TY - JOUR
T1 - India-discovered levonadifloxacin & alalevonadifloxacin
T2 - A review on susceptibility testing methods, CLSI quality control and breakpoints along with a brief account of their emerging therapeutic profile as a novel standard-of-care
AU - Drug Discovery group, Wockhardt
AU - Veeraraghavan, Balaji
AU - Bakthavatchalam, Yamuna Devi
AU - Manesh, Abi
AU - Lal, Binesh
AU - Swaminathan, Subramanian
AU - Ansari, Abdul
AU - Subbareddy, K.
AU - Rangappa, Pradeep
AU - Choudhuri, Anirban Hom
AU - Nagvekar, Vasant
AU - Mehta, Yatin
AU - Appalaraju, Boppe
AU - Baveja, Sujata
AU - Baliga, Shrikala
AU - Shenoy, Suchitra
AU - Bhardwaj, Renu
AU - Kongre, Vaishali
AU - Dattatraya, Gogi Suresh
AU - Verma, Binita
AU - Mukherjee, D. N.
AU - Gupta, Shalini
AU - Shanmugam, Priyadarshini
AU - Iravane, Jyoti
AU - Mishra, Sudhi Ranjan
AU - Barman, Purabi
AU - Chopra, Shimpi
AU - Hariharan, Meenakshi
AU - Surpam, Rajendra
AU - Pratap, Rana
AU - Turbadkar, Dilip
AU - Taklikar, Shripad
N1 - Funding Information:
†Wockhardt Drug Discovery Group: Mahesh Patel, Prasad Deshpande, Satish Bhavsar, Ravindra Yeole, Sachin Bhagwat, Swapna Takalkar, Hariharan Periasamy, Suyog Vaidya, Snehal Palwe, Prashant Joshi, Rajesh Chavan, Vineet Zope, Anasuya Patel, Manohar Nandanwar, Atul Kansagara, Sangita Gupta, Muqtedar Patel, Arvind Merwade, Dinesh Shinde.
Publisher Copyright:
© 2023 Indian Association of Medical Microbiologists
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background: Levonadifloxacin (intravenous) and alalevonadifloxacin (oral prodrug) are novel antibiotics based on benzoquinolizine subclass of fluoroquinolone, licensed for clinical use in India in 2019. The active moiety, levonadifloxacin, is a broad-spectrum antibiotic with a high potency against methicillin-resistant Staphylococcus. aureus, multi-drug resistant pneumococci and anaerobes. Objective: This review, for the first time, critically analyses the antimicrobial susceptibility testing methods, Clinical Laboratory & Standards Institute (CLSI)-quality control of susceptibility testing and breakpoints of levonadifloxacin. Further, the genesis, discovery and developmental aspects as well as therapeutic profile of levonadifloxacin and alalevonadifloxacin are briefly described. Contents: In order to aid the scientific and clinician communities with a single comprehensive overview on all the key aspects of levonadifloxacin and alalevonadifloxacin, the present article covers the reference MIC and disk diffusion methods for levonadifloxacin susceptibility testing that were approved by CLSI and the reference ranges for quality control strains published in the CLSI M100 document. The breakpoints of levonadifloxacin were derived in concordance to US FDA, European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI approaches. Further, the article provides a brief account of challenges encountered during the discovery stages of levonadifloxacin and alalevonadifloxacin, activity spectrum and safety benefits accruing from structural novelty-linked mechanism of action. Further, the review also covers in vitro and in vivo activities, registrational clinical studies and patient-friendly features of levonadifloxacin/alalevonadifloxacin. Cumulatively, levonadifloxacin has a potential to offer a long awaited new standard-of-care treatment for the resistant Gram-positive bacterial infections.
AB - Background: Levonadifloxacin (intravenous) and alalevonadifloxacin (oral prodrug) are novel antibiotics based on benzoquinolizine subclass of fluoroquinolone, licensed for clinical use in India in 2019. The active moiety, levonadifloxacin, is a broad-spectrum antibiotic with a high potency against methicillin-resistant Staphylococcus. aureus, multi-drug resistant pneumococci and anaerobes. Objective: This review, for the first time, critically analyses the antimicrobial susceptibility testing methods, Clinical Laboratory & Standards Institute (CLSI)-quality control of susceptibility testing and breakpoints of levonadifloxacin. Further, the genesis, discovery and developmental aspects as well as therapeutic profile of levonadifloxacin and alalevonadifloxacin are briefly described. Contents: In order to aid the scientific and clinician communities with a single comprehensive overview on all the key aspects of levonadifloxacin and alalevonadifloxacin, the present article covers the reference MIC and disk diffusion methods for levonadifloxacin susceptibility testing that were approved by CLSI and the reference ranges for quality control strains published in the CLSI M100 document. The breakpoints of levonadifloxacin were derived in concordance to US FDA, European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI approaches. Further, the article provides a brief account of challenges encountered during the discovery stages of levonadifloxacin and alalevonadifloxacin, activity spectrum and safety benefits accruing from structural novelty-linked mechanism of action. Further, the review also covers in vitro and in vivo activities, registrational clinical studies and patient-friendly features of levonadifloxacin/alalevonadifloxacin. Cumulatively, levonadifloxacin has a potential to offer a long awaited new standard-of-care treatment for the resistant Gram-positive bacterial infections.
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U2 - 10.1016/j.ijmmb.2022.11.005
DO - 10.1016/j.ijmmb.2022.11.005
M3 - Review article
C2 - 36509611
AN - SCOPUS:85145232220
SN - 0255-0857
VL - 41
SP - 71
EP - 80
JO - Indian Journal of Medical Microbiology
JF - Indian Journal of Medical Microbiology
ER -
