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Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension, 0.6%: microbiological eradication outcomes.

Morris TW, Gearinger LS, Usner DW, Paterno MR, Decory HH, Comstock TL, Haas W - Clin Ophthalmol (2011)

Bottom Line: Visit 2 (day 4 or 5) and visit 3 (day 8) overall microbiological eradication rates were 92.2% and 88.4% for besifloxacin ophthalmic suspension compared with 61.4% and 72.5% for vehicle and 91.6% and 85.7% for moxifloxacin ophthalmic solution.Eradication failures in the besifloxacin treatment group were not associated with lower antimicrobial susceptibility at baseline.The few eradication failures were not due to fluoroquinolone resistance at baseline and/or resistance development during treatment.

View Article: PubMed Central - PubMed

Affiliation: Microbiology and Sterilization Sciences, Bausch & Lomb, Rochester, NY, USA. timothy.w.morris@bausch.com

ABSTRACT

Purpose: To assess clinical antimicrobial efficacy results obtained with besifloxacin ophthalmic suspension, 0.6%, administered three times a day (TID) for 5 days, integrated across three clinical trials of bacterial conjunctivitis and to investigate any microbiological eradication failures.

Methods: Clinical microbiological eradication data from three randomized, double-masked, parallel group studies of patients with bacterial conjunctivitis (two vehicle controlled; one active controlled with moxifloxacin ophthalmic solution, 0.5%) were integrated. All bacterial samples isolated at baseline above the species-specific threshold value were subjected to antimicrobial susceptibility testing. Samples isolated at subsequent visits were subjected to susceptibility testing and pulsed-field gel electrophoresis (PFGE) to investigate the cause of eradication failures and the potential for drug resistance development.

Results: Visit 2 (day 4 or 5) and visit 3 (day 8) overall microbiological eradication rates were 92.2% and 88.4% for besifloxacin ophthalmic suspension compared with 61.4% and 72.5% for vehicle and 91.6% and 85.7% for moxifloxacin ophthalmic solution. Visit 2 and visit 3 microbiological eradication rates for Gram-positive and Gram-negative isolates and for individual species were consistent with the overall eradication rates. The majority of observed eradication failures in any treatment group were due to the persistence of the pathogen isolated at baseline. Eradication failures in the besifloxacin treatment group were not associated with lower antimicrobial susceptibility at baseline. PFGE data showed that the majority of bacterial strains in eyes with eradication failures were identical to the strain isolated at baseline; these eradication failures were not associated with a lower antimicrobial susceptibility at the follow-up visit.

Conclusion: Treatment with besifloxacin ophthalmic suspension, 0.6%, administered TID for 5 days resulted in microbiological eradication rates that were ≥ 90% across the three clinical studies for the common pathogens of bacterial conjunctivitis. The few eradication failures were not due to fluoroquinolone resistance at baseline and/or resistance development during treatment.

No MeSH data available.


Related in: MedlinePlus

Visit 2 microbiological eradication versus MIC distribution at baseline in the active controlled study. (A) Eradication versus besifloxacin MIC distribution for isolates in the besifloxacin ophthalmic suspension treatment group (N = 329). (B) Eradication versus moxifloxacin MIC distribution for isolates in the moxifloxacin ophthalmic solution treatment group (N = 370). θ = nil.Abbreviations: MIC, minimum inhibitory concentration; ND, MIC could not be determined.
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f3-opth-5-1359: Visit 2 microbiological eradication versus MIC distribution at baseline in the active controlled study. (A) Eradication versus besifloxacin MIC distribution for isolates in the besifloxacin ophthalmic suspension treatment group (N = 329). (B) Eradication versus moxifloxacin MIC distribution for isolates in the moxifloxacin ophthalmic solution treatment group (N = 370). θ = nil.Abbreviations: MIC, minimum inhibitory concentration; ND, MIC could not be determined.

Mentions: Figure 2 presents visit 2 microbiological eradication results for isolates from besifloxacin-treated eyes from all three studies relative to the besifloxacin MIC value for pathogens isolated at baseline. Figure 3 presents visit 2 microbiological eradication results for isolates from besifloxacin- and moxifloxacin-treated eyes in the active controlled study relative to the besifloxacin and moxifloxacin MIC values, respectively, for pathogens isolated at baseline in that study. The baseline MIC range for isolates from eyes treated with besifloxacin that were eradicated was 0.008–8 μg/mL. The MIC range for isolates from eyes treated with besifloxacin that resulted in eradication failures (all studies, n = 51; activecontrolled study, n = 22) was 0.015–1 μg/mL, indicating that the besifloxacin MIC at baseline was not the primary determinant of microbial eradication failures. Minimum inhibitory concentration values were higher overall in the moxifloxacin treatment group. The baseline MIC range for the moxifloxacin-treated isolates was 0.015 to >8 μg/ mL for the isolates that were eradicated (n = 339) and 0.03 to >8 μg/mL for the isolates that resulted in eradication failures (n = 31). However, of the latter, four isolates had moxifloxacin MIC values that were ≥2 μg/mL. Thus, 100% (16/16) of isolates from besifloxacin-treated eyes with besifloxacin MIC values of 2–8 μg/mL were successfully eradicated compared with 87.1% (27/31) of isolates from moxifloxacin-treated eyes with moxifloxacin MICs of 2 to >8 μg/mL. Analysis of visit 3 eradication rates for either besifloxacin- or moxifloxacin-treated isolates as a function of baseline MIC resulted in similar findings as those observed for visit 2 (data not shown).


Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension, 0.6%: microbiological eradication outcomes.

Morris TW, Gearinger LS, Usner DW, Paterno MR, Decory HH, Comstock TL, Haas W - Clin Ophthalmol (2011)

Visit 2 microbiological eradication versus MIC distribution at baseline in the active controlled study. (A) Eradication versus besifloxacin MIC distribution for isolates in the besifloxacin ophthalmic suspension treatment group (N = 329). (B) Eradication versus moxifloxacin MIC distribution for isolates in the moxifloxacin ophthalmic solution treatment group (N = 370). θ = nil.Abbreviations: MIC, minimum inhibitory concentration; ND, MIC could not be determined.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198409&req=5

f3-opth-5-1359: Visit 2 microbiological eradication versus MIC distribution at baseline in the active controlled study. (A) Eradication versus besifloxacin MIC distribution for isolates in the besifloxacin ophthalmic suspension treatment group (N = 329). (B) Eradication versus moxifloxacin MIC distribution for isolates in the moxifloxacin ophthalmic solution treatment group (N = 370). θ = nil.Abbreviations: MIC, minimum inhibitory concentration; ND, MIC could not be determined.
Mentions: Figure 2 presents visit 2 microbiological eradication results for isolates from besifloxacin-treated eyes from all three studies relative to the besifloxacin MIC value for pathogens isolated at baseline. Figure 3 presents visit 2 microbiological eradication results for isolates from besifloxacin- and moxifloxacin-treated eyes in the active controlled study relative to the besifloxacin and moxifloxacin MIC values, respectively, for pathogens isolated at baseline in that study. The baseline MIC range for isolates from eyes treated with besifloxacin that were eradicated was 0.008–8 μg/mL. The MIC range for isolates from eyes treated with besifloxacin that resulted in eradication failures (all studies, n = 51; activecontrolled study, n = 22) was 0.015–1 μg/mL, indicating that the besifloxacin MIC at baseline was not the primary determinant of microbial eradication failures. Minimum inhibitory concentration values were higher overall in the moxifloxacin treatment group. The baseline MIC range for the moxifloxacin-treated isolates was 0.015 to >8 μg/ mL for the isolates that were eradicated (n = 339) and 0.03 to >8 μg/mL for the isolates that resulted in eradication failures (n = 31). However, of the latter, four isolates had moxifloxacin MIC values that were ≥2 μg/mL. Thus, 100% (16/16) of isolates from besifloxacin-treated eyes with besifloxacin MIC values of 2–8 μg/mL were successfully eradicated compared with 87.1% (27/31) of isolates from moxifloxacin-treated eyes with moxifloxacin MICs of 2 to >8 μg/mL. Analysis of visit 3 eradication rates for either besifloxacin- or moxifloxacin-treated isolates as a function of baseline MIC resulted in similar findings as those observed for visit 2 (data not shown).

Bottom Line: Visit 2 (day 4 or 5) and visit 3 (day 8) overall microbiological eradication rates were 92.2% and 88.4% for besifloxacin ophthalmic suspension compared with 61.4% and 72.5% for vehicle and 91.6% and 85.7% for moxifloxacin ophthalmic solution.Eradication failures in the besifloxacin treatment group were not associated with lower antimicrobial susceptibility at baseline.The few eradication failures were not due to fluoroquinolone resistance at baseline and/or resistance development during treatment.

View Article: PubMed Central - PubMed

Affiliation: Microbiology and Sterilization Sciences, Bausch & Lomb, Rochester, NY, USA. timothy.w.morris@bausch.com

ABSTRACT

Purpose: To assess clinical antimicrobial efficacy results obtained with besifloxacin ophthalmic suspension, 0.6%, administered three times a day (TID) for 5 days, integrated across three clinical trials of bacterial conjunctivitis and to investigate any microbiological eradication failures.

Methods: Clinical microbiological eradication data from three randomized, double-masked, parallel group studies of patients with bacterial conjunctivitis (two vehicle controlled; one active controlled with moxifloxacin ophthalmic solution, 0.5%) were integrated. All bacterial samples isolated at baseline above the species-specific threshold value were subjected to antimicrobial susceptibility testing. Samples isolated at subsequent visits were subjected to susceptibility testing and pulsed-field gel electrophoresis (PFGE) to investigate the cause of eradication failures and the potential for drug resistance development.

Results: Visit 2 (day 4 or 5) and visit 3 (day 8) overall microbiological eradication rates were 92.2% and 88.4% for besifloxacin ophthalmic suspension compared with 61.4% and 72.5% for vehicle and 91.6% and 85.7% for moxifloxacin ophthalmic solution. Visit 2 and visit 3 microbiological eradication rates for Gram-positive and Gram-negative isolates and for individual species were consistent with the overall eradication rates. The majority of observed eradication failures in any treatment group were due to the persistence of the pathogen isolated at baseline. Eradication failures in the besifloxacin treatment group were not associated with lower antimicrobial susceptibility at baseline. PFGE data showed that the majority of bacterial strains in eyes with eradication failures were identical to the strain isolated at baseline; these eradication failures were not associated with a lower antimicrobial susceptibility at the follow-up visit.

Conclusion: Treatment with besifloxacin ophthalmic suspension, 0.6%, administered TID for 5 days resulted in microbiological eradication rates that were ≥ 90% across the three clinical studies for the common pathogens of bacterial conjunctivitis. The few eradication failures were not due to fluoroquinolone resistance at baseline and/or resistance development during treatment.

No MeSH data available.


Related in: MedlinePlus