Besivance (besifloxacin ophthalmic suspension) / Bausch Health, Sun Pharma - LARVOL DELTA

Hantzsch Reaction-Based Fluorimetric Approach for Sensitive Determination of Besifloxacin in Pharmaceutical Eye Drops and Aqueous Humor. (PubMed, Luminescence) - "The dynamic range for BFC determination in the pure state is 0.15-1.0 (μg/mL), with detection and quantification limits of 0.02 and 0.05 (μg/mL), respectively. The approach exhibits favorable recovery rates in spiked aqueous humor (95.5% ± 1.15%-100.3% ± 0.50%)."

Journal

Clinical Ocular Exposure Extrapolation for a Complex Ophthalmic Suspension Using Physiologically Based Pharmacokinetic Modeling and Simulation. (PubMed, Pharmaceutics) - "Besifloxacin (Bes) suspension is presented as a case study...The O-PBPK model simulations adequately described the observed concentrations in the eye tissues following the topical administration of Bes suspension in rabbits. After adjustment of physiological parameters to represent the human eye, the extrapolation of clinical ocular exposure following a single ocular administration of Bes suspension was successful."

Journal • PK/PD data • Ophthalmology

Antibiotic resistance of bacterial pathogens isolated from the conjunctiva in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study (2009-2021). (PubMed, Diagn Microbiol Infect Dis) - "Staphylococci were commonly resistant to azithromycin (≥54.8%) and oxacillin (≥29.3%)...Among staphylococci, antibiotic resistance increased with patient age, and there were small decreases in resistance to several drugs over the 13-year period. These findings indicate that resistance to antibiotics routinely used in ophthalmic practice remains high among conjunctival isolates."

Journal • Conjunctivitis • Infectious Disease • Influenza • Ocular Infections • Ocular Inflammation • Ophthalmology • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Besifloxacin in Bacterial Keratitis (clinicaltrials.gov) - P=N/A | N=32 | Completed | Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre | Unknown status ➔ Completed

Trial completion • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology

Nano-Formulating Besifloxacin and Employing Quercetin as a Synergizer to Enhance the Potency of Besifloxacin against Pathogenic Bacterial Strains: A Nano-Synergistic Approach. (PubMed, Nanomaterials (Basel)) - "Their potent activity against S. aureus has its own clinical significance, as it is one the main causative agents of ocular infection, and besifloxacin is primarily used for treating infectious eye diseases. Thus, the outcomes of the present study could be explored further to provide better medication for eye infections caused by resistant pathogens."

Journal • Infectious Disease • Ocular Infections • Ophthalmology

Clinical Ocular Exposure Extrapolation Using PBPK Modeling and Simulation: Besifloxacin Suspension Case Study (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Ophthalmology

Retrospective Assessment of the Routine Use of Loteprednol Etabonate Gel 0.38% Following LASIK and PRK Surgery (ASCRS-ASOA 2023) - "Purpose To assess real world experience using loteprednol etabonate ophthalmic gel, 0.38% (LSM) for postoperative pain and inflammation following laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) surgery.MethodsThis was a retrospective chart review conducted at 4 sites in the United States.Cases from patients aged 18 years and above were eligible for inclusion.Data were collected from routine LASIK (N=240 eyes) or PRK (N=80 eyes) surgery cases (165 patients) in which LSM was used postoperatively as the clinician’s routine standard of care and in which patients had a minimum of one (LASIK) or two (PRK) months follow-up.Data evaluated included refractive characteristics, intraocular pressure (IOP) measurements, LSM dosing regimen, adverse events (AEs) and early discontinuations.The primary outcomes of interest included IOP changes, other AEs, and reasons for any early treatment discontinuation.ResultsCommon LSM dosing regimens were TID..."

Retrospective data • Surgery • Inflammation • Ophthalmology • Pain

Keratitis following leech therapy for periocular eczematous dermatitis: a case report. (PubMed, BMC Complement Med Ther) - "MLT should be performed by certified physicians with sterile medicinal leeches and precautious antibiotics should be used before MLT for prevention against potential infections."

Journal • Achromatopsia • Atopic Dermatitis • Corneal Abrasion • Dermatitis • Dermatology • Immunology • Infectious Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Pain

In Vitro Antibiotic Resistance Among Bacterial Pathogens from Pediatric Patients with Eye Infections: 13-year Results from the ARMOR Study (AAP-NCE 2022) - "Among S. aureus and CoNS, respectively, 58% and 74% were resistant to azithromycin and 24% and 46% were methicillin-resistant (MR); multidrug resistance (MDR; resistance to ≥3 drug classes) was found in 15% and 40%, and in 52% and 77% of MR strains thereof (Figure)...Respective MIC90s (MICs that inhibited 90% of isolates, in μg/mL) for besifloxacin/moxifloxacin/ciprofloxacin were 0.25/1/8 for S. aureus, 0.25/1/4 for CoNS, 0.06/0.25/1 for S. pneumoniae, 0.03/0.03/0.015 for H. influenzae, and 2/2/0.25 for P. aeruginosa... In vitro antibiotic resistance is common among staphylococci and pneumococcal isolates collected from pediatric patients, with a high prevalence of MDR among staphylococci, especially in MR strains. Besifloxacin had the lowest MICs against staphylococcal and pneumococcal strains and a comparable MIC to other fluoroquinolones against H. influenzae; ciprofloxacin had the lowest MIC against P. aeruginosa. The clinical significance of these in vitro data is..."

Preclinical • Infectious Disease • Influenza • Ocular Infections • Ophthalmology • Pediatrics • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation. (PubMed, Pharmaceutics) - "The innovative ophthalmic preparation minimum inhibitory concentration (MIC) was 0.0960 µg/mL and 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy. Therefore, besifloxacin nanocrystals revealed the potential for reduced dosing of the drug substance, with a minor occurrence of adverse effects and greater patient adherence to treatment."

Journal • Conjunctivitis • Infectious Disease • Ocular Infections • Ocular Inflammation • Ophthalmology

Association between initiation of fluoroquinolones and hospital admission or emergency department visit for suicidality: population based cohort study. (PubMed, BMJ) - "Initiation of fluoroquinolones was not associated with a substantially increased risk of admission to hospital or emergency department visits for suicidality compared with azithromycin or trimethoprim-sulfamethoxazole."

Journal • CNS Disorders • Infectious Disease • Nephrology • Pneumonia • Psychiatry • Respiratory Diseases • Suicidal Ideation

Genomic Characterization of Antimicrobial Resistance in Gram-Positive Bacteria Causing Keratitis (ASM Microbe 2022) - "Compared with methicillin-susceptible S. aureus, resistance to other antibiotics was more prevalent among MRSA isolates, with rates of resistance higher than 70% for fluoroquinolones (FQ) and azithromycin. The newest FQ (besifloxacin and moxifloxacin) had lower MIC90 compared with the earlier ones...epidermidis were also positive for the dfrC (82.6%) and tetK genes (21.7%) which confers resistance to diaminopyrimidine and tetracycline respectively...These isolates often carried macrolide resistance genes (ermB and mefA/msrD) that are integrated into mobile genetic elements. We provided an overview of current rates of resistance to antibiotics commonly used to treat keratitis caused by GPB and a characterization of the diversity of the associated molecular mechanisms that confer AMR."

Infectious Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Pneumonia

Design of Besifloxacin HCl-Loaded Nanostructured Lipid Carriers: In Vitro and Ex Vivo Evaluation. (PubMed, J Ocul Pharmacol Ther) - "It has the highest drug loading capacity and one of the highest ex vivo corneal passage levels, along with desired drug release. The formulation containing BHL/SBE-CD and chitosan can be a potential alternative for the treatment of bacterial keratitis."

Journal • Preclinical • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology

Minimum inhibitory concentration and mutant prevention concentration for besifloxacin and four other fluoroquinolones tested against ocular pathogens alone or in mixed organism assays (ECCMID 2022) - No abstract available

Killing of ocular pathogens in mixed pathogen assays by besifloxacin using minimum inhibitory concentration and mutant prevention concentration drug concentrations (ECCMID 2022) - No abstract available

Pharmacokinetics of a Hydrogel-based Besifloxacin Intracanalicular Insert in Canines (ARVO 2022) - "A hydrogel-based intracanalicular insert with besifloxacin produced clinically effective drug levels capable of killing the most common isolates of bacterial conjunctivitis for 21 days. A single dose besifloxacin intracanalicular insert may reduce the need for patients to self-administer antimicrobial therapy. Images: Figure 1."

PK/PD data • Conjunctivitis • Ocular Infections • Ocular Inflammation • Ophthalmology

Characterization of the resistome in gram-positive bacteria causing keratitis (ARVO 2022) - "The newest FQ (besifloxacin and moxifloxacin) had lower MIC90 overall compared with the earlier ones... We provided an overview of current rates of resistance to antibiotics commonly used to treat keratitis caused by GPB and a characterization of the diversity of the associated molecular mechanisms that confer antimicrobial resistance."

Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology

Antibiotic Resistance among Ocular Staphylococcal Pathogens: Longitudinal Trends in the ARMOR Study (ARVO 2022) - "Cumulative besifloxacin MIC90s (1 µg/mL for S. aureus and 2 µg/mL for CoNS) were 4- to 128-fold lower than other fluoroquinolones and comparable to vancomycin. Analyses of antibiotic resistance among staphylococci collected over 13 years in ARMOR indicate that in vitro resistance has decreased only slightly over this timeframe for several antibiotics and is still prevalent in 2021. Although the clinical relevance of in vitro data is unclear without consideration of the ocular pharmacokinetics of tested antibiotics, these findings warrant attention when choosing empiric therapy for the management of ocular staphylococcal infections."

Ocular Infections • Ophthalmology

Characterization of Polybacterial versus Monobacterial Conjunctivitis Infections in Pediatric Subjects Across Multiple Studies and Microbiological Outcomes with Besifloxacin Ophthalmic Suspension 0.6. (PubMed, Clin Ophthalmol) - "Treatment with besifloxacin resulted in microbial eradication in 79.1% of polybacterial and 92.3% of monobacterial infections (P≤0.005 vs vehicle). One in four pediatric bacterial conjunctivitis infections is polybacterial, highlighting the need for a broad-spectrum antibiotic when choosing empiric therapy."

Clinical • Journal • Conjunctivitis • Infectious Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Pediatrics • Pneumococcal Infections • Pneumonia • Respiratory Diseases

A novel, sensitive, and widely accessible besifloxacin quantification method by HPLC-fluorescence: Application to an ocular pharmacokinetic study. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Maximum concentrations were 1412 ± 1910 and 0.15 ± 0.12 μg/mL; area under the curve was 1,637 and 1.08 µg·h/g; and half-life was 4.9 and 4.1 h; and pharmacokinetic-to-pharmacodynamic ratios were ≥ 409 and ≤ 17.8 against ocular pathogens in tears and aqueous humor, respectively. This readily available method is sensitive for biosamples and practical for routine use, facilitating besifloxacin therapy development."

Journal • PK/PD data • Infectious Disease

[VIRTUAL] In Vitro Antibiotic Resistance Among Ocular Bacterial Pathogens from Children in the ARMOR Surveillance Study (AAP-NCE 2021) - "Among S. aureus and CoNS, respectively, 57% and 74% were resistant to azithromycin and 22% and 50% were methicillin-resistant (MR); multidrug resistance to ≥3 drug classes (MDR) was prevalent among MR strains (51% and 72%)...Besifloxacin was found to have the lowest MICs against staphylococcal and pneumococcal strains and a comparable MIC to other fluoroquinolones against H. influenzae; ciprofloxacin had the lowest MIC against P. aeruginosa (Table)... In vitro antibiotic resistance appears common among staphylococcal and pneumococcal isolates collected from pediatric patients, with MR staphylococci exhibiting high levels of MDR. The clinical relevance of these data are unclear without additional consideration of the ocular pharmacokinetics of tested antibiotics."

Preclinical • Infectious Disease • Ocular Infections • Ophthalmology • Pediatrics • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones-Shaping the Fifth Generation. (PubMed, Pharmaceutics) - "Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. Antibacterial quinolones class continues to acquire new compounds with antibacterial potential, among other effects. Numerous derivatives, hybrids or conjugates are currently in various stages of research."

Journal • Review

Spatiotemporal profiling of antibiotics and resistance genes in a river catchment: Human population as the main driver of antibiotic and antibiotic resistance gene presence in the environment. (PubMed, Water Res) - "All antibiotics, apart from four fluroquinolones (besifloxacin, lomefloxacin, ulifloxacin, prulifloxacin), were detected within all influent wastewater from the 5 cities (1 city = 1 WWTP), as were the corresponding antibiotic resistance genes (ARGs). The efficiency of ABs and ARGs removal by the WWTPs varied according to site (and treatment process utilized) and target, although strong correlations were maintained between the population size served by WWTPs and daily loads of discharged ABs and ARGs into the environment. We therefore conclude that population size is the main determinant of the magnitude of AB and ARG burden in the environment."

Clinical • Journal • Immunology

In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride. (PubMed, Pharmaceuticals (Basel)) - "In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms."

Combination therapy • Journal • Preclinical • Infectious Disease • Ocular Infections • Ophthalmology • Respiratory Diseases

[VIRTUAL] Analysis of Longitudinal Antibiotic Susceptibility Trends in Staphylococci: Results from 12 Years of the ARMOR Study (ARVO 2021) - "Besifloxacin retained consistently low MICs, with 2020 MIC90s (1 µg/mL for S. aureus and 2 µg/mL for CoNS) up to 128-fold lower than other fluoroquinolones. Over a 12-year span, staphylococci generally exhibited minimal or no change in in vitro antibiotic resistance. Although a small decrease in MR was observed among S. aureus (but not CoNS), the high level of MR in staphylococci warrants attention when selecting empiric antibiotic therapy, particularly with respect to multidrug resistance in these organisms."

Ocular Infections • Ophthalmology