Update on nifurtimox for treatment of Chagas disease.

Chagas disease is a vector-borne neglected tropical disease caused by Trypanosoma cruzi. It is a systemic and chronic parasitic infection which is endemic in 21 countries with 10 million cases worldwide and 12,000 annual deaths. Around 70 million people in the Americas are at risk of contracting this disease, and less than 1% of infected people are treated due to low disease awareness and limited access to treatment. The current treatment for Chagas disease consists of benznidazole and nifurtimox under the World Health Organization (WHO) authorization protocol. The current treatment has limitations in terms of efficacy against the chronic phase of infection and side effects associated with prolonged therapy. This review provides an update on nifurtimox progress over the years and its recent approval by the U.S. Food and Drug Administration (FDA) in 2020 for the treatment of Chagas disease in pediatric patients under 18 years of age.

Pretomanid for the treatment of pulmonary tuberculosis.

Discovering novel drugs active against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is currently one of the most unmet medical needs. In this context, pretomanid (PA-824), a novel nitroimidazole prodrug that targets both replicating and nonreplicating cells, is being developed by TB Alliance under license from Novartis. In replicating Mtb, pretomanid inhibits mycolic acid biosynthesis, which is an important building block of Mtb cell wall. Under nonreplicating conditions, pretomanid is reduced by deazaflavin-dependent nitroreductase, leading to generation of reactive nitrogen species exhibiting potent antimycobacterial activity. The U.S. Food and Drug Administration (FDA) has approved pretomanid under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway) for treatment of adult patients with treatment-intolerant or nonresponsive multidrug-resistant TB and extensively drug-resistant TB in combination with bedaquiline and linezolid as part of the oral.

Lascufloxacin hydrochloride to treat bacterial infection.

Lascufloxacin hydrochloride (AM-1977) is a novel 8-methoxy fluoroquinolone antibacterial agent with a unique pharmacophore at the 1st and 7th positions of the quinoline nucleus developed by Kyorin Pharmaceutical Co., Ltd. (Tokyo, Japan). It has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of respiratory tract and ear, nose and throat infections including community-acquired pneumonia and otorhinolaryngological infections, and shows great promise against fluoroquinolone-resistant strains of major pathogens which infect the respiratory tract. It is suitable for treating infections caused by Staphylococcus, Streptococcus, Pneumococcus, Moraxella (Branhamella) catarrhalis, Klebsiella, Enterobacter, Haemophilus influenzae, Legionella pneumophila, Prevotella and Mycoplasma pneumoniae that are sensitive to this drug.

Imipenem/cilastatin sodium/relebactam fixed combination to treat urinary infections and complicated intra-abdominal bacterial infections.

Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and ß-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative microorganisms in adult patients with limited or no alternative treatment options. The product was also approved by the European Medicines Agency (EMA) in 2020 for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.

Triclabendazole for the treatment of fascioliasis.

Fascioliasis is a neglected tropical disease that is commonly caused by flatworms affecting both domestic ruminants and humans. Fascioliasis currently affects roughly 17 million people globally with additional 180 million people at risk of developing infection. Despite the gigantic patient pool, clinicians typically have very few treatment options available. In this context, triclabendazole (Fasinex, Egaten) is the only medication approved by the Food and Drug Administration (FDA) for the treatment of fascioliasis. The FDA approval has been granted in 2019 although the drug was already utilized in the veterinary setting. Recently, three hits from the Pathogen Box have been identified in vitro as exhibiting potent anti-fascioliasis activity in an effort to identify other drugs active against fascioliasis.

Eravacycline for the treatment of patients with bacterial infections.

Eravacycline is a novel, broad-spectrum, synthetic fluorocycline antibiotic for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to multidrug-resistant Gram-positive, Gram-negative and anaerobic bacteria that has demonstrated superior potency to that of currently marketed antibiotics. Tetraphase Pharmaceuticals has submitted a new drug application for eravacycline for the treatment of cIAI due to drug-resistant bacteria. In 2013, the U.S. Food and Drug Administration (FDA) granted eravacycline qualified infectious disease product designation for the treatment of cUTI and cIAI.

An update on benznidazole for the treatment of patients with Chagas disease.

Chagas disease is a vector-borne, systemic and chronic parasitic infection caused by Trypanosoma cruzi with approximately 8 million cases worldwide. The treatment for acute phase of Chagas disease consists of benznidazole and nifurtimox, although this treatment combination falls short in terms of efficacy against chronic phases of infection. This review provides an update on benznidazole progress and approval by the U.S. Food and Drug Administration in 2017 for the treatment of Chagas disease along with its lacunae.

Bezlotoxumab for the treatment of Clostridium difficile-associated diarrhea.

Diarrhea caused by Clostridium difficile is one of the major emerging threats to modern healthcare systems worldwide. Although C. difficile spores are present in the gut innocuously, because of repeated broad-spectrum antibiotic therapy, the spores germinate with concomitant release of exotoxin A and B, resulting in mild to severe diarrhea. Antibiotic therapy is augmented by addition of the humanized antibodies actoxumab and bezlotoxumab to prevent the action of exotoxins A and B, respectively, since they provide passive immunity. Bezlotoxumab, a fully humanized monoclonal antibody developed against C. difficile toxin B, was approved by the U.S. Food and Drug Administration in 2016 to prevent the recurrence of C. difficile infections (CDI) in patients above 18 years of age who are receiving antibiotics for CDI and are at a higher risk of recurrence.

Delamanid for the treatment of pulmonary multidrug-resistant tuberculosis.

Out of a handful of new drugs currently in clinical trials for the treatment of tuberculosis, delamanid, a nitro-dihydro-imidazole derivative, has successfully emerged. Delamanid is a novel mycolic acid biosynthesis inhibitor that is equally potent against drug-sensitive as well as drug-resistant Mycobacterium tuberculosis. One of the strongest points for delamanid is its inability to be metabolized by cytochrome P450 enzymes, making it a promising candidate to be used in combination therapies for the treatment of tuberculosis and HIV. Additionally, it has successfully completed phase II efficacy trials and has received conditional marketing authorization from the European Medicines Agency.

Study of intercropping in periwinkle.

An experiment to study the feasibility of intercropping the short duration agronomical crops in periwinkle was conducted at Nagarjun Medicinal Plants Garden, P.K.V. Akola during 1988 - 89, 89 - 90 and 90 - 91. The highest monetary return of Rs. 15,604/ per hectare was obtained from an intercropping system of periwinkle and groundnut is row proportion of 2:1.

Varietal trial on palmarosa.

Field and laboratory investigations were undertaken at Nagarjun Medicinal Plants Garden from 1984 - 1987 with object to find out the suitable variety of palmarosa having high yield of foliage and oil. From the pooled analysis the variety IW - 3631 showed highest dry foliage yield (10271 KG / ha) which was significantly superior over all varieties i.e, IW 3632, IW-3630, IW RRL (B) - 65 and IW - 3629 except IW RRL (B) - 49. Oil contents and oil yield was also found to be more in variety IW 3631. Varieties IW - 3629 gave lowest oil yield and was at par with varieties IW - 3630 and IW - 3632.