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Doripenem
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Doripenem is currently approved by the FDA for use in patients with complicated intraabdominal infection and complicated urinary tract infection (Shionogi, 2015). The indications vary somewhat by market, with a very broad list of conditions contained in the Japanese product information (Shionogi, 2013). Due to the evanescent nature of the agent in many markets, it seems unlikely there will be further large randomized trials undertaken to better inform the indications for use of doripenem in the foreseeable future. The failure in many markets most likely relates to the inferior efficacy of doripenem compared with imipenem–cilastatin for therapy of ventilator associated pneumonia in a 2012 clinical trial (Kollef et al., 2012), as discussed in section 7c, Hospital-acquired pneumonia, including ventilator-associated pneumonia.
Selected strategies to fight pathogenic bacteria
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Aiva Plotniece, Arkadij Sobolev, Claudiu T. Supuran, Fabrizio Carta, Fredrik Björkling, Henrik Franzyk, Jari Yli-Kauhaluoma, Koen Augustyns, Paul Cos, Linda De Vooght, Matthias Govaerts, Juliana Aizawa, Päivi Tammela, Raivis Žalubovskis
Doripenem is a new thienamycin-inspired antibiotic, which can be used parenterally. Thienamycin, isolated from Streptomyces cattleya in 1976, was found highly activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase, however, this compound was too metabolically unstable to be further developed9. The thienamycin analogue doripenem has an enhanced metabolic stability to renal dehydropeptidase-1 due to the 1β-methyl substituent in the carbapenem skeleton10. Doripenem is a broad-spectrum antibiotic against many pathogenic bacteria, including the Gram-negative Pseudomonas aeruginosa. The key synthetic step (Scheme 3) is a coupling between the 4-nitrobenzyl-protected enol phosphate and substituted 3-mercaptopyrrolidine11.
New insights on the phytochemical intervention for the treatment of neuropsychiatric disorders using the leaves of Michelia champaca: an in vivo and in silico approach
Published in Pharmaceutical Biology, 2022
Pushpa V. H., Jayanthi M. K., Rashmi H. R., Veeresh Kumar N. Shivamurthy, Shashank M. Patil, Prithvi S. Shirahatti, Ramith Ramu
Based on the biological result interpretations, M. champaca leaves extracted using ethanol as a solvent is a rich source of compounds with potential antidepressant and anxiolytic properties. In vivo findings also support their traditional importance as potent formulations in the treatment of depression and anxiety. Besides, the molecular docking study revealed that doripenem showed good interaction with both human potassium channel KSCA-FAB and human serotonin transporter proteins docking simulations, in comparison with reference drugs, thereby showing in silico anxiolytic and antidepressant activities, respectively. The drug-likeness and toxicity profile of doripenem also favours it as an effective potential drug candidate, whereas reference drugs were reported with toxicity predictions. Overall, this study paves way for future research in understanding the ethnomedicinal uses of M. champaca leaves in the treatment of anxiety and depression.
Pharmacotherapeutic advances for recurrent urinary tract infections in women
Published in Expert Opinion on Pharmacotherapy, 2020
Mohamad Moussa, Mohamed Abou Chakra, Athanasios Dellis, Yasmin Moussa, Athanasios Papatsoris
Ceftazidime-avibactam (C-A) is a novel β-lactam/β-lactamase inhibitor combination that was recently approved by FDA for the cUTIs. C-A may offer a significant advance over previously developed antimicrobials with in vitro activity against CRE, such as colistin, gentamicin, and tigecycline, which are limited by concerns over the efficacy and/or toxicity [135]. Phase 3 RECAPTURE trial was done to compare the efficacy and safety of C-A and doripenem in patients with cUTIs, including acute pyelonephritis. C-A 2000 mg/500 mg every 8 hours or doripenem 500 mg every 8 hours (doses adjusted for renal function) were used. Noninferiority of C-A vs. doripenem was demonstrated for the FDA co-primary endpoints. C-A was found to be highly effective for the empiric treatment of cUTIs (including acute pyelonephritis), and may offer an alternative to carbapenems [136].