative tool for transporting multiple drugs with augmented biocompatibility. Antibacterial efficiency may be enhanced; by modifying or conjugating surface topology. Intensified NP structure shows effective potency than unmodified ones. This review encompasses how antibacterial activity of NPs offers a novel approach in reducing threats due to MDR bacteria and how their structural changes can affect its antimicrobial activity against MDR. [ABSTRACT FROM AUTHOR]

The current healthcare environment is at risk due to the facilitated transmission and empowerment of the ESKAPE pathogens, comprising of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These pathogens have posed significant challenges to global public health and the threat has only amplified over time. These multidrug-resistant bacteria have become adept at escaping the effects of conventional antibiotics utilized, leading to severe healthcare-associated infections and compromising immunocompromised patient outcomes to a greater extent. The impact of ESKAPE pathogens is evident in the rapidly rising rates of treatment failures, increased mortality, and elevated healthcare costs. To combat this looming crisis, diverse strategies have been adopted, ranging from the development of novel antimicrobial agents and combination therapies to the implementation of stringent infection control measures. Additionally, there has been a growing emphasis on promoting antimicrobial stewardship programs to optimize the use of existing antibiotics and reduce the selective pressure driving the evolution of resistance. While progress has been made to some extent, the rapid adaptability of these pathogens and the enhancement of antimicrobial resistance mechanisms proves to be a major hurdle yet to be crossed by healthcare professionals. In this viewpoint, the impending threat heralded by the proliferation of ESKAPE pathogens, and the need for a concerted global effort via international collaborations for the assurance of effective and sustainable solutions, are explored. To curb the possibility of outbreaks in the future and to safeguard public health, better preparation via global awareness and defense mechanisms should be given paramount importance. [ABSTRACT FROM AUTHOR]

The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites. Twelve trials were used to screen for critical variables influencing productivity using the Placket-Burman Design method. S. baarensis MH-133 is significantly influenced by elicitation, yeast extract, inoculum size, and incubation period in terms of antibacterial activity. A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken design. The analyses revealed that the model was highly significant (p < 0.001), with a lack-of-fit of 0.212 and a coefficient determination (R2) of 0.9224. Additionally, the model predicted that the response as inhibition zone diameter would reach a value of 27 mm. Under optimal conditions, S. baarensis MH-133 produced 18.0 g of crude extract to each 35L and was purified with column chromatography. The active fraction exhibiting antibacterial activity was characterized using spectroscopic analysis. The MIC and MBC values varied between 37.5 and 300 µg/ml and 75 and 300 µg/ml, respectively. In conclusion, the biostatistical optimization of the active fraction critical variables, including environmental and nutritional conditions, enhances the production of bioactive molecules by Streptomyces species. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase-producing Klebsiella pneumoniae (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a ceftazidime/avibactam (CAZ-AVI)-resistant K. pneumoniae isolate obtained from a patient previously exposed to CAZ-AVI expressing a novel K. pneumoniae carbapenemase (KPC)-3 variant. Methods: Antimicrobial susceptibility testing was performed using reference broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina and Nanopore Technologies. Short- and long-reads were combined with Unicycler. Assemblies were investigated for multilocus sequence typing (MLST), antimicrobial resistance genes, porins, and plasmids. Results: The K. pneumoniae isolate (KP_RM_1) was resistant to CAZ-AVI, expanded-spectrum cephalosporins, amikacin, ertapenem, and cefiderocol (FDC) but was susceptible to tigecycline, colistin, trimethoprim/sulfamethoxazole, meropenem–vaborbactam, and imipenem–relebactam. WGS revealed that the KP_RM_1 genome is composed of a single chromosome of 5 Mbp and five circular plasmids. Further analysis showed the presence of novel blaKPC-216 located on a 72 kb plasmid. KPC-216 differs from KPC-3 by a Lysin (K) insertion at position 168 (+K168). Conclusions: We report the identification of a new KPC-3 variant associated with CAZ-AVI resistance. The KPC variants associated with CAZ-AVI resistance should be determined to promptly inform clinicians and start the appropriate antimicrobial therapy. [ABSTRACT FROM AUTHOR]

The current healthcare environment is at risk due to the facilitated transmission and empowerment of the ESKAPE pathogens, comprising of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These pathogens have posed significant challenges to global public health and the threat has only amplified over time. These multidrug-resistant bacteria have become adept at escaping the effects of conventional antibiotics utilized, leading to severe healthcare-associated infections and compromising immunocompromised patient outcomes to a greater extent. The impact of ESKAPE pathogens is evident in the rapidly rising rates of treatment failures, increased mortality, and elevated healthcare costs. To combat this looming crisis, diverse strategies have been adopted, ranging from the development of novel antimicrobial agents and combination therapies to the implementation of stringent infection control measures. Additionally, there has been a growing emphasis on promoting antimicrobial stewardship programs to optimize the use of existing antibiotics and reduce the selective pressure driving the evolution of resistance. While progress has been made to some extent, the rapid adaptability of these pathogens and the enhancement of antimicrobial resistance mechanisms proves to be a major hurdle yet to be crossed by healthcare professionals. In this viewpoint, the impending threat heralded by the proliferation of ESKAPE pathogens, and the need for a concerted global effort via international collaborations for the assurance of effective and sustainable solutions, are explored. To curb the possibility of outbreaks in the future and to safeguard public health, better preparation via global awareness and defense mechanisms should be given paramount importance.

Global health is seriously threatened by an increase in antibiotic resistance among ESKAPE pathogens- E- E. faecium, S- S.aureus, K- K.pneumoniae, A-A.baumannii, P- P.aeruginosa, and E-Enterobacter. The resistance of many bacteria to traditional antibiotics is increasing, making the search for novel approaches critical. In order to minimize the effect of these diseases, early detection, diagnosis, and treatment are important. However, there are drawbacks to traditional detection techniques such molecular-based, biochemical, and microbiological assays. These include the inability to detect on-site, as well as their time-consuming, expensive, and labour-intensive nature. Viral agents that target bacteria exclusively, known as bacteriophages, have shown promise in combating over infections resistant to antibiotics. Bacteriophage-based biosensors are adaptable to many environmental conditions and offer special features such as host specificity and ability to identify active infections. They're very accurate, very specific, and have quick assay times, which makes them beneficial tools for detection. Also, phages are more easily produced than antibodies and can withstand high pH, temperature, and chemical solvents. The potential of bacteriophage-based biosensors in the fight against ESKAPE pathogens is highlighted by this review. Bacteriophage-based biosensors provide simplified detection processes in contrast to conventional approaches, which makes them invaluable in environmental and clinical situations. Numerous platforms, including electrochemical, magnetoelastic, quartz crystal microbalance, and surface plasmon resonance sensors, being investigated for their potential use to detect pathogenic bacteria in a range of sample types.

ABSTRACTThe escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. – were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People’s Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People’s Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What’s more, as a vast nation, People’s Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.

Background: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one. [ABSTRACT FROM AUTHOR]

The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and/or applying innovative drug formulations. Hence, bacterial iron acquisition systems and bacterial Fe2+/3+-containing enzymes have been identified as a plausible target of great potential. The intriguing "Trojan horse" approach deprives microorganisms from the essential iron. Recently, gallium's potential in medicine as an iron mimicry species has attracted vast attention. Different Ga3+ formulations exhibit diverse effects upon entering the cell and thus supposedly have multiple targets. The aim of the current study is to specifically distinguish characteristics of great significance in regard to the initial gallium-based complex, allowing the alien cation to effectively compete with the native ferric ion for binding the siderophores pyochelin and pyoverdine secreted by the bacterium P. aeruginosa. Therefore, three gallium-based formulations were taken into consideration: the first-generation gallium nitrate, Ga(NO3)3, metabolized to Ga3+-hydrated forms, the second-generation gallium maltolate (tris(3-hydroxy-2-methyl-4-pyronato)gallium), and the experimentally proven Ga carrier in the bloodstream—the protein transferrin. We employed a reliable in silico approach based on DFT computations in order to understand the underlying biochemical processes that govern the Ga3+/Fe3+ rivalry for binding the two bacterial siderophores. [ABSTRACT FROM AUTHOR]

Patients in burns centres are at high risk of acquiring multi-drug-resistant organisms (MDROs) due to the reduced skin barrier and long hospital stay. This study reports the investigation and control of an outbreak of MDR Acinetobacter baumannii in a burns centre. The 27 patients hospitalized in the centre during the outbreak were screened regularly, and a total of 132 environmental samples were analysed to identify a potential source. Fourier-transform infra-red (FT-IR) spectroscopy and multi-locus sequence typing were applied to characterize the outbreak strain. Between August and November 2022, the outbreak affected eight patients, with 11 infections and three potentially related fatal outcomes. An interdisciplinary and multi-professional outbreak team implemented a bundle strategy with repetitive admission stops, isolation precaution measures, patient screenings, enhanced cleaning and disinfection, and staff education. FT-IR spectroscopy suggested that the outbreak started from a patient who had been repatriated 1 month previously from a country with high prevalence of MDR A. baumannii. Environmental sampling did not identify a common source. Acquisition of the outbreak strain was associated with a higher percentage of body surface area with burn lesions ≥2a [per percent increase: odds ratio (OR) 1.05, 95% confidence interval (CI) 0.99–1.12; P =0.09], and inversely associated with a higher nurse-to-patient ratio (per 0.1 increase: OR 0.34, 95% CI 0.10–1.12; P =0.06). Burn patients with a higher percentage of body surface area with burn lesions ≥2a are at high risk of colonization and infection due to MDROs, particularly during periods of high workload. A multi-faceted containment strategy can successfully control outbreaks due to MDR A. baumannii in a burns centre. [ABSTRACT FROM AUTHOR]

The study screened the occurrence of VanA,VanB,Vanc genes in Staph aureus vancomycin-resistant isolates recovered in Hilla -hospitals. From various clinical samples, 160 isolates from patients between July and November of 2022 were included in the search. Among these samples are (65) burn samples, (55) urine samples, and (40) samples from Blood. 40 (or 25%) of the 160 isolates were Staph aureus. Characterization of the VanA, VanB, and VanC genes in Staph aureus isolates obtained from various specimens is the main goal of the work. The RESULTS of samples were obtained from a variety of clinical specimens, including 20 (40.625%) burn swabs, 10 (25%) urine samples, and 10 (34.375%) blood. Staph aureus was resistant to Cefepime (91.7%), Piperacillin (73.3%), and Ceftazidime (71.7%), although little relationship was detected with Aztreonam resistance (35%). 40 isolates were used for antibiotic sensitivity test (AST). Only 18.3% and 15% of isolates, respectively, were resistant to meropenem and imipenem. Fluoroquinolone resistance to lomefloxacin, ciprofloxacin, ofloxacin, and levofloxacin was 51.7%, 48.3%, 35%), and 30%, respectively. While the most prevalent vancomycin resistance genes were found in 40 isolates of S. aureus and were discovered by VanC 40 (100%), VanA 20 (100%), and VanB28 (70%), according to the current investigation.In Conclusion :The PCR-reaction method was discovered to be an easy-to- use tool for detecting staph aureus by pcr that can be regularly used for identifying staph aureus and detection the molecular resistance apparatuses to vancomycin in staph aureus by VanA, VanB, VanC), efflux systems plays To choose the best antibiotics, prevent the establishment of resistant strains, and create novel antimicrobial. medications, it is beneficial to research the particular resistance mechanisms vancomycin to staph aureus. [ABSTRACT FROM AUTHOR]

Both honey and fish oil have been historically used in medicine and identified as having antimicrobial properties. Although analyses of the substances have identified different components within them, it is not fully understood how these components interact and contribute to the observed effect. With the increase in multi-drug resistant strains of bacteria found in infections, new treatment options are needed. This study aimed to assess the antimicrobial abilities of fish oil components, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and derived resolvins (RvE1, RvD2, and RvD3), as well as two varieties of manuka honey, against a panel of medically relevant microorganisms and antimicrobial resistant organisms, such as Methicillin Resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were identified; further minimum biofilm eradication concentrations (MBEC) were investigated for responsive organisms, including S. aureus, E. coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent with the existing literature, manuka honey was found to be a broad-spectrum antimicrobial with varied potency according to methylglyoxal content. DHA and EPA were both effective against Gram-positive and negative bacteria, but some drug-resistant strains or pathogens were not protected by a capsule. Only E. coli was inhibited by the resolvins. [ABSTRACT FROM AUTHOR]

Introduction: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. are microorganisms referred as the ESKAPE group pathogens. These microorganisms have generated great concern in health institutions around the world since most of them have resistance to multiple antibiotics and cause most infections associated with healthcare, as well as community infections. The aim of this study was the analysis of antibiotic resistance in microorganisms of the ESKAPE group, recovered from clinical samples in 11 health institutions from Hermosillo and Ciudad Obregón in the State of Sonora, México, during the period from 2019 to 2020. Methods: A cross-sectional, descriptive, observational, and temporality epidemiological study was carried out. A comparative and statistical analysis of antibiotic resistance was carried out using the chi-square test, and small values were analyzed using Fisher's exact test p ≤ 0.05. Results and discussion: All the ESKAPE group microorganisms showed significant differences in antibiotic resistance percentages between both cities. High resistance percentages for some antibiotics, like cephalosporins and ciprofloxacin were detected for Klebsiella pneumoniae and Acinetobacter baumannii. [ABSTRACT FROM AUTHOR]

The ESKAPE pathogen-associated antimicrobial resistance is a global public health issue, and novel therapeutic strategies are urgently needed. The short cationic antimicrobial peptide (AMP) family represents an important subfamily of scorpion-derived AMPs, but high hemolysis and poor antimicrobial activity hinder their therapeutic application. Here, we recomposed the hydrophilic face of Ctriporin through lysine substitution. We observed non-linear correlations between the physiochemical properties of the peptides and their activities, and significant deviations regarding the changes of antimicrobial activities against different bacterial species, as well as hemolytic activity. Most importantly, we obtained two Ctriporin analogs, CM5 and CM6, these two have significantly reduced hemolytic activity and more potent antimicrobial activities against all tested antibiotic-resistant ESKAPE pathogens. Fluorescence experiments indicated they may perform the bactericidal function through a membrane-lytic action model. Our work sheds light on the potential of CM5 and CM6 in developing novel antimicrobials and gives clues for optimizing peptides from the short cationic AMP family. [ABSTRACT FROM AUTHOR]

Acinetobacter pittii has increasingly been associated with several types of hospital-acquired severe infections. Genes implicated in carbapenem resistance, tigecycline resistance, or genes encoding extended spectrum cephalosporinases, such as blaADC, are commonly found in isolates implicated in these infections. A. pittii strains that are pandrug resistant have occasionally been identified. Food for human consumption, animals and plants are environmental sources of this pathogen. An alarming situation is that A. pitti has been identified as responsible for outbreaks in different regions worldwide. In this study, 384 genomes of A. pittii were analyzed, comprising sequences from clinical and non-clinical origins from 32 countries. The objective was to investigate if clinical strains possess genetic traits facilitating hospital adaptation. Results indicate significant genomic variability in terms of size and gene content among A. pittii isolates. The core genome represents a small portion (25–36%) of each isolate’s genome, while genes associated with antibiotic resistance and virulence predominantly belong to the accessory genome. Notably, antibiotic resistance genes are encoded by a diverse array of plasmids. As the core genome between environmental and hospital isolates is the same, we can assume that hospital isolates acquired ARGs due to a high selective pressure in these settings. The strain’s phylogeographic distribution indicates that there is no geographical bias in the isolate distribution; isolates from different geographic regions are dispersed throughout a core genome phylogenetic tree. A single clade may include isolates from extremely distant geographical areas. Furthermore, strains isolated from the environment or animal, or plant sources frequently share the same clade as hospital isolates. Our analysis showed that the clinical isolates do not already possess specific genes, other than antibiotic-resistant genes, to thrive in the hospital setting.

Codon usage of each genome is closely correlated with the abundance of tRNA isoacceptors. How codon usage bias is resolved by tRNA post-transcriptional modifications is largely unknown. Here we demonstrate that the N1-methylation of guanosine at position 37 (m1G37) on the 3-side of the anticodon, while not directly responsible for reading of codons, is a neutralizer that resolves differential decoding of proline codons. A genome-wide suppressor screen of a non-viable Escherichia coli strain, lacking m1G37, identifies proS suppressor mutations, indicating a coupling of methylation with tRNA prolyl-aminoacylation that sets the limit of cell viability. Using these suppressors, where prolyl-aminoacylation is decoupled from tRNA methylation, we show that m1G37 neutralizes differential translation of proline codons by the major isoacceptor. Lack of m1G37 inactivates this neutralization and exposes the need for a minor isoacceptor for cell viability. This work has medical implications for bacterial species that exclusively use the major isoacceptor for survival.

ObjectiveTo conduct a bibliometric visual analysis of studies on Enterococcus faecium， Staphylococcus aureus， Klebsiella pneumoniae， Acinetobacter baumannii， Pseudomonas aeruginosa and Enterobacter species （ESKAPE） in the past 10 years at home and abroad， and to analyze current research status and future research directions in this field based on the concept of “One health”.MethodsRelated literature on ESKAPE drug resistant bacteria from 2013 to 2022 was searched on CNKI and WoS， respectively. Furthermore， a metrological visualization analysis of authors， source of agencies， countries， and keywords was conducted by the CiteSpace 6.1.R6 software.ResultsA total of 2 991 pieces of Chinese-language and 24 497 pieces of English-language literature were included in this study. Although the number and growth rate of English-language publications were higher than those of Chinese-language publications， the number of English-language papers authored by Chinese scholars showed a significant upward trend. The level of collaboration between authors and institutions in Chinese-language publications was weaker than that in English-language publications. Overall， the country with the highest number of publications was the United States （6 623）， followed by China （3 776）. However， China’s annual publication volume （851） exceeded that of the United States （600） in 2022. China had collaborations with 25 countries， indicating good global cooperation， but its level of international cooperation was still slightly weaker than that of the United States. High-frequency keywords in Chinese-language literature mainly included drug resistance， nosocomial infection， and antibiotics， while high-frequency keywords in English-language literature included Staphylococcus aureus， Klebsiella pneumoniae， and methicillin-resistant.ConclusionCarbapenem-resistant Klebsiella pneumoniae， carbapenem-resistant Enterobacteriaceae， and "One health" are research hotspots. In the future， cross-sectoral and multi-regional collaboration should be deepened to strengthen the control of infections of important drug-resistant bacteria， and infection treatment strategies should be optimized as well.

ABSTRACTIntroduction Antimicrobial resistance (AMR) is responsible for the death of millions worldwide and stands as a major threat to our healthcare systems, which are heavily reliant on antibiotics to fight bacterial infections. The development of vaccines against the main pathogens involved is urgently required as prevention remains essential against the rise of AMR.Areas covered A systematic research review was conducted on MEDLINE database focusing on the six AMR pathogens defined as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli), which are considered critical or high priority pathogens by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). The analysis was intersecated with the terms carbohydrate, glycoconjugate, bioconjugate, glyconanoparticle, and multiple presenting antigen system vaccines.Expert opinion Glycoconjugate vaccines have been successful in preventing meningitis and pneumoniae, and there are high expectations that they will play a key role in fighting AMR. We herein discuss the recent technological, preclinical, and clinical advances, as well as the challenges associated with the development of carbohydrate-based vaccines against leading AMR bacteria, with focus on the ESKAPE pathogens. The need of innovative clinical and regulatory approaches to tackle these targets is also highlighted.

Pseudomonas aeruginosa is a pathogen of critical priority importance according to the WHO. Due to its multi-resistance and expression of various virulence factors, it is the causal agent of severe healthcare-acquired infections (HAIs). Effective strategies to control infections caused by P. aeruginosa must include early and specific detection of the pathogen for early and timely antibiotic prescription. The need to develop a specific and reproducible diagnostic technique is urgent, which must often be more sensitive and faster than current clinical diagnostic methods. In this study, we implement and standardize the loop-mediated isothermal amplification (LAMP) technique, coupled with the reverse line blot hybridization (RLBH) technique for the detection of P. aeruginosa. A set of primers and probes was designed to amplify a specific region of the P. aeruginosa 16s rRNA gene. The sensitivity of the LAMP-RLBH method was 3 × 10−4 ng/μL, 1000 times more sensitive than the PCR and LAMP technique (this work), with a sensitivity of 3 × 10−3 ng/μL. The LAMP-RLBH and LAMP techniques showed specific amplification and no cross-reaction with members of the ESKAPE group and other Pseudomonas species. The present investigation provides a technique that can be easily performed in less time, achieving a faster and more reliable alternative compared to traditional microbial diagnostic methods for the detection of P. aeruginosa.

The World Health Organization announced critically important bacterial and fungal pathogens displaying alarming levels of antimicrobial resistance, which currently represent difficult-to-treat cases of morbidity. Within this grouping, the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are causative of significant morbidity and mortality. Studies described herein demonstrate the presence of critically important fungal and ESKAPE bacterial species in companion animals which are zoonotic in nature. The relationship between the environment, animals, and human infectious disease has long been recognized as part of One Health. This research investigates the resistance patterns of isolated zoonotic pathogens using recognized in vitro methodologies, namely disk diffusion, minimum inhibitory concentration testing, and genetic screening. Antibiotic susceptibility testing and gene analysis demonstrated an association between multi-drug resistance and extended beta spectrum lactamase production in critical-priority bacteria. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa exhibit great levels of multi-drug resistance. Fungal isolates demonstrated high levels of resistance, with Amphotericin B proving the most effective antifungal agent investigated. The level of antimicrobial resistance present in clinically relevant bacterial and fungal pathogens isolated from animal cases of morbidity in this study is alarming. In conclusion, this study shows that animals can act as a reservoir facilitating the transmission of antibiotic-resistant pathogens and genes zoonotically.

Background: Extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing Enterobacterales and Acinetobacter spp. pose significant challenges as nosocomial pathogens, demonstrating resistance against various antimicrobials. Their presence in food suggests that hospital kitchens could serve as antibiotic resistance reservoirs leading to patients’ infection. Objectives: The aim of this study was to assess the prevalence and characteristics of β-lactam-resistant strains of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter spp. isolated from the kitchen environment and from the staff of two Greek hospitals. Methods: Strains were recovered after selective isolation with β-lactams and were identified with MALDI–TOF MS. Antimicrobial susceptibility and presence of common β-lactamase genes were evaluated. Protein profiles were examined to analyze potential relationships of the strain with those from hospital patients. E. coli strains were further categorized into phylogenetic groups. Results: The overall prevalence in the kitchen environment was 4.5%, 1.5%, and 15.0% for E. coli, K. pneumoniae, and Acinetobacter spp., respectively, whereas the prevalence of Acinetobacter spp. in human skin was 4.0%. Almost all strains were multidrug-resistant. All E. coli strains were ESBL producers and belonged to phylogroups A and B1. All K. pneumoniae and seven Acinetobacter strains were carbapenemase-producers. A protein profile analysis showed relatedness between chicken and kitchen environment strains, as well as between kitchen environment and patient strains originated either from the same or from different hospitals. Conclusions: The results suggest that hospital kitchens may act as important pathogen hotspots contributing to the circulation of resistant strains in the hospital environment.

Background/Objectives: Wastewater treatment plants (WWTPs) are hotspots for the spread of antimicrobial resistance into the environment. This study aimed to estimate the proportion of clinically relevant antimicrobial-resistant bacteria in two Spanish urban WWTPs, located in the region of La Rioja (Spain); Methods: Ninety-four samples (48 water/46 sludge) were collected and streaked on ten different selective media, in order to recover the culturable bacterial diversity with relevant resistance phenotypes: Extended-Spectrum β-Lactamase-producing Escherichia coli/Klebsiella pneumoniae (ESBL-Ec/Kp), Carbapenem-resistant Enterobacteriaceae (CR-E), Methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococcus faecium/faecalis (VR-E. faecium/faecalis). Isolates were identified by MALDI-TOF and were tested for antimicrobial susceptibility using the disk diffusion method. The confirmation of ESBL production was performed by the double-disk test; Results: A total of 914 isolates were recovered (31 genera and 90 species). Isolates with clinically relevant resistance phenotypes such as ESBL-Ec/Kp and CR-E were recovered in the effluent (0.4 × 100–4.8 × 101 CFU/mL) and organic amendment samples (1.0–101–6.0 × 102 CFU/mL), which are discharged to surface waters/agricultural fields. We reported the presence of VR-E. faecium in non-treated sludge and in the digested sludge samples (1.3 × 101–1 × 103 CFU/mL). MRSA was also recovered, but only in low abundance in the effluent (0.2 × 101 CFU/mL); Conclusions: This study highlights the need for improved wastewater technologies and stricter regulations on the use of amendment sludge in agriculture. In addition, regular monitoring and surveillance of WWTPs are critical for early detection and the mitigation of risks associated with the spread of antimicrobial resistance.

The leading cause of hospital-acquired infections worldwide includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) infections. These bacteria are commonly isolated from clinical settings and linked to a number of potentially fatal diseases associated with hospitals. The objective of this study was to review the prevalence of ESKAPE pathogens in Africa. We gathered and systematically reviewed the literature concerning the prevalence of ESKAPE pathogens, published in the English language from January 2014 to February 2024, from three databases (PubMed, Web of Science and ScienceDirect). Our overall results revealed that S. aureus was the most prevalent species (79.5%), followed by A. baumannii (27.6%), K. pneumoniae (24.2%), Enterobacter spp. (20%), P. aeruginosa (9.0%), and E. faecium (5.1%). Moreover, stool samples had the highest Pooled Prevalence Estimates (PPEs) of 44.0%, followed by urine, nasal, and blood samples with 37.3%, 26.9%, and 22.9%, respectively. For the diagnostic method used to identify these ESKAPE pathogens, VITEK-MS had the highest PPE of 55.2%, followed by whole genome sequencing and PCR with 37.1% and 33.2%, respectively. The highest PPE of ESKAPE pathogens was recorded in West Africa with 77.3%, followed by Central/Middle Africa and East Africa with 43.5% and 25.1%, respectively. The overall PPE of ESKAPE pathogens from humans, animals, the environment (water, soil, and surfaces) and food sources was 35.8%, 37.3%, 47.7%, and 34.2%, respectively. Despite their prevalence in nosocomial settings, studies have shown that the ESKAPE pathogens may be isolated from a range of environmental reservoirs, including soil, dumping sites, beach sand, wastewater, food, and fish farms, among others. This wide source of ESKAPE pathogens substrates indicates the need for a multidisciplinary collaborative partnership for epidemiological studies and intervention efforts by the human, veterinary, and environmental health sectors in Africa.

Background/Objectives: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. Methods: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ‘‘Ruggi D’Aragona’’ Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. Results: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. Conclusions: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.

Aim Hospital-acquired infections (HAIs) caused by antimicrobial-resistant ESKAPE pathogens are a significant concern for the healthcare industry, with an estimated cost of up to $45 billion per year in the US alone. Clostridioides difficile is an additional opportunistic pathogen that also poses a serious threat to immunocompromised patients in hospitals. Infections caused by these pathogens lead to increased hospital stays and repeated readmission, resulting in a significant economic burden. Disinfectants and sporicidals are essential to reduce the risk of these pathogens in hospitals, but commercially available products can have a number of disadvantages including inefficacy, long contact times, short shelf lives, and operator health hazards. In this study, we evaluated the effectiveness of Rosin (a natural substance secreted by coniferous trees as a defence mechanism against wounds in tree bark) and its commercial derivative Rosetax-21 as disinfectants and sporicidal against the six ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species) and spore preparations from C. difficile. Methods and Results Both Rosin and Rosetax-21 were tested under simulated clean and dirty conditions [with Bovine Serum Albumin (BSA)] against the ESKAPE pathogens, and C. difficile spore preparations. In clean conditions, Rosin (5% weight/volume: w/v) demonstrated significant efficacy against five of the ESKAPE pathogens, with A. baumannii and Enterococcus faecium being the most susceptible, and K. pneumoniae the most resistant, showing only a 1-log reduction after a 5 min treatment. However, in dirty conditions, all pathogens including K. pneumoniae exhibited at least a 3-log reduction to Rosin within 5 min. Rosetax-21 (5% w/v) was found to be less effective than Rosin in clean conditions, a trend that was exacerbated in the presence of BSA. Additionally, both Rosin and Rosetax-21 at 2.5% (w/v) achieved complete eradication of C. difficile spores when combined with 0.5% glutaraldehyde, though their standalone sporicidal activity was limited. Conclusions The findings from this study highlight the potential of Rosin and Rosetax-21 as both bactericidal and sporicidal disinfectants, with their efficacy varying based on the conditions and the pathogens tested. This presents an avenue for the development of novel healthcare disinfection strategies, especially against HAIs caused by antimicrobial-resistant ESKAPE pathogens and C. difficile. [ABSTRACT FROM AUTHOR]

Healthcare-associated infections caused by multi-drug-resistant pathogens are increasing globally, and current antimicrobial options have limited efficacy against these robust species. The WHO details the critically important bacterial and fungal species that are often associated with medical device HAIs. The effective sterilization of medical devices plays a key role in preventing infectious disease morbidity and mortality. A lack of adherence to protocol and limitations associated with each sterilization modality, however, allows for the incidence of disease. Furthermore, issues relating to carcinogenic emissions from ethylene oxide gas (EtO) have motivated the EPA to propose limiting EtO use or seeking alternative sterilization methods for medical devices. The Food and Drug Administration supports the sterilization of healthcare products using low-temperature VH2O2 as an alternative to EtO. With advances in biomaterial and medical devices and the increasing use of combination products, current sterilization modalities are becoming limited. Novel approaches to disinfection and sterilization of medical devices, biomaterials, and therapeutics are warranted to safeguard public health. Bacteriophages, endolysins, and antimicrobial peptides are considered promising options for the prophylactic and meta-phylactic control of infectious diseases. This timely review discusses the application of these biologics as antimicrobial agents against critically important WHO pathogens, including ESKAPE bacterial species. [ABSTRACT FROM AUTHOR]

Introduction: Healthcare-associated infections in the post-pandemic era are as important as they were before COVID-19. The dominant route of transmission of microorganisms in health care units is the contact route, for which hand hygiene is of cardinal importance, but also effective disinfection of touch surfaces. Traditional disinfection based on chemical compounds is sensitive to human errors. Therefore, a valuable supplement to it can be contactless disinfection methods, including the use of UV-C. The aim of the study was to assess the effectiveness of UV-C radiation in eliminating selected, most important pathogens of particular epidemic importance from surfaces made of various materials: stainless steel, plastic and glass, most often found in hospital conditions. Material and Method: In laboratory conditions, the study was conducted using bacterial strains of great epidemiological importance and Candida auris. In hospital wards, samples were taken before and after disinfection for comparisons of the composition and quantity of bacteria. In laboratory conditions, carriers made of steel, plastic and glass were contaminated with a bacterial suspension with a density of approx. 0.5 McFarland, and then the density of persistent microorganisms was assessed after 10 min of UV-C irradiation. Results: The high effectiveness of UV-C radiation in eliminating bacteria contaminating touch surfaces in hospital wards and in laboratory conditions has been confirmed. The elimination efficiency in laboratory conditions was slightly lower (statistically insignificant) on the plastic surface, which is probably related to subtle differences in the thickness of the contaminating layer. Hydrophobic properties and the smallest suspension diameter were confirmed for the tested plastic carriers. Conclusions: UV-C disinfection is a desirable element to support traditional, chemical methods of disinfection in hospital conditions, effective against multidrug-resistant bacteria and C. auris. [ABSTRACT FROM AUTHOR]

Ultrashort cationic lipopeptides (USCLs) and quaternary ammonium salts constitute two groups of cationic surfactants with high antimicrobial activity. This study aimed to investigate the influence of quaternization of the amino group of the lysine side chain in USCLs on their antimicrobial, hemolytic and cytotoxic activities. To do this, two series of lipopeptides were synthesized, USLCs and their quaternized analogues containing trimethylated lysine residues — qUSCLs (quaternized ultrashort cationic lipopeptides). Quaternization was performed on a resin during a standard solid-phase peptide synthesis with CH3I as the methylating agent. According to our knowledge, this is the first study presenting on-resin peptide quaternization. The lipopeptides were tested for their antibacterial and antifungal activities against the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella aerogenes) bacteria and Candida glabrata yeast-like fungus. Most of the compounds proved to be active antimicrobial agents with enhanced activity against Gram-positive strains and fungi and a lower against Gram-negative species. In addition, the antimicrobial activity of lipopeptides was increasing with an increase in hydrophobicity but qUSCLs exhibited usually a poorer antimicrobial activity than their parent molecules. Furthermore, the toxicity against red blood cells and human keratinocytes was assessed. It's worth emphasizing that qUSCLs were less toxic than the parent molecules of comparative hydrophobicity. The results of the study proved that qUSCLs can offer a higher selectivity to pathogens over human cells than that of USCLs. Last but not least, quaternization of the peptides could increase their solubility and therefore their bioavailability and utility. [ABSTRACT FROM AUTHOR]

IntroductionEnterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. are microorganisms referred as the ESKAPE group pathogens. These microorganisms have generated great concern in health institutions around the world since most of them have resistance to multiple antibiotics and cause most infections associated with healthcare, as well as community infections. The aim of this study was the analysis of antibiotic resistance in microorganisms of the ESKAPE group, recovered from clinical samples in 11 health institutions from Hermosillo and Ciudad Obregón in the State of Sonora, México, during the period from 2019 to 2020.MethodsA cross-sectional, descriptive, observational, and temporality epidemiological study was carried out. A comparative and statistical analysis of antibiotic resistance was carried out using the chi-square test, and small values were analyzed using Fisher’s exact test p ≤ 0.05.Results and discussionAll the ESKAPE group microorganisms showed significant differences in antibiotic resistance percentages between both cities. High resistance percentages for some antibiotics, like cephalosporins and ciprofloxacin were detected for Klebsiella pneumoniae and Acinetobacter baumannii.