India-discovered levonadifloxacin & alalevonadifloxacin: 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.

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.

Comparative evaluation of antifungal action of tea tree oil, chlorhexidine gluconate and fluconazole on heat polymerized acrylic denture base resin - an in vitro study.

OBJECTIVE: Candida albicans-associated denture stomatitis is the most common type of denture stomatitis seen in denture wearers. This study evaluates and compares the antifungal action of fluconazole, chlorhexidine gluconate and tea tree oil on heat-polymerised denture base resin, which has been previously contaminated with C. albicans grown in BHI broth. MATERIAL AND METHODS: Seventy-five specimens were immersed in BHI broth previously inoculated with C. albicans and stored for 3 h at 37°C. They were divided into five groups (n = 15): G1: 2% chlorhexidine solution; G2: 100% pure pharmaceutical grade tea tree oil; G3: 65 µg/ml fluconazole solution; C1: specimens not disinfected; C2: specimens not contaminated with Candida. Each specimen was then transferred to individual tubes containing BHI broth and incubated for 24 h. Culture media turbidity was evaluated for absorbance over a period of 14 days using a microplate reader. It was observed that the lower the absorbance, the stronger the antimicrobial action. Statistical analysis was performed (two-way anova and Bonferroni test, p < 0.001). RESULTS: Chlorhexidine and tea tree oil inhibited Candida up to the 14th day, whereas antifungal effect of fluconazole was not significant after the 7th day. CONCLUSION: Tea tree oil and chlorhexidine gluconate are more effective than fluconazole in inhibiting C. albicans growth on heat-polymerised acrylic resin.