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Background: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. Method: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed. Results: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes. Conclusions: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens. [ABSTRACT FROM AUTHOR]

The common intestinal pathogen Klebsiella pneumoniae (K. pneumoniae) is one of the leading causes of fatal superbug infections that can resist the effects of commonly prescribed medicines. The uncontrolled use or misuse of antibiotics has increased the prevalence of drug-resistant K. pneumoniae strains in the environment. In the quest to search for alternative therapeutics for treating these drug-resistant infections, bacteriophages (bacterial viruses) emerged as potential candidates for in phage therapy against Klebsiella. The effective formulation of phage therapy against drug-resistant Klebsiella infections demands thorough characterization and screening of many bacteriophages. To contribute effectively to the formulation of successful phage therapy against superbug infections by K. pneumoniae, this study includes the isolation and characterization of a novel lytic bacteriophage MKP-1 to consider its potential to be used as therapeutics in treating drug-resistant Klebsiella infections. Morphologically, having a capsid attached to a long non-contractile tail, it was found to be a siphovirus that belongs to the class Caudoviricetes and showed infectivity against different strains of the target host bacterium. Comparatively, this double-stranded DNA phage has a large burst size and is quite stable in various physiological conditions. More interestingly, it has the potential to degrade the tough biofilms formed by K. pneumoniae (Klebsiella pneumoniae subsp. pneumoniae (Schroeter) Trevisan [ATCC 15380]) significantly. Thus, the following study would contribute effectively to considering phage MKP-1 as a potential candidate for phage therapy against Klebsiella infection. [ABSTRACT FROM AUTHOR]

Introduction: Real-life experience with imipenem/cilastatin/relebactam (IMI/REL) for the treatment of KPC-producing Klebsiella pneumoniae complex (KPCKp) and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa (DTR-PA) infections is herein described. Methods: Adult patients with KPC-Kp or DTR-PA infections who received =48 h of IMI/REL were included. Clinical and microbiological outcomes were retrieved through the medical records. Primary outcome was clinical cure. Secondary outcomes included mortality from infection onset and adverse effects attributable to IMI/REL. Results: We included 10 patients with different infections caused by DTRPA (n = 4), KPC-Kp [n = 5, of which 3 ceftazidime/avibactam-resistant (CTV-R KPC-Kp), 2 CTV susceptible (CTV-S KPC-Kp)] or both DTR-PA/KPC-Kp (n = 1) successfully treated with IMI/REL: 3 hospital-acquired pneumonia, 1 ventilatorassociated pneumonia, 2 skin and soft tissue infections, 1 osteomyelitis, 2 bloodstream infections, 1 complicated urinary tract infection. Clinical cure was achieved in all cases. No patients died and no side effect were reported. Discussion: We reported the preliminary real-life experience on the successful and safe use of IMI/REL for the treatment of KPC-Kp or DTR-PA complicated infections, including pneumonia and bone infections. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91–1.71) and 4.95 million (95% UI: 3.62–6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K. pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K. pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public–private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K. pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance is a global concern, linking bacterial genotype and phenotype. However, variability in antibiotic susceptibility within bacterial populations can lead to misclassification. Heteroresistance exemplifies this, where isolates have subpopulations less susceptible than the main population. This study explores heteroresistance in Gram-negative bacteria, distinguishing between carbapenem-sensitive isolates and stable heteroresistant isolates (SHIs). Methods: A total of 151 Gram-negative clinical isolates including Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii and Proteus mirabilis from various sources were included. Heteroresistant isolates and their stability were detected by disc-diffusion technique while genotypic analysis was carried out by PCR and efflux activity was assessed by ethidium bromide (EtBr)-agar cartwheel method. Results: A total of 51 heteroresistant subpopulations were detected, producing 16 SHIs upon stability-detection. Amplified resistance genes and EtBr-agar cartwheel method showed a significant difference between resistant subpopulations and their corresponding-sensitive main populations. Conclusion: Genotypic analysis confirmed that genetic mutation can lead to resistance development although the main populations were sensitive, thereby leading to treatment failure. This is a neglected issue which should be highly considered for better treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae is a Gram-negative pathogen that has become a threat to public health worldwide due to the emergence of hypervirulent and multidrug-resistant strains. Cell-surface components, such as polysaccharide capsules, fimbriae, and lipopolysaccharides (LPS), are among the major virulence factors for K. pneumoniae. One of the genes involved in LPS biosynthesis is the uge gene, which encodes the uridine diphosphate galacturonate 4-epimerase enzyme. Although essential for the LPS formation in K. pneumoniae, little is known about the mechanisms that regulate the expression of uge. Ferric uptake regulator (Fur) is an iron-responsive transcription factor that modulates the expression of capsular and fimbrial genes, but its role in LPS expression has not yet been identified. This work aimed to investigate the role of the Fur regulator in the expression of the K. pneumoniae uge gene and to determine whether the production of LPS by K. pneumoniae is modulated by the iron levels available to the bacterium. Results: Using bioinformatic analyses, a Fur-binding site was identified on the promoter region of the uge gene; this binding site was validated experimentally through Fur Titration Assay (FURTA) and DNA Electrophoretic Mobility Shift Assay (EMSA) techniques. RT-qPCR analyses were used to evaluate the expression of uge according to the iron levels available to the bacterium. The iron-rich condition led to a down-regulation of uge, while the iron-restricted condition resulted in up-regulation. In addition, LPS was extracted and quantified on K. pneumoniae cells subjected to iron-replete and iron-limited conditions. The iron-limited condition increased the amount of LPS produced by K. pneumoniae. Finally, the expression levels of uge and the amount of the LPS were evaluated on a K. pneumoniae strain mutant for the fur gene. Compared to the wild-type, the strain with the fur gene knocked out presented a lower LPS amount and an unchanged expression of uge, regardless of the iron levels. Conclusions: Here, we show that iron deprivation led the K. pneumoniae cells to produce higher amount of LPS and that the Fur regulator modulates the expression of uge, a gene essential for LPS biosynthesis. Thus, our results indicate that iron availability modulates the LPS biosynthesis in K. pneumoniae through a Fur-dependent mechanism. [ABSTRACT FROM AUTHOR]

The surge in mobile colistin-resistant genes (mcr) has become an increasing public health concern, especially in carbapenem-resistant Enterobacterales (CRE). Prospective surveillance was conducted to explore the genomic characteristics of clinical CRE isolates harbouring mcr in 2015–2020. In this study, we aimed to examine the genomic characteristics and phonotypes of mcr-8 and mcr-9 harbouring carbapenem-resistant K. pneumoniae complex (CRKpnC). Polymerase chain reaction test and genome analysis identified CRKpnC strain AMR20201034 as K. pneumoniae (CRKP) ST147 and strain AMR20200784 as K. quasipneumoniae (CRKQ) ST476, harbouring mcr-8 and mcr-9, respectively. CRKQ exhibited substitutions in chromosomal-mediated colistin resistance genes (pmrB, pmrC, ramA, and lpxM), while CRKP showed two substitutions in crrB, pmrB, pmrC, lpxM and lapB. Both species showed resistance to colistin, with minimal inhibitory concentrations of 8 µg/ml for mcr-8-carrying CRKP isolate and 32 µg/ml for mcr-9-carrying CRKQ isolate. In addition, CRKP harbouring mcr-8 carried blaNDM, while CRKQ harbouring mcr-9 carried blaIMP, conferring carbapenem resistance. Analysis of plasmid replicon types carrying mcr-8 and mcr-9 showed FIA-FII (96,575 bp) and FIB-HI1B (287,118 bp), respectively. In contrast with the plasmid carrying the carbapenemase genes, the CRKQ carried blaIMP-14 on an IncC plasmid, while the CRKP harboured blaNDM-1 on an FIB plasmid. This finding provides a comprehensive insight into another mcr-carrying CRE from patients in Thailand. The other antimicrobial-resistant genes in the CRKP were blaCTX-M-15, blaSHV-11, blaOXA-1, aac(6′)-Ib-cr, aph(3′)-VI, ARR-3, qnrS1, oqxA, oqxB, sul1, catB3, fosA, and qacE, while those detected in CRKQ were blaOKP-B-15, qnrA1, oqxA, oqxB, sul1, fosA, and qacE. This observation highlights the importance of strengthening official active surveillance efforts to detect, control, and prevent mcr-harbouring CRE and the need for rational drug use in all sectors. [ABSTRACT FROM AUTHOR]

Background: (R,R)-2,3-butanediol (BDO) is employed in a variety of applications and is gaining prominence due to its unique physicochemical features. The use of glycerol as a carbon source for 2,3-BDO production in Klebsiella pneumoniae has been limited, since 1,3-propanediol (PDO) is generated during glycerol fermentation. Results: In this study, the inactivation of the budC gene in K. pneumoniae increased the production rate of (R,R)-2,3-BDO from 21.92 ± 2.10 to 92.05 ± 1.20%. The major isomer form of K. pneumoniae (meso-2,3-BDO) was shifted to (R,R)-2,3-BDO. The purity of (R,R)-2,3-BDO was examined by agitation speed, and 98.54% of (R,R)-2,3-BDO was obtained at 500 rpm. However, as the cultivation period got longer, the purity of (R,R)-2,3-BDO declined. For this problem, a two-step agitation speed control strategy (adjusted from 500 to 400 rpm after 24 h) and over-expression of the dhaD gene involved in (R,R)-2,3-BDO biosynthesis were used. Nevertheless, the purity of (R,R)-2,3-BDO still gradually decreased over time. Finally, when pure glycerol was replaced with crude glycerol, the titer of 89.47 g/L of (R,R)-2,3-BDO (1.69 g/L of meso-2,3-BDO), productivity of 1.24 g/L/h, and yield of 0.35 g/g consumed crude glycerol was achieved while maintaining a purity of 98% or higher. Conclusions: This study is meaningful in that it demonstrated the highest production and productivity among studies in that produced (R,R)-2,3-BDO with a high purity in Klebsiella sp. strains. In addition, to the best of our knowledge, this is the first study to produce (R,R)-2,3-BDO using glycerol as the sole carbon source. [ABSTRACT FROM AUTHOR]

Introduction Methodology Results Conclusion Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2‐mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS.We undertook a cross‐sectional study of AFRS patients and non‐fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short‐read next‐generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full‐length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT).Thirty‐two AFRS and 29 non‐fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p = .07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p = .03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p = .005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p = .008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi.A low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia, Aspergillus and Curvularia. While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross‐kingdom pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Background: The emergence of plasmid-mediated mobile colistin resistance (mcr) gene poses a great challenge to the clinical application of polymyxins. To date, mcr-1 to mcr-10 have been found in animals, humans, and the environment. Among them, mcr-8 was first identified in Klebsiella pneumoniae (K. pneumoniae) of swine origin, and then mcr-8.1 to mcr-8.5 were successively identified. Notably, K. pneumoniae is the major host of the mcr-8 gene in both animals and humans. This study aims to explore the characteristics of K. pneumoniae strains carrying the mcr-8 gene and tmexCD1-toprJ1 gene cluster and investigate the correlation between these two antibiotic resistance genes. Methods: The isolates from the poultry farms and the surrounding villages were identified by mass spectrometer, and the strains positive for mcr-1 to mcr-10 were screened by polymerase chain reaction (PCR). The size of the plasmid and the antimicrobial resistance genes carried were confirmed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization, and the transferability of the plasmid was verified by conjugation experiments. Antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS) were used to characterize the strains. Results: Two K. pneumoniae isolates (KP26 and KP29) displaying polymyxin resistance were identified as mcr-8 gene carriers. Besides that, tigecycline-resistant gene cluster tmexCD1-toprJ1 was also found on the other plasmid which conferred strain resistance to tigecycline. Through epidemiological analysis, we found that the mcr-8 gene has dispersed globally, circulating in the human, animals, and the environment. Furthermore, our analysis suggests that the coexistence of mcr-8 and tmexCD1-toprJ1 on a single plasmid might evolved through plasmid recombination. Conclusions: Although the mcr-8 and tmexCD1-toprJ1 gene clusters in the two strains of K. pneumoniae in this study were on two different plasmids, they still pose a potential threat to public health, requiring close monitoring and further study. [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]

Background: Neonatal sepsis is still a global health concern as it contributes to a high burden of neonatal morbidity and mortality especially in developing countries. The aim of the study is to give an insight into neonatal sepsis: risk factors, sepsis types, clinical features, pathogen burden with their antibiotic sensitivities, and outcome of admission in our facility. The study was a prospective hospital-based study conducted over 10 months, October 2018–July 2019. Result: Of the 248 term neonates with features of sepsis enrolled in the study 94 (37.9%) were confirmed to have sepsis. Late-onset sepsis LOS (68%) was found to be the most common, and most of the neonates were delivered elsewhere. Clinical features were non-specific for both early-onset (EOS) and LOS and include fever, jaundice, poor suck, and depressed primitive reflexes. Infections were mostly caused by gram-negative bacteria, and while Staphylococcus aureus was the single most common isolate for both EOS and LOS. Antibiotic sensitivity was highest with ciprofloxacin for both EOS and LOS. Mortality was high at 14.9% and was mostly contributed to by Staphylococcus aureus infection. Conclusion: Neonatal sepsis is still a burden with mostly non-specific clinical features. The local prevalent organisms were Staphylococcus aureus, Enterobacter agglomerans and Klebsiella pneumonia with good antibiotic susceptibility to ciprofloxacin. Most presented with late-onset sepsis and therefore infection is likely to be community-acquired which to a great extent can be prevented with robust public health interventions. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2), such as empagliflozin, used to treat type 2 diabetes mellitus (DM), can increase the risk of infections, including urinary tract infections and osteomyelitis, especially in elderly patients. The use of SGLT2 inhibitors has been increasing dramatically in the last few years. Therefore, their adverse effects and complications have also been increasing. Herein, this report describes a 73-year-old man with type 2 DM treated with empagliflozin presenting with asymptomatic bacteriuria, vertebral osteomyelitis and iliopsoas abscess due to Klebsiella pneumoniae. Case Report: We report a 73-year-old man with DM on empagliflozin who presented with back pain of 1-month duration with elevated inflammatory markers. On lumbar spine magnetic resonance imaging (MRI), he was found to have lumbar vertebral osteomyelitis and left iliopsoas abscess. His symptoms were improved with abscess drainage and antimicrobial therapy. The source of infection was most likely asymptomatic bacteriuria, which may have been secondary to empagliflozin treatment, as evidenced by the urine, the blood, the bone and abscess cultures revealing growth of Klebsiella pneumoniae with the same susceptibility profile. Conclusions: This particular case reinforces the significance of potential complications of DM and SGLT2 inhibitors’ adverse effects, especially the increased risk of infections, and can aid clinicians in expanding the differential and enabling them to reach an accurate diagnosis and appropriate management. Although vertebral osteomyelitis is a less common cause of back pain, physicians should keep it in the differential diagnosis whenever a patient’s back pain is chronic and associated with motor weakness. [ABSTRACT FROM AUTHOR]

Background: The emergence of fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae is a growing concern. To investigate the mechanisms behind this resistance, we studied a total of 215 K. pneumoniae isolates from hospitals in Bushehr province, Iran, collected between 2017 and 2019. Antimicrobial susceptibility test for fluoroquinolones was determined. The presence of plasmid mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining region (QRDR) of gyrA and parC genes in ciprofloxacin-resistant K. pneumoniae isolates were identified by PCR and sequencing. Results: Out of 215 K. pneumoniae isolates, 40 were resistant to ciprofloxacin as determined by E-test method. PCR analysis revealed that among these ciprofloxacin-resistant isolates, 13 (32.5%), 7 (17.5%), 40 (100%), and 25 (62.5%) isolates harbored qnrB, qnrS, oqxA and aac(6')-Ib-cr genes, respectively. Mutation analysis of gyrA and parC genes showed that 35 (87.5%) and 34 (85%) of the ciprofloxacin-resistant isolates had mutations in these genes, respectively. The most frequent mutations were observed in codon 83 of gyrA and codon 80 of parC gene. Single gyrA substitution, Ser83→ Ile and Asp87→Gly, and double substitutions, Ser83→Phe plus Asp87→Ala, Ser83→Tyr plus Asp87→Ala, Ser83→Ile plus Asp87→Tyr, Ser83→Phe plus Asp87→Asn and Ser83→Ile plus Asp87→Gly were detected. In addition, Ser80→Ile and Glu84→Lys single substitution were found in parC gene. Conclusions: Our results indicated that 90% of isolates have at least one mutation in QRDR of gyrA orparC genes, thus the frequency of mutations was very significant and alarming in our region. [ABSTRACT FROM AUTHOR]

Background: K. pneumoniae liver abscess (KPLA) mostly involves the right lobe. We present a case of K. pneumoniae caudate liver abscess with invasive liver abscess syndrome (ILAS) was rarely identified. Case presentation: A 53-year-old man with elevated glycated hemoglobin with chills, rigors and a fever of five days. The patient presented with tachycardia and fever. Physical examination revealed tenderness over the right abdomen was elicited. In particular, the inflammatory markers were markedly elevated, and computerized tomography (CT) showed pulmonary abscess, pulmonary embolism and caudate liver abscess. The patient's sequential organ failure assessment (SOFA) score was 10 points. Klebsiella pneumoniae was isolated from sputum, urine and blood. With the suspicion of liver abscesses, ILAS and sepsis. The patient was successfully treated with antibiotics. He returned to close to his premorbid function. Conclusion: K. pneumoniae caudate liver abscess was rare. This is the first detailed report of K. pneumoniae caudate liver abscess with invasive liver abscess syndrome. Patients with cryptogenic K. pneumoniae liver abscess are advised to undergo an examination of intestinal barrier function. The study indicates that in patients with K. pneumoniae liver abscess, a caudate liver abscess size of ≤ 9.86 cm² may be characteristic of those suitable for conservative treatment of invasive liver abscess syndrome. [ABSTRACT FROM AUTHOR]

In this study, we define Szeged-like topological coindices in which formulas are constructed by a complement of a given graph. We introduce two new co-polynomials of two variables, denoted by $ \overline {SMP} ({x,y}) $ SMP ¯ (x , y) and $ \overline {SM{P_e}} ({x,y}) $ SM P e ¯ (x , y) briefly, to compute modifications and edge versions of these molecular descriptors. In order to the perform the effect of the topological descriptors, firstly we obtain the graph structures of five novel diamide derivatives which are considered potential agents for Alzheimer's disease. After completing the computation process of each index from some modifications of the polynomials mentioned above, we correlate the coindices values with the pMIC values of the compounds against three Gram-negative bacteria E. coli, P. aeruginosa, K. pneumoniae, and three Gram-positive bacteria E. faecalis, B. cereus, S. aeurus to predict the bioactivity properties. As a result of the QSAR analysis, we get good correlations among the bioactivity data and topologic values which shows the effectiveness of our newly created coindices. Also we give mathematical equations giving the best approach to predict the relation between the topological coindices and bioactivity properties obtained by exponential regression analysis. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae is a nosocomial pathogen that causes severe infections in immunocompromised patients. The aim of the study was to conduct a microbiological and clinical analysis of K. pneumoniae infections in children with malignancies or undergoing hematopoietic cell transplantation in Poland. Methods: We conducted a retrospective, multicenter study including children and adolescents under 19 years old treated between 2012 and 2021. We analyzed patients' characteristics, microbiological data, and the outcomes of antibiotic therapy. Results: A total of 9121 newly diagnosed children were treated for malignancy and 1697 pediatric patients underwent hematopoietic cell transplantation. K. pneumoniae infections were diagnosed in 527 patients. Their overall incidence was 4.86% in pediatric hematology and oncology patients and 4.95% in patients who underwent hematopoietic cell transplantation. The incidence of infection was higher in patients with acute leukemia than with solid tumors (7.8% vs. 4.1%; OR = 2.0; 95% CI = 1.6–2.4; p < 0.0001). The most frequent source of infection was in the urinary tract at 55.2%. More than 57% of K. pneumoniae strains were extended-spectrum β-lactamase-positive and almost 34% were multidrug-resistant. Infections with K. pneumoniae contributed to death in 3.22% of patients. Conclusions: K. pneumoniae is one of the most critical pathogens in children suffering from malignancies or undergoing hematopoietic cell transplantation. The incidence of multidrug-resistant K. pneumoniae strains is increasing and contributing to poor clinical outcome. [ABSTRACT FROM AUTHOR]

Urine pH reflects the functional integrity of the body and may influence the virulence of uropathogenic Escherichia coli and Klebsiella pneumoniae, the main causes of urinary tract infections (UTIs). This study evaluated the effects of acidic pH on the pathogenicity of uropathogenic E. coli and K. pneumoniae strains, in vitro and in vivo. Four uropathogenic E. coli and four K. pneumoniae strains were used. Biofilm formation, growth competition indices, motility, and adhesion and invasion of human renal cells were analyzed in media with acidic, neutral, and alkaline pH. A murine lower UTI model was used, with urine adjusted to acidic, neutral, or alkaline pH. At acidic pH, E. coli and K. pneumoniae exhibited higher bacterial concentrations in the kidneys and systemic symptoms, including bacteremia. Alkaline urine pH did not affect bacterial concentrations of any strain. In mice with UTIs caused by E. coli Nu14 and K. pneumoniae HUVR42 and acidic urine pH, histopathological studies of the kidneys showed acute inflammation affecting the urothelium and renal parenchyma, which are traits of acute pyelonephritis. These results indicate that acidic pH could increase the pathogenicity of E. coli and K. pneumoniae in murine models of lower UTI, promoting renal infection and acute inflammation. [ABSTRACT FROM AUTHOR]

Background: Neutrophilic myocarditis often stems from bacterial or fungal infections, and it is typically detectable through blood cultures or analyses of the primary infection site. However, research specifically addressing the morphological features of acute myocarditis in complex sepsis cases is scarce, with existing studies primarily dating back to the pre-antibiotic era. Methods: This study constitutes a retrospective and descriptive analysis encompassing 22 forensic cases. We collected data from forensic reports emphasising clinical details, disease history, gross observations, and histopathological findings. Results: The results show that using positive-air-pressure ventilation could be related to cardiac inflammation (45.45%, 10/22). Despite large-spectrum antibiotic therapy, the blood samples were positive for Staphylococcus aureus (MRSA strain), Klebsiella pneumoniae (ESBL strain), Acinetobacter baumannii, and Pseudomonas aeruginosa. Colonies developed in the myocardium of 36% of the patients (8/22), where 4 of them had septic emboli. Fungal myocarditis accompanied bacterial infections (2/8) and were unsuspected clinically. Background changes, such as interstitial fibrosis and arteriosclerosis, were associated with a greater degree of inflammation and septic embolism. Conclusion: Neutrophilic myocarditis in patients with emerging sepsis is linked to fatal virulent infections, where bacteria and/or fungi contaminate and impair the myocardium syncytium. Prolonged hospitalisation and positive-air-pressure ventilation may be a risk factor for this condition and needs further research. [ABSTRACT FROM AUTHOR]

Background Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of imipenemase (IMP)–encoding CPE among diverse Enterobacterales species between 2016 and 2019 across a London regional network. Methods We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE–positive patients. Genomes of IMP-encoding CPE isolates were overlaid with patient contacts to imply potential transmission events. Results Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, and Escherichia coli); 86% (72 of 84) harbored an IncHI2 plasmid carrying bla IMP and colistin resistance gene mcr-9 (68 of 72). Phylogenetic analysis of IncHI2 plasmids identified 3 lineages showing significant association with patient contacts and movements between 4 hospital sites and across medical specialties, which was missed in initial investigations. Conclusions Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of bla IMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multimodal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks. Summary This was an investigation, using integrated pathway networks and genomics methods, of the emergence of imipenemase-encoding carbapenemase-producing Enterobacterales among diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network, which was missed on routine investigations. [ABSTRACT FROM AUTHOR]

Background Klebsiella pneumoniae carbapenemase–producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection. Methods We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model. Results We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice. Conclusions Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence. [ABSTRACT FROM AUTHOR]

Objective: Piperacillin/tazobactam (PIP/TAZ) is used for the treatment of lower respiratory tract bacterial infections in children. This study was performed to evaluate if the current dosing regimen results in therapeutic drug concentrations. Patients and methods: Patients suspected or proven to have lower respiratory tract bacterial infection and administrated PIP/TAZ intravenously for a duration of no less than 0.5 h, q6h-q12h daily, were enrolled. Blood samples were collected, and PIP concentrations were determined by high-performance liquid chromatography. The individual predicted concentration of PIP was evaluated using the individual empirical Bayesian estimate method. The evaluated PK/PD targets included (1) 70% time when the predicted free drug concentration exceeds the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. Probability of target attainment (PTA) was assessed by the proportion of patients who reached the PK/PD targets. The PIP concentrations between different groups of patients were compared. Results: A total of 57 samples were collected from 57 patients with a median age of 2.26 years (0.17-12.58). For the PK/PD targets of 70% fT > MIC and 50% fT > 4× MIC for Pseudomonas aeruginosa and Klebsiella pneumoniae, the PTA was all 0. The median Cmin of PIP was significantly higher in infants than in children, and the median Cmin after administration in q8h was significantly higher than that after administration in q12h. Conclusion: The current dose regimen of PIP/TAZ leads to extremely low plasma concentrations in most children with lower respiratory tract bacterial infections. More optimized dosing regimens or better alternative therapies need to be further explored. [ABSTRACT FROM AUTHOR]

Background: The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear. Results: Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions. Conclusions: Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella's enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts. 2NMbQE6jVjinwr48dC_rNo Video Abstract [ABSTRACT FROM AUTHOR]

Objective: The emergence of clinical Klebsiella pneumoniae strains harboring acrAB-tolC genes in the chromosome, along with the presence of two repetitive tandem core structures for blaKPC-2 and blaCTX-M-65 genes on a plasmid, has presented a significant clinical challenge. Methods: In order to study the detailed genetic features of K. pneumoniae strain SC35, both the bacterial chromosome and plasmids were sequenced using Illumina and nanopore platforms. Furthermore, bioinformatics methods were employed to analyze the mobile genetic elements associated with antibiotic resistance genes. Results: K. pneumoniae strain SC35 was found to possess a class A betalactamase and demonstrated resistance to all tested antibiotics. This resistance was attributed to the presence of efflux pump genes, specifically acrAB-tolC, on the SC35 chromosome. Additionally, the SC35 plasmid p1 carried the two repetitive tandem core structures for blaKPC-2 and blaCTX-M-65, as well as blaTEM-1 with rmtB, which shared overlapping structures with mobile genetic elements as In413, Tn3, and TnAs3. Through plasmid transfer assays, it was determined that the SC35 plasmid p1 could be successfully transferred with an average conjugation frequency of 6.85 × 10-4. Conclusion: The structure of the SC35 plasmid p1 appears to have evolved in correlation with other plasmids such as pKPC2_130119, pDD01754-2, and F4_plasmid pA. The infectious strain SC35 exhibits no susceptibility to tested antibioticst, thus effective measures should be taken to prevent the spread and epidemic of this strain. [ABSTRACT FROM AUTHOR]

Most Escherichia coli isolates from humans do not utilize D-sucrose as a substrate for fermentation or growth. Previous work has shown that the Csc pathway allows some E. coli to utilize sucrose for slow growth, and this pathway has been engineered in E. coli W strains to enhance use of sucrose as a feedstock for industrial applications. An alternative sucrose utilization pathway, Scr, was first identified in Klebsiella pneumoniae and has been reported in some E. coli and Salmonella enterica isolates. We show here that the Scr pathway is native to an important subset of E. coli phylogroup B2 lineages that lack the Csc pathway but grow rapidly on sucrose. Laboratory E. coli strains derived from MG1655 (phylogroup A, ST10) are unable to utilize sucrose and lack the scr and csc genes, but a recombinant plasmid-borne scr locus enables rapid growth on and fermentation of sucrose. Genome analyses of Enterobacteriaceae indicate that the scr locus is widespread in other Enterobacteriaceae; including Enterobacter and Klebsiella species, and some Citrobacter and Proteus species. In contrast, the Csc pathway is limited mostly to E. coli, some Shigella species (in which csc loci are rendered non-functional by various mutations), and Citrobacter freundii. The more efficient Scr pathway likely has greater potential than the Csc pathway for bioindustrial applications of E. coli and other Enterobacteriaceae using sucrose as a feedstock. [ABSTRACT FROM AUTHOR]

Background: Deep neck infections (DNIs) can compromise the airway and are associated with high morbidity and mortality rates. Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia that is associated with several comorbidities. We compared the clinical characteristics of DNI patients with and without DM. Methods: This study recorded the relevant clinical variables of 383 patients with DNIs between November 2016 and September 2022; of those patients, 147 (38.38%) had DM. The clinical factors between DNI patients with and without DM were assessed. Results: Patients with DM were older (p < 0.001), had higher white blood cell counts (p = 0.029) and C-reactive protein levels (CRP, p < 0.001), had a greater number of deep neck spaces (p = 0.002) compared to patients without DM, and had longer hospital stays (p < 0.001). Klebsiella pneumoniae was cultured more frequently from patients with DM than those without DM (p = 0.002). A higher CRP level (OR = 1.0094, 95% CI: 1.0047–1.0142, p < 0.001) was a significant independent risk factor for DM patients with prolonged hospitalization. The lengths of hospital stays in patients with poorly controlled DM were longer than those with well-controlled DM (p = 0.027). Conclusions: DNI disease severity and outcomes were worse in patients with DM than those without DM. Antibiotics effective against Klebsiella pneumoniae should be used for DNI patients with DM. DNI patients with DM and high CRP levels had more prolonged hospitalizations. Appropriate blood glucose control is essential for DNI patients with DM. [ABSTRACT FROM AUTHOR]

Background: Metastatic brain abscesses caused by Klebsiella pneumoniae are extremely rare but life-threatening conditions. To depict a unique case of the middle-aged hypertensive man with an unusual presentation of metastatic brain abscesses originating from a pleural abscess caused by Klebsiella pneumoniae and subsequently leading to loss of consciousness (LOC). Case report: A 52-year-old Iranian man with a history of hypertension presented to the emergency department with a five-day history of worsening cough, high-grade fever, shortness of breath, chest pain, fatigue, and a productive cough. Laboratory tests revealed leukocytosis, elevated C-reactive protein, and respiratory alkalosis. A chest computed tomography scan confirmed pneumonia, and a brain scan revealed multiple hypodense lesions. Despite antibiotic therapy, the patient's condition worsened, leading to confusion, disorientation, and loss of consciousness. Magnetic resonance imaging revealed multiple ring-enhancing lesions, suggesting an abscess formation. Bronchial washings and BAL samples confirmed a lower respiratory tract infection. Cultures from the bronchial washings grew Klebsiella pneumoniae. Conclusions: Metastatic brain abscesses caused by Klebsiella pneumoniae are exceedingly rare but life-threatening conditions. Timely diagnosis and effective antimicrobial treatment are critical for patient outcomes. This case underscores the significance of recognizing atypical presentations of bacterial infections, as early detection and appropriate management can significantly impact patient outcomes. [ABSTRACT FROM AUTHOR]

Community‐acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. It also contributes significantly to hospital admissions, particularly in low‐income countries such as Ethiopia, where it accounts for major public health problems. This could be attributed to the increasing prevalence of antibiotic‐resistant pathogens in CAP patients. This study aimed to identify and assess the antibiotic resistance patterns of bacterial isolates from CAP patients at the Adama Hospital Medical College in Adama City, Ethiopia. A cross‐sectional study was conducted from November 10, 2022, to November 30, 2023. Demographic, clinical data, and sputum samples were collected from patients with CAP (n = 369). Sputum samples were subjected to standard microbiological procedures, including culture, Gram staining, and a panel of different biochemical tests for the identification of pathogenic bacterial isolates. The Kirby–Bauer disc diffusion method was used for drug susceptibility testing. Descriptive statistics were computed by using SPSS (version 26). Of the 369 patients with CAP, bacterial pathogens were identified in 31.7% (n = 117, 95% CI: 27.0%–36.7%). The most common isolates were Moraxella catarrhalis (n = 15; 12.8%), Staphylococcus aureus (n = 15; 12.8%), Klebsiella pneumoniae (n = 12; 10.3%), Escherichia coli (n = 11; 9.4%), Pseudomonas aeruginosa (n = 11; 9.4%), Enterobacter species (n = 11; 9.4%), and Citrobacter species (n = 11; 9.4%). Among the identified isolates, resistance rates were high in Enterobacteriaceae, followed by Gram‐positive bacteria, and non‐Enterobacteriaceae. Overall, 68 (58.1%) of the identified bacterial isolates were multidrug resistant (MDR), with K. pneumoniae accounting for the highest proportion of multidrug resistant isolates (91.7%), while P. aeruginosa accounted for the lowest proportion (9.1%) of MDR isolates. This study revealed a high prevalence (31.7%) of bacterial pathogens in CAP patients and higher (58.1%) MDR bacterial pathogens. Therefore, regular surveillance and monitoring systems are warranted for assessing predominant pathogens and antibiotic resistance patterns. [ABSTRACT FROM AUTHOR]

Patients with cancer have weakened immune systems, making them more vulnerable to infections. This study was carried out to determine the bacterial origins of enteric disorders in cancer patients and noncancer patients at the Oncology Department of Laquintinie Hospital in Douala. A cross‐sectional study was conducted from October 2021 to March 2023. Stool samples from 307 cancer patients with enteric disorders and 200 noncancer patients with enteric disorders were examined to diagnose the presence of bacteria using various techniques. Among all participants in this study, 62.13% were female and 37.87% were male. The average age of the participants was 46.38 ± 15.81 years, with a minimum age of 10 years and a maximum age of 84 years. The average age of participants was significantly higher (p < 0.000) in cancer patients (49.54 ± 14.65 years) compared to noncancer patients (41.53 ± 16.33 years). Proteus mirabilis, Proteus vulgaris, Salmonella typhi, Enterobacter cloacae, Klebsiella pneumoniae, Yersinia intemedia, and Klebsiella oxytoca were more frequently isolated in cancer patients than in noncancer patients, with the respective percentages of 56.25% versus 43.75%, 50.00% versus 50.00%, 61.66% versus 38.34%, 66.66% versus 33.34%, 72.22% versus 27.78%, 80.00 versus 20.00%, and 100% versus 0.00%. Most isolates were sensitive to imipenem (IMP), gentamicin (GEN), and amikacin (AMK). Proteus vulgaris, the most prevalent isolate, showed significantly high resistance (with p < 0.05) in cancer patients compared to noncancer patients at amoxicillin/clavuranic acid (AMC) (89.13% versus 41.30%), ceftriaxone (CTR) (63.04% versus 39.13%), ciprofloxacin (CIP) (65.22% versus 34.18%), and tetracycline (TET) (93.48% versus 63.04%). Multidrug resistance was observed in cancer patients compared to noncancer patients for Klebsiella pneumoniae (85.00% versus 60.00%), Salmonella typhi (84.62% versus 60.00%), and Klebsiella oxytoca (86.49% versus 43.48%). The increase in the number of Gram‐negative infections among cancer patients, as shown in the present study, highlights the need for broad‐spectrum therapy and effective planning of control programs to reduce bacterial diseases among cancer patients. [ABSTRACT FROM AUTHOR]

Microbes maneuver strategies to become incessant and biofilms perfectly play a role in scaling up virulence to cause long-lasting infections. The present study was designed to assess the use of an eco-friendly formulation of functionalized silver nanoparticles generated from Mentha longifolia leaf extract (MℓE) for the treatment of biofilm-producing microbes. Nanoparticles synthesized using MℓE as a reducing agent were optimized at different strengths of AgNO3 (1 mM, 2 mM, 3 mM, and 4 mM). Synthesis of M. longifolia silver nanoparticles (MℓAgNPs) was observed spectrophotometrically (450 nm) showing that MℓAgNPs (4 mM) had the highest absorbance. Various techniques e.g., Fourier transforms Infrared spectroscopy (FTIR), Dynamic light scattering (DLS), zeta potential (ZP), X-ray Diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) were used to characterize MℓAgNPs. In the present study, the Kirby—Bauer method revealed 4mM was the most detrimental conc. of MℓAgNPs with MIC and MBC values of 0.62 μg/mL and 1.25 μg/mL, 0.03 μg/mL and 0.078 μg/mL, and 0.07 μg/mL and 0.15 μg/mL against previously isolated and identified clinical strains of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, respectively. Moreover, the MℓAgNP antibiofilm activity was examined via tissue culture plate (TCP) assay that revealed biofilm inhibition of up to 87.09%, 85.6%, 83.11%, and 75.09% against E. coli, P. aeruginosa, K. pneumonia, and S. aureus, respectively. Herbal synthesized silver nanoparticles (MℓAgNPs) tend to have excellent antibacterial and antibiofilm properties and are promising for other biomedical applications involving the extrication of irksome biofilms. For our best knowledge, it is the first study on the use of the green-synthesized silver nanoparticle MℓAgNP as an antibiofilm agent, suggesting that this material has antibiotic, therapeutic, and industrial applications. [ABSTRACT FROM AUTHOR]

Background: The emergence of multi-drug-resistant Klebsiella pneumoniae (MDR-KP) represents a serious clinical health concern. Antibiotic resistance and virulence interactions play a significant role in the pathogenesis of K. pneumoniae infections. Therefore, tracking the clinical resistome and virulome through monitoring antibiotic resistance genes (ARG) and virulence factors in the bacterial genome using computational analysis tools is critical for predicting the next epidemic. Methods: In the current study, one hundred extended spectrum β-lactamase (ESBL)-producing clinical isolates were collected from Mansoura University Hospital, Egypt, in a six-month period from January to June 2022. One isolate was selected due to the high resistance phenotype, and the genetic features of MDR-KP recovered from hospitalized patient were investigated. Otherwise, the susceptibility to 25 antimicrobials was determined using the DL Antimicrobial Susceptibility Testing (AST) system. Whole genome sequencing (WGS) using Illumina NovaSeq 6000 was employed to provide genomic insights into K. pneumoniae WSF99 clinical isolate. Results: The isolate K. pneumoniae WSF99 was phenotypically resistant to the antibiotics under investigation via antibiotic susceptibility testing. WGS analysis revealed that WSF99 total genome length was 5.7 Mb with an estimated 5,718 protein-coding genes and a G + C content of 56.98 mol%. Additionally, the allelic profile of the WSF99 isolate was allocated to the high-risk clone ST147. Furthermore, diverse antibiotic resistance genes were determined in the genome that explain the high-level resistance phenotypes. Several β-lactamase genes, including blaCTX−M−15, blaTEM−1, blaTEM−12, blaSHV−11, blaSHV−67, and blaOXA−9, were detected in the WSF99 isolate. Moreover, a single carbapenemase gene, blaNDM−5, was predicted in the genome, positioned within a mobile cassette. In addition, other resistance genes were predicted in the genome including, aac(6')-Ib, aph(3')-VI, sul1, sul2, fosA, aadA, arr-2, qnrS1, tetA and tetC. Four plasmid replicons CoIRNAI, IncFIB(K), IncFIB(pQil), and IncR were predicted in the genome. The draft genome analysis revealed the occurrence of genetic mobile elements positioned around the ARGs, suggesting the ease of dissemination via horizontal gene transfer. Conclusions: This study reports a comprehensive pathogenomic analysis of MDR-KP isolated from a hospitalized patient. These findings could be relevant for future studies investigating the diversity of antimicrobial resistance and virulence in Egypt. [ABSTRACT FROM AUTHOR]

Background. Bacterial bloodstream infections (BSIs) are the leading cause of sepsis‐related morbidity and mortality worldwide. The emergence and spread of antimicrobial resistance (AMR) in bacteria is also a growing global concern. As a result, data on bacterial profile and their antibiogram are essential for strategies to contain drug resistance, improve the quality of patient care, and strengthen health systems. Methods. Retrospective data from bacteriological results of blood samples of BSI‐suspected patients from 2018 to 2021 were collected using a data collection sheet. Standard bacteriological techniques were followed during sample collection, culture preparation, bacterial identification, and antibiotic susceptibility testing (AST). We used Epi Info version 7 to enter and clean the data and then exported it to SPSS version 26 for analysis. Logistic regression models were used to measure the association between variables. A p value <0.05 with a 95% confidence interval was considered as statistically significant. Result. Of the total 2,795 blood culture records, 455 (16.3%) were culture positive for bacteria, with Klebsiella pneumoniae (26%) and Staphylococcus aureus (24.6%) being the leading isolates. The isolates were highly resistant to common antibiotics, with more than 80% of them being resistant to ceftriaxone and penicillin. Moreover, about 43% of isolates were multidrug resistant (MDR), with Klebsiella pneumoniae (65.5%), Acinetobacter species (56.7%), and Citrobacter species (53.8%) being the most common MDR isolates. Age and diagnosis year were significantly associated with the presence of bacterial BSIs (p value <0.05). Conclusion. Bacterial BSI and AMR were growing concerns in the study area. Bacteremia was more common in children under the age of five, and it decreased as the patient's age increased. The alarming rate of AMR, such as MDR blood isolates, calls for periodic and continuous monitoring of antibiotic usage in the study area. [ABSTRACT FROM AUTHOR]

Background: ESBL-producing Escherichia coli pose a growing health risk in community and healthcare settings. We investigated the resistome, virulome, mobilome, and genetic relatedness of multidrug-resistant (MDR) E. coli isolates from patients and their environment in a Ghanaian teaching hospital. Materials and methods: Twenty-three MDR ESBL-producing or carbapenem-resistant E. coli isolates from a collection of MDR Gram-negative bacteria (GNB) from patients and environments were selected for genomic analyses. Whole genome sequencing and bioinformatics tools were used to analyze genomic characteristics and phylogeny. Results: The prevalence and incidence of rectal carriage of ESBL E. coli among patients were 13.65% and 11.32% respectively. The β-lactamase genes, blaTEM−1B (10 isolates) and blaCTX−M−15 (12 isolates) were commonly associated with IncFIB plasmid replicons and co-occurred with aminoglycoside, macrolide, and sulfamethoxazole/trimethoprim resistance. Insertion sequences, transposons, and class I integrons were found with blaCTX−M−15. Carriage and environmental isolates carried multiple virulence genes, with terC being the most prevalent in 21 isolates. Seventeen sequence types (STs) were identified, including a novel ST (ST13846). Phylogenetic analysis grouped the isolates into four main clusters, with one outlier. High genetic relatedness was observed between two carriage isolates of ST940 and between a carriage isolate and an environmental isolate of ST648. Isolates with different STs, collected at different times and locations, also showed genetic similarities. Conclusion: We identified ESBL-producing E. coli with diverse genomic characteristics circulating in different hospital directorates. Clonal relatedness was observed among isolates from patients and the environment, as well as between different patients, suggesting transmission within and between sources. [ABSTRACT FROM AUTHOR]

The bacterium Klebsiella pneumoniae (Kp) was the primary pathogen of hospitalacquired infection, but the current detection method could not rapidly and conveniently identify Kp. Recombinase polymerase amplification (RPA) was a fast and convenient isothermal amplification technology, and the clustered regularly interspaced short palindromic repeats (CRISPR) system could rapidly amplify the signal of RPA and improve its limit of detection (LOD). In this study, we designed three pairs of RPA primers for the rcsA gene of Kp, amplified the RPA signal through single-strand DNA reporter cleavage by CRISPR/Cas12a, and finally analyzed the cleavage signal using fluorescence detection (FD) and lateral flow test strips (LFTS). Our results indicated that the RPA-CRISPR/Cas12a platform could specifically identify Kp from eleven common clinical pathogens. The LOD of FD and LFTS were 1 fg/µL and 10 fg/µL, respectively. In clinical sample testing, the RPA-CRISPR/Cas12a platform was consistent with the culture method and qPCR method, and its sensitivity and specificity were 100% (16/16) and 100% (9/9), respectively. With the advantages of detection speed, simplicity, and accuracy, the RPA-CRISPR/Cas12a platform was expected to be a convenient tool for the early clinical detection of Kp. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in the use of bacteriophages, which have great potential as antimicrobial agents but also carry the risk of inducing resistance. The objective of the present study was to minimize the development of phage resistance in Klebsiella pneumoniae strains by inhibiting quorum sensing (QS) and thus demonstrate the role of QS in regulating defense mechanisms. Results: Cinnamaldehyde (CAD) was added to K. pneumoniae cultures to inhibit QS and thus demonstrate the role of the signaling system in regulating the antiphage defense mechanism. The QS inhibitory activity of CAD in K. pneumoniae was confirmed by a reduction in the quantitative expression of the lsrB gene (AI-2 pathway) and by proteomic analysis. The infection assays showed that the phage was able to infect a previously resistant K. pneumoniae strain in the cultures to which CAD was added. The results were confirmed using proteomic analysis. Thus, anti-phage defense-related proteins from different systems, such as cyclic oligonucleotide-based bacterial anti-phage signaling systems (CBASS), restriction-modification (R-M) systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) system, and bacteriophage control infection (BCI), were present in the cultures with phage but not in the cultures with phage and CAD. When the QS and anti-phage defense systems were inhibited by the combined treatment, proteins related to phage infection and proliferation, such as the tail fiber protein, the cell division protein DamX, and the outer membrane channel protein TolC, were detected. Conclusion: Inhibition of QS reduces phage resistance in K. pneumoniae, resulting in the infection of a previously resistant strain by phage, with a significant increase in phage proliferation and a significant reduction in bacterial growth. QS inhibitors could be considered for therapeutic application by including them in phage cocktails or in phage-antibiotic combinations to enhance synergistic effects and reduce the emergence of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)−165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice. The function of circular RNA (circRNA) in the innate immune system is not fully understood. Here the authors characterise a cell division cycle 42 (CDC42)-165aa protein encoded by circRNA circCDC42 that promotes Pyrin-inflammasome mediated pyroptosis in Klebsiella pneumoniae (KP) infection and inhibition of circCDC42 reduces KP induced lung injury in mice. [ABSTRACT FROM AUTHOR]

Introduction: The rapid spread of plasmid-mediated tet(X4) conferring high tigecycline resistance poses a significant threat to public health. Escherichia coli as the most common pathogen which carries tet(X4) has been widely disseminated in China. Thus, comprehensive investigations are required to understand the mechanism of transmission of tet(X4)-positive E. coli. Methods: In this study, a total of 775 nonduplicate samples were collected in Guangdong, China from 2019 to 2020. We screened for tet(X4)-positive E. coli by PCR amplification and species identification. Furthermore, we analyzed the phylogenetics and genetic context of tet(X4)-positive E. coli through wholegenome sequencing and long-reads sequencing. Results: Overall, 146 (18.84%) tet(X4)-positive E. coli were isolated, comprising 2 isolates from humans and 144 isolates from pigs. The majority of tet(X4)-positive E. coli exhibited resistance to multiple antibiotics but all of them were susceptible to amikacin and colistin. Phylogenetic analysis showed that ST877, ST871, and ST195 emerged as the predominant sequence types in tet(X4)-positive E. coli. Further analysis revealed various genetic environments associated with the horizontal transfer of tet(X4). Notably, a 100-kbp large fragment insertion was discovered downstream of tet(X4), containing a replicon and a 40-kbp gene cluster for the bacterial type IV secretion system. Discussion: The high colonization rate of tet(X4)-positive E. coli in animals suggests that colonization as a key factor in its dissemination to humans. Diverse genetic context may contribute to the transfer of tet(X4). Our findings underline the urgent need for controlling the spread of plasmid-mediated tigecycline resistance. [ABSTRACT FROM AUTHOR]

Biological agents are getting a noticeable concern as efficient eco-friendly method for nanoparticle fabrication, from which fungi considered promising agents in this field. In the current study, two fungal species (Embellisia spp. and Gymnoascus spp.) were isolated from the desert soil in Saudi Arabia and identified using 18S rRNA gene sequencing then used as bio-mediator for the fabrication of silver nanoparticles (AgNPs). Myco-synthesized AgNPs were characterized using UV–visible spectrometry, transmission electron microscopy, Fourier transform infrared spectroscopy and dynamic light scattering techniques. Their antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae were investigated. In atrial to detect their possible antibacterial mechanism, Sodium dodecyl sulfate (SDS-PAGE) and TEM analysis were performed for Klebsiella pneumoniae treated by the myco-synthesized AgNPs. Detected properties of the fabricated materials indicated the ability of both tested fungal strains in successful fabrication of AgNPs having same range of mean size diameters and varied PDI. The efficiency of Embellisia spp. in providing AgNPs with higher antibacterial activity compared to Gymnoascus spp. was reported however, both indicated antibacterial efficacy. Variations in the protein profile of K. pneumoniae after treatments and ultrastructural changes were observed. Current outcomes suggested applying of fungi as direct, simple and sustainable approach in providing efficient AgNPs. [ABSTRACT FROM AUTHOR]

Objectives: Genomic surveillance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is crucial for virulence, drug-resistance monitoring, and outbreak containment. Methods: Genomic analysis on 87 KPC-Kp strains isolated from 3 Northern Italy hospitals in 2019-2021 was performed by whole genome sequencing (WGS), to characterize resistome, virulome, and mobilome, and to assess potential associations with phenotype resistance and clinical presentation. Maximum Likelihood and Minimum Spanning Trees were used to determine strain correlations and identify potential transmission clusters. Results: Overall, 15 different STs were found; the predominant ones included ST307 (35, 40.2%), ST512/1519 (15, 17.2%), ST20 (12, 13.8%), and ST101 (7, 8.1%). 33 (37.9%) KPC-Kp strains were noticed to be in five transmission clusters (median number of isolates in each cluster: 5 [3-10]), four of them characterized by intra-hospital transmission. All 87 strains harbored Tn4401a transposon, carrying blaKPC-3 (48, 55.2%), blaKPC-2 (38, 43.7%), and in one case (1.2%) blaKPC-33, the latter gene conferred resistance to ceftazidime/avibactam (CZA). Thirty strains (34.5%) harbored porin mutations; of them, 7 (8.1%) carried multiple Tn4401a copies. These strains were characterized by significantly higher CZA minimum inhibitory concentration compared with strains with no porin mutations or single Tn4401a copy, respectively, even if they did not overcome the resistance breakpoint of 8 ug/mL. Median 2 (IQR:1-2) virulence factors per strain were detected. The lowest number was observed in ST20 compared to the other STs (p<0.001). While ST307 was associated with infection events, a trend associated with colonization events could be observed for ST20. Conclusions: Integration of genomic, resistance score, and clinical data allowed us to define a relative diversification of KPC-Kp in Northern Italy between 2019 and 2021, characterized by few large transmission chains and rare inter-hospital transmission. Our results also provided initial evidence of correlation between KPC-Kp genomic signatures and higher MIC levels to some antimicrobial agents or colonization/infection status, once again underlining WGS's importance in bacterial surveillance. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTI) by antibiotic resistant and virulent K. pneumoniae are a growing concern. Understanding the genome and validating the genomic profile along with pangenome analysis will facilitate surveillance of high-risk clones of K. pneumoniae to underpin management strategies toward early detection. The present study aims to correlate resistome with phenotypic antimicrobial resistance and virulome with pathogenicity in Klebsiella spp. The present study aimed to perform complete genome sequences of Klebsiella spp. and to analyse the correlation of resistome with phenotypic antimicrobial resistance and virulome with pathogenicity. To understand the resistome, pangenome and virulome in the Klebsiella spp, the ResFinder, CARD, IS Finder, PlasmidFinder, PHASTER, Roary, VFDB were used. The phenotypic susceptibility profiling identified the uropathogenic kp3 to exhibit multi drug resistance. The resistome and in vitro antimicrobial profiling showed concordance with all the tested antibiotics against the study strains. Hypermucoviscosity was not observed for any of the test isolates; this phenotypic character matches perfectly with the absence of rmpA and magA genes. To the best of our knowledge, this is the first report on the presence of ste, stf, stc and sti major fimbrial operons of Salmonella enterica serotype Typhimurium in K. pneumoniae genome. The study identifies the discordance of virulome and virulence in Klebsiella spp. The complete genome analysis and phenotypic correlation identify uropathogenic K. pneumoniae kp3 as a carbapenem-resistant and virulent pathogen. The Pangenome of K. pneumoniae was open suggesting high genetic diversity. Diverse K serotypes were observed. Sequence typing reveals the prevalence of K. pneumoniae high-risk clones in UTI catheterised patients. The study also highlights the concordance of resistome and in vitro susceptibility tests. Importantly, the study identifies the necessity of virulome and phenotypic virulence markers for timely diagnosis and immediate treatment for the management of high-risk K. pneumoniae clones. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectivesMethodsResultsConclusionKlebsiella pneumoniae (KP) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs).To investigate incidence, antimicrobial resistance and risk factors for mortality of KP BSIs in East China.A retrospective study of patients with KP BSIs was conducted in a tertiary care hospital from 2018 to 2022. Medical records of all hospitalised patients with KP BSIs were reviewed and analysed. The incidence, antimicrobial resistance and mortality of KP BSIs were evaluated. The Kaplan-Meier method was used to plot survival curves and logistic regression was used to analyse risk factors for crude 30-day mortality.A total of 379 inpatients with KP BSIs were enrolled. The incidence of patients with KP BSIs was fluctuating between 4.77 and 9.40 per 100,000 patient-days. The crude 30-day mortality rate of these patients was 26.39%. Of the 379 KPisolates, 197 (51.98%) were carbapenem-resistant (CR) and 252 (66.49%) were multidrug-resistant (MDR). All isolates showed the lowest resistance to tigecycline (13.77%) and polymyxin B (14.61%). Cases with MDR/CR isolates had significantly longer length of hospital stay, higher crude 30-day mortality and medical costs than non-MDR/non-CR isolates. Age, CR phenotype, paracentesis, indwelling central venous catheter (CVC), use of carbapenems, tetracyclines, polymyxins B, and irrational empiric treatment were independently associated with crude 30-day mortality.MDR/CR KP BSIs are associated with increased mortality, healthcare costs and prolonged hospitalisation. Patients with advanced age, CR phenotype, paracentesis, CVC, exposure to some antibiotics, and irrational empirical antibiotic treatment are at higher mortality risk. [ABSTRACT FROM AUTHOR]

Objective: We explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks. Methods: 932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and blaKPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems. Results: We found a significant inverse correlation between the presence of CRISPR and R-M systems and blaKPC plasmids in K. pneumoniae, especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in blaKPC-IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder blaKPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of blaKPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity. Conclusions: Our results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP. [ABSTRACT FROM AUTHOR]

Background: Infections due to Citrobacter species are increasingly observed in hospitalized patients and are often multidrug-resistant. Yet, the magnitude and burden of Citrobacter spp. resistance in the hospital setting have not been reported. We aimed to evaluate the epidemiology of Citrobacter spp. infections among hospitalized patients, their main resistance patterns and Citrobacter spp. involvement in hospital outbreaks. Methods: We conducted a systematic review and meta-analysis of published literature (PROSPERO registration Jan-2023, CRD42023390084). We searched Embase, Medline and grey literature for studies on hospitalized patients diagnosed with Citrobacter spp. infections, and nosocomial outbreaks due to Citrobacter spp. published during the years 2000–2022. We included observational, interventional, surveillance studies and outbreak reports. Outcomes of interest were the frequency of Citrobacter spp. infections among hospitalized patients and 3rd generation cephalosporin and/or carbapenem resistance percentages in these infections. We used random-effects models to generate pooled outcome estimates and evaluated risk of bias and quality of reporting of outbreaks. Results: We screened 1609 deduplicated publications, assessed 148 full-texts, and included 41 studies (15 observational, 13 surveillance and 13 outbreak studies). Citrobacter spp. urinary tract- and bloodstream infections were most frequently reported, with Citrobacter freundii being the main causative species. Hospital-acquired infection occurred in 85% (838/990) of hospitalized patients with Citrobacter infection. After 2010, an increasing number of patients with Citrobacter spp. infections was reported in observational studies. Pooled frequency estimates for Citrobacter spp. infections could not be generated due to lack of data. The pooled prevalence of ESBL and carbapenemase producers among Citrobacter isolates were 22% (95%CI 4–50%, 7 studies) and 18% (95%CI 0–63%, 4 studies), respectively. An increased frequency of reported Citrobacter outbreaks was observed after 2016, with an infection/colonization ratio of 1:3 and a case-fatality ratio of 7% (6/89 patients). Common outbreak sources were sinks, toilets, contaminated food and injection material. Implemented preventive measures included environmental cleaning, isolation of positive patients and reinforcement of hand hygiene. Only seven out of 13 outbreaks (54%) were definitively controlled. Conclusion: This review highlights the clinical importance of endemic and epidemic Citrobacter spp. in healthcare settings. As an emerging, multidrug‑resistant nosocomial pathogen it requires heightened awareness and further dedicated surveillance efforts. [ABSTRACT FROM AUTHOR]

Background: Colistin is regarded as the final option for treating Gram-negative bacteria that are resistant to several drugs. A common resistance mechanism for colistin in Klebsiella pneumoniae is mgrB gene inactivation. Inactivation of mgrB activates the PhoPQ which upregulates the PmrAB leading to resistance by lipopolysaccharide modification. Colistin resistance has been reported in Klebsiella pneumoniae still studies related to molecular mechanisms of this resistance are lacking. Aim: Role of mgrB in colistin resistance Methods: In this study, eight colistin-resistant clinical K. pneumoniae were selected, and performed broth microdilution was followed by a rapid polymyxin nordmann poirel test for screening of colistin resistance. PCR was performed for different types of mcr genes. MgrB was amplified and sequenced. Quantitative real-time PCR was performed for mgrB, PmrA, PmrB, PhoP, and PhoQ genes. Furthermore, clonal analysis by enterobacterial repetitive intergenic consensus PCR was done. Results: Colistin minimum inhibitory concentration of 4 µg/ml has been shown by the isolates. No mcr gene was detected. Positive amplification for the mgrB gene was found in all the isolates. Sequence analysis of the mgrB gene found no mutation however, higher expression in the mgrB, PmrA, PmrB, PhoP, and PhoQ genes of all the eight colistin-resistant isolates could be observed when the isolates were exposed to colistin and Mg2+ pressure. Clonal analysis exhibited seven different haplotypes of K. pneumoniae. Conclusion: This study provides firsthand knowledge about molecular mechanisms of colistin resistance in K. pneumoniae in this geographical area. Enhancement in mgrB expression in the presence of colistin and Mg2+ pressure regardless of any mutation has a remarkable impact in the context of colistin resistance mechanisms in clinical K. pneumoniae. [ABSTRACT FROM AUTHOR]

Acalypha is a valuable genus that has interesting pharmaceutical applications. This study investigated the phytochemical composition and thin layer chromatography (TLC) profile, as well as the antioxidant and antibacterial activities of the ethanolic leaf extract of Acalypha angatensis Blanco, Fl. Filip. Qualitative phytochemical screening revealed the presence of tannins, phenolics, flavonoids, saponins, steroids, and triterpenoids. Nutrient analysis showed that potassium and calcium contents were at 1.499 g/100g and 1.38 g/100g, respectively. The determination of the total phenolic content (TPC) showed that this species has an average of 282.24 ± 3.56 mg GAE/g and a total flavonoid content (TFC) of 36.24 ± 3.77 mg QE/g of dried extract. These values are higher than other Acalypha species that have already been studied. Antioxidant activity, measured using the DPPH antioxidant assay, showed a concentration-dependent radical scavenging effect, with an IC50 of 34.02 µg/mL. The ethanolic extract exhibited substantial antibacterial activity against the gram-positive bacteria, Enterococcus faecium (NCTC 12204) and MRSA (ATCC 33592), with a minimum inhibitory concentration (MIC) of 4 mg/mL. Higher concentrations (>20 mg/mL) were needed for inhibition of the gram-negative strains (Klebsiella pneumoniae and Enterobacter cloacae). These results suggest that A. angatensis has good antioxidant and antibacterial activities against gram positive bacteria, supporting its use in traditional medicine. This species has the potential to be a raw material for pharmaceutical and nutraceutical products. [ABSTRACT FROM AUTHOR]

This paper investigates the efficacy of photodynamic activation (PDA) using herbal extract in combination with low-power laser treatment against both gram-positive (Streptococcus mutans) and gram-negative (Klebsiella pneumoniae) bacteria. The study explores the threats posed by these bacteria and highlights their resistance mechanisms. Various experiments, including colony formation assays, minimal inhibitory concentration tests, and bacterial viability assays, were conducted to assess the antibacterial effects of PDA in the presence and absence of laser irradiation. Additionally, spectroscopic analysis of the herbal extract was performed to elucidate their composition and potential synergistic interactions with PDA. [ABSTRACT FROM AUTHOR]

This study synthesizes nano composite (Ea-AgNPs-Si) using Euphorbia antisyphilitica(Ea), employing it as a poultry reformer, sorptive material, pathogen suppressor and sprouting catalyst. Characterization involved XRD, SEM, TEM, Zetasizer, UV-Visible and FT-IR techniques. Ea-AgNPs-Si adopted a face centered cubic arrangement with average crystalline size of 20.34 nm. Zeta potential assessed stability. PDI value of Ea-AgNPs-Si nanocomposite is 1 indicating the polydisperse distribution. SEM revealed flower shape (Ea-AgNPs-Si), ranging 70-100 nm in diameter. The disc diffusion method reveals that Ea-AgNPs-Si exhibits potent antimicrobial activity at 60 μl against Staphylococcus aureus, Actinomycetes, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa, attributed to its deep diffusion and release of silver ions and silica. It is unequivocally evident from the data that Langmuir isotherm and Pseudo II order model provides a superior fit approaching R² value as 0.9972, 0.9461, 0.916, 0.9827, 0.9455 and 0.9534 for LA(I), LA(II), LA(III) describing monolayer chemisorption onto surfaces with uniform adsorption energies than Freundlich, Tempkin and BET models, which is synonymous with the results obtained from R2011a Matlab neuro solution. Through final germination (FG) we concluded that among 130 corriandrum seeds sown,109 sprouted in 20 days. Higher germination index (GI) T2>T4>T1>T3> expedited that Ea-AgNPs-Si shall be used as a nutrient to boost the growth of crops. Ordinarily, it necessitates a span of 45 days for a single batch to attain harvest readiness; however, through our efforts, we have accomplished this feat in a mere 20 days. Henceforth, Ea-AgNPs-Si shall be employed as a Poultry Reformer, Pathogen Suppressor, Sprouting Catalyst and Adsorbent. [ABSTRACT FROM AUTHOR]

Objectives 1. To determine the etiological profile of suspected cases of bacteremia 2. To establish the antibiotic susceptibility pattern of bacterial isolates Materials and Methods: The retrospective study was carried out from January 2022 to December 2022 at Islamabad International Hospital. A total of 639 blood culture isolates were processed manually onto blood agar, chocolate agar, MacConkey’s agar, and bile-esculin agar and were identified on their morphological appearance using gram staining. Isolates were further identified at the species level using the Analytic Profile Index (API). Antibiotic susceptibility testing was performed using the Disk Diffusion method as per Clinical and Laboratory Standards Institute guidelines (M-100 Version 2021) Results: Amongst 639 blood culture isolates, only 66 (10.32%) were culture-positive. Prevalent gram-negative bacilli included Salmonella typhi (n= 19) and Escherichia coli (n= 8) whilst Enterococcus (n=4), and Staphylococcus aureus (n=4) were the predominant gram-positive cocci. Salmonella typhi and S. aureus showed 100% resistance to ciprofloxacin whilst enterococcus displayed 75% resistance. Overall, all strains (n=6) of K. pneumoniae and 63% of E. coli showed resistance to over 4 antibiotics. Conclusion: Gram-negative bacteria were the main cause of BSIs, where the predominant microorganism was S. typhi. Remarkably all S. typhi isolates were completely resistant to ciprofloxacin. [ABSTRACT FROM AUTHOR]

Introduction Nanoniosomes are multi-layered vesicles that are used as one of the new targeted drug delivery systems today. In this study, the extract of the Artemisia deserti L. was encapsulated in nanonisomes and its antimicrobial and cytotoxic effects were studied. Materials and Methods In this experimental study, nanonisomes containing the extract of Artemisia deserti were synthesized and their appearance and structural characteristics were investigated. After confirming the structure, its antimicrobial and anti-biofilm effects on Klebsiella pneumoniae pathogenic strains were investigated. Finally, in order to check the biocompatibility, the colorimetric method of nanonisomes cytotoxicity was used on HFF normal fibroblast cell line. Results The results of niosomes synthesis showed that the synthesized nanoniosomes have a spherical structure and have a size of 125.4 ± 29.3 nm. In addition, FTIR results confirmed the synthesis of niosomes. The results of the antimicrobial effects showed that the nanoniosomes containing the medicinal extract have more significant antimicrobial and anti-biofilm effects than the extract alone, so that the minimum inhibitory concentration (MIC) of the niosomes was reduced between 2 and 4 times. Also, the cytotoxicity results showed that the synthesized niosomes do not have significant cytotoxicity effects. Conclusion In general, the results of this study showed that nanonisomes can act as a suitable drug delivery system for medicinal plant extract to increase the amount of antimicrobial and anti-biofilm effects. Therefore, with further studies, this system can be used as an optimal drug delivery system for medicinal purposes. [ABSTRACT FROM AUTHOR]

Aquaculture is one of the major economic activities in India, providing livelihoods and nutritional security to millions of people. In recent times, fish diseases have come to the limelight resulting in significant economic losses. We aimed to identify pathogenicity and virulence profiling of thirty-six pathogenic bacterial strains isolated from diseased Labeo rohita in the district of Hooghly, West Bengal, India. The bacterial strains were characterized through a comprehensive approach involving the examination of morphological features, biochemical properties, amplification, and sequencing of the 16S rRNA, species-specific genes, and virulence genes. Considering the prevalence frequency, virulence potential, and statistical significance Aeromonas hydrophila and Pseudomonas aeruginosa were selected for a survival assay followed by the examination of histopathological features to elucidate their effects. The identified bacterial isolates were arranged based on their predominance frequency, i.e., Aeromonas hydrophila (25%), Aeromonas veronii (22%), Pseudomonas aeruginosa (22%), Enterococcus faecalis (14%), Klebsiella pneumoniae (6%), Staphylococcus aureus (6%) and Escherichia coli (5%). Sixteen virulence-associated genes related to pathogenicity were amplified across the thirty-six isolates; aer, alt, lip and hlyA for A. hydrophila; exoS, lasB, toxA, oprL and phzM for P. aeruginosa; entB, fimH and uge in K. pneumoniae; aer in A. veronii; hlyA in E. coli; hlb in S. aureus and gelE for E. faecalis. The log-probit analysis revealed that A. hydrophila was notably more pathogenic than P. aeruginosa, as indicated by its lower lethal dose of 1.5x104 CFU/mL. Additionally, histological examination revealed notable pathological changes, including tissue degeneration, inflammatory cell infiltration and vacuolation observed in the liver, kidney, gill and intestine of the challenged fish. We highlighted several potent aquatic microbial pathogens in order to manage and prevent such aquacultural maladies. [ABSTRACT FROM AUTHOR]