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The accelerated dispersion of multidrug-resistant (MDR) Escherichia coli due to the production of extended-spectrum β-lactamases (ESBLs) or AmpC enzymes has been noted in Egypt, presenting a serious treatment challenge. In this study, we investigate the prevalence of ESBLs and AmpC enzymes among 48 E. coli isolates collected from patients with urinary tract infections admitted to a teaching hospital in Alexandria. Phenotypic and genotypic methods of detection are conducted. Isolates producing both enzymes are tested for the mobilization of their genes by a broth mating experiment. Whole genome sequencing (WGS) is performed for isolate EC13655. The results indicate that 80% of the isolates are MDR, among which 52% and 13% were ESBL and AmpC producers, respectively. Conjugation experiments fail to show the mobilization of blaCMY-2 in EC13655, which was chosen for WGS. In silico analysis reveals that the isolate belongs to a ST410-H24Rx high-risk clone. It coharbors the ESBL-encoding genes blaCTX-M-15, blaTEM-1, blaOXA-1 and blaNDM-5 on an IncFIA/IncFIB/IncFII/IncQ1 multireplicon plasmid. The chromosomal location of blaCMY-2 is detected with a flanking upstream copy of ISEcp1. This chromosomal integration of blaCMY-2 establishes the stable maintenance of the gene and thus, necessitates an imperative local surveillance to reduce further spread of such strains in different clinical settings. [ABSTRACT FROM AUTHOR]

Recently, Egypt has witnessed the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae, which has posed a serious healthcare challenge. The accelerated dissemination of blaCTX-M genes among these MDR K. pneumoniae, particularly blaCTX-M-14 and blaCTX-M-15, have been noted. In this study, we investigated the occurrence of blaCTX-M-IV among K. pneumoniae recovered from the laboratory of a major hospital in Alexandria. The 23 tested isolates showed an MDR phenotype and the blaCTX-M-IV gene was detected in ≈22% of the isolates. The transformation of plasmids harboring blaCTX-M-IV to chemically competent cells of Escherichia coli DH5α was successful in three out of five of the tested blaCTX-M-IV-positive isolates. Whole genome sequencing of K22 indicated that the isolate belonged to the high-risk clone ST383, showing a simultaneous carriage of blaCTX-M-14 on IncL/M plasmid, i.e., pEGY22_CTX-M-14, and blaCTX-M-15 on a hybrid IncHI1B/IncFIB plasmid, pEGY22_CTX-M-15. Alignment of both plasmids revealed high similarity with those originating in the UK, Germany, Australia, Russia, China, Saudi Arabia, and Morocco. pEGY22_CTX-M-15 was a mosaic plasmid that demonstrated convergence of MDR and virulence genes. The emergence of such a plasmid with enhanced genetic plasticity constitutes the perfect path for the evolution of K. pneumoniae isolates causing invasive untreatable infections especially in a country with a high burden of infectious diseases such as Egypt. Therefore there is an imperative need for countrywide surveillances to monitor the prevalence of these superbugs with limited therapeutic options. [ABSTRACT FROM AUTHOR]

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) having an increased rate of fluoroquinolone resistance is currently noted in Egypt necessitating the implication of new strategies to restrain the rapid spread of this resistance. The approach of repurposing could present a solution to this problem. In the current study, the efficacy of the antifungal agent, caspofungin, in increasing the susceptibility of MRSA isolated from Alexandria Main University Hospital (AMUH) to a novel fluoroquinolone, zabofloxacin, was investigated. A percentage of 30.3% of tested isolates were found to be resistant to zabofloxacin. Upon treatment with subinhibitory concentration of caspofungin, these isolates had their zabofloxacin minimum inhibitory concentration values decreased by a range varying from 2- to 32-fold. Proteomic approach was performed to provide insights into the involved mechanism of caspofungin sensitization. The profiles of cellular proteins generated by electrophoretic techniques varied between treated and untreated MRSA samples with polymorphism values ranging from 82.4 to 94.1%. Homology was detected between 1,3-beta-glucan synthase (the fungal target enzyme of caspofungin) and SdrM, a multidrug efflux pump in S. aureus. This homology was elaborated by immunoblotting analysis which showed downregulation of SdrM efflux pump proteins. The percentage of reduction in the SdrM proteins expression level varied from 18 to 61%. Caspofungin succeeded in sensitizing zabofloxacin-resistant MRSA clinical isolates by blocking the action of SdrM efflux pump and inhibiting its extrusion. Further research is urgently required to endorse the repositioning of caspofungin as an agent used in combination with zabofloxacin in the management of MRSA infections with higher efficiency. [ABSTRACT FROM AUTHOR]

Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a-n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a-n was assessed using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against a panel of Gram-negative bacteria, Gram-positive bacteria and fungi. Most of the synthesized compounds 5a-n showed weak activities against Gram-negative bacteria while compounds 5b and 5c exhibited good activities against Gram-positive bacteria. On the other hand, compound 5j emerged as the most active compound towards Candida albicans (C. albicans), with an MIC value of 3.9 µg/mL, and compound 5g as the most active congener towards Asperagillus niger (A. niger), with an MIC value of 15.6 µg/mL. Moreover, compound 5h manifested the best anti-P. notatum effect, with an MIC value of 7.8 µg/mL, making it equipotent with compound 5g. [ABSTRACT FROM AUTHOR]

In an attempt to reach better treatment of skin infections, gel formulations containing Cefotaxime (CTX) were prepared. The gel was formulated using Carbopol 934 (C934), Hydroxypropyl Methylcellulose 4000 (HPMC 4000), Carboxymethylcellulose Sodium (Na CMC), Pectin (PEC), Xanthan Gum (XG), or Guar Gum (GG). Thirteen different formulas were prepared and characterized physically in terms of color, syneresis, spreadability, pH, drug content, and rheological properties. Drug-excipients compatibility studies were confirmed by FTIR and then in vitro drug release study was conducted. In vitro and in vivo antibacterial activities of CTX were studied against wound pathogens such as, Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), using either pure drug or Fucidin® cream as control. F13 provides better spreadability compared to F1 (XG) or F11 (HPMC). Moreover, the release of the drug from hydrogel F13 containing C934 was slower and sustained for 8 h. Stability study revealed that, upon storage, there were no significant changes in pH, drug content, and viscosity of the gels. Also, F13 showed the larger inhibition zone and highest antibacterial activity among other formulations. Histological analysis demonstrated that after single treatment with F13 gel formulation, a noticeable reduction in microbial bioburden occurred in case of both Gram positive and Gram negative bacterial isolates. [ABSTRACT FROM AUTHOR]

Anti-Candida activities of certain new oximes 4a-d and their respective aromatic esters 5a-l are reported. The tested compoundsyl)-1- phenylpropan-1-one O-4-chlorobenzoyl oxime emerged as the most active congener, with a MIC value of 0.0054 μmol/mL being more potent tha 4a-d and 5a-l exhibited better anti-Candida profiles than fluconazole. Compound 5j, namely (E)-3-(1H-imidazol-1-n both fluconazole (MIC > 1.6325 μmol/mL) and miconazole (MIC value = 0.0188 μmol/mL) as a new anti-Candida albicans agent. [ABSTRACT FROM AUTHOR]

N-(2-{[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamides (5a–h) and N-[2-(2-{[2-(acetylamino)phenyl](oxo)acetyl}hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides (5i–l) were synthesized and characterized with different analytical tools. N-Acetylisatines 4a–d were subjected to ring opening at their C2 carbons with the aid of different indole-bearing hydrazides 3a,b and 7 to afford the respective glyoxylamides 5a–l. The antimicrobial activity of the target compounds 5a–l was assessed with the aid of Diameter of the Inhibition Zone (DIZ) and Minimum Inhibitory Concentration (MIC) assays against a panel of Gram-positive and Gram-negative bacteria and certain fungal strains. The antimicrobial screening revealed that Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans are the most sensitive microorganisms towards the synthesized compounds 5a–l. In addition, compounds 5c and 5h emerged as the most active congeners towards Staphylococcus aureus and Candida albicans, respectively. Molecular docking studies revealed the possible binding mode of compounds 5c and 5h to their target proteins. [ABSTRACT FROM AUTHOR]

Synthesis, characterization, and anti-Candida activity of ({(E)-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]amino}oxy)(4-nitrophenyl)methanone (4) are reported. Compound 4 showed anti-Candida albicans activity (MIC = 0.6862 µmol/mL) being nearly 5-fold more potent than the gold standard antifungal drug, fluconazole (MIC > 3.265 µmol/mL), on the clinical isolates of Candida albicans. Single crystal X-ray structure of the title compound 4 confirmed its assigned (E)-configuration. The compound crystallizes in the triclinic, P-1 (no. 2), a = 6.4633 (1) Å, b = 11.1063 (2) Å, c = 12.9872 (2) Å, α = 67.650 (1)°, β = 86.415 (1)°, γ = 86.776 (1)°, V = 860.01 (3)ų, Z = 2, R(F) = 0.046, wR(F²) = 0.139, T = 296 K. The crystal structure is stabilized by weak intermolecular C--H•••O hydrogen interactions. [ABSTRACT FROM AUTHOR]