Recent Patents on Anti-Infective Drug Discovery - Volume 12, Issue 1, 2017

Background: Recently, increasing antibiotic resistance is causing serious publichealth concerns worldwide. This phenomenon increased patient's morbidity and mortality rate, particularly in immunocompromised individuals. Methods: Considering that antimicrobial resistance can vary according to geographical location, we investigated the status of antibiotic resistance in Ilam province from 2008 to 2013. Results: The results of our study showed that antibiotic resistance rates to aztreonam, cefotaxime, ceftazidime and ceftriaxone were 38%, 39%, 43% and 48% respectively. Conclusion: Antibiotic resistance had increased (except for aztreonam) during the period from 2008 to 2013.

Background: Critically ill patients are very susceptible to a variety of disorders and infections during hospitalization in Intensive Care Units [ICU]. Among these problems, nosocomial infections are major causes of morbidity and mortality. Methods: Nosocomial pneumonias, specifically ventilator associated pneumonias have become a major health care issue. The implication of oral care in hospital presents challenges that can prevent or reduce the risk of nosocomial pneumonias in ICU. In this review article, we reviewed the most important nosocomial pathogens which colonize the oral cavity and causes severe infections during hospitalization in ICU. Conclusion: Finally, we discuss that the prevention strategies against oral colonization of nosocomial pathogens include classical methods and novel methods such as Photodynamic therapy, NO based therapy, anti-virulence therapy and other new under investigation antimicrobial strategies.

Background: Orf virus is a DNA virus that belongs to the Parapoxvirus genus. The virus is a causative agent of orf in humans or contagious ecthyma in animals which is mostly seen in sheep, goat and cattle. Discussion: Orf is an emerging zoonosis with an increasing number of worldwide outbreaks that have been reported. It is a contagious disease that tends to spread very fast among livestock. The morbidity rate is very high, particularly among young unvaccinated animals. The fatality rate is low but can be seen due to secondary infections. The disease has a significant effect on livestock health and may lead to economical losses. Humans may become infected if they have a direct contact with animal lesions. The disease is seen as a cutaneous lesion with a mild clinical outcome. Human to human transmission exists but is very rare. Nosocomial transmission was reported with one outbreak in a burn unit. The diagnosis is mostly based on the history of animal contact and clinical findings. Molecular tests are used to confirm clinical diagnose. There is no specific treatment but a live vaccine is available for animals. Surveillance implementations and infection control measurements are very important for the prevention of infection. Currently, there are limited studies on orf or contagious ecthyma. It has been observed that there are few studies that have resulted in patents. Conclusion: The aim of this paper was to review the current relevant patents, epidemiological features, clinical presentations, the diagnosis and treatment of orf.

Background: With an increase in comprehension of the molecular biology of viruses, there has been a recent surge in the application of virus sequences and viral gene expression strategies towards the diagnosis and treatment of diseases. Results: The scope of the patenting landscape has widened as a result and the current review discusses patents pertaining to live / attenuated viral vaccines. The vaccines addressed here have been developed by both conventional means as well as by the state-of-the-art genetic engineering techniques. Conclusion: This review also addresses the applications of these patents for clinical and biotechnological purposes.

Background: Loperamide is an anti-diarrheal drug prescribed for non-infectious diarrhea. The drug is an opioid receptor agonist, blocker of voltage-dependent calcium channel (Cav) and calmodulin (CaM) inhibitor on human cells. Loperamide has been reported to exert anti-amoebic effects against pathogenic strains of Acanthamoeba castellanii. Objectives: The precise mode of antibiotic action, cellular target homology with human counterparts and the pattern of cell death induced by loperamide in Acanthamoeba castellanii remain to be established. Additionally, we attempt to establish the presence a primitive Cav in Acanthamoeba castellanii. Methods: Bioinformatics, 3D structural modelling, ligand binding predictions and apoptotic/ amoebicidal assays were used in this study to answer the above queries. Amino acid sequences and structural models were compared between human and A. castellanii proteins that are involved in the regulation of calcium (Ca+2) homeostasis. Results: Our results show that A. castellanii expresses similar, to near identical types of primitive calcium channels Cav Ac and CaM that are well known targets of loperamide in humans. The growth assays showed anti-amoebic effects of loperamide at different doses, both alone and in combinations with other Ca+2- CaM inhibitors. The synergistic actions of loperamide with haloperidol showed to be more amoebicidal than when either of them used alone. Imaging with Annexin V, Acridine orange and Propidium iodide showed apoptosis in A. castellanii at a dose of 100 µg/ml and necrosis at higher doses of 250 µg/ml. Conclusion: Though, Acanthamoeba does not express a homolog of the human mu-opioid receptor, but does shows evidence of the homologs for other known human targets of loperamide that are involved in Ca+2 uptake and Ca+2 signal transduction pathways. This suggests optimization of similar drug interactions with these targets may be useful in developing new approaches to control the growth of this parasite and possibly the diseases caused by it.

Background: Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective: Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Method: Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Results: Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16% through egg membrane, 95.23% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. Conclusion: It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency.