Study of Multidrug Resistance Pattern among Escherichia coli isolated from patients with Urinary tract infection

Objective: Urinary tract infections (UTIs) are some of the most common bacterial infections encountered in community and cause of significant morbidity and high medical cost. Escherichia coli is the most common pathogen belongs to Enterobacteriaceae family responsible for majority of UTI infections. Antimicrobial drugs have been routinely prescribed for empirical treatment of UTIs which has led to a dramatic increase in antibiotic resistance pattern of E. coli. The aim of present study was to analyse the multidrug resistance patterns (MDR) of E. coli isolated from UTI patients.Methods: A total of 80 urine samples collected from the patients suspected of having UTI attending Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala were cultured using standard microbiological techniques. Antibiotic susceptibility testing of E.coli was done by using minimum inhibitory concentration (MIC). MIC of tetracycline, doxycycline, azithromycin, erythromycin, ciprofloxacin, levofloxacin, ampicillin, amoxicillin and amikacin was done by agar dilution method.Results: Of the total 46 isolates contributing 33 females and 13 males were confirmed as E. coli. About 51.34% of the female patients belonged to the age group 21-40 yr and 53.84% of the male population belonged to 41-80 yr were found to be more susceptible to UTI infection. All isolates confirmed as E.coli were found to be multidrug resistant. 80% of the isolates exhibited MICs higher than 1000mg/L against β-lactams. 20% of the E. coli isolates exhibited MICs higher than 1000mg/L against ciprofloxacin, amikacin and erythromycin. 23% and 95% of E. coli isolates exhibited MICs less than 128 mg/L against doxycycline and levofloxacin respectively.Conclusion: The present study revealed the decreased susceptibility of the E.coli to all drugs. E. coli resistance profile to beta lactams, quinolones, macrolides, tetracyclines and aminoglycosides were also found to be quite high in this study emphasizing the need to educate public about appropriate use of antibiotics.N

Linear cyclodextrin polymer prodrugs as novel yherapeutics for Niemann-Pick type C1 disorder

Niemann-Pick Type C1 disorder (NPC) is a rare lysosomal storage disease characterized by the accumulation of cholesterol in lysosomes. NPC has no FDA approved treatments yet, however 2-hydroxypropyl-β-cyclodextrin (HPβCD) has shown efficacy for treating the disease in both mouse and feline NPC models and is currently being investigated in late stage clinical trials. Despite promising results, therapeutic use of HPβCD is limited by the need for high doses, ototoxicity and intrathecal administration. These limitations can be attributed to its poor pharmacokinetic profile. In the attempt to overcome these limitations, we have designed a β-cyclodextrin (βCD) based polymer prodrugs (ORX-301) for an enhanced pharmacokinetic and biodistribution profile, which in turn can potentially provide an improved efficacy at lower doses. We demonstrated that subcutaneously injected ORX-301 extended the mean lifespan of NPC mice at a dosage 5-fold lower (800 mg/kg, body weight) the HPβCD dose proven efficacious (4000 mg/kg). We also show that ORX-301 penetrates the blood brain barrier and counteracts neurological impairment. These properties represent a substantial improvement and appear to overcome major limitations of presently available βCD-based therapy, demonstrating that this novel prodrug is a valuable alternative/complement for existing therapies

Exploring the Potential of <em>Calotropis procera</em> in Pharmacological Approaches

Medicinal plants have been a source of treatments for many ailments for thousands of years. The WHO estimates that 80% of worldwide population use traditional medicines to treat common health issues. Plant derived bioactive substances constitute 50% of Western medications. The increase in incidents of emerging medical challenges, including post-COVID syndrome, rising multidrug-resistant (MDR), and many more, has raised annual fatalities. To address these issues, novel medications and strategic approaches are urgently required. Designing novel drugs relies on exploring medicinal plants, which have great scope in combating diseases. Calotropis procera is a medicinal plant belongs to Apocynaceae family and subfamily Asclepiadoideae that have been exploring for developing novel drugs. C. procera consists of numerous phytochemicals including flavonoids, terpenoids, cardenolides, steroids and oxypregnanes. Therefore, its phytoconstituents have been used to treat a variety of conditions including cancer, asthma, epilepsy and snake bite. C. procera is reported to have anti-inflammatory, anti-tumor, anthelmintic, antibacterial, antinociceptive and antimalarial properties. Roots, leaves and flower of C. procera have been used in wide range of ethnomedicinal and pharmacological actions including leukoderma, malaria and eczema. Recent ongoing techniques including computational tools using the phytoconstituents of C. procera against various diseases will open up avenues for developing novel drugs

L'Avenir de Luchon : journal scientifique, littéraire, annonces et réclames : guide général des baigneurs et des touristes aux eaux thermales, bains de mer de la France et de l'étranger

14 février 19261926/02/14 (N279)-1926/02/14.Appartient à l’ensemble documentaire : MidiPyren

Analytical profiling of mutations in quinolone resistance determining region of <i>gyrA</i> gene among UPEC

<div><p>Mutations in <i>gyrA</i> are the primary cause of quinolone resistance encountered in gram-negative clinical isolates. The prospect of this work was to analyze the role of <i>gyrA</i> mutations in eliciting high quinolone resistance in uropathogenic <i>E</i>.<i>coli</i> (UPEC) through molecular docking studies. Quinolone susceptibility testing of 18 <i>E</i>.<i>coli</i> strains isolated from UTI patients revealed unusually high resistance level to all the quinolones used; especially norfloxacin and ciprofloxacin. The QRDR of <i>gyrA</i> was amplified and sequenced. Mutations identified in <i>gyrA</i> of <i>E</i>.<i>coli</i> included Ser83Leu, Asp87Asn and Ala93Gly/Glu. Contrasting previous reports, we found Ser83Leu substitution in sensitive strains. Strains with S83L, D87N and A93E (A15 and A26) demonstrated norfloxacin MICs ≥1024mg/L which could be proof that Asp87Asn is necessary for resistance phenotype. Resistance to levofloxacin was comparatively lower in all the isolates. Docking of 4 quinolones (ciprofloxacin, ofloxacin, levofloxacin and norfloxacin) to normal and mutated <i>E</i>.<i>coli</i> gyrase A protein demonstrated lower binding energies for the latter, with significant displacement of norfloxacin in the mutated GyrA complex and least displacement in case of levofloxacin.</p></div

Accession numbers, quinolone susceptibility and GyrA mutations of <i>E</i>.<i>coli</i> isolates.

<p>Accession numbers, quinolone susceptibility and GyrA mutations of <i>E</i>.<i>coli</i> isolates.</p

Docking structures of norfloxacin with (a) normal and (b) mutated GyrA QRDR.

<p>Docking structures of norfloxacin with (a) normal and (b) mutated GyrA QRDR.</p

DNA sequence similarity among <i>gyrA</i> QRDR of <i>E</i>. <i>coli</i> strains.

<p>Substitutions leading to amino acid changes are highlighted. Amino acid mutations are mentioned above specific codon. A38, A55 -sensitive strains, A21- intermediate & remaining strains are resistant. Identical nucleotides are dotted while those different from sensitive strain are highlighted.</p