Skip to main content
SpringerLink
Log in

Treatment of rabbit corneal infections with ophthalmic gatifloxacin: A concentration dependence study

  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

This study was designed to determine the most effective dose of gatifloxacin in ophthalmic solution for control of methicillin-resistantStaphylococcus aureus (MRSA) corneal infections in rabbits. Rabbits were inoculated by injecting 9300 colonyforming units of MRSA into the corneal stroma of the eye (n=43). They were then randomly assigned to topical administration of saline, ofloxacin 0.3%, or gatifloxacin 0.02%, 0.1%, 0.3%, or 0.5% ophthalmic solutions. Infection severity 48 hours postinoculation was assessed by masked observers using standard scales. After treatment completion, viable MRSA in corneal tissue were counted, and pathologic examinations of ocular tissues were conducted. Relative to saline, treatment with gatifloxacin 0.3% or 0.5% decreased mean infection scores at every time point from 16 to 48 hours after inoculation (P≤.012) and reduced area-underthe-curve values for infection scores by 50.3% and 54.2%, respectively (P=.00005). Rabbits treated with gatifloxacin 0.3% and 0.5% had lower areaunder-the-curve values than those treated with ofloxacin 0.3% (P≤.039). Viable MRSA in corneal tissue after gatifloxacin 0.3% or 0.5% treatment were decreased to less than 1% of those found after ofloxacin 0.3% treatment. Gram-positive colony formation and abscesses found in saline-treated corneas were distinctly alleviated by treatment with gatifloxacin 0.3% or 0.5%. No significant differences were observed between treatments with gatifloxacin 0.3% or 0.5% ophthalmic formulations and they were equally effective. Topical administration of gatifloxacin 0.3% or 0.5% ophthalmic solutions controlled MRSA corneal infections in rabbits significantly better than saline or ofloxacin 0.3%.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Drlica K. Mechanism of fluoroquinolone action.Curr Opin Microbiol. 1999;2:504–508.

    Article  PubMed  CAS  Google Scholar 

  2. Everett SL, Kowalski RP, Karenchak LM, Landsittel D, Day R, Gordon YJ. An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics.Cornea. 1995;14:382–387.

    Article  PubMed  CAS  Google Scholar 

  3. Osato MS, Jensen HG, Trousdale MD, et al. The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates.Am J Ophthalmol. 1989; 108:380–386.

    PubMed  CAS  Google Scholar 

  4. Bauernfeind A. Comparison of the antibacterial activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin.J Antimicrob Chemother. 1997;40:639–651.

    Article  PubMed  CAS  Google Scholar 

  5. Hoellman DB, Lin G, Jacobs MR, Appelbaum PC. Anti-pneumococcal activity of gatifloxacin compared with other quinolone and non-quinolone agents.J Antimicrob Chemother. 1999;43: 645–649.

    Article  PubMed  CAS  Google Scholar 

  6. Beck R, van Keyserlingk J, Fischer U, Guthoff R, Drewelow B. Penetration of ciprofloxacin, norfloxacin, and ofloxacin into the aqueous humor using different topical application modes.Graefe’s Arch Clin Exp Ophthalmol. 1999;237:89–92.

    Article  CAS  Google Scholar 

  7. Cekic O, Batman C, Totan Y, et al. Aqueous humor levels of topically applied ciprofloxacin and ofloxacin in the same subjects.Eye. 1999;13:656–659.

    PubMed  Google Scholar 

  8. Fung-Tomc J, Minassian B, Kolek B, Washo T, Huczko E, Bonner D. In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin.J Antimicrob Chemother. 2000; 45:437–446.

    Article  PubMed  CAS  Google Scholar 

  9. Huczko E, Conetta B, Bonner D, et al. Susceptibility of bacterial isolates to gatifloxacin and ciprofloxacin from clinical trials 1997–1998.Int J Antimicrob Agents. 2000;16:401–405.

    Article  PubMed  CAS  Google Scholar 

  10. Wise R, Brenwald NP, Andrews JM, Boswell F. The activity of the methylpiperazinyl fluoroquinolone CG 5501: a comparison with other fluoroquinolones.J Antimicrob Chemother. 1997;39:447–452.

    Article  PubMed  CAS  Google Scholar 

  11. Fung-Tomc J, Gradelski E, Huczko E, Minassian B, Bonner DP. Activity of gatifloxacin against strains resistant to ofloxacin and ciprofloxacin and its ability to select for less susceptible bacterial variants.Int J Antimicrob Agents. 2001;18:77–80.

    Article  PubMed  CAS  Google Scholar 

  12. Schmitz FJ, Boos M, Mayer S, et al. Propensity of fluoroquinolones with different moieties at position 8 to cause resistance development in clinical isolates ofStreptococcus pneumoniae.Antimicrob Agents Chemother. 2001;45:2666–2667.

    Article  PubMed  CAS  Google Scholar 

  13. Fukuda H, Kishii R, Takei M, Hosaka M. Contributions of the 8-methoxy group of gatifloxacin to resistance selectivity, target preference, and antibacterial activity againstStreptococcus pneumoniae.Antimicrob Agents Chemother. 2001;45:1649–1653.

    Article  PubMed  CAS  Google Scholar 

  14. Ince D, Hooper DC. Mechanisms and frequency of resistance to gatifloxacin in comparison to AM-1121 and ciprofloxacin inStaphylococcus aureus.Antimicrob Agents Chemother. 2001;45: 2755–2764.

    Article  PubMed  CAS  Google Scholar 

  15. Takei M, Fukuda H, Kishii R, Hosaka M. Target preference of 15 quinolones againstStaphylococcus aureus, based on antibacterial activities and target inhibition.Antimicrob Agents Chemother. 2001;45: 3544–3547.

    Article  PubMed  CAS  Google Scholar 

  16. Breen J, Skuba K, Grasela D. Safety and tolerability of gatifloxacin, an advanced generation 8-methoxy fluoroquinolone.J Resp Dis. 1999;20:S70-S76.

    Google Scholar 

  17. Gajjar DA, LaCreta FP, Uderman HD, et al. A dose-escalation study of the safety, tolerability, and pharmacokinetics of intravenous gatifloxacin in healthy adult men.Pharmacotherapy. 2000;20:49S-58S.

    Article  PubMed  CAS  Google Scholar 

  18. Grasela DM. Clinical pharmacology of gatifloxacin, a new fluoroquinolone.Clin Infect Dis. 2000; 31:S51-S58.

    Article  PubMed  CAS  Google Scholar 

  19. Domagala JM. Structure-activity and structure-side-effect relationships for the quinolone antibacterials.J Antimicrob Chemother. 1994;33:685–706.

    Article  PubMed  CAS  Google Scholar 

  20. Takei M, Fukuda H, Yasue T, Hosaka M, Oomori Y. Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases.Antimicrob Agents Chemother. 1998;42:2678–2681.

    PubMed  CAS  Google Scholar 

  21. Yamamoto T, Tsurumaki Y, Takei M, Hosaka M, Oomori Y. In vitro method for prediction of the phototoxic potentials of fluoroquinolones.Toxicol In Vitro. 2001;15:721–727.

    Article  PubMed  CAS  Google Scholar 

  22. Aguilar HE, Meredith TA, Drews C, Grossniklaus H, Sawant AD, Gardner S. Comparative treatment of experimentalStaphylococcus aureus endophthalmitis.Am J Ophthalmol. 1996;121:310–317.

    PubMed  CAS  Google Scholar 

  23. Tungsiripat T, Sarayba MA, Kaufman MB, et al. Fluoroquinolone therapy in multiple-drug resistant staphylococcal keratitis after lamellar keratectomy in a rabbit model.Am J Ophthalmol. 2003;136: 76–81.

    Article  PubMed  CAS  Google Scholar 

  24. Solomon R, Donnenfed ED, Perry HD, Biser S. Bilateral methicillin-resistantStaphylococcus aureus keratitis in a medical resident following an uneventful bilateral photorefractive keratectomy.Eye Contact Lens. 2003;29:187–189.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Laboratories, Senju Pharmaceutical Co., Ltd., 1-5-4, Murotani, Nishiku Kobe, Hyogo, Japan

    Tomoyuki Wada MSc, Hiroaki Naka MSc, Hideki Tokushige MSc, Hideyuki Sakaki PhD & Takahiro Ogawa PhD

  2. Allergan Inc., Irvine, California

    Harold Jensen PhD & Scott M. Whitcup MD

Authors
  1. Tomoyuki Wada MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroaki Naka MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideki Tokushige MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hideyuki Sakaki PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takahiro Ogawa PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Harold Jensen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Scott M. Whitcup MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wada, T., Naka, H., Tokushige, H. et al. Treatment of rabbit corneal infections with ophthalmic gatifloxacin: A concentration dependence study. Adv Therapy 21, 1–12 (2004). https://doi.org/10.1007/BF02850260

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02850260

Keywords

Search

Navigation