Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model

Patel, Anasuya; Sangle, Ganesh V.; Trivedi, Jinal; Shengule, Sushant; Thorve, Deepak; Patil, Mohan; Deshmukh, Nitin; Choudhari, Bhushan; Karade, Avinash; Gupta, Sapna; Bhagwat, Sachin; Patel, Mahesh

doi:10.1128/aac.00084-20

Cited by 8 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This immunomodulatory finding was corroborated using histopathological evidence that suggested minimal infiltration of neutrophils into the lung tissue by levonadifloxacin after a lipopolysaccharide challenge. This feature may play a role in augmenting the clinical efficacy [17] . Levonadifloxacin has comparable antibacterial activity with other quinolones against Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

Prabhudesai

Jain

Borade

et al. 2021

ijirms

View full text Add to dashboard Cite

Background: Community-acquired bacterial pneumonia (CABP) remains a global public health threat and is a leading cause of hospitalization and infection-linked mortality. Levonadifloxacin is a novel benzoquinolizine antibiotic with a broad-spectrum activity including methicillin-resistant Staphylococcus aureus (MRSA) and CABP-pathogens. Methods: This multi-centre, retrospective, post-marketing, real-world study assessed the efficacy and safety of levonadifloxacin oral and/or intravenous therapy in the treatment of CABP. Data from 338 patients above 17 years-of-age who received levonadifloxacin (oral or intravenous or both) was collected from 89 healthcare facilities across India. Information on clinical condition, comorbidities, complications, and details of concurrent therapy (including antimicrobial agents) was also collected. Study outcomes were clinical and microbial success at the end of therapy while safety was assessed based on clinical and laboratory adverse events. Results: Of the 338 patients, 244 (72.2%) were male, 93 (27.5%) were female and 1 (0.43%) was a transgender. About 294 (87.0%) patients were hospital-treated and 44 (13%) received outpatient treatment. About 248 (73.4%) patients received intravenous levonadifloxacin treatment, 79 (23.4%) received oral and 11 (3.3%) received intravenous followed by oral levonadifloxacin therapy. The common comorbid conditions were diabetes (14.2%) and hypertension (8.6%). Mean duration of levonadifloxacin therapy was 6.4 days. Clinical and microbial success in levonadifloxacin-treated patients was 95.0% (321/388) and 96.8% (150/155), respectively. Conclusions: Levonadifloxacin showed promising clinical outcomes and safety when used as an intravenous and/or oral for the treatment of CABP, both in outpatients as well as hospitalized patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

Prabhudesai

Jain

Borade

et al. 2021

ijirms

View full text Add to dashboard Cite

show abstract

“…In light of the fact that COVID-19 patients may present with immunosuppression, anti-inflammatory activity of levonadifloxacin involving inhibition of proinflammatory cytokines, as established through nonclinical studies, could potentially offer clinical benefits in terms of early resolution of symptoms and restricting the progression towards severe respiratory disease. 23 The main strength of our study is that it includes data on real-word scenario for COVID-19 management from hospitals across the country and thus, this study provides insights on the use of AMAs in COVID-19 patients. Also, very few studies are reported from India regarding use of antibiotic in COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of intravenous and/or oral levonadifloxacin in the management of secondary bacterial pulmonary infections in COVID-19 patients: findings of a retrospective, real-world, multi-center study

Saseedharan

Aneja

Chowti³

et al. 2021

Int J Res Med Sci

View full text Add to dashboard Cite

Background: Owing to dysregulated immune response, secondary bacterial pulmonary infections involving both gram-positive and gram-negative pathogens are common in COVID-19 patients and are often associated with higher mortality. This is a first ever report on the safety and efficacy of levonadifloxacin in the treatment of secondary bacterial pulmonary infections in patients with COVID-19 pneumonia.Methods: This multi-center, retrospective, post-marketing and real-world study assessed the safety and efficacy of IV and/or oral levonadifloxacin in the treatment of bacterial infections encountered in COVID-19 patients. Data for 154 male/female patients above 18 years of age who received levonadifloxacin (injectable and/or oral) was collected from 44 participating sites. Study outcomes were the clinical and microbial success at the end of therapy. Safety was assessed based on clinical and laboratory adverse events.Results: Among the 154 patients assessed, 121 (78.6%) were males and 142 (92.2%) were hospitalized. Majority of the patients (119) received all-IV therapy while 11 patients were prescribed with IV followed by oral regimen. All-oral therapy was received by 24 patients. The most common co-morbid conditions were diabetes (19.6%) and hypertension (19.2%). Post-treatment with levonadifloxacin, clinical and microbial success rates were 96.8% and 97.0% respectively.Conclusions: Levonadifloxacin showed promising safety and efficacy when used as IV and/or oral therapy for the treatment of secondary bacterial pulmonary infections in COVID-19 patients. Clinically relevant features of levonadifloxacin such as availability of both IV and oral options, broad spectrum coverage and reassuring safety in patients with significant co-morbidities could help simplify the management.Trial registration no. CTRI/2020/09/028152 [Registered on: 30/09/2020].

show abstract

“…There is also activity against quinolone-susceptible Gram-negative bacteria including Escherichia coli, Klebsiella pneumoniae, Pseudomonas spp and Acinetobacter spp. Furthermore, after systemic administration, levonadifloxacin has inhibitory action against proinflammatory cytokines 74. Due to their antibacterial and anti-inflammatory properties, they are used topically for the treatment of acne vulgaris and may have a role in the role of ocular rosacea and related lid disease 75.…”

Section: Fluoroquinolonesmentioning

confidence: 99%

“…Furthermore, after systemic administration, levonadifloxacin has inhibitory action against proinflammatory cytokines. 74 Due to their antibacterial and anti-inflammatory properties, they are used topically for the treatment of acne vulgaris and may have a role in the role of ocular rosacea and related lid disease. 75 There are no data regarding its use as a topical ophthalmic medication, but it is a promising candidate.…”

Section: Fluoroquinolonesmentioning

confidence: 99%

Potential new fluoroquinolone treatments for suspected bacterial keratitis

et al. 2022

View full text Add to dashboard Cite

Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such asStaphylococcus aureus,Pseudomonas aeruginosa,Streptococcus pneumoniaeand several of theEnterobacteriaceae. However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.

show abstract

Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model

Cited by 8 publications

References 23 publications

Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

Efficacy and safety of intravenous and/or oral levonadifloxacin in the management of secondary bacterial pulmonary infections in COVID-19 patients: findings of a retrospective, real-world, multi-center study

Potential new fluoroquinolone treatments for suspected bacterial keratitis

Contact Info

Product

Resources

About