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In Vitro Effect of New Antibiotics Against Clinical Isolates of Salmonella Enterica Subspecies Enterica

Thesis Info

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Author

Malik, Nasrullah

Program

PhD

Institute

Baqai Medical University

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Microbiology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12863/1/PhD%20Thesis%20Nasrullah%20Malik%20-%20Baqai%20Medical%20University%20-HEC.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726443271

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Background: Typhoid fever is caused by Salmonella enterica serovar Typhi (S, Typhi, T is capital because Typhi is serotype and not species) a gram negative bacterium (1). It continues to be a global health problem with over 21.6 million cases and more than 200,000 deaths occurring annually (2;3). Most of these deaths occur in Asia (4). Salmonella enterica serotype Paratyphi is traditionally associated with relatively milder illness as compared to Salmonella enterica serotype Typhi. Aim & Objectives: The aim of this study was to determine in vitro MIC patterns of various therapeutic alternatives available for the treatment of enteric fever and non-typhoidal salmonellae in an endemic region reporting a recent increase in ciprofloxacin resistance. Study design: It is a cross sectional research carried out at Armed Forces Institute of Pathology Rawalpindi. Research was conducted from June 2011 to May 2013. Materials and Methods: Samples of blood, bone marrow, pus, urine, stool and fluids were collected from suspected cases of salmonella infections. Standard protocols were observed during collection and transportation. Culture was applied on Bactec 9050 special and/or standard media. Suspected salmonella colonies were tested by API 20E and confirmed by serology. The isolates were also tested for resistance to antibiotics ampicillin, cotrimoxazole, ciprofloxacin, ceftriaxone, doripenem, imipenem, ertapenem, aztreonam, moxifloxacin, cefpirome, cefepime, gatifloxacin, and chloramphenicol by Kirby-Bauer disc diffusion method (5). MIC (Minimum Inhibitory concentration) was done on MDR and ciprofloxacin intermediate or resistant cases by E-strips. Results: 316 isolates of Salmonella were recovered from 2230 specimens. Resistance by disk diffusion technique was determined, for Salmonella Typhi against Ampicillin 72%, Chloramphenicol 62%, Cotrimoxazole 41.2%, ceftriaxone 2.4%, ciprofloxacin 8%, cefpodoxime 4.7%, doripenem 2.3%, ertapenem 3.5%, aztreonam 3.5%, and moxifloxacin 3.5%. No resistance was noted for imipenem, cefepime and gatifloxacin. Resistance noted in Salmonella Paratyphi A was ampicillin 60%, chloramphenicol 40%, cotrimoxazole 38%, ceftriaxone 7.9%, ciprofloxacin 8%, cefpodoxime 7.9%, imipenem and ertapenem 2.6%, aztreonam 1.3%, moxifloxacin 6.6%, and gatifloxacin1.3%. No resistance was noted for doripenem and cefepime. For non-typhoidal salmonellae resistance was noted only against cotrimoxazole 66.6% and ciprofloxacin 7%. For S. Typhi imipenem MIC90 was 0.38 and MIC50 was 0.25. For cefpirome MIC90 was 0.64 and MIC50 was 0.09. For aztreonam MIC90 was 0.12 and MIC50 was 0.09. For cefpodoxime MIC90 was 0.75 and MIC50 was 0.38. For azithromycin these values were 16.0 and 7.0 and for tigecycline they were 0.25 and 0.09
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حکیم الیاس کٹھوری

حکیم الیاس کٹھوری
حکیم الیاس کٹھوری مقیم میرٹھ پچھلے دنوں اچانک انتقال فرماگئے۔ مرحوم بڑے حاذق و فائق طبیب تھے۔مزاحیہ انداز میں اپنے چاہنے والوں کو ہمیشہ خوش رکھا کرتے تھے۔قاری محمدطیب اورحضرت مفتی عتیق الرحمن عثمانیؒ کے خاص شیدائی و معتقد تھے۔عالموں سے انھیں زیادہ ہی محبت تھی خلوص کے ساتھ ہمہ وقت ان کی خدمت میں جٹے رہتے ۔نیکی وشرافت کی تصویر تھے۔
ادارہ ندوۃ المصنفین دہلی کے خصوصی نمبر ’’مفکرملّت ‘‘ میں بھی حکیم الیاس صاحبؒ نے مفتی عتیق الرحمن عثمانی ؒ کے سلسلے میں بڑا ہی پراز معلوماتی مضمون برائے اشاعت ارسال فرمایاتھا ۔
ادارہ ندوۃ المصنفین دہلی حامد الانصاری غازی ،حکیم عبدالقوی دریابادی اورحکیم الیاس کٹھوری کے انتقال پرملال پراپنے گہرے رنج وغم کااظہار کرتا ہے اور اﷲ تعالیٰ سے دعاہے کہ تمام متعلقین کوان کی وفات کے صدمہ کوبرداشت کرنے کی توفیق عطا فرمائے ۔آمین۔ [نومبر ۱۹۹۲ء]

 

مکی دور نبوت اور مسلم اقلیت کافقہ السیرۃ کی روشنی میں سماجی مطالعہ

The life of Holy Prophet (peace be upon him) is described as role model in Holy Quran for all the Muslims and known as Uswa.e. Hasna. So, the importance of the life history of the Holy Prophet (peace be upon him) in every period before prophet hood and as a prophet cannot be denied in any walk of life. But the makki period of the Prophet’s life has not enlightened in such a way as it has importance. Many aspects of makki period has been discussed in history and seerah writing but along with this a lot of aspects has been not given due importance in contemporary seerah writing. The basic sources of hadith o seerah provides lots of material on this aspect. In the makki period, Muslims were in minority and they had to face a lot of religious, social, economic and political issues in their lives. Now a days, in modern world majority of Muslims lives in western and non. Muslim societies and have to spend their lives as minority in that socities. In a state of minority, they have to face a lot of religious, social and economical issues in their lives. These problems can be solved in the light of seerah especially from the teachings of makki period, it can provide a lot of religious solutions in contemporary societies in a better way. This article will throw light on teachings of makki period and discuss the solutions of Muslim’s problems as minority in the light of fiqh. Ul. Seerah.

Evaluation of Pharmacological Potential of Bioactive Compounds Isolated from a Selected Medicinal Plant

Plants are rich source of therapeutic compounds that have tremendous applications in the pharmaceutical industry. To identify appropriate plants for isolation of bioactive compounds, methanol/chloroform (M/C) and aqueous (aq.) extracts of 61 medicinal plants were evaluated systematically for their biological activities. Antimicrobial activity was assessed against six bacterial and five fungal strains, while natural antioxidants were studied by using reducing power (RP), total antioxidant capacity (TAC) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Six plants exhibited broad spectrum antibacterial activity while two exerted significant antifungal activity. Antioxidant potential, total phenolic content (TPC) and total flavonoid content (TFC) of plant species varied among extracts as well as in assays used for antioxidant evaluation. Significant linear correlation (p < 0.01) of TPC with antioxidant activities suggested their contribution to antioxidant potential. Based on the results of antimicrobial and antioxidant assays and traditional information Ficus microcarpa was selected for isolation of bioactive compounds. Through chromatographic techniques two pure compounds were isolated from ethyl acetate fraction of Ficus microcarpa and identified through NMR as Plectranthoic acid (PA), a pentacyclic triterpenoid, and 3,4,5,7-Flavantetrol (FL), a flavonoid. These compounds are isolated first time from Ficus microcarpa. Moreover, FL is isolated first time from any natural source. Inhibition of α-glucosidase, α-amylase and dipeptidyl peptidase 4 (DPP-4) is an important therapeutic approach for treating diabetes mellitus (DM). The bioactivity of PA and FL was evaluated to inhibit these enzymes. Among both the compounds, PA possessed pleotropic inhibitory activity with IC50 values of 39.5, 55.5 and 51.4 μM against α-glucosidase, α amylase and DPP-4, respectively. As first line antidiabetic drug metformin activates 5′AMP-activated kinase (AMPK), the potential of PA to enhance AMPK activity was assessed using hepatocytes. AMPK is a well-studied therapeutic target for metabolic syndrome, type-2 diabetes. Our results showed that PA is an activator of AMPK. Epidemiologic studies indicated that diabetics treated with metformin had a lower incidence of cancer than those taking other anti-diabetes drugs. This led to a surge in the efforts to explore the anticancer potential of PA, which has potent AMPK activating properties. We found that treatment of prostate cancer (PCa) cells with PA inhibited proliferation and induced G1 phase arrest in cell cycle that was accompanied with up- Abstract Evaluation of Pharmacological Potential of Bioactive Compounds Isolated from a Selected Medicinal Plant xxiv regulation of cyclin kinase inhibitors p27/KIP1 and p21/CIP1. PA treatment suppressed mTOR/S6K signaling and induced apoptosis in PCa cells in an AMPK-dependent manner. Interestingly, PA-induced autophagy in PCa cells was found to be independent of AMPK activation. Combination studies of PA and metformin demonstrated that metformin had an inhibitory effect on PA-induced AMPK activation and suppressed PA-mediated apoptosis. Then we designed the study to determine the putative targets of PA in PCa cells and employed a quantitative proteomics approach i.e. nano-LC/MS/MS. Results were processed with the SIEVE software to identify proteins with differential expression. A total of 98 unique peptides, showing > 2 fold change, were analyzed by using IPA and PANTHER software’s which identified mTOR pathway is the major canonical pathway. The biological process modulated by PA with the high percentage, i.e. 51.0% proteins, was a metabolic process. Epithelial-to-mesenchymal transition (EMT) plays a crucial role in PCa metastasis. We next identified PA as an inhibitor of EMT which inhibited cell migration, invasion and expression of mesenchymal markers in PCa cells. We presented that PA reverse EMT by using a PCa cell culture model of transforming growth factor-β (TGF-β)-induced EMT. To inhibit migration PA used adherin-junction signalling as a major target and Rac1 was identified as the major protein modulated by PA. PA also affected NEDD9, which activates Rac1 and was identified as a major protein involved in progression and migration of PCa cells. This study identifies plants with antimicrobial and antioxidant properties which could be important for isolation of desired therapeutic compounds and to improve infusions, nutraceuticals and pharmaceuticals. The study suggests that Ficus microcarpa and its isolate PA could be an important natural source for alleviating the symptoms of type 2 DM. Given the anti-proliferative role of PA in cancer and its potent anti-hyperglycemic activity, we suggest that PA should be explored further as a novel activator of AMPK for its ultimate use for the treatment of cancers and inhibition of EMT. This study also deserves further investigation in order to isolate more bioactive secondary metabolites from Ficus microcarpa with anticancer and antidiabetic potential.