Recent patents on anti-infective drug discovery最新文献

Introduction: Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are among the highly antimicrobial resistant gram negative bacteria and infections due to them are an increasingly major health problem worldwide.

Methods: In this study we have detected the blaKPC and blaGES carbapenemase genes in Klebsiella pneumoniae isolated from hospitalized patients in Kashan, Iran. In a cross-sectional study, a total of 181 K. pneumoniae isolates were recovered from clinical specimens during November 2013 to October 2014.

Result: Antimicrobial susceptibility profiles were determined using disk diffusion method according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI guidelines. Carbapenem-resistant K. pneumoniae isolates were identified. PCR method and sequencing were used for detection of blaKPC and blaGES carbapenemase genes. Of the 181 K. pneumoniae isolates, 35 (19.3%) were found to be resistant to imipenem and 150 (82.9%) were identified as MDR strains. Among carbapenems, the most resistant rate 39 (21.5%) was seen against ertapenem using disk diffusion method. Of K. pneumoniae isolates 21 (11.6%) and 42 (23.2%) carried blaKPC and blaGES genes, respectively and 19(10.5%) carried both genes simultaneously.

Conclusion: The data of current study revealed that the frequency of resistance to carbapenems and production of carbapenemase enzymes especially GES type was high among clinical isolates of K pneumoniae in Kashan, Iran.

Background: According to the World Health Organization, as of 2014 9% of the world's adult population is affected by diabetes. Uncontrolled diabetes is a pro-inflammatory process that increases generation of reactive oxygen species (ROS).

Methods: The production of ROS leads to a chronic increase in oxidative stress which results in an increased susceptibility to infections. Individuals with type 2 diabetes mellitus (T2DM) are highly susceptible to Mycobacterium tuberculosis (M. tb) infection. Previous research has demonstrated that glutathione (GSH) plays an important role in the control of M. tb infection. Recent studies have demonstrated that phagocytosis of M.tb is diminished in patients with T2DM. Phagocytosis in macrophages is thought to be mediated in part by complement protein 3b (C3b)-complement protein receptor 3b (C3R) interactions. Since C3b production is not diminished in patients with T2DM we propose that C3R production is reduced and is the cause for impaired macrophage phagocytosis as well as IL-12 and IFN-γ signaling.

Conclusion: This study utilizes a quantitative PCR (qPCR), demonstrating decreased transcription of C3R mRNA in patients with T2DM as compared to non-diabetics.

Background: Inflammatory bowel disease (IBD) is one of the five most prevalent gastrointestinal disease burdens which commonly require lifetime care. Worldwide incidence rate of ulcerative colitis and Crohn's disease is about 16.8% and 13.4% respectively. Colitis is an inflammation of the colon. Colon targeted drug delivery will direct the drug to the colon. The drug will reach at the site of action and hence its side effects as well as dose can be reduced. Recent patent describes treatment of ulcerative colitis using anti CD3 antibodies, with nicotine and anti-depressant drugs, budesonide foam etc.

Objective: Present study deals with optimization of site targeted methylprednisolone delivery for treatment of colitis.

Method: Chitosan and Eudragit RS 100 were used as coating polymers. Tablets were prepared by press coated technology. The core tablets contain drug, avicel as binder, croscarmellose sodium as super disintegrant and dicalcium phosphate as diluent. Drug excipient compatibility was carried out using FTIR, UV and DSC. Design of experiment was used to optimize the formulation. Tablets were evaluated for thickness, weight variation, hardness, swelling index, in-vitro drug release and release of drug in simulated media.

Results: Optimized batch (B2) contained chitosan 40% and eudragit RS 100 17.5%. B2 showed in-vitro drug release 85.65 ± 7.6% in 6.8 pH phosphate buffer and 96.7 ±9.1% in simulated media after 7.5 hours.

Conclusion: In-vivo x-ray placebo study for formulation B2 had shown that the tablet reached to the ascending colon after 5 hours. This indicated a potential site targeted delivery of optimized batch B2.

Background: Rheumatoid arthritis (RA) is an immune mediated joint-based chronic inflammatory disorder recognized by joint inflammation, destruction, pain and remission. Currently, numerous pharmacotherapeutic strategies have gained immense popularity in RA therapy and improving the patient life.

Methods: Besides, it exhibits numerous drawbacks such as requirement of high dose of drugs, unavoidable adverse effects and diseases remission. Thus, use of currently available pharmacotherapeutics employing conventional formulations can only provide therapeutic effects to a certain extent.

Results: Recent advancements in nanotechnology-based lipidic vesicular nanocarriers have led provided improved efficacy and safety for the anti-rheumatic drugs. These include liposomes, stealth liposomes, ethosomes, transfersomes, etc., which have shown their potential to improve the therapeutic efficacy of antirheumatic drugs with lesser toxicity. Although the results of animal models for use of lipid vesicular nanocarriers for drug targeting in RA have been found to be highly promising, but lack of sufficient data in a clinical setup are still evident to demonstrate their practical utility in patient populations. In this regard, considerable research studies are required for evaluating the efficacy and safety of the aforementioned nanocarriers in RA through clinical studies.

Conclusion: The present review, therefore, covers the brief pathophysiology of RA, current medication and their challenges in RA therapy. Besides, an extensive account on recent advancements in novel lipid vesicular nanocarriers in RA therapy has also been addressed with special emphasis on the patent literature too.

Background: Treatment of human hydatidosis is mainly surgical, with chemical treatment being reserved as a coadjuvant treatment. Use of effective protoscolicidal agents during surgery of hydatid disease is essential to reduce the recurrence rate.

Objective: The aim of this study was to investigate the scolicidal effects of Pistacia atlantica leaf and fruit hydroalcoholic extracts on protoscolices of hydatid cyst.

Method: Echinococcus granulosus protoscolices were obtained from 50 sheep infected with hydatid cysts. Various concentrations of plant hydroalcoholic extracts were used in different exposure times for viability assay of protoscolices.

Results: The scolicidal effects of the hydroalcoholic extracts of the leaf, fresh and dried fruits were significant compared to the control groups (P < 0.05). Among the Pistacia atlantica extracts tested, 0.1% (mg/ml) concentrations of fresh fruit extract (99.09 ± 1.27) and leaf extract (89.25 ± 18.42) had strong scolicidal effects in 360 min, of exposure times and the mortality rate decreased with the lower concentration.

Conclusion: Information from the current study has the strong scolicidal effect of fresh fruit hydroalcoholic extract of Pistacia atlantica on protoscoleces, which may be used as a scolicidal agent during the surgery techniques.

Introduction: Antiseptics and disinfectants have been used widely in hospitals and other health care settings to control the growth of microorganisms. However, some disinfectant resistant strains were reported. The objectives of our study were to evaluate correlation between the efflux pump genes, drugs and disinfectant resistant among clinical isolates of E.coli.

Methods: A total of 102 of E. coli strains were isolated from urine sample of hospitalized patients. The antibiotic susceptibility was carried out by disc diffusion method. Didecyl di-methyl ammonium chloride (DDDMAC) was used as Quaternary ammonium compound (QAC) disinfectant which was used in Heart Center Hospital. PCR reaction was carried out for detection of qacE and qac∆E efflux pump genes.

Result: Almost all the strains had higher resistance to ampicillin, ciproflaxacin, cotrimaxazole and cephalothin. Totally 49% (n: 50) of strains were produced ESBL. Almost all the strains have MIC value between 0.00195 to 0.0078 mg/l for DDDMAC. Correlation between presence of qacE and qac∆E genes and antibiotic resistance was perceived. Presence of qacE and qac∆E genes among strains that have high disinfectant MIC value were 96.9% and 93.7% respectively. In addition, 98% of ESBL producing strains harbored qacE gene and 94% of ESBL producing strains harbored qac∆E gene.

Conclusion: Our study indicated that there was a strong correlation between presence of qacE and qac∆E genes with resistance to some antibiotics and growth in media which contain high concentration of disinfectant. In conclusion, other mechanisms also play important role in resistant to antimicrobial agents but the role of efflux pumps in resistant to antimicrobial agents should not be neglected.

The colonization and infection with methicillin-resistant Staphylococcus aureus is a major health problem in hospitals and long-term care facilities. Although bacteriaemias with MRSA (methicillin-resistant Staphylococcus aureus) can be treated with vancomycin and other reserve antibiotics, 20% of patients cannot be successfully cured. Inpatients colonized with MRSA are isolated in hospitals according to the guidelines of the Robert-Koch-Institute, althouth in long-term care facilities these patients are not urgently isolated. Active decolonization measures are taken to eradicate colonization with MRSA. In order to reduce MRSA colonization, it could be possible to administer cultures of Staphylococcus epidermidis which have no anbitiotic resistance, so that physiological genes could be conferred from Staphylococcus epidermis to MRSA bacteria.