22 research outputs found
Resensitization of Fluconazole-Resistant Urinary Candida spp. Isolates by Amikacin through Downregulation of Efflux Pump Genes
In Vitro and In Vivo Activity of Zabofloxacin and Other Fluoroquinolones Against MRSA Isolates from A University Hospital in Egypt
A Promising Approach to Provide Appropriate Colon Target Drug Delivery Systems of Vancomycin HCL: Pharmaceutical and Microbiological Studies
Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested
Genomic Characterization of International High-Risk Clone ST410 Escherichia coli Co-Harboring ESBL-Encoding Genes and blaNDM-5 on IncFIA/IncFIB/IncFII/IncQ1 Multireplicon Plasmid and Carrying a Chromosome-Borne blaCMY-2 from Egypt
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
Pathogenicity Islands in Uropathogenic <i>Escherichia coli</i> Clinical Isolate of the Globally Disseminated O25:H4-ST131 Pandemic Clonal Lineage: First Report from Egypt
Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). The pathogenesis of UTIs relies upon UPEC’s acquisition of virulence determinants that are commonly inserted into large chromosomal blocks which are termed ‘pathogenicity islands’ (PAIs). In this study, we investigated the virulence-associated genes embedded in the chromosome of a UPEC Egyptian strain, EC14142. Additionally, we present a detailed characterization of the PAIs in the EGY_EC14142 chromosome. The isolate displayed a multidrug-resistant phenotype, and whole genome sequencing indicated that it belonged to the globally disseminated O25:H4-ST131 pandemic lineage and the H30-Rx clade. EGY_EC14142 carried genes that are responsible for resistance to aminoglycosides, fluoroquinolones, extended-spectrum β-lactams, macrolides, folate pathway antagonists, and tetracyclines. It encoded five PAIs with a high similarity to PAI II536, PAI IV536, PAI V536, PAI-536-icd, and PAIusp. The genome analysis of EGY_EC14142 with other closely related UPEC strains revealed that they have a high nucleotide sequence identity. The constructed maximum-likelihood phylogenetic tree showed the close clonality of EGY_EC14142 with the previously published ST131 UPEC international isolates, thus endorsing the broad geographical distribution of this clone. This is the first report characterizing PAIs in a UPEC Egyptian strain belonging to the globally disseminated pandemic clone O25:H4-ST131
Antifungal Caspofungin Sensitizes MRSA Isolates Towards Zabofloxacin, A Proteomic Study
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
Newly Developed Topical Cefotaxime Sodium Hydrogels: Antibacterial Activity and In Vivo Evaluation
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
Synthesis, Spectroscopic Characterization and Antimicrobial Potential of Certain New Isatin-Indole Molecular Hybrids
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
In Vitro Anti-Candida Activity of Certain New 3-(1H-Imidazol-1-yl)propan-1-one Oxime Esters
Anti-Candida activities of certain new oximes 4a–d and their respective aromatic esters 5a–l are reported. The tested compounds 4a–d and 5a–l exhibited better anti-Candida profiles than fluconazole. Compound 5j, namely (E)-3-(1H-imidazol-1-yl)-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 than both fluconazole (MIC > 1.6325 µmol/mL) and miconazole (MIC value = 0.0188 µmol/mL) as a new anti-Candida albicans agent
In Vitro Anti-Candida Activity of Certain New 3-(1H-Imidazol-1-yl)propan-1-one Oxime Esters
Anti-Candida activities of certain new oximes 4a–d and their respective aromatic esters 5a–l are reported. The tested compounds 4a–d and 5a–l exhibited better anti-Candida profiles than fluconazole. Compound 5j, namely (E)-3-(1H-imidazol-1-yl)-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 than both fluconazole (MIC > 1.6325 µmol/mL) and miconazole (MIC value = 0.0188 µmol/mL) as a new anti-Candida albicans agent