Search

Background: The perennial plant Hypericum perforatum is widely distributed around the world. It has been used for many years in conventional medicine to treat a variety of illnesses, including stress, mild to moderate depression, and minor injuries. This study examined the antimicrobial activity of the H. perforatum total extract and its fractions (n-hexane, ethyl acetate, chloroform, and aqueous) against multi-drug-resistant (MDR) isolates that were gathered from clinical samples, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis , Escherichia coli , and Klebsiella pneumonia ., Materials and Methods: Aerial parts of H. perforatum were collected and extracted using various solvents and were tested versus different isolated bacterial species. The inhibition zone of tested extracts was detected using an agar diffusion assay, and MICs were measured. Phytochemical analysis of promising H. perforatum extract was done using LC-ESI-MS/MS. Ultrastructure examination for the most altered bacteria used transmission electron microscopy. Antioxidant assays were done using DPPH and ABTS scavenging capacity methods. Cytotoxicity was reported versus Vero cells., Results: Different extracts of H. perforatum showed promising antibacterial activity against the pathogens. While the subfractions of the total extract were observed to show lesser inhibition zones and higher MIC values than the total extract of H. perforatum against MDR strains, the total extract of H. perforatum demonstrated the most potent antimicrobial action with an inhibition zone range of 17.9-27.9 mm. MDR- K. pneumoniae was discovered to be the most susceptible strain, which is consistent with the antibacterial inhibitory action of H. perforatum whole extract. Additionally, after treatment at the minimum inhibitory concentration (MIC 3.9  μ g/ml), the transmission electron microscope showed alterations in the ultrastructure of the K. pneumoniae cells. Methanol extract from H. perforatum has a CC 50 value of 976.75  μ g/ml., Conclusion: Future inhibitors that target MDR strains may be revealed by these findings. Additionally, the extracts that were put to the test demonstrated strong antioxidant effects as shown by DPPH or ABTS radical-scavenging assays., Competing Interests: The authors claim to have no conflicts of interest., (Copyright © 2023 Momen M. Sherif et al.)

Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids ( 5a-m and 9a-c ) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d , 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49-7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.

Herein, molecular hybridization strategy was utilized in the design of new benzosuberone-thiazole derivatives. The structures of the synthesized hybrids were determined on the basis of elemental and spectral analyses. These compounds were evaluated for their antibacterial activities against five bronchitis causing bacteria in addition to their anti-tubercular activities. Most compounds revealed promising activities. Amongst active compounds, benzosuberone-dithiazole derivatives 22a and 28 with MIC value = 1.95 µg/ml against H. influenza, M. pneumonia, and B. pertussis displayed four times the activity of ciprofloxacin (MIC = 7.81 µg/ml) against H. influenza, twice the activity of ciprofloxacin (MIC = 3.9 µg/ml) against M. pneumonia and were equipotent to ciprofloxacin against B. pertussis (MIC = 1.95 µg/ml). Additionally, benzosuberone-dithiazole derivatives 22a and 27 were the most promising anti-tubercular among the tested compounds with MIC values of 0.12 and 0.24 µg/ml, respectively against sensitive M. tuberculosis in addition to high activity against resistant strain of M. tuberculosis (MIC = 0.98 and 1.95 µg/ml, respectively) compared to isoniazid (MIC = 0.12 µg/ml against sensitive M. tuberculosis and no activity against resistant M. tuberculosis). Cytotoxicity study of the active dithiazole derivatives 22a, 27 and 28 against normal human lung cells (WI-38) indicated their high safety profile as showed from their high IC 50 values (IC 50  = 107, 74.8, and 117 µM, respectively). Furthermore, DNA gyrase supercoiling and ATPase activity assays showed that 22a, 27 and 28 have the potential to inhibit DNA gyrase at low micromolar levels (IC 50  = 3.29-15.64 µM). Molecular docking analysis was also carried out to understand the binding profiles of the synthesized compounds into the ATPase binding sites of bacterial and mycobacterial DNA gyraseB., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective : Inappropriate use of antibiotics is one of the main causes of antibiotic resistance around the globe. The present study was aimed to assess the knowledge, attitude, and practices toward antibiotics and antibiotic resistance among consumers. Methods : A cross-sectional study was conducted from April 2019 to September 2019. The participants visiting community pharmacies to buy the antibiotics were approached by data collectors. The descriptive analysis, Kruskal Wallis, and Mann-Whitney statistical tests were used for data analysis through SPSS. Results : 399 participants at three pharmacies with male (n = 352, 88.2%), age (years) group between 34 to 41(n = 138, 34.6%), uneducated (n = 128, 32.1%), and higher education (n = 76, 19.0%) level of the participants were noted. Poor to moderate knowledge were observed; participants were unaware of the risk and misuse of antibiotics at all three pharmacies. By some means, a positive attitude noted, but the storage of antibiotics at home (Median = 2, IQR = 2) was preferred to use when needed. Most of the respondents didn't follow the actual dosage regimen as prescribed (n = 266, 66.7%, p < 0.05). Conclusion : A lack of knowledge and malpractices toward antibiotics use among consumers were observed. Education and awareness of the public about antibiotic resistance is the need of the hour.

Prickly pear fruit peel constitutes a high percentage of the fruit and could be a natural, economic agro-industrial waste of potential use in the nutraceutical industry. This study aimed to isolate and characterize the main constituents of the fruit peel and evaluate its antibacterial activity. A methanol extract was successively fractionated using hexane, chloroform and ethyl acetate. The n-hexane fraction was evaluated for its fatty acid content using gas chromatography mass spectrometry (GC-MS), revealing linolenic acid (omega-3) as the major fatty acid (60.56%), while an ethyl acetate fraction was analyzed using ultra-performance liquid chromatography electrospray tandem mass spectrometry (UPLC-ESI-MS/MS), resulting in the identification of 6 phenolic acids and 9 flavonoids, where caffeic acid (43.69%) and quercetin (14%) were found the most abundant. The ethyl acetate fraction was subjected to column chromatography, resulting in the isolation of four flavanols, viz. astragalin (1), quercetin 5,4'-dimethyl ether (2), isorhamnetin-3-O-glucoside (3) and isorhamnetin (4). Antibacterial evaluation revealed that the EtOAc fraction is the most potent active fraction against the selected pneumonia pathogens, and quercetin 5,4'-dimethyl ether (2) is the most active among the isolated compounds. Virtual docking of the isolated compounds showed promising in silico anti-quorum sensing efficacy, indicating that they could represent natural antibacterial agents. These findings indicate that the unused waste from prickly pear fruits contains valuable constituents that have beneficial potential against some pneumonia pathogens.

Streptococcus mutans has been considered as the major etiological agent of dental caries, mostly due to its arsenal of virulence factors, including strong biofilm formation, exopolysaccharides production, and high acid production. Here, we present the antivirulence activity of fatty acids derived from the endophytic fungus Arthrographis kalrae isolated from Coriandrum sativum against Streptococcus mutans . The chemical composition of the fatty acids was analyzed by gas chromatography-mass spectrometry GC-MS and revealed nine compounds representing 99.6% of fatty acids, where unsaturated and saturated fatty acids formed 93.8% and 5.8 % respectively. Oleic and linoleic acids were the major unsaturated fatty acids. Noteworthy, the fatty acids at the concentration of 31.3 mg L -1 completely inhibited Streptococcus mutans biofilm, and water insoluble extracellular polysaccharide production in both polystyrene plates, and tooth model assay using saliva-coated hydroxyapatite discs. Inhibition of biofilm correlated significantly and positively with the inhibition of water insoluble extracellular polysaccharide (R=1, p <0.0001). Furthermore, Arthrographis kalrae fatty acids at a concentration of 7.8 mg L -1 exhibited acidogenesis-mitigation activity. They did not show bactericidal activity against Streptococcus mutans and cytotoxic activity against human oral fibroblast cells at the concentration used. On the other hand, saliva-coated hydroxyapatite discs treated with sub-minimum biofilm inhibitory concentration of fatty acids showed disturbed biofilm architecture with a few unequally distributed clumped matrices using fluorescence microscopy. Our findings revealed that the intracellular fatty acid arrays derived from endophytic Arthrographis kalrae could contribute to the biofilm-preventing alternatives, specifically Streptococcus mutans biofilms.

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.

Ammi majus L.; Family Apiaceae; is a plant indigenous to Egypt. Its fruits contain bioactive compounds such as furanocoumarins and flavonoids of important biological activities. An endophytic fungus was isolated from the fruits and identified as Aspergillus amstelodami (MK215708) by morphology, microscopical characterization, and molecular identification. To our knowledge this is the first time an endophytic fungus has been isolated from the fruits. The antimicrobial activity of the Ammi majus ethanol fruits extract (AME) and fungal ethyl acetate extract (FEA) were investigated, where the FEA showed higher antimicrobial activity, against all the tested standard strains. Phytochemical investigation of the FEA extract yielded five prenylated benzaldehyde derivative compounds isolated for the first time from this species: Dihydroauroglaucin (1), tetrahydroauroglaucin (2), 2-(3,6-dihydroxyhepta-1,4-dien-1-yl)-3,6-dihydroxy-5-(dimethylallyl)benzaldehyde (3), isotetrahydroauroglaucin )4), and flavoglaucin (5). Structure elucidation was carried out using (1H- and 13C-NMR). Fractions and the major isolated compound 1 were evaluated for their antimicrobial and antibiofilm activity. Compound 1 showed high antimicrobial activity against Escherichia coli with minimum inhibitory concentration (MIC) = 1.95 µg/mL, Streptococcus mutans (MIC = 1.95 µg/mL), and Staphylococcus aureus (MIC = 3.9 µg/mL). It exhibited high antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) = 7.81 µg/mL against Staphylococcus aureus and Escherichia coli biofilms and MBIC = 15.63 µg/mL against Streptococcus mutans and Candida albicans and moderate activity (MBIC = 31.25 µg/mL) against Pseudomonas aeruginosa biofilm. This reveals that dihydroauroglaucin, a prenylated benzaldehyde derivative, has a broad spectrum antimicrobial activity. In conclusion, it was observed that the MICs of the FEA are much lower than that of the AME against all susceptible strains, confirming that the antimicrobial activity of Ammi majus may be due to the ability of its endophytic fungi to produce effective secondary metabolites.

Background: Antimicrobial resistance (AMR) is a global threat and the antimicrobial stewardship program (ASP) is a globally used tool to combat AMR. There is little information on the views among Pakistani physicians regarding AMR and the benefits of hospital antimicrobial stewardship implementation. This study was designed to explore the physicians' views about ASP. Methods: Qualitative face-to-face and telephonic interviews were conducted by using purposive sampling method with 22 physicians working in seven tertiary care public hospitals of Punjab, Pakistan. All interviews were audio recorded and transcribed verbatim. Qualitative software was used, and a thematic analysis was conducted. Results: Three broad themes were identified: (1) the growing concern of antimicrobial resistance in Pakistan, (2) the role(s) of healthcare professionals in antibiotic prescribing, and (3) managing antibiotic resistance in hospitals. Inadequate resources, poor healthcare facilities, and insufficiently trained medical staff were the major hurdles in ASP implementation in Pakistan. Conclusions: Our study found a poor familiarity of hospital ASP among physicians working in public sector tertiary care teaching hospitals, and a number of distinct themes emerged during this study that could be helpful in establishing the concept of hospital ASP in Pakistan. Overall, physicians showed a positive attitude towards the enforcement of ASP in all healthcare settings, including teaching hospitals.

Background: Diabetes mellitus is the most common disease in Egypt. In this context, Beta vulgaris subspecies cicla L. var. flavescens is an edible plant that has been used in traditional medicine as a therapy for treating some diseases., Objectives: The current study was performed to evaluate the antibacterial and potential anti-diabetic activities of different extracts and isolated flavone C-glycoside compounds isolated from Beta vulgaris subspecies cicla L. var. flavescens leaves., Methods: Phytochemical investigation of n-butanol extract led to the isolation of five phytoconstituents. Their structures were determined by spectroscopic tools, including 1D-NMR (1H- & 13C-NMR) and 2D-NMR (HMQC & HMBC) besides the comparison of the data with the literature. The extracts and phytoconstituents were evaluated in vitro for their activity against some bacterial pathogens, which represent prominent human pathogens, particularly in hospital settings. The antibacterial activity was examined against three Gram-positive bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis & Enterococcus faecalis) and five Gram-negative ones (Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae, Proteus mirabilis & Salmonella typhimurium) relative to Ciprofloxacin as a reference drug. Furthermore, the in vitro antidiabetic activity (Type II) was evaluated using the alpha-glucosidase inhibitory assay., Results: Five flavone C-glycosides namely; Apigenin 8-C-β-D-glucopyranoside (vitexin) (1), 2''-Oxylopyranosylvitexin (2), acacetin 8-C-β-D-glucopyranoside (3), acacetin 8-C-α-L-rhamnoside (4), and 6,8-di-C-β-D-glucopyranosylapigenin (vecinin-II) (5) were isolated from n-butanol extract of B. vulgaris subspecies cicla L. var. flavescens. Compound 1 showed a promising antibacterial activity against most of the test bacterial strains with respect to the minimum inhibitory concentration values (MIC) ranged from 1.95 to 15.63 µg ml-1. On the other hand, compounds 1 and 3 demonstrated superior antidiabetic activities with IC50 values of 35.7 and 42.64 µg ml-1, respectively, while an inferior potential antidiabetic activity was recorded for compound 4 (IC50 = 145.5 µg ml-1) in comparison with Acarbose as a reference drug., Conclusion: B. vulgaris L. is an edible plant, which could be used as a natural source of antibiotic and hypoglycemic drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In connection with our research program on the development of novel anti-tubercular candidates, herein we report the design and synthesis of two different sets of indole-thiazolidinone conjugates (8a,b; 11a-d) and (14a-k; 15a-h). The target compounds were evaluated for their in vitro antibacterial and antifungal activities against selected human pathogens viz. Staphylococcus aureus (Gram positiveve), Pseudomonas aeruginosa, Escherichia coli (Gram negative), Mycobacterium tuberculosis (Acid-fast bacteria), Aspergillus fumigates and Candida albicans (fungi). Moreover, eukaryotic cell-toxicity was tested via an integrated ex vivo drug screening model in order to evaluate the selective therapeutic index (SI) towards antimicrobial activity when microbes are growing inside primary immune cells. Also, the cytotoxicity towards a panel of cancer cell lines and human lung fibroblast normal cell line, WI-38 cells, was explored to assure their safety. Compound 15b emerged as a hit in this study with potent broad spectrum antibacterial (MIC: 0.39-0.98 μg/mL) and antifungal (MIC: 0.49-0.98 μg/mL) activities, in addition to its ability to kill mycobacteria M. aurum inside an infected macrophage model with good therapeutic window. Moreover, compound 15b displayed promising activity towards resistant bacteria strains MRSA and VRE with MIC values equal 3.90 and 7.81 μg/mL, respectively. These results suggest compound 15b as a new therapeutic lead with good selectivity for further optimization and development., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Non-prescription use of antibiotics in children is an important public health problem. We aimed to investigate primary caregivers' knowledge, attitudes, and practices of antibiotics use among children in urban China., Methods: Knowledge, attitudes, and practices regarding antibiotics use in children were assessed through a cross-sectional questionnaire survey of 4200 caregivers of children under-7 years from three cities in China. Data were analyzed using descriptive statistics and multivariate analysis., Results: Caregivers' knowledge gaps and undesirables attitudes regarding appropriate use of antibiotics were identified. 48.2% of respondents reported non-prescription use of antibiotics for children in the past 6 months. The most common sources of antibiotics used without a prescription are community pharmacies and leftovers. Storing antibiotics at home and caregivers' supportive attitude were positively and significantly associated with non-prescription use of antibiotics in children, while significant inverse associations were found for caregiver's knowledge of prescription-only regulation on antibiotics sales at community pharmacies., Conclusions: There was a high proportion of primary caregivers self-medicate antibiotics for children in urban China, despite their insufficient knowledge about antibiotic use. Public health initiatives are needed such as public education campaigns and stricter government regulation of antibiotic use and availability in community pharmacies.

The increased development of highly resistant bacterial strains and tuberculosis, constitute a serious public health threat, highlighting the urgent need of novel antibacterial agents. In this work, two novel series of nicotinic acid hydrazone derivatives (6a-r) and quinolone hydrazide derivatives (12a-l) were synthesized and evaluated as antimicrobial and antitubercular agents. The synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antimycobacterial activities. Compounds 6f and 6p bearing the 3,4,5- (OCH3)3 and 2,5-(OCH3)2 benzylidene motifs were the most potent and as antibacterial, antifungal (MIC: 0.49-1.95 μg/mL) and (MIC: 0.49-0.98 μg/mL) respectively and antimycobacterial activity (MIC = 0.76 and 0.39 μg/mL) respectively. Besides, several derivatives, 6e, 6h, 6l-6o, 6q, 6r, 12a, 12b, 12e, 12h, 12k and 12l, exhibited significant antibacterial and antifungal activities with MIC values ranging from 1.95 to 7.81 μg/mL, they also displayed excellent to good activity against Mycobacterium tuberculosis with MIC range from 0.39 to 3.12 μg/mL. In addition, some of the most active compounds were tested for cytotoxic activities against human lung fibroblast normal cells (WI-38) and displayed low toxicity. Moreover, 2D-QSAR models to characterize the descriptors controlling the observed activities, were generated and validated., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background Resistance to antibiotics is a major threat to global health and general public play a significant role in the fight against antimicrobial resistance. Objective The present study aimed to identify the knowledge, attitudes, and practice of the general public towards antibiotic use in China. Setting Randomly selected parks in three cities of western, central and eastern China: Xi'an, Changsha, and Nanjing. Method A cross-sectional survey was conducted on a sample of 1400 residents, from January to June 2015. Main outcome measures Knowledge, attitudes and practices scores toward self-medication with antibiotics and compliance with antibiotic regimens. Results The response rate was 86.0% (n = 1204). Only 192 (19.5%) respondents gained a score of 3 or above, and the maximum score of 4, reflecting poor knowledge towards antibiotics. Just over half (54.8%) of respondents incorrectly believed antibiotics were effective against viral infections and only one-third (34.3%) knew that antibiotics were not anti-inflammatories. Nearly half of the respondents (49.0%) had changed the dosage when taking antibiotics, 35.6% switched to another class, 33.4% had not finished the full treatment course and over 60.0% kept leftover antibiotics for future use. Almost half of the respondents (45.7%) stated they had used antimicrobials during the last 6 months and 64.4% of them had self-medicated. Conclusion This study identified serious misconceptions regarding antibiotics use in the Chinese general public. Effective interventions should be developed to provide practical and appropriate advice to effect behaviour change within this population.

Background: Group B Streptococcus (GBS) is a cause of neonatal sepsis, pneumonia, and meningitis that can lead to neurological sequelae in infants less than 3 months of age. The GBS disease burden is not known in China, therefore it cannot receive major attention. The main objectives of this study are the evaluation of the incidence of neonatal GBS infection, GBS case-fatality ratio, its serotypes and genotypes, bacterial resistance, clinical treatment and outcomes in China., Methods: We are conducting a nation-wide, population-based, multi-center, prospective, observational cohort study in China from May 2016 to December 2017. Eighteen large urban tertiary care hospitals from 16 provinces were selected that cover the eastern, southern, western, northern and central regions of China. Meanwhile, we retrospectively collected data and GBS strains from January 2015 to April 2016 from selected hospitals. The incidence rate per 1000 live births will be defined as the total number of confirmed GBS cases born in the selected hospitals divided by the number of live births in the hospitals during the study period. All GBS cases detected in selected hospitals will be used to calculate the case-fatality ratio and for the typing analysis. GBS isolates will be serotyped using the Strep-B-Latex® rapid latex agglutination test for serotyping of Group B streptococci. Multi-locus sequence typing (MLST) will be performed by sequencing the internal fragments of seven house-keeping genes. Antimicrobial susceptibility will be tested per interpretive standards established by the Clinical and Laboratory Standards Institute. The presence of the common resistance genes ermA, ermB, mefA, tetI, tetO and tetM will be tested by PCR., Discussion: We are conducting the first national study to estimate the invasive GBS disease burden and antimicrobial resistance of GBS among infants in China. Study findings will provide important evidence for improving clinical practice to ensure timely diagnosis of GBS disease and decisions for preventive measures. Surveillance of antimicrobial resistance will promote the rational use of antimicrobials., Trial Registration: The study was retrospectively registered at http://clinicaltrials.gov on June 13, 2016. It was granted a registration number of "NCT02812576".

RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Sugar hydrazones from 2-hydrazinoquinoline, 2-hydrazino-6-methyllepidine, 6-chloro-2-hydrazino lepidine, 7-chloro-2-hydrazinolepidine, and 7-chloro-2-hydrazino-3-nitroquinoline were prepared. Their acetylation, benzoylation, periodate oxidation, oxidation with lead tetraacetate and bromination have been investigated. The antimicrobial activities of the hydrazones were evaluated. Some compounds showed moderate activity.