Clinical Drug Investigation

, Volume 32, Issue 5, pp 303–317 | Cite as

Besifloxacin Ophthalmic Suspension 0.6% Administered Twice Daily for 3 Days in the Treatment of Bacterial Conjunctivitis in Adults and Children

  • Jesse DeLeon
  • Bruce E. Silverstein
  • Catherine Allaire
  • Lynne S. Gearinger
  • Kirk M. Bateman
  • Timothy W. Morris
  • Timothy L. ComstockEmail author
Original Research Article


Background and Objective: Besifloxacin ophthalmic suspension 0.6% given thrice daily for 5 days is safe and effective in the treatment of patients with bacterial conjunctivitis. This study evaluated the safety and efficacy of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days compared with vehicle in the treatment of bacterial conjunctivitis.

Study Design: This was a multicenter, double-masked, randomized, vehicle-controlled, parallel-group study.

Methods: A total of 474 patients aged ≥1 year with bacterial conjunctivitis were randomized in a 1 : 1 ratio to receive either besifloxacin ophthalmic suspension 0.6% or vehicle administered twice daily for 3 days. There were three study visits: day 1 (the baseline visit), day 4/5 (visit 2), and day 7±1 (visit 3). The co-primary efficacy endpoints were bacterial eradication and clinical resolution at day 4/5 in designated study eyes of patients with culture-confirmed bacterial conjunctivitis. Secondary efficacy endpoints were bacterial eradication and clinical resolution at day 7±1, individual clinical outcomes of ocular discharge and bulbar conjunctival injection at all visits; and microbial and clinical outcomes for overall bacterial species and individual Gram- positive and Gram-negative bacterial species at each follow-up visit. Safety endpoints included adverse events (AEs), changes in visual acuity and biomicroscopy findings at each visit, and changes in ophthalmoscopy findings at day 7±1.

Results: Bacterial eradication and clinical resolution rates were significantly higher in the besifloxacin group than in the vehicle group (115/135 [85.2%] vs 77/141 [54.6%], p<0.001, and 89/135 [65.9%] vs 62/141 [44.0%], p<0.001, respectively) at day 4/5. Rates of bacterial eradication continued to be significantly greater in the besifloxacin group (115/135 [85.2%] vs 91/141 [64.5%], respectively; p<0.001) at day 7±1; however, the rates of clinical resolution did not differ significantly between the groups (103/135 [76.3%] and 94/141 [66.7%], p =0.209) at this visit. Ocular discharge and bulbar conjunctival injection at each visit were consistent with the primary outcomes. Clinical resolution and bacterial eradication with Gram-positive or Gram-negative organisms were consistent with the overall findings. All AEs in both groups were of mild or moderate severity and were considered unrelated to the treatment.

Conclusion: Treatment with besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days was effective and safe in adults and children with bacterial conjunctivitis.


Clinical Resolution Bacterial Eradication Bacterial Conjunctivitis Besifloxacin Ocular Discharge 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was sponsored by Bausch & Lomb, Inc., who designed and managed the study. All authors had full access to the study data. Dr Allaire, Mr Bateman, Ms Gearinger, Dr Morris and Dr Comstock are employees of Bausch & Lomb. The authors thank Raman Bedi, MD, for the critical review of the manuscript and IrisARC-Analytics, Research & Consulting (Chandigarh, India) for writing and editing assistance. Statistical analysis was conducted by Howard Proskin & Associates (Rochester, NY, USA).


  1. 1.
    Diamant JI, Hwang DG. Therapy for bacterial conjunctivitis. Ophthalmol Clin North Am 1999; 12(1): 15–20CrossRefGoogle Scholar
  2. 2.
    Sheikh A, Hurwitz B. Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database Syst Rev 2006; (2): CD001211Google Scholar
  3. 3.
    Hovding G. Acute bacterial conjunctivitis. Acta Ophthalmol 2008; 86(1): 5–17PubMedCrossRefGoogle Scholar
  4. 4.
    Weiss A. Acute conjunctivitis in childhood. Curr Probl Pediatr 1994; 24(1): 4–11PubMedGoogle Scholar
  5. 5.
    Syed NA, Hyndiuk RA. Infectious conjunctivitis. Infect Dis Clin North Am 1992; 6(4): 789–805PubMedGoogle Scholar
  6. 6.
    Adebayo A, Parikh JG, McCormick SA, et al. Shifting trends in in vitro antibiotic susceptibilities for common bacterial conjunctival isolates in the last decade at the New York Eye and Ear Infirmary. Graefes Arch Clin Exp Ophthalmol 2011; 249(1): 111–9PubMedCrossRefGoogle Scholar
  7. 7.
    Cavuoto K, Zutshi D, Karp CL, et al. Update on bacterial conjunctivitis in South Florida. Ophthalmology 2008; 115(1): 51–6PubMedCrossRefGoogle Scholar
  8. 8.
    Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterial keratitis: a 5-year review. Ophthalmology 1999; 106(7): 1313–8PubMedCrossRefGoogle Scholar
  9. 9.
    Haas W, Pillar CM, Torres M, et al. Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance Monitoring in Ocular MicRorganisms (ARMOR) 2009 surveillance study. Am J Ophthalmol 2011; 152(4): 567–74 e3PubMedCrossRefGoogle Scholar
  10. 10.
    McDonald M, Blondeau JM. Emerging antibiotic resistance in ocular infections and the role of fluoroquinolones. J Cataract Refract Surg 2010; 36(9): 1588–98PubMedCrossRefGoogle Scholar
  11. 11.
    Morrissey I, Burnett R, Viljoen L, et al. Surveillance of the susceptibility of ocular bacterial pathogens to the fluoroquinolone gatifloxacin and other antimicrobials in Europe during 2001/2002. J Infect 2004; 49(2): 109–14PubMedCrossRefGoogle Scholar
  12. 12.
    Parmar P, Salman A, Kalavathy CM, et al. Comparison of topical gatifloxacin 0.3% and ciprofloxacin 0.3% for the treatment of bacterial keratitis. Am J Ophthalmol 2006; 141(2): 282–6PubMedCrossRefGoogle Scholar
  13. 13.
    Recchia FM, Busbee BG, Pearlman RB, et al. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch Ophthalmol 2005; 123(3): 341–6PubMedCrossRefGoogle Scholar
  14. 14.
    Haas W, Gearinger LS, Usner DW, et al. Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension 0.6%: etiology of bacterial conjunctivitis and antibacterial susceptibility profile. Clin Ophthalmol 2011; 5: 1369–79PubMedGoogle Scholar
  15. 15.
    Haas W, Pillar CM, Hesje CK, et al. In vitro time-kill experiments with besifloxacin, moxifloxacin and gatifloxacin in the absence and presence of benzalkonium chloride. J Antimicrob Chemother 2011; 66(4): 840–4PubMedCrossRefGoogle Scholar
  16. 16.
    Haas W, Pillar CM, Zurenko GE, et al. Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteria. Antimicrob Agents Chemother 2009; 53(8): 3552–60PubMedCrossRefGoogle Scholar
  17. 17.
    Sanfilippo CM, Hesje CK, Haas W, et al. Topoisomerase mutations that are associated with high-level resistance to earlier fluoroquinolones in Staphylococcus aureus have less effect on the antibacterial activity of besifloxacin. Chemotherapy 2011; 57(5): 363–71PubMedCrossRefGoogle Scholar
  18. 18.
    Ward KW, Lepage JF, Driot JY. Nonclinical pharmacodynamics, pharmacokinetics, and safety of BOL-303224-A, a novel fluoroquinolone antimicrobial agent for topical ophthalmic use. J Ocul Pharmacol Ther 2007; 23(3): 243–56PubMedCrossRefGoogle Scholar
  19. 19.
    Cambau E, Matrat S, Pan XS, et al. Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother 2009; 63(3): 443–50PubMedCrossRefGoogle Scholar
  20. 20.
    Comstock TL, Karpecki PM, Morris TW, et al. Besifloxacin: a novel anti-infective for the treatment of bacterial conjunctivitis. Clin Ophthalmol 2010; 4: 215–25PubMedCrossRefGoogle Scholar
  21. 21.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23(8): 1296–310PubMedCrossRefGoogle Scholar
  22. 22.
    Richter A, Anton SE, Koch P, et al. The impact of reducing dose frequency on health outcomes. Clin Ther 2003; 25(8): 2307–35; discussion 6PubMedCrossRefGoogle Scholar
  23. 23.
    Bertino Jr JS. Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics. Clin Ophthalmol 2009; 3: 507–21PubMedCrossRefGoogle Scholar
  24. 24.
    Blondeau JM, Hansen G, Metzler K, et al. The role of PK/PD parameters to avoid selection and increase of resistance: mutant prevention concentration. J Chemother 2004; 16Suppl. 3: 1–19PubMedGoogle Scholar
  25. 25.
    Burgess DS. Pharmacodynamic principles of antimicrobial therapy in the prevention of resistance. Chest 1999; 115(3 Suppl.): 19S–23SPubMedCrossRefGoogle Scholar
  26. 26.
    Harbarth S, Samore MH. Antimicrobial resistance determinants and future control. Emerg Infect Dis 2005; 11(6): 794–801PubMedCrossRefGoogle Scholar
  27. 27.
    Hwang DG, Schanzlin DJ, Rotberg MH, et al. A phase III, placebo controlled clinical trial of 0.5% levofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis. Br J Ophthalmol 2003; 87(8): 1004–9PubMedCrossRefGoogle Scholar
  28. 28.
    Sharma S. Antibiotic resistance in ocular bacterial pathogens. Indian J Med Microbiol 2011; 29(3): 218–22PubMedCrossRefGoogle Scholar
  29. 29.
    Pichichero ME. Bacterial conjunctivitis in children: antibacterial treatment options in an era of increasing drug resistance. Clin Pediatr (Phila) 2011; 50(1): 7–13CrossRefGoogle Scholar
  30. 30.
    Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed? A novel assessment technique. JAMA 1989; 261(22): 3273–7PubMedCrossRefGoogle Scholar
  31. 31.
    Friedlaender MH, Protzko E. Clinical development of 1% azithromycin in DuraSite, a topical azalide anti-infective for ocular surface therapy. Clin Ophthalmol 2007; 1(1): 3–10PubMedGoogle Scholar
  32. 32.
    Levison ME. Pharmacodynamics of antimicrobial drugs. Infect Dis Clin North Am 2004; 18(3): 451–65, viiPubMedCrossRefGoogle Scholar
  33. 33.
    Karpecki P, Depaolis M, Hunter JA, et al. Besifloxacin ophthalmic suspension 0.6% in patients with bacterial conjunctivitis: a multicenter, prospective, randomized, double-masked, vehicle-controlled, 5-day efficacy and safety study. Clin Ther 2009; 31(3): 514–26PubMedCrossRefGoogle Scholar
  34. 34.
    Tepedino ME, Heller WH, Usner DW, et al. Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis. Curr Med Res Opin 2009; 25(5): 1159–69PubMedCrossRefGoogle Scholar
  35. 35.
    Proksch JW, Granvil CP, Siou-Mermet R, et al. Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans. J Ocul Pharmacol Ther 2009; 25(4): 335–44PubMedCrossRefGoogle Scholar
  36. 36.
    Silverstein BE, Allaire C, Bateman KM, et al. Efficacy and tolerability of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days in the treatment of bacterial conjunctivitis: a multicenter, randomized, double-masked, vehicle-controlled, parallel-group study in adults and children. Clin Ther 2011; 33(1): 13–26PubMedCrossRefGoogle Scholar
  37. 37.
    Leibowitz HM. Antibacterial effectiveness of ciprofloxacin 0.3% ophthalmic solution in the treatment of bacterial conjunctivitis. Am J Ophthalmol 1991; 112(4 Suppl.): 29S–33SPubMedGoogle Scholar
  38. 38.
    Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard-eighth edition. CLSI document M07-A8. Wayne (PA): CLSI, 2009Google Scholar
  39. 39.
    Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; nineteenth informational supplement. CLSI document M100-S19. Wayne (PA): CLSI, 2009Google Scholar
  40. 40.
    Agresti A. Categorical data analysis. New York (NY): John Wiley & Sons, 1990Google Scholar
  41. 41.
    Masterton RG. The new treatment paradigm and the role of carbapenems. Int J Antimicrob Agents 2009; 33(2): 105–10PubMedCrossRefGoogle Scholar
  42. 42.
    Giorgio JM, Sanflippo J, Kleiman E, et al. An experiential avoidance conceptualization of depressive rumination: three tests of the model. Behav Res Ther 2010; 48(10): 1021–31PubMedCrossRefGoogle Scholar
  43. 43.
    Besivance™ (besifloxacin ophthalmic suspension) 0.6% [package insert]. Tampa (FL): Bausch & Lomb Inc., Apr 2009Google Scholar
  44. 44.
    ZYMAXID™ (gatifloxacin ophthalmic solution) 0.5% [package insert]. Irvine (CA): Allergan, Inc., May 2010Google Scholar
  45. 45.
    Katz HR, Andrews W, Creager D, et al. Moxifloxacin ophthalmic solution 0.5% hastens cure and eradicates the causative pathogens of bacterial conjunctivitis in pediatric and adult patients [abstract]. Invest Ophthal Vis Sci; 2003; 44: E-abstract 2114Google Scholar
  46. 46.
    ZYMAR® (gatifloxacin ophthalmic solution) 0.3% [package insert]. Irvine (CA): Allergan, Inc., January 2010Google Scholar
  47. 47.
    VIGAMOX® (moxifloxacin hydrochloride ophthalmic solution) 0.5% [package insert]. Fort Worth (TX): Alcon Laboratories, Inc., July 2011Google Scholar
  48. 48.
    Schlech BA, Stroman DW, Gower L, et al. Eradication of bacteria from infected eyes by a three day BID treatment with moxifloxacin ophthalmic solution, 0.5% [abstract]. Invest Ophthal Vis Sci 2003; 44: ARVO E-abstract 2116Google Scholar
  49. 49.
    Gross RD, Lichtenstein SJ, Schlech BA. Early clinical and microbiological responses in the treatment of bacterial conjunctivitis with moxifloxacin ophthalmic solution 0.5% (vigamox) using BID dosing. Todays Ther Trends 2003; 21: 227–37Google Scholar
  50. 50.
    Tauber S, Cupp G, Garber R, et al. Microbiological efficacy of a new ophthalmic formulation of moxifloxacin dosed twice-daily for bacterial conjunctivitis. Adv Ther 2011; 28(7): 566–74PubMedCrossRefGoogle Scholar
  51. 51.
    MOXEZA™ (moxifloxacin hydrochloride ophthalmic solution) 0.5% [package insert]. Fort Worth (TX): Alcon Laboratories, Inc., 2010Google Scholar
  52. 52.
    McDonald MB, Protzko EE, Brunner LS, et al. Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis. Ophthalmology 2009; 116(9): 1615–23 e1PubMedCrossRefGoogle Scholar
  53. 53.
    Szaflik J, Szaflik JP, Kaminska A. Clinical and microbiological efficacy of levofloxacin administered three times a day for the treatment of bacterial conjunctivitis. Eur J Ophthalmol 2009; 19(1): 1–9PubMedGoogle Scholar
  54. 54.
    Yee RW, Tepedino M, Bernstein P, et al. A randomized, investigator- masked clinical trial comparing the efficacy and safety of gatifloxacin 0.3% administered BID versus QID for the treatment BID versus QID for the treatment of acute bacterial conjunctivitis of acute bacterial conjunctivitis. Curr Med Res Opin 2005; 21(3): 425–31PubMedCrossRefGoogle Scholar
  55. 55.
    Haas W, Pillar CM, Morris TW, et al. Antibiotic resistance trends in ocular pathogens: an update from the ARMOR 2009 and ARMOR 2010 surveillance studies [abstract]. Invest Ophthal Vis Sci; 2011; 52: E-abstract 5844Google Scholar
  56. 56.
    Comstock TL, Paterno MR, Decory HH, et al. Safety and tolerability of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis: data from six clinical and phase I safety studies. Clin Drug Investig 2010; 30(10): 675–85PubMedCrossRefGoogle Scholar
  57. 57.
    Comstock TL, Paterno MR, Usner DW, et al. Efficacy and safety of besifloxacin ophthalmic suspension 0.6% in children and adolescents with bacterial conjunctivitis: a post hoc, subgroup analysis of three randomized, double-masked, parallel-group, multicenter clinical trials. Paediatr Drugs 2010; 12(2): 105–12PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  • Jesse DeLeon
    • 1
  • Bruce E. Silverstein
    • 2
  • Catherine Allaire
    • 3
  • Lynne S. Gearinger
    • 3
  • Kirk M. Bateman
    • 3
  • Timothy W. Morris
    • 3
  • Timothy L. Comstock
    • 3
    Email author
  1. 1.Center for Clinical TrialsLLCParamountUSA
  2. 2.Shasta Eye Medical Group, Inc.ReddingUSA
  3. 3.Global PharmaceuticalBausch & Lomb, Inc.RochesterUSA

Personalised recommendations