Recent Patents on Anti-Infective Drug Discovery - Volume 16, Issue 1, 2021

An infectious disease of the colon, recurrent Clostridium difficile infection (RCDI), is hitherto considered insurmountable leading to significant morbidity and mortality. Gut dysbiosis, generally resulting from frequent use of antibiotics, is considered to be responsible for the etiopathogenesis of RCDI. Ironically, the conventional treatment strategies for the disease also include the use of anti- infective drugs such as metronidazole, vancomycin and fidaxomycin. As a result of the efforts to overcome the limitations of these treatment options to control the recurrence of disease, faecal microbiota transplant (FMT) has emerged as an effective and safe alternative. It is pertinent to add here that FMT is defined as the process of engraftment of fecal suspension from the healthy person into the gastrointestinal tract of the diseased individual aiming at the restoration of gut microbiota. FMT has proved to be quite successful in the treatment of recurrent and resistant Clostridium difficile infections. In the last three decades, a lot of information has been generated on the use of FMT for RCDI. A number of clinical trials have been reported with generally very high success rates. However, a very small number of patents could be found in the area, indicating that there still exists lacuna in the knowledge about FMT with respect to its preparation, regulation, mode of delivery and safety. The current review attempts to dive deeper to discuss the patents available in the area while supporting the information contained therein with the non-patent literature.

Aim: To formulate and preliminary evaluated polysaccharide based mucoadhesive floating tablets of Cinnarizine. Background: Gastro-retentive drug delivery systems has proved to be a successful approach to enhance the gastric residence with site specific targeting for achieving local or generalized effect. Various patents has also been filed globally employing gastro-retentive approach. Objective: The study is designed to explore the mucoadhesive and low density characteristics of corn fibre gum (CFG) for the preparation of gastro-retentive floating tablets of cinnarizine. Methods: Floating tablets were prepared by direct compression technique using different concentrations of CFG (45, 50, 60% w/w). The formulated floating tablet batches were evaluated for their hardness, friability, drug content, floating duration/lag time, swelling behavior, bioadhesive strength and in-vitro drug release. Results: Mucoadhesive strength was found to increase with an increment in the polysaccharide concentration. Swelling index was found to increase both with the increase in CFG concentration and with duration for which tablet remains in medium. The in-vitro drug release studies indicated decrease in drug release (91% to 77%) with the increase in polymer concentration. The release data was further fitted to various kinetic models which revealed the drug release to be in accordance with zero order and Higuchi models, indicating polymer to exhibit the swellable matrix forming abilities. The value of n (between 0.458 and 0.997) from Korsemeyer-Peppas model depicted the possibility of drug to follow more than one mechanism of release from the formulation i.e. diffusion and erosion. Stability studies revealed the preparations to retain their integrity and pharmaceutical characteristics at variable storage conditions. Conclusion: Thus from the research findings, CFG could be concluded to possess potential binder, release retardant and mucoadhesive characteristics which could be successfully employed for the formulation of gastro-retentive floating tablets.

Background: Cutaneous candidiasis is a deep-seated skin fungal infection that is most commonly observed in immunocompromised patients. This fungal infection is conventionally treated with various formulations like gels and creams which are having different side effects and the least therapeutic efficacy. Hence, it becomes necessary to develop a novel carrier system for the treatment of this deep-seated skin fungal infection. Econazole nitrate is the most widely used antifungal for the treatment of cutaneous candidiasis and many patents have been granted by various pharmaceutical scientists around the globe related to nanocarrier systems for transdermal delivery of antifungal drugs like econazole nitrate (ECN) therefore, we developed and evaluated econazole nitrate loaded oleic acid vesicles in the present research work for treatment of cutaneous candidiasis through transdermal route. Methods: Econazole nitrate loaded oleic acid vesicles were prepared by thin-film hydration and characterized for drug entrapment, vesicle size, zeta potential, polydispersity index (PDI), Fourier Transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. Furthermore, the oleic acid vesicular gel was evaluated for ex-vivo skin permeation/retention and in-vitro and in-vivo antifungal activity in Wistar rats. Results: Econazole nitrate loaded oleic acid vesicles showed high encapsulation of drug (74.76 ± 3.0%), acceptable size (373.4 ± 2.9 nm), and colloidal characteristics (PDI = 0.231 ± 0.078, and zeta potential = -13.27 ± 0.80 mV). The oleic acid vesicular gel showed high skin permeation (Transdermal flux = 61.98 ± 2.45 μg/cm²/h), skin retention (35.90 ± 2.06%), in-vitro, and in-vivo antifungal activity compared to marketed cream (Ecoderm ^R) of econazole nitrate for a prolonged time (4 days). Conclusion: Developed econazole nitrate loaded oleic acid vesicles could be used effectively in the treatment of cutaneous candidiasis with minimization of side effects of econazole nitrate with increased therapeutic efficacy.

Aim: This study tries to find new antimicrobial agents using some Nigerian plants. Background: Antimicrobial compounds from fungi endophytes have shown great promise in mitigating the threats of resistant pathogens. Objective: The study evaluated the in vitro antimicrobial property of secondary metabolites of endophytic fungi isolated from Newbouldia laevis and Cassia tora leaves. Methods: Ten endophytic fungi were isolated from the two plants’ leaves and later fermented on local rice for 21 days. Thereafter, their secondary metabolites were extracted using ethyl acetate. The antibacterial activity of the extracts on the test organisms were determined using agar diffusion and agar dilution methods, while the bioactive constituents were identified using high performance liquid chromatography coupled to diode array detector. Results: Nine of the crude extracts (NL1, NL3, NL6, NL10, NL12, CT2, CT7, CT9 and CT10) of the fungi isolates inhibited at least one of the microorganisms studied with maximum and minimum inhibition-zone-diameter of 14 mm and 2 mm, respectively while CT1 did not inhibit any of the tested microorganisms at tested concentrations. The extracts exhibited good antifungal activity, inhibiting the growth of both C. albicans and Trichophyton tested with an inhibition-zone-diameter ranging between 4-8 mm and 7-14 mm, respectively. The endophytic fungi extracts-CT2 and NL1-exhibited the best antimicrobial activity, inhibiting most of the tested microorganisms. HPLC-DAD analysis of the endophytic fungal extracts identified some classes of compounds such as catechin derivatives, benzoic acid derivatives and apigenin, which were previously reported to have antimicrobial potentials. Conclusion: Newbouldia laevis and Cassia tora leaves house endophytic fungi capable of yielding secondary metabolites with potential as anti-infective agents.

Background: Methicillin-resistant coagulase-negative staphylococci is responsible for hospital and community-acquired infections. Objective: This study aimed to investigate the antibiotic-resistance patterns, antibiotic-resistance genes, namely, ermA, ermB, ermC, blaZ, msrA, tetK, tetM, mup, and vanA, biofilm formation, and prevalence of different SCCmec types among the Staphylococcus cohnii strains isolated from clinical samples in Tehran, Iran. Methods: In this study, S. cohnii isolates were screened from the clinical samples from March 2012 to February 2013 in Tehran, Iran. Antimicrobial susceptibility test and inducible clindamycin resistance were evaluated by disc diffusion method, and resistance genes were examined using Polymerase Chain Reaction (PCR) assays. Then, biofilm formation assay was analyzed by Microtiter-plate test to detect the icaA and icaD genes. The SCCmec and the Arginine Catabolite Mobile Element (ACME) typing were performed using the PCR method. Results: From twenty S. cohnii, all isolates were resistant to cefoxitin. 95% of the S. cohnii was defined as Multidrug Resistance (MDR) strains. The ermB, ermC, and vanA genes were not detected in any isolates; however, the blaZ gene had the highest frequency. 95% of the S. cohnii isolates produced biofilm. Also, 4 SCCmec types, including V, IV, III+ (C2), VIII+ (AB1), were identified. Therefore, the majority of SCCmec were untypable. Based on the ACME typing, arcA and opp3 genes were positive in 13 (65%) and 1 (5%) isolates, respectively. Conclusion: Due to the high antimicrobial resistance and the spread of untypable SCCmec among the isolates studied, the control and treatment of methicillin-resistant S. cohnii in hospitals and public health centers is a significant concern.

Background: Brucellosis is a highly infectious multi-systemic zoonosis, and it is caused by Gram-negative bacteria, Brucella. Despite the low incidence of neurobrucellosis, it is the most dangerous consequence of brucellosis. Case Presentation: A 30-year-old Sudanese male patient presented to our hospital with a complaint of fever associated with confusion for three days. He had signs of meningeal irritation in the form of neck stiffness, positive Kernig’s, and Lesage’s sign. The computerized tomography of the brain was normal. The CSF analysis showed a clear colorless sample with normal tension, decreased glucose, and slightly increased CSF protein level. We reviewed his occupational history; the patient was a farmer with regular contact with cattle and camels. The patient had positive Brucella antibodies for both B. Abortus and B. melitensis with a high titer (1/640). As described in various patents, we administered triple therapy for brucellosis for two weeks. A marked improvement in the conscious level was observed, and the patient was back to normal within a few days post-treatment. Conclusion: We encouraged physicians to consider the diagnosis of neurobrucellosis with any neurologic sign without a known cause. Our case highlights the importance of occupational history in clinical medicine.

Background: The global outbreak of COVID-19 was first reported in Wuhan, China, in the late 2019. The origin of the infection is still unclear. Over time, it spread to 150 countries in the world, due to which, the World Health Organization (WHO) declared the infectious disease to be pandemic. Objective: COVID-19 transmitted to India due to the arrival of travelers from other countries. The transmissibility and epidemicity of COVID-19 in India are exponential. So, in order to understand the above characteristics, specifically COVID-19 status in India has to be analyzed. To gain better insight on the matter, the state of Kerala is selected. The epidemiological characteristics of patients in Kerala, South India, and the possible transmission of COVID-19 from asymptomatic members to other peers are shown describing certain cases. Methodology: The COVID-19 dataset is taken from the Kaggle dataset. This dataset contains the details of the infected patients from different states of India. Statistical analysis techniques were used to analyze the distribution of the affected cases in a particular state. Case Presentation: The analysis shows that there is a possibility of the transmission of infection even during the incubation period. The recent trend in the number of infected cases in India is discussed. Conclusion: The transmissibility of COVID-19 and its epidemicity in India are discussed. Specifically, a case study on COVID-19 cases in the state of Kerala relating transmissibility is also summarized. Further, data related to patents on coronavirus is also discussed. From the analysis, it can be concluded that there is a possibility of COVID-19 transmission even during the incubation period. The preventive measures to overcome COVID-19 and methods to increase immunity are discussed.