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Timothy W Morris - One of the best experts on this subject based on the ideXlab platform.
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clinical and antibacterial efficacy and safety of Besifloxacin ophthalmic suspension compared with moxifloxacin ophthalmic solution
Asia-Pacific journal of ophthalmology, 2017Co-Authors: Prashant Garg, Timothy W Morris, Umang Mathur, Parul Sony, Radhika Tandon, Timothy L. ComstockAbstract:PURPOSE To evaluate the efficacy of Besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% in the treatment of bacterial conjunctivitis in an Indian population. DESIGN Multicenter, randomized, double-masked, active-controlled, parallel-group, clinical trial, including 6 clinical sites in India. METHODS Patients were randomized to receive 1 drop of Besifloxacin or moxifloxacin in the infected eye(s), 3 times daily, for 5 days. Primary efficacy end points included clinical resolution and bacterial eradication at day 5. Secondary efficacy end points included clinical resolution and bacterial eradication at day 8, ocular discharge, bulbar conjunctival injection, investigator's global assessment, and bacterial eradication by species. Efficacy was analyzed using the Cochran-Mantel-Haenszel and Pearson χ2 tests. Safety was assessed by the incidence of ocular and nonocular treatment-emergent adverse events (AEs), changes in visual acuity, and biomicroscopy and ophthalmoscopy findings. Data presented are that for the subset of patients from India. RESULTS Of the 123 patients randomized at clinical sites in India, 96.7% completed the study. Day 5 differences in microbial eradication (100% Besifloxacin vs 96.3% moxifloxacin) and in clinical resolution (78.9% Besifloxacin vs 71.4% moxifloxacin) were not statistically significant. No statistically significant between-group differences were observed for secondary end points. All ocular AEs in both groups were mild or moderate in severity. There were no drug-related ocular AEs with Besifloxacin. CONCLUSIONS Treatment of bacterial conjunctivitis with Besifloxacin 0.6% produces similar antibacterial and clinical efficacy as that with moxifloxacin 0.5% in an Indian population, with no clinically meaningful safety concerns.
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© 2013 Haas et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Clinical Ophthalmology 2013:7 821–830
2016Co-Authors: Clinical Ophthalmology, Christine K Hesje, Wolfgang Haas, Timothy W MorrisAbstract:Contribution of the R8 substituent to the in vitro antibacterial potency of Besifloxacin and comparator ophthalmic fluoroquinolone
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antibacterial efficacy of prophylactic Besifloxacin 0 6 and moxifloxacin 0 5 in patients undergoing cataract surgery
Clinical Ophthalmology, 2015Co-Authors: Frank A Bucci, Timothy W Morris, Heleen H Decory, Christine M Sanfilippo, R E Evans, L M Amico, Angel T Fluet, Timothy L. ComstockAbstract:Background The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of Besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients. Methods This was a prospective, randomized, laboratory-masked clinical trial. Patients received Besifloxacin or moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints. Results Fifty-nine patients (n=28 Besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only Besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer Besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of Besifloxacin against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin. Conclusion Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacin. Besifloxacin was more active in vitro against MRSE.
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clinical outcomes with Besifloxacin ophthalmic suspension 0 6 in the treatment of bacterial conjunctivitis due to potentially consequential pathogens
Clinical Optometry, 2014Co-Authors: Timothy L. Comstock, Timothy W Morris, Lynne S. Gearinger, Heleen H DecoryAbstract:Purpose: Besifloxacin is a chlorofluoroquinolone approved for use in the treatment of bacterial conjunctivitis. This study assessed the clinical efficacy of Besifloxacin ophthalmic suspension 0.6% against conjunctivitis infections caused by potentially consequential pathogens. Design: Post hoc analysis of clinical outcomes for patients with conjunctival infections due to Pseudomonas aeruginosa, Serratia marcescens, Neisseria spp., methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE) who were treated with Besifloxacin in four multicenter, double-masked, randomized clinical trials. Methods: Minimum inhibitory concentrations (MICs) of Besifloxacin against potentially conse quential pathogens were pooled. Clinical outcome data for patients treated with Besifloxacin with baseline infections due to these pathogens were pooled and summarized. Bacterial eradication was defined as the absence of ocular bacterial species present at or above threshold at baseline. Results: A total of 1,317 patients had culture-confirmed bacterial conjunctivitis across the four studies, and 151 infections were due to the aforementioned pathogens (P. aeruginosa n=9; S. marcescens n=10; Neisseria spp. n=16; MRSA n=35; MRSE n=81). Among MRSA and MRSE infections, 48.3% demonstrated concurrent ciprofloxacin resistance (ciprofloxacinresistant [CipR]-MRSA n=24; CipR-MRSE n=32). The MIC 90 (MIC for 90% of isolates) for Besifloxacin was 1 µg/mL for S. marcescens, 0.25 µg/mL for Neisseria spp., 0.06 µg/mL for both ciprofloxacin-sensitive MRSA and ciprofloxacin-sensitive MRSE, and 4 µg/mL for both CipR-MRSA and CipR-MRSE. Against P. aeruginosa, the MIC range was 1–4 µg/mL. Bacterial eradication rates in patients treated with Besifloxacin were 100% by the first follow-up visit for infections due to P. aeruginosa, S. marcescens, and Neisseria spp. and 87.8% by the second follow-up visit for infections due to MRSA and MRSE. Conclusion: The use of Besifloxacin ophthalmic suspension 0.6% in the treatment of conjunc tival infections due to potentially consequential pathogens resulted in high rates of bacterial
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the safety of Besifloxacin ophthalmic suspension 0 6 used three times daily for 7 days in the treatment of bacterial conjunctivitis
Drugs in R & D, 2013Co-Authors: Ranjan Malhotra, Timothy W Morris, Lynne S. Gearinger, Stacey Ackerman, Catherine AllaireAbstract:Background Besifloxacin ophthalmic suspension 0.6 % (Besivance®; Bausch & Lomb, Rochester, NY, USA) was approved by the FDA in 2009 for the treatment of bacterial conjunctivitis, with a recommended 7-day dosing regimen.
Timothy L. Comstock - One of the best experts on this subject based on the ideXlab platform.
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clinical and antibacterial efficacy and safety of Besifloxacin ophthalmic suspension compared with moxifloxacin ophthalmic solution
Asia-Pacific journal of ophthalmology, 2017Co-Authors: Prashant Garg, Timothy W Morris, Umang Mathur, Parul Sony, Radhika Tandon, Timothy L. ComstockAbstract:PURPOSE To evaluate the efficacy of Besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% in the treatment of bacterial conjunctivitis in an Indian population. DESIGN Multicenter, randomized, double-masked, active-controlled, parallel-group, clinical trial, including 6 clinical sites in India. METHODS Patients were randomized to receive 1 drop of Besifloxacin or moxifloxacin in the infected eye(s), 3 times daily, for 5 days. Primary efficacy end points included clinical resolution and bacterial eradication at day 5. Secondary efficacy end points included clinical resolution and bacterial eradication at day 8, ocular discharge, bulbar conjunctival injection, investigator's global assessment, and bacterial eradication by species. Efficacy was analyzed using the Cochran-Mantel-Haenszel and Pearson χ2 tests. Safety was assessed by the incidence of ocular and nonocular treatment-emergent adverse events (AEs), changes in visual acuity, and biomicroscopy and ophthalmoscopy findings. Data presented are that for the subset of patients from India. RESULTS Of the 123 patients randomized at clinical sites in India, 96.7% completed the study. Day 5 differences in microbial eradication (100% Besifloxacin vs 96.3% moxifloxacin) and in clinical resolution (78.9% Besifloxacin vs 71.4% moxifloxacin) were not statistically significant. No statistically significant between-group differences were observed for secondary end points. All ocular AEs in both groups were mild or moderate in severity. There were no drug-related ocular AEs with Besifloxacin. CONCLUSIONS Treatment of bacterial conjunctivitis with Besifloxacin 0.6% produces similar antibacterial and clinical efficacy as that with moxifloxacin 0.5% in an Indian population, with no clinically meaningful safety concerns.
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2016Co-Authors: Clinical Ophthalmology, Joel W Proksch, Gail Torkildsen, Aron Shapiro, Stephanie K Lynch, Timothy L. ComstockAbstract:Concentrations of Besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administratio
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antibacterial efficacy of prophylactic Besifloxacin 0 6 and moxifloxacin 0 5 in patients undergoing cataract surgery
Clinical Ophthalmology, 2015Co-Authors: Frank A Bucci, Timothy W Morris, Heleen H Decory, Christine M Sanfilippo, R E Evans, L M Amico, Angel T Fluet, Timothy L. ComstockAbstract:Background The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of Besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients. Methods This was a prospective, randomized, laboratory-masked clinical trial. Patients received Besifloxacin or moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints. Results Fifty-nine patients (n=28 Besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only Besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer Besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of Besifloxacin against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin. Conclusion Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacin. Besifloxacin was more active in vitro against MRSE.
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clinical outcomes with Besifloxacin ophthalmic suspension 0 6 in the treatment of bacterial conjunctivitis due to potentially consequential pathogens
Clinical Optometry, 2014Co-Authors: Timothy L. Comstock, Timothy W Morris, Lynne S. Gearinger, Heleen H DecoryAbstract:Purpose: Besifloxacin is a chlorofluoroquinolone approved for use in the treatment of bacterial conjunctivitis. This study assessed the clinical efficacy of Besifloxacin ophthalmic suspension 0.6% against conjunctivitis infections caused by potentially consequential pathogens. Design: Post hoc analysis of clinical outcomes for patients with conjunctival infections due to Pseudomonas aeruginosa, Serratia marcescens, Neisseria spp., methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE) who were treated with Besifloxacin in four multicenter, double-masked, randomized clinical trials. Methods: Minimum inhibitory concentrations (MICs) of Besifloxacin against potentially conse quential pathogens were pooled. Clinical outcome data for patients treated with Besifloxacin with baseline infections due to these pathogens were pooled and summarized. Bacterial eradication was defined as the absence of ocular bacterial species present at or above threshold at baseline. Results: A total of 1,317 patients had culture-confirmed bacterial conjunctivitis across the four studies, and 151 infections were due to the aforementioned pathogens (P. aeruginosa n=9; S. marcescens n=10; Neisseria spp. n=16; MRSA n=35; MRSE n=81). Among MRSA and MRSE infections, 48.3% demonstrated concurrent ciprofloxacin resistance (ciprofloxacinresistant [CipR]-MRSA n=24; CipR-MRSE n=32). The MIC 90 (MIC for 90% of isolates) for Besifloxacin was 1 µg/mL for S. marcescens, 0.25 µg/mL for Neisseria spp., 0.06 µg/mL for both ciprofloxacin-sensitive MRSA and ciprofloxacin-sensitive MRSE, and 4 µg/mL for both CipR-MRSA and CipR-MRSE. Against P. aeruginosa, the MIC range was 1–4 µg/mL. Bacterial eradication rates in patients treated with Besifloxacin were 100% by the first follow-up visit for infections due to P. aeruginosa, S. marcescens, and Neisseria spp. and 87.8% by the second follow-up visit for infections due to MRSA and MRSE. Conclusion: The use of Besifloxacin ophthalmic suspension 0.6% in the treatment of conjunc tival infections due to potentially consequential pathogens resulted in high rates of bacterial
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Aron Shapiro 3
2013Co-Authors: Joel W Proksch, Stephanie K Lynch, Timothy L. ComstockAbstract:Concentrations of Besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administratio
Wolfgang Haas - One of the best experts on this subject based on the ideXlab platform.
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© 2013 Haas et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Clinical Ophthalmology 2013:7 821–830
2016Co-Authors: Clinical Ophthalmology, Christine K Hesje, Wolfgang Haas, Timothy W MorrisAbstract:Contribution of the R8 substituent to the in vitro antibacterial potency of Besifloxacin and comparator ophthalmic fluoroquinolone
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Bactericidal activity of Besifloxacin against staphylococci, Streptococcus pneumoniae and Haemophilus influenzae
2013Co-Authors: Wolfgang Haas, Chris M Pillar, Christine K Hesje, Timothy W MorrisAbstract:Objectives: Besifloxacin is a novel fluoroquinolone that was recently approved for topical treatment of bacterial conjunctivitis. The compound was shown to be active in vitro against a broad spectrum of bacteria, including isolates resistant to other antibacterials. Here, the bactericidal activity of Besifloxacin was evaluated against the most common bacterial conjunctivitis pathogens. Methods: MIC, MBC and time–kill experiments with Besifloxacin and comparators were performed according to CLSI guidelines. Quinolone resistance-determining regions (QRDRs) were sequenced using standard PCR-based techniques. Results: MIC and MBC data indicated that Besifloxacin was the most potent fluoroquinolone tested against Staphylococcus aureus (n30), Staphylococcus epidermidis (n15) and Streptococcus pneumoniae (n35), while all fluoroquinolones were highly active against Haemophilus influenzae (n40). Besifloxacin MBC:MIC ratios were ≤4 for 97.5 % of all isolates tested (n120). All fluoroquinolones tested, as well as tobramycin, were bactericidal, while azithromycin was bactericidal against S. pneumoniae and H. influenzae, but bacteriostatic against the staphylococci. Time–kill assays with all four species showed that Besifloxacin caused ≥1000-fold killing within 2 h for 11 of 12 isolates. Only one isolate treated with moxifloxacin and three ciprofloxacin-treated isolates achieved the same level of bactericidal activity under the same conditions
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Pharmaceutical Medical Affairs, Bausch
2013Co-Authors: Wolfgang Haas, Lynne S. Gearinger, Dale W. Usner, Heleen H Decory, Timothy W MorrisAbstract:Integrated analysis of three bacterial conjunctivitis trials of Besifloxacin ophthalmic suspension, 0.6%: etiology of bacterial conjunctivitis and antibacterial susceptibility profil
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contribution of the r8 substituent to the in vitro antibacterial potency of Besifloxacin and comparator ophthalmic fluoroquinolones
Clinical Ophthalmology, 2013Co-Authors: Wolfgang Haas, Christine M Sanfilippo, Christine K Hesje, Timothy W MorrisAbstract:INTRODUCTION Previous work has shown that Besifloxacin, an 8-chloro-fluoroquinolone, has more potent activity against gram-positive pathogens than moxifloxacin and gatifloxacin, which carry an 8-methoxy group. This study was conducted to determine the contribution of the R7 and R8 substituent to fluoroquinolone antibacterial activity. MATERIALS AND METHODS Besifloxacin, moxifloxacin, gatifloxacin, their R8 structural analogs, and ciprofloxacin were tested against representative isolates of various gram-positive and gram-negative species and previously characterized fluoroquinolone-resistant mutants of Staphylococcus aureus. Minimum inhibitory and minimum bactericidal concentrations were determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Reserpine was used to determine the effect of efflux pumps on antibacterial activity. RESULTS In general, exchanging the R8 residue in Besifloxacin slightly reduced the molecule's potency, while introducing an 8-chloro group in moxifloxacin increased its potency. A similar change in gatifloxacin had little to no effect. Substituting the R8 residues did not increase the susceptibility to the efflux pump inhibitor reserpine or result in a loss of bactericidal activity. In contrast, the positive control, ciprofloxacin, was shown to be a substrate for reserpine and lost bactericidal activity against some fluoroquinolone-resistant isolates of S. aureus. CONCLUSION The data presented here show that, depending on the R7 substituent, replacing an 8-methoxy group with an 8-chloro substituent can improve potency or can have little-to-no effect. These findings highlight the importance of the interplay between the R7 and R8 substituents in determining antibacterial potency.
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microbiological etiology and susceptibility of bacterial conjunctivitis isolates from clinical trials with ophthalmic twice daily Besifloxacin
Advances in Therapy, 2012Co-Authors: Wolfgang Haas, Lynne S. Gearinger, Christine M Sanfilippo, Christine K Hesje, Timothy W MorrisAbstract:Bacterial conjunctivitis is a contagious infection of the surface of the eye usually treated empirically with topical antibiotics. Since the etiologic agent is rarely identified, it is important to monitor which bacteria cause conjunctivitis and determine their antibacterial resistance profiles. A total of 496 bacterial samples were isolated during a randomized, double-masked, vehicle-controlled, parallel-group study conducted in the United States with Besifloxacin ophthalmic suspension 0.6% dosed twice daily. Species were determined by standard biochemical and/or molecular identification methods. Minimum inhibitory concentrations were determined according to Clinical and Laboratory Standards Institute standards. The most prevalent species was Haemophilus influenzae, followed by Staphylococcus epidermidis, Staphylococcus aureus, the Streptococcus mitis group, and Streptococcus pneumoniae. One species identified in this study, which was not previously noted as a common cause of bacterial conjunctivitis, was Dolosigranulum pigrum. Ampicillin resistance was common among H. influenzae isolates, while macrolide resistance was high among S. pneumoniae, S. epidermidis, and S. aureus. The latter two species also included a number of isolates resistant to methicillin and ciprofloxacin. Antibiotic resistance among isolates remains a concern and the appearance of an emerging ocular pathogen, D. pigrum, suggests the need for continued observation. The topical ophthalmic fluoroquinolones continue to provide a good balance of low to moderate (i.e., manageable) levels of resistance plus broad-spectrum coverage for empiric treatment of ocular infections.
Christine M Sanfilippo - One of the best experts on this subject based on the ideXlab platform.
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characterization of baseline polybacterial versus monobacterial infections in three randomized controlled bacterial conjunctivitis trials and microbial outcomes with Besifloxacin ophthalmic suspension 0 6
PLOS ONE, 2020Co-Authors: Heleen H Decory, Christine M Sanfilippo, Howard M Proskin, Joseph M BlondeauAbstract:Background/Purpose To date, studies examining polymicrobial infections in ocular disease have mostly been limited to keratitis or endophthalmitis. We characterized polybacterial infections compared to monobacterial infections in prior clinical studies evaluating Besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial conjunctivitis and report on associated microbiological outcomes. Methods In this post-hoc analysis, microbiological data for subjects with conjunctivitis due to one or more than one bacterial species in three previous studies (two vehicle-, one active-controlled) of Besifloxacin were extracted. Bacterial species identified at baseline were deemed causative if their colony count equaled or exceeded species-specific prespecified threshold criteria. In subjects with polybacterial infections, the fold-increase over threshold was used to rank order the contribution of individual species. Baseline pathogens and their minimum inhibitory concentrations (MICs) for common ophthalmic antibiotics were compared by infection type, as were microbial eradication rates following treatment with Besifloxacin. Results Of 1041 subjects with culture-confirmed conjunctivitis, 17% had polybacterial and 83% had monobacterial conjunctivitis at baseline. In polybacterial compared to monobacterial infections, Haemophilus influenzae and Streptococcus pneumoniae were identified less frequently as the dominant infecting species (P = 0.042 and P<0.001, respectively), whereas Streptococcus mitis/S. mitis group was identified more frequently as dominant (P<0.001). Viral coinfection was also identified more frequently in polybacterial infections (P<0.001). Staphylococcus aureus was the most common coinfecting species in polybacterial infections and the second most common dominant species in such infections. With few exceptions, MICs for individual species were comparable regardless of infection type. Clinical microbial eradication rates with Besifloxacin were high regardless of infection type (P≤0.016 vs vehicle at follow-up visits). Conclusions Approximately one in five subjects with bacterial conjunctivitis are infected with more than one bacterial species underscoring the need for a broad-spectrum antibiotic for such infections. Besifloxacin treatment resulted in robust eradication rates of these infections comparable to monobacterial infections. Trial registration NCT000622908, NCT00347932, NCT00348348
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an evaluation of staphylococci from ocular surface infections treated empirically with topical Besifloxacin antibiotic resistance molecular characteristics and clinical outcomes
Ophthalmology and therapy, 2020Co-Authors: Barry A Schechter, Heleen H Decory, Christine M Sanfilippo, John D Sheppard, Penny A AsbellAbstract:Understanding antibiotic resistance and toxin profiles among staphylococcal isolates in ocular infections can aid in therapeutic management and infection prevention strategies. We evaluated in vitro antibiotic resistance patterns and molecular traits of staphylococci isolated from patients with ocular surface infections. We also report on clinical outcomes for these patients following empirical treatment with topical Besifloxacin ophthalmic suspension 0.6%. This was a small observational study. Participating investigators from three clinical sites collected an initial ocular culture from the affected eye of patients presenting with ocular surface infections with presumed staphylococcal etiology. Clinical outcome data for patients with confirmed staphylococcal infections were collated later through retrospective review of patient medical records. Staphylococcal species identification in ocular cultures, in vitro antibiotic susceptibility testing, and PCR-based determination of methicillin resistance cassettes and toxin genotypes were conducted at a central laboratory. Isolates were categorized as susceptible or resistant based on systemic breakpoints, where available. Cultures were collected from 43 patients, and staphylococcal infections were confirmed in 25 patients. Two isolates of Staphylococcus aureus and 27 isolates of Staphylococcus epidermidis were identified. Both S. aureus isolates were methicillin-susceptible, lacked the gene encoding Panton-Valentine leukocidin, and carried few enterotoxin genes. Eight (30%) S. epidermidis were methicillin-resistant (MRSE), and 10 (37%) were ciprofloxacin-resistant. All but two MRSE isolates demonstrated multidrug resistance (MDR), and the staphylococcal cassette chromosome mec (SCCmec) type IVa was detected in five of the eight MRSE isolates. Clinical resolution of the ocular surface infection was reported in all 25 patients following treatment with Besifloxacin. In this study, S. aureus contained few toxins, while SCCmec IVa and MDR was predominant among MRSE from ocular surface infections. Despite significant in vitro fluoroquinolone resistance, there were no cases of treatment failure with topical Besifloxacin ophthalmic suspension 0.6%. Bausch Health US, LLC.
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Besifloxacin ophthalmic suspension 0 6 compared with gatifloxacin ophthalmic solution 0 3 for the treatment of bacterial conjunctivitis in neonates
Drugs in R & D, 2017Co-Authors: Christine M Sanfilippo, Catherine Allaire, Heleen H DecoryAbstract:The aim of this study was to evaluate the safety and efficacy of topical Besifloxacin ophthalmic suspension 0.6% compared with gatifloxacin ophthalmic solution 0.3% in the treatment of bacterial conjunctivitis in neonates. This was a multicenter, randomized, double-masked, parallel group study. Subjects ≤31 days of age with severity grade ≥1 (scale 0–3) for both conjunctival discharge and conjunctival hyperemia were randomized to Besifloxacin or gatifloxacin instilled three times daily for 7 days, and completed five study visits (three clinic visits and two phone calls). Primary endpoints included clinical resolution (absence of both conjunctival discharge and conjunctival hyperemia) at visit 5 (day 8 or 9) and ocular and non-ocular treatment-emergent adverse events (AEs). Bacterial eradication was a secondary endpoint. Thirty-three subjects were included in the intent-to-treat (ITT) population. All were aged <28 days, with a mean (standard deviation) age of 15.5 days (6.0), and 57.6% were female. Twenty-two subjects had culture-confirmed conjunctivitis in at least one eye (modified ITT [mITT] population), most often with Gram-positive bacteria. Visit 5 clinical resolution and bacterial eradication rates were comparable among Besifloxacin- and gatifloxacin-treated study eyes (clinical resolution: 12/16 [75.0%] vs. 12/17 [70.6%] for the ITT population, and 11/13 [84.6%] vs. 7/9 [77.8%] for the mITT population; bacterial eradication: 12/13 [92.3%] vs. 8/9 [88.9%] for the mITT population, respectively). No AEs were reported in the Besifloxacin treatment group, and AEs reported in the gatifloxacin group were considered not treatment-related. In this small study in neonates, both Besifloxacin and gatifloxacin appeared effective and safe in the treatment of bacterial conjunctivitis. Larger studies are warranted.
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Besifloxacin: Efficacy and Safety in Treatment and Prevention of Ocular Bacterial Infections
Ophthalmology and Therapy, 2016Co-Authors: Francis S. Mah, Christine M SanfilippoAbstract:This comprehensive review summarizes the mechanism of action, pharmacokinetics, efficacy, and safety of Besifloxacin ophthalmic suspension, 0.6% and examines its role in the treatment of ocular surface bacterial infections. Besifloxacin possesses balanced activity against bacterial topoisomerase II (also called DNA gyrase) and topoisomerase IV. It has shown a low potential to select for bacterial resistance in vitro and demonstrated strong in vitro activity against many Gram-positive, Gram-negative, and anaerobic organisms, including methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis (MRSA and MRSE, respectively). Ocular pharmacokinetic studies have shown that Besifloxacin achieves high, sustained concentrations in the tear fluid and conjunctiva following topical administration, with negligible systemic exposure. Large randomized, controlled clinical trials have established the efficacy and safety of Besifloxacin administered three times daily for 5 days for treatment of acute bacterial conjunctivitis in both adults and children, with high rates of clinical resolution (up to more than 70% by day 5) and bacterial eradication (more than 90% by day 5), and a low incidence of adverse events. Additionally, Besifloxacin applied twice daily for 3 days demonstrated greater efficacy than vehicle in treating bacterial conjunctivitis. Case reports, a large retrospective chart review, and animal studies have provided supporting evidence for the efficacy of Besifloxacin in the management of acute bacterial keratitis. There is some evidence to suggest that Besifloxacin may provide an advantage over other current-generation fluoroquinolones in antimicrobial prophylaxis for ocular surgery. Besifloxacin is an appropriate option for treatment of bacterial conjunctivitis, and its use in the treatment of bacterial keratitis and lid disorders, as well as for surgical prophylaxis, appears promising and warrants further evaluation.
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antibacterial efficacy of prophylactic Besifloxacin 0 6 and moxifloxacin 0 5 in patients undergoing cataract surgery
Clinical Ophthalmology, 2015Co-Authors: Frank A Bucci, Timothy W Morris, Heleen H Decory, Christine M Sanfilippo, R E Evans, L M Amico, Angel T Fluet, Timothy L. ComstockAbstract:Background The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of Besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients. Methods This was a prospective, randomized, laboratory-masked clinical trial. Patients received Besifloxacin or moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints. Results Fifty-nine patients (n=28 Besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only Besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer Besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of Besifloxacin against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin. Conclusion Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacin. Besifloxacin was more active in vitro against MRSE.
Heleen H Decory - One of the best experts on this subject based on the ideXlab platform.
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in vitro time kill of common ocular pathogens with Besifloxacin alone and in combination with benzalkonium chloride
Pharmaceuticals, 2021Co-Authors: Joseph M Blondeau, Heleen H DecoryAbstract:Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of Besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of Besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of Besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log10 CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to Besifloxacin increased the rate of killing compared to Besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: 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.
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characterization of baseline polybacterial versus monobacterial infections in three randomized controlled bacterial conjunctivitis trials and microbial outcomes with Besifloxacin ophthalmic suspension 0 6
PLOS ONE, 2020Co-Authors: Heleen H Decory, Christine M Sanfilippo, Howard M Proskin, Joseph M BlondeauAbstract:Background/Purpose To date, studies examining polymicrobial infections in ocular disease have mostly been limited to keratitis or endophthalmitis. We characterized polybacterial infections compared to monobacterial infections in prior clinical studies evaluating Besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial conjunctivitis and report on associated microbiological outcomes. Methods In this post-hoc analysis, microbiological data for subjects with conjunctivitis due to one or more than one bacterial species in three previous studies (two vehicle-, one active-controlled) of Besifloxacin were extracted. Bacterial species identified at baseline were deemed causative if their colony count equaled or exceeded species-specific prespecified threshold criteria. In subjects with polybacterial infections, the fold-increase over threshold was used to rank order the contribution of individual species. Baseline pathogens and their minimum inhibitory concentrations (MICs) for common ophthalmic antibiotics were compared by infection type, as were microbial eradication rates following treatment with Besifloxacin. Results Of 1041 subjects with culture-confirmed conjunctivitis, 17% had polybacterial and 83% had monobacterial conjunctivitis at baseline. In polybacterial compared to monobacterial infections, Haemophilus influenzae and Streptococcus pneumoniae were identified less frequently as the dominant infecting species (P = 0.042 and P<0.001, respectively), whereas Streptococcus mitis/S. mitis group was identified more frequently as dominant (P<0.001). Viral coinfection was also identified more frequently in polybacterial infections (P<0.001). Staphylococcus aureus was the most common coinfecting species in polybacterial infections and the second most common dominant species in such infections. With few exceptions, MICs for individual species were comparable regardless of infection type. Clinical microbial eradication rates with Besifloxacin were high regardless of infection type (P≤0.016 vs vehicle at follow-up visits). Conclusions Approximately one in five subjects with bacterial conjunctivitis are infected with more than one bacterial species underscoring the need for a broad-spectrum antibiotic for such infections. Besifloxacin treatment resulted in robust eradication rates of these infections comparable to monobacterial infections. Trial registration NCT000622908, NCT00347932, NCT00348348
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an evaluation of staphylococci from ocular surface infections treated empirically with topical Besifloxacin antibiotic resistance molecular characteristics and clinical outcomes
Ophthalmology and therapy, 2020Co-Authors: Barry A Schechter, Heleen H Decory, Christine M Sanfilippo, John D Sheppard, Penny A AsbellAbstract:Understanding antibiotic resistance and toxin profiles among staphylococcal isolates in ocular infections can aid in therapeutic management and infection prevention strategies. We evaluated in vitro antibiotic resistance patterns and molecular traits of staphylococci isolated from patients with ocular surface infections. We also report on clinical outcomes for these patients following empirical treatment with topical Besifloxacin ophthalmic suspension 0.6%. This was a small observational study. Participating investigators from three clinical sites collected an initial ocular culture from the affected eye of patients presenting with ocular surface infections with presumed staphylococcal etiology. Clinical outcome data for patients with confirmed staphylococcal infections were collated later through retrospective review of patient medical records. Staphylococcal species identification in ocular cultures, in vitro antibiotic susceptibility testing, and PCR-based determination of methicillin resistance cassettes and toxin genotypes were conducted at a central laboratory. Isolates were categorized as susceptible or resistant based on systemic breakpoints, where available. Cultures were collected from 43 patients, and staphylococcal infections were confirmed in 25 patients. Two isolates of Staphylococcus aureus and 27 isolates of Staphylococcus epidermidis were identified. Both S. aureus isolates were methicillin-susceptible, lacked the gene encoding Panton-Valentine leukocidin, and carried few enterotoxin genes. Eight (30%) S. epidermidis were methicillin-resistant (MRSE), and 10 (37%) were ciprofloxacin-resistant. All but two MRSE isolates demonstrated multidrug resistance (MDR), and the staphylococcal cassette chromosome mec (SCCmec) type IVa was detected in five of the eight MRSE isolates. Clinical resolution of the ocular surface infection was reported in all 25 patients following treatment with Besifloxacin. In this study, S. aureus contained few toxins, while SCCmec IVa and MDR was predominant among MRSE from ocular surface infections. Despite significant in vitro fluoroquinolone resistance, there were no cases of treatment failure with topical Besifloxacin ophthalmic suspension 0.6%. Bausch Health US, LLC.
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Besifloxacin ophthalmic suspension 0 6 compared with gatifloxacin ophthalmic solution 0 3 for the treatment of bacterial conjunctivitis in neonates
Drugs in R & D, 2017Co-Authors: Christine M Sanfilippo, Catherine Allaire, Heleen H DecoryAbstract:The aim of this study was to evaluate the safety and efficacy of topical Besifloxacin ophthalmic suspension 0.6% compared with gatifloxacin ophthalmic solution 0.3% in the treatment of bacterial conjunctivitis in neonates. This was a multicenter, randomized, double-masked, parallel group study. Subjects ≤31 days of age with severity grade ≥1 (scale 0–3) for both conjunctival discharge and conjunctival hyperemia were randomized to Besifloxacin or gatifloxacin instilled three times daily for 7 days, and completed five study visits (three clinic visits and two phone calls). Primary endpoints included clinical resolution (absence of both conjunctival discharge and conjunctival hyperemia) at visit 5 (day 8 or 9) and ocular and non-ocular treatment-emergent adverse events (AEs). Bacterial eradication was a secondary endpoint. Thirty-three subjects were included in the intent-to-treat (ITT) population. All were aged <28 days, with a mean (standard deviation) age of 15.5 days (6.0), and 57.6% were female. Twenty-two subjects had culture-confirmed conjunctivitis in at least one eye (modified ITT [mITT] population), most often with Gram-positive bacteria. Visit 5 clinical resolution and bacterial eradication rates were comparable among Besifloxacin- and gatifloxacin-treated study eyes (clinical resolution: 12/16 [75.0%] vs. 12/17 [70.6%] for the ITT population, and 11/13 [84.6%] vs. 7/9 [77.8%] for the mITT population; bacterial eradication: 12/13 [92.3%] vs. 8/9 [88.9%] for the mITT population, respectively). No AEs were reported in the Besifloxacin treatment group, and AEs reported in the gatifloxacin group were considered not treatment-related. In this small study in neonates, both Besifloxacin and gatifloxacin appeared effective and safe in the treatment of bacterial conjunctivitis. Larger studies are warranted.
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antibacterial efficacy of prophylactic Besifloxacin 0 6 and moxifloxacin 0 5 in patients undergoing cataract surgery
Clinical Ophthalmology, 2015Co-Authors: Frank A Bucci, Timothy W Morris, Heleen H Decory, Christine M Sanfilippo, R E Evans, L M Amico, Angel T Fluet, Timothy L. ComstockAbstract:Background The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of Besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients. Methods This was a prospective, randomized, laboratory-masked clinical trial. Patients received Besifloxacin or moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints. Results Fifty-nine patients (n=28 Besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only Besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer Besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of Besifloxacin against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin. Conclusion Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacin. Besifloxacin was more active in vitro against MRSE.