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• Presenting a facile method using pink flower petals as a new source of green synthesis of silver nanoparticles. • SEM analysis showed that the biosynthesized nanoparticles with pink rose petals had a spherical shape and an average size of 26 nm. • Biosynthesized nanoparticles have Ag0 structure. • Biosynthesized silver nanoparticles with a new synthesis source have antibacterial effects, the lowest minimum inhibitory concentration (MIC) of silver nanoparticles is 400 μg/ml against multidrug-resistant Staphylococcus aureus and MIC on multidrug-resistant Escherichia coli, Acinetobacter baumannii , and resistant Acinetobacter. It was 800 µg/ml, 3200 µg/ml and 1600 µg/ml, respectively, to several drugs and Klebsiella pneumoniae. Drug resistant bacterial infections can be fatal for disabled people needing multiple medications and new effective antibacterial drugs such as biosynthesized nanoparticles are needed. A cost-effective and green method was studied for the biosynthesis of silver nanoparticles using pink rose petals. Silver nanoparticles (AgNP) were synthesized using the petals of pink rose flowers. The AgNPs were characterized using FITR, SEM, XRD, and EDS analyses. The antibacterial activity of the AgNPs against multidrug-resistant bacterial pathogens Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii , and colistin-resistant Klebsiella pneumoniae were studied using the microplate method. Th AgNPs had a spherical shape and an average size of 26 nm. XRD analysis showed that the nanoparticles were Ag0. Antibacterial activity was the highest against the multidrug-resistant S. aureus the minimum inhibitory concentration (MIC) being 400 µg/ml AgNPs. The multidrug-resistant E. coli , multidrug-resistant A. baumannii , and colistin-resistant K. pneumoniae MICs were 800 µg/ml, 3200 µg/ml, and 1600 µg/ml, respectively. The green synthesized of AgNPS using pink rose petals and their antibacterial effects offer material for the treatments of common multidrug-resistant bacterial pathogens. [ABSTRACT FROM AUTHOR]

Anti-microbial resistance has emerged as the leading cause of death worldwide with the rise of multidrug-resistant (MDR) bacteria, the need for novel anti-microbials to treat serious illnesses has become a great necessity. Hence, in this study, we aimed to design and synthesize benzothiazole-coupled azetidinone derivatives (GD1-GD12) as novel antibacterial agents. The synthesized compounds were elucidated by nuclear magnetic resonance, infrared and mass spectroscopy. The antibacterial activities of these compounds were tested against antibiotic-susceptible and MDR strains of bacteria. In addition, we performed ADME profiling, molecular docking and molecular dynamic simulations, principle component analysis, dynamic cross-correlation map and free-energy landscape to assess the binding of synthesized compounds with the β -lactamase. Among the synthesized compounds GD6 and GD5 displayed minimum inhibitory concentrations of 12.5 μ g/mL and 50 μ g/mL against MDR strains of E. coli; more effective than standard. The molecular docking of designed molecules was performed against μ -lactamase enzyme and the stability of the complex was vali-dated. The pharmacokinetic profile displayed the compounds to possess druggable properties within the suitable ranges. The in silico approach displayed compound GD6 to be stable with β -lactamase enzyme; indicating the mechanism for these compounds to be via inhibition of β -lactamase. The novel anti-microbial compounds assessed against susceptible and MDR strains of bacteria possess antibacterial potential via the inhibition of β -lactamase. The aforementioned data will be crucial to the development of novel broad-spectrum antibacterial compounds. A novel method was used to design the ligands: Benzothiazole-coupled azetidinone (GD1-12). Their binding affinity and stability to the β -lactamase enzyme inhibitor (3FV7) were assessed using molecular docking and dynamics. Subsequently, compounds (GD1-12) were synthesized, purified, characterized, and tested for antimicrobial activity. Among all the compounds, GD6 exhibited promising antimicrobial activity. [ABSTRACT FROM AUTHOR]

Introduction: The Seraph® 100 Microbind® Affinity Filter is a biomimetic adsorbent device that can remove pathogens from the blood. Case Presentation: Here, we report the successful use of the Seraph® 100 to treat both a SARS-CoV-2 reinfection leading to severe COVID-19 pneumonia as well as subsequent secondary lung infections including Acinetobacter baumannii, Serratia marcescens, and Pseudomonas aeruginosa multidrug-resistant bacteria. To our knowledge, this 46-year-old black male is the first patient in which four treatments with this pathogen adsorber, one for a viral and three for different bacterial infections, have been successfully used. Conclusion: The Seraph® 100 can be easily and successfully used in conjunction with standard (anti-infective) treatment. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a harmful pathogen that causes a variety of acute and chronic infections through quorum sensing (QS) mechanisms. The increasing resistance of this bacterium to numerous antibiotics has created a demand for new medications that specifically target QS. Endophytes can be the source of compounds with antibacterial properties. This research is the first to examine tannic acid (TA) produced by endophytic fungus as a potential biotherapeutic agent. A novel endophytic fungal isolate identified as Penicillium oxalicum was derived from the cladodes of Opuntia ficus-indica (L.). The species identification for this isolate was confirmed through sequencing of the internal transcribed spacer region. The metabolites from the culture of this isolate were extracted using ethyl acetate, then separated and characterized using chromatographic methods. This led to the acquisition of TA, a compound that shows strong anti-QS and excellent antibacterial effects against extensively drug-resistant P. aeruginosa strains. Furthermore, it was shown that treating P. aeruginosa with the obtained TA reduced the secretion of virulence factors controlled by QS in a dose-dependent manner, indicating that TA inhibited the QS characteristics of P. aeruginosa. Simultaneously, TA significantly inhibited the expression of genes associated with QS, including rhlR/I, lasR/I, and pqsR. In addition, in silico virtual molecular docking showed that TA could efficiently bind to QS receptor proteins. Our results showed that P. oxalicum could be a new source of TA for the treatment of infections caused by extensively drug-resistant P. aeruginosa. [ABSTRACT FROM AUTHOR]

[Display omitted] Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (B BR) and epigallocatechin gallate (E GCG) from natural plant extracts, named as BE NPs , which is successively coated with manganese dioxide nanoshells (M nO 2 NSs) and glucose oxidase (G OX) to form the final BEMG NPs. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMG NPs to produce gluconic acid and hydrogen peroxide (H 2 O 2). That is subsequently to decompose MnO 2 NSs in the BEMG NPs to generate oxygen (O 2). The BEMG NPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O 2. Under the synergistic function of the cascaded reaction, the BEMG NPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (particularly bacterial resistance to antibiotics) represents a major public health issue worldwide. There is growing concern that more and more bacteria are becoming resistant to antibiotics as a result of genetic mutations. In this article, we describe the main mechanisms through which bacteria can resist the action of antibiotics and the transfer of resistance between bacteria of the same species or different species. Some bacteria acquire resistance to multiple antibiotics from different classes, becoming multidrug- resistant bacteria, which are increasing globally and can cause severe infections, making them difficult to treat and contributing to the spread of this resistance (examples: methicillin- resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum β-lactamase-producing Enterobacteriaceae, etc.). The major causes of antibiotic resistance development are the excessive use of antibiotics and the transmission of resistant pathogens in human and animal populations, as well as between humans, animals and the environment. It is important to note the transmission of resistant bacteria within healthcare-associated institutions. Globally, antibiotic resistance is a serious threat due to its continuous increase and the diminishing effectiveness of common antibiotics, with the risk of returning to the pre-antibiotic era. Thus, international health organizations are raising the alarm, highlighting the urgent need to improve surveillance, prevention, and control of bacterial resistance to antibiotics, as well as the need for research development to identify rapid and accurate diagnostic tests for detecting infections caused by resistant bacteria and to develop new medications. [ABSTRACT FROM AUTHOR]

Background/Objectives: Intestinal colonization by multidrug-resistant (MDR) bacteria is considered one of the main risk factors for invasive infections in the hematopoietic stem-cell transplant (HSCT) setting, associated with hard-to-eradicate microorganisms. The aim of this study was to assess the rate of intestinal colonization by MDR bacteria and their microbial spectrum in a group of post-HSCT patients to study the genetic determinants of beta-lactam and glycopeptide resistance in the recovered isolates, as well as to determine the epidemiological relation between them. Methods: The intestinal colonization status of 74 patients admitted to the transplantation center of University Hospital "St. Marina"—Varna in the period January 2019 to December 2021 was investigated. Stool samples/rectal swabs were screened for third-generation cephalosporin and/or carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Stenotrophomonas maltophilia. Identification and antimicrobial susceptibility testing were performed by Phoenix (BD, Sparks, MD, USA) and MALDI Biotyper sirius (Bruker, Bremen, Germany). Molecular genetic methods (PCR, DNA sequencing) were used to study the mechanisms of beta-lactam and glycopeptide resistance in the collected isolates, as well as the epidemiological relationship between them. Results: A total of 28 patients (37.8%) were detected with intestinal colonization by MDR bacteria. Forty-eight non-duplicate MDR bacteria were isolated from their stool samples. Amongst them, the Gram-negative bacteria prevailed (68.8%), dominated by ESBL-producing Escherichia coli (30.3%), and followed by carbapenem-resistant Pseudomonas sp. (24.2%). The Gram-positive bacteria were represented exclusively by Enterococcus faecium (31.2%). The main beta-lactam resistance mechanisms were associated with CTX-M and VIM production. VanA was detected in all vancomycin-resistant enterococci. A clonal relationship was observed among Enterobacter cloacae complex and among E. faecium isolates. Conclusions: To the best of our knowledge, this is the first Bulgarian study that presents detailed information about the prevalence, resistance genetic determinants, and molecular epidemiology of MDR gut-colonizing bacteria in HSCT patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment.We performed a retrospective single‐center study of all LTs performed between 2016 and 2019 with a minimum 4‐year follow‐up and a standardized protocol for the evaluation of LTBI.Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow‐up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin‐treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant‐days; p =  .8) and multidrug‐resistant gram‐negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant‐days; p =  .08) were not significantly higher in comparison to patients who did not receive moxifloxacin.A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations. [ABSTRACT FROM AUTHOR]

Studies on the conditions and pollution routes of antibiotic-resistant bacteria (ARB) in rivers can help provide countermeasures against the spread of ARB. This study focused on the pristine uppermost stream of a river, where Escherichia coli (E. coli) and enterococci were detected, although the stream flows through a pristine forest catchment. Antibiotic resistance of E. coli and enterococci isolated from the river water, riverbed sediment, and feces of waterside animals, such as birds and Mustelidae, were investigated throughout the year in the pristine uppermost sites. Antibiotic resistance was present in 1.4% (7/494) of the E. coli strains and 3.0% (24/812) of the enterococcal strains, and was low throughout the year. Although antibiotic resistance of bacteria isolated from feces was not detected in this watershed, the prevalence of multidrug-resistant E. coli was 0.4% (1/246) and 0.6% (1/172) in river water and riverbed sediment samples, respectively were observed. The presence of extended-spectrum β-lactamase (ESBL)-producing E. coli was confirmed in river water samples, and genomic analysis revealed that the samples possessed the CTX-M-15 group. Multidrug-resistant strains and ESBL-producing strains were classified as phylogroups B1 and A, respectively, which are E. coli phenotypes isolated from wild animals. Pulsed-field gel electrophoresis revealed analysis targeting enterococci that strains isolated from river water and bird feces were in the same cluster with 100% similarity. Therefore, bird feces are a source of enterococci in the uppermost stream of the river. Because multidrug-resistant bacteria and ESBL-producing bacteria were present in the pristine uppermost stream of the pristine river, urgent elucidation of the spreading routes of ARB is important. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is an opportunistic Gram-negative bacterium in the Enterobacteriaceae family associated with a wide range of diseases, such as pneumonia, bloodstream infections, meningitis and urinary tract infections. Infections caused by drug-resistant strains of Klebsiella pneumoniae pose a significant threat to the effectiveness of conventional antibiotics. Hence, this has led to the need to explore alternative antimicrobial therapies, especially natural products derived from plant sources. This study assessed the phytochemical composition and antibacterial properties and performed a molecular docking analysis of Henna leaves (Lawsonia inermis L.) extracts on strains of Klebsiella pneumoniae. Crude ethanol and methanol extracts of L. inermis L. were prepared at different concentrations (25, 50, 75 and 100 mg/mL) and tested on extended spectrum beta-lactamases (ESBLs)-producing strains of Klebsiella pneumoniae. Phytocompounds were identified using gas chromatography–mass spectrometry (GC-MS) and further subjected to virtual ligands screening with DataWarrior (v05.02.01) and a molecular docking analysis using AutoDock4.2 (v4.2.6). The active compounds of L. inermis L. were determined by the docking analysis, including phytochemical, physicochemical, pharmacokinetics and docking score. The GC-MS analysis identified 27 phytoconstituents, including ethyl acetate, sclareol, 2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine, α-bisabolol and 2-Isopropyl-5-methylcyclohexyl 3-(1-(4-chlorophenyl)-3-oxobutyl)-coumarin-4-yl carbonate. The 27 compounds were then screened for their physicochemical and pharmacokinetic properties. The results revealed that the methanol extracts at 100 mg/mL showed significantly higher (p < 0.05) zones of inhibition (13.7 ± 1.2 mm), while the ethanol extracts at 50 mg/mL were significantly lower (6.3 ± 0.6 mm) compared to all the other treatments. The docking analysis revealed that out of the 27 compounds identified, only twelve (12) compounds have a drug-likeness activity. The 12 compounds were further subjected to docking analysis to determine the binding energies with the CTX-M protein of Klebsiella pneumoniae. Only one compound [CID_440869; (2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine)] had the best binding energy of −9.76 kcal/mol; hence, it can be considered a potentially suitable treatment for infections caused by ESBLs-producing strains of Klebsiella pneumoniae. This study has demonstrated that L. inermis L. extracts have antibacterial effects. Further research could explore the potential antimicrobial applications of L. inermis L. extracts to many bacterial strains. [ABSTRACT FROM AUTHOR]

The increasing incidence of antibiotic resistance in bacteria is a major problem in terms of therapeutic options, especially in immunocompromised patients, such as patients from intensive care units (ICUs), HIV-positive patients, patients with malignancies or transplant patients. Commensal bacteria, especially anaerobes, serve to maintain microbial stability by preventing overpopulation with pathogenic bacteria. In immunocompromised patients, microbiota imbalance caused by antibiotic therapy and decreased host immunity favors intestinal overpopulation with pathogenic species, leading to increased bacterial translocation and susceptibility to systemic infections. Infections with multidrug-resistant (MDR) bacteria pose major challenges to the establishment of appropriate treatment and lead to increased mortality. Asymptomatic colonization with MDR bacteria usually precedes infection and tends to persist for long periods of time, and in immunocompromised patients, colonization with MDR bacteria is a risk factor for systemic infections. This review aims to assess the relation between colonization and infection with MDR bacteria in immunocompromised patients such as ICU patients, HIV-positive patients and cancer patients and to identify the prevalence and patterns of MDR bacterial colonization and infection in this category of patients. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid β-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure–activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin's antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) is a rare disease in children and is associated with significant morbidity and mortality. In recent years, significant changes have occurred in pediatric care that could have influenced the microbiology and presentation of IE. The aim of this work was to study epidemiological, microbiological, and clinical features of IE treated at a Pediatric Cardiac Surgery Reference Center located in Madrid (Spain) in a 10-years' period. A descriptive observational retrospective study was performed, including pediatric patients < 16 years old with definite or possible IE admitted to a reference center between January 2012 and December 2021. Thirty-two IE episodes were identified. Twenty-eight (87.5%) had congenital heart disease (CHD), 8 (25.0%) were preterm infants, 1 (3.1%) was immunocompromised and 6 (18.8%) had other chronic conditions; in 11 (34.4%) episodes more than one underlying condition was associated. In 20 (62.5%) episodes there was an indwelling central venous catheter (CVC); children with other comorbidities (preterm, immunocompromised, other chronic conditions) were more likely to have a CVC at diagnosis compared with patients with isolated CHD (p < 0.001). Thirty-six microbiological isolates were obtained in the 32 episodes; 4 (12.5%) episodes had 2 isolated microorganisms. Microbiological isolates were 20 (55.6%) Gram-positive bacteria (GPB), 10 (27.8%) non-HACEK Gram-negative bacteria (GNB), 1 (2.8%) HACEK-group bacterium, 4 (11.1%) fungi and 1 (2.8%) Coxiella burnetii. In 10 (31.3%) episodes, patients were colonized by multidrug-resistant bacteria (MDRB) and the etiology of IE in 3 (30.0%) of those episodes was the colonizing MDRB. MDRB colonization was associated with MDRB IE (p = 0.007). The most common complication was septic embolism: 11 (34.4%) episodes (9 pulmonary and 2 cerebral). In-hospital mortality was 6.3% (n = 2), all of them due to underlying conditions and not to IE or its complications. Clinical features and complications of IE episodes caused by non-HACEK GNB and those caused by GPB were compared, finding no statistically significant differences. Conclusion: Risk factors for developing IE, the proportion of embolic complications, and mortality rate were consistent with previously published findings. Proportion of IE cases attributed to non-HACEK GNB was higher than previously reported, suggesting an evolving epidemiology of IE. One-third of children colonized with MDRB subsequently developed IE caused by the same MDRB strains, so empirical coverage of MDRB organisms must be considered when IE is suspected in MDRB colonized patients. No significant differences in clinical features and complications were observed when comparing IE episodes caused by non-HACEK GNB and those caused by GPB, however larger cohort studies are needed. What is Known: • Infective endocarditis (IE) is a rare disease in children, associated with significant morbidity and mortality. • The main risk factor for developing IE in children is an underlying congenital heart disease. What is New: • With current changing epidemiology in pediatric IE, a higher proportion of IE caused by non-HACEK Gram-negative bacteria should be expected. • A significant percentage of children colonized by multidrug-resistant bacteria can develop an IE due to those bacteria. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading causative pathogen of nosocomial pneumonia with an alarming in-hospital mortality rate of 30%. Last resort antibiotic, vancomycin, has been increasingly used to treat MRSA infections, but the rapid emergence of vancomycin-resistant strains urges the development of alternative treatment strategies against MRSA-associated pneumonia. The bacteriolytic enzyme, lysostaphin, targeting the cell wall peptidoglycan of S. aureus, has been considered as a promising alternative for MRSA infections. Its proteinaceous nature is likely benefit from direct delivery to the lungs, but the challenges for successful pulmonary delivery of lysostaphin lying on a suitable inhalation device and a formulation with sufficient storage stability. In this study, the applicability of a vibrating mesh nebulizer (Aerogen Solo®) and a soft mist inhaler (Respimat®) was investigated. Both devices were capable of aerosolizing lysostaphin solution into inhalable droplets and caused minimum antibacterial activity loss. In addition, lysostaphin stabilized with phosphate-buffered saline and 0.1% Tween 80 was proved to have acceptable stability for at least 12 months when stored at 4 °C. These promising data encourage further clinical development of lysostaphin for management of MRSA-associated lung infections. Lysostaphin had insignificant activity loss after aerosol generation by a vibrating mesh nebulizer and a soft mist inhaler. Most of the lysostaphin aerosols generated by the vibrating mesh nebulizer and soft mist inhaler are inhalable. The vibrating mesh nebulizer and soft mist inhaler are suitable device for pulmonary delivery of lysostaphin. [ABSTRACT FROM AUTHOR]

Abstract Using plant extracts in the green synthesis of nanoparticles has become an environmentally acceptable approach. In our study, copper oxide nanoparticles (CuO NPs) were synthesized using ethanolic extracts of Azadirachta indica and Simmondsia chinensis. CuO NP formation was confirmed by the change in color and by UV‒visible spectroscopy (CuO NPs peaked at a wavelength of 344 nm). TEM images confirmed the semispherical shape of the CuO NPs, with particle sizes ranging from 30.9 to 10.7 nm. The antibacterial activity of these NPs was evaluated by using the agar diffusion method against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Pseudomonas aeruginosa, Acinetobacter spp., Klebsiella pneumoniae, and Stenotrophomonas maltophilia. The minimum inhibitory concentration (MIC) of CuO NPs ranged from 62.5 to 125 µg/ml. In contrast, the antioxidant activity and antibiofilm activity of CuO NPs ranged from 31.1 to 92.2% at 125–500 µg/ml and 62.2–95%, respectively, at 125 –62.5 µg/ml. Our results confirmed that CuO NPs had IC50s of 383.41 ± 3.4 and 402.73 ± 1.86 at 250 µg/mL against the HBF4 cell line. Molecular docking studies with CuO NPs suggested that penicillin-binding protein 4 (PBP4) and beta-lactamase proteins (OXA-48) strongly bind to S. aureus and K. pneumoniae, respectively, with CuO NPs. Our study confirms the promising use of CuO NPs in treating pathogenic bacteria and that CuO NPs could be possible alternative antibiotics. This study supports the pharmaceutical and healthcare sectors in Egypt and worldwide.

Introduction: The Seraph® 100 Microbind® Affinity Filter is a biomimetic adsorbent device that can remove pathogens from the blood. Case Presentation: Here, we report the successful use of the Seraph® 100 to treat both a SARS-CoV-2 reinfection leading to severe COVID-19 pneumonia as well as subsequent secondary lung infections including Acinetobacter baumannii, Serratia marcescens, and Pseudomonas aeruginosa multidrug-resistant bacteria. To our knowledge, this 46-year-old black male is the first patient in which four treatments with this pathogen adsorber, one for a viral and three for different bacterial infections, have been successfully used. Conclusion: The Seraph® 100 can be easily and successfully used in conjunction with standard (anti-infective) treatment.

Klebsiella pneumoniae is an opportunistic Gram-negative bacterium in the Enterobacteriaceae family associated with a wide range of diseases, such as pneumonia, bloodstream infections, meningitis and urinary tract infections. Infections caused by drug-resistant strains of Klebsiella pneumoniae pose a significant threat to the effectiveness of conventional antibiotics. Hence, this has led to the need to explore alternative antimicrobial therapies, especially natural products derived from plant sources. This study assessed the phytochemical composition and antibacterial properties and performed a molecular docking analysis of Henna leaves (Lawsonia inermis L.) extracts on strains of Klebsiella pneumoniae. Crude ethanol and methanol extracts of L. inermis L. were prepared at different concentrations (25, 50, 75 and 100 mg/mL) and tested on extended spectrum beta-lactamases (ESBLs)-producing strains of Klebsiella pneumoniae. Phytocompounds were identified using gas chromatography–mass spectrometry (GC-MS) and further subjected to virtual ligands screening with DataWarrior (v05.02.01) and a molecular docking analysis using AutoDock4.2 (v4.2.6). The active compounds of L. inermis L. were determined by the docking analysis, including phytochemical, physicochemical, pharmacokinetics and docking score. The GC-MS analysis identified 27 phytoconstituents, including ethyl acetate, sclareol, 2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine, α-bisabolol and 2-Isopropyl-5-methylcyclohexyl 3-(1-(4-chlorophenyl)-3-oxobutyl)-coumarin-4-yl carbonate. The 27 compounds were then screened for their physicochemical and pharmacokinetic properties. The results revealed that the methanol extracts at 100 mg/mL showed significantly higher (p < 0.05) zones of inhibition (13.7 ± 1.2 mm), while the ethanol extracts at 50 mg/mL were significantly lower (6.3 ± 0.6 mm) compared to all the other treatments. The docking analysis revealed that out of the 27 compounds identified, only twelve (12) compounds have a drug-likeness activity. The 12 compounds were further subjected to docking analysis to determine the binding energies with the CTX-M protein of Klebsiella pneumoniae. Only one compound [CID_440869; (2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine)] had the best binding energy of −9.76 kcal/mol; hence, it can be considered a potentially suitable treatment for infections caused by ESBLs-producing strains of Klebsiella pneumoniae. This study has demonstrated that L. inermis L. extracts have antibacterial effects. Further research could explore the potential antimicrobial applications of L. inermis L. extracts to many bacterial strains.

Enas M Al-Khlifeh,1 Ibrahim S Alkhazi,2 Majed Abdullah Alrowaily,3 Mansoor Alghamdi,4 Malek Alrashidi,4 Ahmad S Tarawneh,5 Ibraheem M Alkhawaldeh,6 Ahmad B Hassanat5 1Department of Medical Laboratory Science, Al-Balqa Applied University, Al-salt, 19117, Jordan; 2College of Computers & Information Technology, University of Tabuk, Tabuk, 47512, Saudi Arabia; 3Department of Computer Science, College of Computer and Information Sciences, Jouf University, Sakaka, 72341, Saudi Arabia; 4Computer Science Department, Applied College, University of Tabuk, Tabuk, 71491, Saudi Arabia; 5Faculty of Information Technology, Mutah University, Al-Karak, Jordan; 6Faculty of Medicine, Mutah University, Al-Karak, JordanCorrespondence: Enas M Al-Khlifeh, Parasitology laboratory, Department of Medical Laboratory Science, Faculty of Science, Al-Balqa Applied University, Al-Salt (19117), Jordan, Tel +962795856110, Email Al-khlifeh.en@bau.edu.joBackground: The incidence of microorganisms with extended-spectrum beta-lactamase (ESBL) is on the rise, posing a significant public health concern. The current application of machine learning (ML) focuses on predicting bacterial resistance to optimize antibiotic therapy. This study employs ML to forecast the occurrence of bacteria that generate ESBL and demonstrate resistance to multiple antibiotics (MDR).Methods: Six popular ML algorithms were initially trained on antibiotic resistance test patient reports (n = 489) collected from Al-Hussein/Salt Hospital in Jordan. Trained outcome models predict ESBL and multidrug resistance profiles based on microbiological and patients’ clinical data. The results were utilized to select the optimal ML method to predict ESBL’s most associated features.Results: Escherichia coli (E. coli, 82%) was the most commonly identified microbe generating ESBL, displaying multidrug resistance. Urinary tract infections (UTIs) constituted the most frequently observed clinical diagnosis (68.7%). Classification and Regression Trees (CART) and Random Forest (RF) classifiers emerged as the most effective algorithms. The relevant features associated with the emergence of ESBL include age and different classes of antibiotics, including cefuroxime, ceftazidime, cefepime, trimethoprim/ sulfamethoxazole, ciprofloxacin, and gentamicin. Fosfomycin nitrofurantoin, piperacillin/tazobactam, along with amikacin, meropenem, and imipenem, had a pronounced inverse relationship with the ESBL class.Conclusion: CART and RF-based ML algorithms can be employed to predict the most important features of ESBL. The significance of monitoring trends in ESBL infections is emphasized to facilitate the administration of appropriate antibiotic therapy. Keywords: ESBL, machine learning, multidrug-resistant bacteria, E. coli, cefuroxime, CART and RF

The use of antibiotics against a range of pathogenic bacteria has increased in recent years, leading to the development of drug resistance, which makes disease control challenging. Thus, the need for the development of new antibacterial medications is critical. Natural resources, such as entomopathogenic bacteria (EPB), provide a rich source of metabolites with well-known antibacterial properties. The present study aimed to investigate the antibacterial activity of symbiotic (n = 1) and non-symbiotic (n = 8) entomopathogenic bacterial species associated with the entomopathogenic nematode (EPN) Steinernema feltiae against four multidrug-resistant bacterial species. Bacterial cells and filtrates from Xenorhabdus bovienii strongly inhibited the growth of Staphylococcus aureus (33.3 and 28.9 mm) and Escherichia coli (24.6 and 21.6 mm) in disk diffusion, minimum inhibitory concentration (MIC) (2 and 8 µl/ml) and minimal bactericidal concentration (MBC) (4 and 12.5 µl/ml) assays. In conclusion, the direct application of endogenous S. feltiae-associated EPB, especially X. bovienii, appears promising as an antibacterial agent against multidrug-resistant bacteria (MRBs).

The challenge in treating diabetic foot infections caused by drug‐resistant bacteria is rapidly eradicating bacteria and accelerating wound healing. NIR‐II‐induced photothermal therapy (PTT) offers notable advantages over conventional treatments, such as broad‐spectrum bactericidal efficacy, better penetration depth in biological tissues, and higher skin tolerance thresholds, making it particularly suitable for addressing diabetic foot infections. Herein, it is found that NIR‐II dye IR26 exhibited good photothermal effects but poor photothermal stability. By modifying IR26 with methoxy and triphenylamine groups, a novel D–A–D‐type NIR‐II small molecule photothermal agent (IRC) is developed, with high photothermal stability and photothermal conversion efficiency (44.3%). IRC exhibited a maximum absorption wavelength of 1166 nm and a maximum emission wavelength of 1238 nm. However, PTT alone cannot effectively promote diabetic wound healing. Therefore, a novel nanoplatforms (Cur‐IRC@PCM) are developed by coloading IRC and curcumin, a natural wound–healing compound, into thermosensitive liposomes to treat MRSA‐infected diabetic wounds. Under 980 nm laser irradiation, Cur‐IRC@PCM provided PTT and controlled the precise release of curcumin, effectively synergizing to eradicate drug‐resistant bacteria and accelerate wound closure. The intelligent antibacterial nanoplatforms Cur‐IRC@PCM also exhibits excellent biocompatibility, rendering it a promising therapeutic tool in biomedical fields for combating drug‐resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Multidrug-resistant organism (MDRO) outbreaks have been steadily increasing in intensive care units (ICUs). Still, healthcare institutions and workers (HCWs) have not reached unanimity on how and when to implement infection prevention and control (IPC) strategies. We aimed to provide a pragmatic physician practice-oriented resume of strategies towards different MDRO outbreaks in ICUs. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios; education, isolation, decolonization, screening, and hygiene practices; outbreak reporting; cost-effectiveness; reproduction numbers (R0); and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician lose sight of the big picture. IPC strategies have proven their cost-effectiveness regardless of typology, country, and pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, the elaboration of a rapid outbreak recognition tool (i.e., an easy-to-use mathematical model) would improve early diagnosis and prevent spreading. Further studies are needed to express views in favor or against MDRO decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategy application has made and still makes ICUs major MDRO reservoirs in the community. In a not-too-distant future, genetic engineering and phage therapies could represent a plot twist in MDRO IPC strategies. [ABSTRACT FROM AUTHOR]

Given the urgent need for novel methods to control the spread of multidrug-resistant microorganisms, this study presents a green synthesis approach to produce silver nanoparticles (AgNPs) using the bark extract from Anadenanthera colubrina (Vell.) Brenan var. colubrina. The methodology included obtaining the extract and characterizing the AgNPs, which revealed antimicrobial activity against MDR bacteria. A. colubrina species is valued in indigenous and traditional medicine for its medicinal properties. Herein, it was employed to synthesize AgNPs with effective antibacterial activity (MIC = 19.53–78.12 μM) against clinical isolates from the ESKAPEE group, known for causing high hospitalization costs and mortality rates. Despite its complexity, AgNP synthesis is an affordable method with minimal environmental impacts and risks. Plant-synthesized AgNPs possess unique characteristics that affect their biological activity and cytotoxicity. In this work, A. colubrina bark extract resulted in the synthesis of nanoparticles measuring 75.62 nm in diameter, with a polydispersity index of 0.17 and an average zeta potential of −29 mV, as well as low toxicity for human erythrocytes, with a CC50 value in the range of 961 μM. This synthesis underscores its innovative potential owing to its low toxicity, suggesting applicability across several areas and paving the way for future research. [ABSTRACT FROM AUTHOR]

Multidrug-resistant bacteria present a significant public health challenge; such pathogens exhibit reduced susceptibility to conventional antibiotics, limiting current treatment options. Cationic non-ribosomal peptides (CNRPs) such as brevicidine and polymyxins have emerged as promising candidates to block Gram-negative bacteria. To investigate the capability of bacteria to biosynthesize CNRPs, and specifically polymyxins, over 11,000 bacterial genomes were mined in silico. Paenibacillus polymyxa was identified as having a robust biosynthetic capacity, based on multiple polymyxin gene clusters. P. polymyxa biosynthetic competence was confirmed by metabolite characterization via HPLC purification and MALDI TOF/TOF analysis. When grown in a selected medium, the metabolite yield was 4 mg/L with a 20-fold specific activity increase. Polymyxin B (PMB) was assayed with select nosocomial pathogens, including Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumaii, which exhibited minimum inhibitory concentrations of 4, 1, and 1 µg/mL, respectively. [ABSTRACT FROM AUTHOR]

Bacterial infections, especially caused by multidrug‐resistant bacteria, pose a big challenge to the healthcare system. As a group of historic agents, metals with broad‐spectrum antibacterial activity are regarded as promising alternatives to tackle antibiotic resistance. Among them, gallium ions have presented encouraging antibacterial effects in research and preclinic studies. However, utilization of gallium ions has difficulty in achieving high targeting and long‐term effectiveness. With the renaissance of liquid metal, here, a novel and facile antibacterial gallium nanostructure is proposed in which polydopamine‐modified gallium nanocore serves as an ion reservoir for enhanced metal ion release and the surface also permits secondary reaction, allowing for in situ formation of Ag nanoparticles to improve the antibacterial property, ROS generation, and photothermal performance. Notably, ≈100% bacterial killing efficacy can be achieved when combined with NIR laser irradiation. The in vivo treatment results of methicillin‐resistant Staphylococcus aureus (MRSA)‐infected mice demonstrate that the microneedle patch loaded with nanoparticles exhibits outstanding bacterial elimination and inflammation alleviation, and promotes angiogenesis and collagen deposition, further accelerating wound healing. This gallium‐based nanostructure offers an effective nanoplatform for antibacterial treatments and combinatory strategies, which holds significant promise for refractory multidrug‐resistant bacteria and related infections. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter baumannii is a multidrug-resistant bacterium commonly associated with hospital-acquired infections. The rapid spread of A. baumannii has raised concerns, as it has been linked to the emergence of clones in healthcare facilities worldwide. The challenges of treating and controlling infections caused by this bacterium in hospital settings are exacerbated by its resistance profile. The proliferation of clones worldwide highlights the need for careful infection control procedures and new tactics to fight illnesses caused by drug-resistant A. baumannii strains. Materials and Methods: Between January 2019 and December 2020, a total of 26,250 specimens were collected by personnel from the Department of Microbiology at King Fahad Specialist Hospital. Results: Our study highlights a significant surge in antimicrobial resistance, indicating a relative increase in multidrug-resistant A. baumannii isolates. Despite extensive resistance, azithromycin, cefoxitin, norfloxacin, penicillin, piperacillin, tetracycline, ceftriaxone, nitrofurantoin and aztreonam showed 91.2%-100% efficacy against these strains. Conclusions: This study emphasises the critical need for stringent infection control measures and judicious antibiotic strategies to curb multidrug-resistant A. baumannii outbreaks in healthcare settings. The identification of alternative therapies is imperative for improved management of infections caused by multidrug-resistant A. baumannii. [ABSTRACT FROM AUTHOR]

Objective: To explore peripheral blood indicators that may serve as early indicators for multidrug‐resistant bacteria (MDR) infections in this demographic, with the goal of providing reference suggestions for the clinical prevention of MDR infections in elderly inpatients. Methods: Clinical data of patients were divided into the MDR‐infected group (n = 488) and the MDR‐uninfected group (n = 233) according to the results of drug sensitivity experiments, risk factors for MDR infection, and peripheral blood indicators related to MDR infections were analyzed using univariate and multivariate logistic regression in conjunction with the construction of a Chi‐squared automatic interaction detector (CHAID) decision tree model, considering statistical significance at p <.05. Results: Of 721 patients, 488 multidrug‐resistant strains were identified. Among them, with Staphylococcus spp. the most prevalent in 148 strains. The most frequent detection of MDR occurred in puncture fluid samples (167 cases). Univariate and multivariate regression analyses revealed that prolonged hospitalization, use of antibiotics preadmission, duration of antibiotics, invasive procedures or recent surgery, and coexisting lung disease were independent risk factors for contracting MDR. Subsequent analysis comparing the aforementioned influences with peripheral blood cells revealed associations between the number of antibiotic treatment days and increased neutrophil‐to‐lymphocyte ratio (NLR), platelet count‐to‐lymphocyte ratio (PLR), neutrophils, decreased lymphocytes, and increased eosinophils; preadmission antibiotic use correlated with increased PLR, NLR, neutrophils, and decreased lymphocytes; and invasive manipulation or surgery correlated with increased PLR and NLR. Conclusions: Elevated NLR, PLR, neutrophils, lowered lymphocytes, and eosinophils may serve as early indicators of MDR infections in elderly hospitalized patients. [ABSTRACT FROM AUTHOR]

The aim of this review is to synthesise the key aspects of the epidemiology, current microbiological diagnostic challenges, antibiotic resistance rates, optimal antimicrobial management, and most effective prevention strategies for Stenotrophomonas maltophilia (SM) in the intensive care unit (ICU) population. In recent years, resistance surveillance data indicate that SM accounts for less than 3% of all healthcare-associated infection strains, a percentage that doubles in the case of ventilator-associated pneumonia (VAP). Interestingly, SM ranks as the third most isolated non-glucose fermenter Gram-negative bacilli (NFGNB). Although this NFGNB genus has usually been considered a bystander and colonising strain, recently published data warn about its potential role as a causative pathogen of severe infections, particularly pneumonia and bloodstream infections (BSI), not only for the classical immunocompromised susceptible host patients but also for critically ill ones even without overt immunosuppression. Indeed, it has been associated with crude 28-day mortality as high as 54.8%, despite initial response following targeted therapy. Additionally, alongside its intrinsic resistance to a wide range of common antimicrobials, various worldwide and local surveillance studies raise concerns about an increase in ICU settings regarding resistance to first-line drugs such as cotrimoxazole or tigecycline. This scenario alerts ICU physicians to the need to reconsider the best stewardship approach when SM is isolated in obtained samples from critically ill patients. Despite the coverage of this multidrug-resistant bacterium (MDRB) provided by some traditional and a non-negligible number of current pipeline antimicrobials, an ecological and cost-effective strategy is needed in the present era. [ABSTRACT FROM AUTHOR]

Background: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. Methods: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). Results: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). Conclusion: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs. [ABSTRACT FROM AUTHOR]

Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium , are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation. [Display omitted] • MDRB infections are frequent in patients with cirrhosis after LT and are associated with increased mortality. • Urinary tract infections are the most common MDRB infections, followed by bacteremia and respiratory infections. • Gram-negative bacteria are the most frequently isolated, but infections caused by gram-positive enterococci are increasing. • Recent ICU admission or MDRB infection (0-3 months before LT) and RBC transfusions are risk factors for post-LT MDRB infection. [ABSTRACT FROM AUTHOR]

The use of antibiotics against a range of pathogenic bacteria has increased in recent years, leading to the development of drug resistance, which makes disease control challenging. Thus, the need for the development of new antibacterial medications is critical. Natural resources, such as entomopathogenic bacteria (EPB), provide a rich source of metabolites with well-known antibacterial properties. The present study aimed to investigate the antibacterial activity of symbiotic (n = 1) and non-symbiotic (n = 8) entomopathogenic bacterial species associated with the entomopathogenic nematode (EPN) Steinernema feltiae against four multidrug-resistant bacterial species. Bacterial cells and filtrates from Xenorhabdus bovienii strongly inhibited the growth of Staphylococcus aureus (33.3 and 28.9 mm) and Escherichia coli (24.6 and 21.6 mm) in disk diffusion, minimum inhibitory concentration (MIC) (2 and 8 µl/ml) and minimal bactericidal concentration (MBC) (4 and 12.5 µl/ml) assays. In conclusion, the direct application of endogenous S. feltiae-associated EPB, especially X. bovienii, appears promising as an antibacterial agent against multidrug-resistant bacteria (MRBs). [ABSTRACT FROM AUTHOR]

Healthcare-associated infections (HAIs) can pose significant risks to patients with cardiovascular disease due to the compromised nature of their health and potential vulnerabilities. In order to reduce the incidence of HAIs and prevent the spread of antibiotic-resistant organisms, it is mandatory to develop surveillance systems. We undertook a retrospective case–control study of all patients presenting HAIs who were admitted to the intensive care unit (ICU) to assess risk factors associated with death among patients with cardiovascular disease. Patients admitted to the ICU who died were more likely to present an infection with a multidrug-resistant bacterium, an infection with Acinetobacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain Gram-negative pathogens such as Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The longer the patient remains admitted in the ICU, the higher the risk of acquiring an infection that can often become fatal. A nosocomial infection, particularly in patients with cardiovascular disease, also increases the length of hospitalization, which will lead to increased expenditure. For this reason, new prophylactic methods and therapeutic approaches are needed, and researchers' efforts should be directed in this direction. [ABSTRACT FROM AUTHOR]

Aims: Multidrug-resistant bacteria urinary tract infections (MDR-UTI) are a global concern, leading to increased morbidity, mortality and financial costs. The aim of this study was to determine the prevalence of MDR-UTI and establish the epidemiological profile of UTI due to different phenotypes of MDR-UTI. Methodology and results: This is a retrospective study of MDR-UTI assessed at the microbiology laboratory of Mohammed VI University Hospital Center of Oujda over 37 months from March 2016 to April 2019. The study included all requests for cytobacteriological examination of urine (CBEU) according to the instructions of the medical microbiology guidelines. An agar medium was utilized for bacterial culture experimentation. Antibiotic susceptibility testing was performed according to the European Committee on Antimicrobial Susceptibility Testing guidelines. CBEU in UTIs allowed the isolation of 1078 isolates. They were dominated by Gram-negative bacteria (87.65%; n=945), followed by Gram-positive bacteria for 12.34% (n=133). This included 181 (16.80%) multidrug-resistant strains, which were dominated by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) (n=144; 79.55%). Young male adults exhibited a higher occurrence of isolated ESBL-E and carbapenem-resistant Acinetobacter baumannii (CRAB). As for the distribution by department, there was a near equality between the MDR isolates isolated from outpatients (n= 88; 49%) versus the inpatients (n= 93; 51%). Exactly 152 (84%) isolated MDR cases were observed in patients who did not have a urinary catheter, 157 (87%) and 141 (78%) cases of MDR of UTI were not associated with care and occurred in non-immunocompromised patients, respectively. Prior antibiotic exposure was observed in only 58 (32%) cases. Conclusion, significance and impact of study: This study confirmed the increasing prevalence of multidrug-resistant urinary tract infections in the community and hospitals. The fight against this problem will require all stakeholders' involvement to achieve the goals from one health perspective in line with international agenda. [ABSTRACT FROM AUTHOR]

Morbidity and mortality associated with multidrug-resistant (MDR) bacterial infections remain very high. There is a need to assess the in vitro antibacterial efficacy of novel therapeutic agents against MDR bacteria. Silver nanoparticles (AgNPs) were intracellularly synthesized by inoculating 2 g biomass of Lysinibacillus fusiformis into 300 mL of 1 mM AgNO3 solution and incubated at 30 °C for 72 h. The AgNPs colloidal suspension was monitored via color change and UV–vis spectroscopy and subsequently characterized via scanning electron microscope (SEM), dynamic light scattering (DLS), transmission electron microscope (TEM), energy dispersive x-ray (EDX), Fourier transform infrared (FTIR), and x-ray diffractometer (XRD), analyses. Antibacterial activities of AgNPs against the MDR bacteria isolated from chronic wounds were assessed using the well-diffusion method, and the minimum inhibitory and bactericidal concentrations were determined. The biomass of Lysinibacillus fusiformis produced AgNPs colloidal suspension with dark brown color and UV–vis absorption peaks between 381 and 404 nm. The AgNPs are spherical and isolated, with a size distribution of 98.88 ± 1.46 nm and a polydispersity index of 0.231 ± 0.003. However, TEM revealed the AgNPs had an average diameter of 18.42 ± 1.47 nm and 73.89% of zerovalent silver with a strong signal at 3.0 keV. FTIR showed the presence of primary amines, while sharp Bragg's peaks matching with the planes (111, 200, 220, and 311) of face-centered, cubic, and crystalline silver were detected for XRD. The AgNPs showed effective antibacterial efficacy against the tested MDR bacterial pathogens with P. aeruginosa (11) and Enterobacter hormaechei (19) being the most sensitive (MIC 156.25 µg/mL; MBC 312.5 – 625 µg/mL). This suggests that in vivo studies should be conducted to further establish their efficacy and possible translation to human clinical use. [ABSTRACT FROM AUTHOR]

IntroductionMultidrug-resistant Enterobacteriaceae are among the most urgent global public health threats associated with various life-threatening infections. In the absence of a rapid method to identify antimicrobial susceptibility, empirical use of broad-spectrum antimicrobials such as carbapenem monotherapy has led to the spread of resistant organisms. Rapid determination of antimicrobial resistance is urgently needed to overcome this issue.MethodsBy capturing dynamic single-cell morphological features, including growth-independent, antibiotic-induced changes, of cells from 19 strains of Klebsiella pneumoniae, we evaluated data processing strategies based on time and concentration differentials to develop models for classifying its susceptibility to a commonly used carbapenem, meropenem, and predicting their minimum inhibitory concentrations (MIC).Results and discussionWe report morphometric antimicrobial susceptibility testing (MorphoAST), a growth independent, computer vision-based machine learning workflow, for rapid determination of antimicrobial susceptibility by single-cell morphological analysis within sub-doubling time of K. pneumoniae. We demonstrated the technological feasibility of predicting MIC/antimicrobial susceptibility in a fraction of the bacterial doubling time (

The global emergency of antimicrobial resistance has drawn several efforts to evaluate new drug candidates, such as natural defensive biomolecules. Ocellatins are a group of antimicrobial peptides found in anurans of the Leptodactylidae family. This work investigated the presence of antimicrobial peptides in the skin secretion of Leptodactylus vastus from the Brazilian northeast. The secretion was fractionated by RP-HPLC, and the fractions were screened for antibacterial activity. A peptide isolated from the most active fraction was characterized for primary structure and evaluated for antibacterial activity, cytotoxicity to murine melanoma cells (B16-F10), and hemolytic activity. The RP-HPLC profile displayed 26 fractions, with fraction 25 being the most active. One of the two peptides present in this fraction had the primary structure determined, belonging to the group of ocellatins. Since it was not identical to other ocellatins previously reported, it was named ocellatin-VT. This peptide especially inhibited Gram-negative bacteria growth, with the highest activity against Acinetobacter baumannii and Escherichia coli (growth inhibition was higher than 95% at 8 and 16 µM, respectively). Ocellatin-VT was weakly cytotoxic to B16-F10 cells and showed low hemolytic activity. In conclusion, a new ocellatin was isolated from L. vastus skin secretion that was active against non-resistant and multidrug-resistant bacteria.

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G–) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G– bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.

Microbial resistance is a rapidly escalating phenomenon worldwide, with complex mechanisms and important involvement in the determinants of healthcare-associated and in-hospital infections. At European level, it is estimated that 80.000 hospitalised patients have at least one HAI every day with multi-antimicrobial resistant germs, leading to an extension of hospital stay by 16 million days every year. In high-income countries, the prevalence is around 7.5%, and in low- and middle-income countries, the prevalence ranges from 5.7% to 19.2%. Material and method. Through a retrospective, descriptive study carried out in the Clinc Emergency Hospital ,,Prof.Dr. Nicolae Oblu” in Iasi, Romania in the period 2020-2021, the 602 identified and reported intra-hospital infections were investigated, focusing on the etiology and microbial resistance of the pathogens involved.Results. The most frequent etiological agents of HAI identified in our study were K. pneumoniae (13.45%), A. calcoaceticus (10.11%), S. aureus (8.45%), E. coli (7.62%), P. aeruginosa (5.47%), noting the predominance of Gram-negative bacteria (GN) and the fact that they are part of the ESKAPE group of pathogens, the percentages obtained being similar to the European average. Klebsiella pneumoniae (13.45 %) was the most common in the aetiological palette of HAIs, allowing us to highlight certain peculiarities regarding its antimicrobial resistance.Conclusions. The present study provides useful data for monitoring the resistance of pathogens involved in HAIs at hospital level, for guiding antibiotic therapy in healthcare-associated infections and for substantiating the implementation of a set of measures related to antibiotic therapy and antibiotic prophylaxis.

Abstract Enterotoxigenic E. coli is one of the bacterial pathogens contributing to the global resistance crisis in public health and animal husbandry. The problem of antibiotic resistance is becoming more and more serious, and phage is considered one of the potential alternatives to antibiotics that could be utilized to treat bacterial infections. Our study isolated and identified a lytic phage PGX1 against multidrug-resistant enterotoxigenic E. coli EC6 strain from sewage. The phage lysis profile revealed that PGX1 exhibited a lytic effect on multidrug-resistant enterotoxigenic E. coli strains of serotype O60. Through phage whole genome sequencing and bioinformatics analysis, PGX1 was found to be the class Caudoviricetes, family Autographiviridae, genus Teseptimavirus. The length of the PGX1 genome is about 37,009 bp, containing 54 open reading frames (ORFs). Notably, phage PGX1 lacks any lysogenic-related genes or virulence genes. Furthermore, phage PGX1 demonstrates strong adaptability, tolerance, and stability in various pH (pH4-10) and temperatures (4–40°C). The in vivo and in vitro tests demonstrated that phage PGX1 significantly removes and inhibits the formation of multidrug-resistant EC6 biofilm and effectively controls the Galleria mellonella larvae and enterotoxigenic E. coli EC6 during mice infection. In conclusion, the above findings demonstrated that phage PGX1 may be a novel antimicrobial agent to control multidrug-resistant E. coli infections.