• 1

    Drlica K. Mechanism of fluoroquinolone action. Curr Opin Microbiol 1999;2:504508.

  • 2

    McGee DH, Holt WF, Kastner PR, et al. Safety of moxifloxacin as shown in animal and in vitro studies. Surv Ophthalmol 2005;50:S46S54.

  • 3

    Kowalski RP, Dhaliwal DK, Karenchak LM, et al. Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial keratitis isolates. Am J Ophthalmol 2003;136:500505.

    • Search Google Scholar
    • Export Citation
  • 4

    Guzek JP, Chacko D, Kettering JD, et al. Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of experimental Pseudomonas aeruginosa keratitis. Cornea 1994;13:500504.

    • Search Google Scholar
    • Export Citation
  • 5

    Tolar EL, Hendrix DV, Rohrbach BW, et al. Evaluation of clinical characteristics and bacterial isolates in dogs with bacterial keratitis: 97 cases (1993–2003). J Am Vet Med Assoc 2006;228:8085.

    • Search Google Scholar
    • Export Citation
  • 6

    Sauer P, Andrew SE, Lassaline M, et al. Changes in antibiotic resistance in equine bacterial ulcerative keratitis (1991–2000): 65 horses. Vet Ophthalmol 2003;6:309313.

    • Search Google Scholar
    • Export Citation
  • 7

    Ince D, Hooper DC. Mechanisms and frequency of resistance to gatifloxacin in comparison to AM-1121 and ciprofloxacin in Staphylococcus aureus. Antimicrob Agents Chemother 2001;45:27552764.

    • Search Google Scholar
    • Export Citation
  • 8

    Fung-Tomc J, Minassian B, Kolek B, et al. In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin. J Antimicrob Chemother 2000;24:437446.

    • Search Google Scholar
    • Export Citation
  • 9

    Saravolatz LD, Leggett J. Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones. Clin Infect Dis 2003;37:12101215.

    • Search Google Scholar
    • Export Citation
  • 10

    Blondeau JM, Laskowski R, Bjarnason J, et al. Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 gram-negative and gram-positive organisms. Int J Antimicrob Agents 2000;14:4550.

    • Search Google Scholar
    • Export Citation
  • 11

    Kowalski RP, Pandya AN, Karenchak LM, et al. An in vitro resistance study of levofloxacin, ciprofloxacin, and ofloxacin using keratitis isolates of Staphylococcus aureus and Pseudomonas aeruginosa. Ophthalmology 2001;108:18261829.

    • Search Google Scholar
    • Export Citation
  • 12

    Thibodeaux BA, Dajcs JJ, Caballero AR, et al. Quantitative comparison of fluoroquinolone therapies of experimental gram-negative bacterial keratitis. Curr Eye Res 2004;28:337342.

    • Search Google Scholar
    • Export Citation
  • 13

    Jensen H, Zerouala C, Carrier M, et al. Comparison of ophthalmic gatifloxacin 0.3% and ciprofloxacin 0.3% in healing of corneal ulcers associated with Pseudomonas aeruginosa-induced ulcerative keratitis in rabbits. J Ocul Pharmacol Ther 2005;21:3643.

    • Search Google Scholar
    • Export Citation
  • 14

    Robertson SM, Curtis MA, Schlech BA, et al. Ocular pharmaco-kinetics of moxifloxacin after topical treatment in animals and humans. Surv Ophthalmol 2005;50 (suppl 1):S32S45.

    • Search Google Scholar
    • Export Citation
  • 15

    Kreger AS. Pathogenesis of Pseudomonas aeruginosa ocular diseases. Rev Infect Dis 1983;5 (suppl 5):931935.

  • 16

    Gerding PA Jr, McLaughlin SA, Troop MW. Pathogenic bacteria and fungi associated with external ocular disease in dogs: 131 cases (1981–1986). J Am Vet Med Assoc 1988;193:242244.

    • Search Google Scholar
    • Export Citation
  • 17

    Fleiszig SM, Evans DJ. The pathogenesis of bacterial keratitis: studies with Pseudomonas aeruginosa. Clin Exp Optom 2002;85:271278.

  • 18

    Wyman M, Swanson C, Kowalski JJ, et al. Experimental Pseudomonas aeruginosa ulcerative keratitis model in the dog. Am J Vet Res 1983;44:11351140.

    • Search Google Scholar
    • Export Citation
  • 19

    Van Horn DL, Davis SD, Hyndiuk RA, et al. Experimental Pseudomonas keratitis in the rabbit: bacteriologic, clinical, and microscopic observations. Invest Ophthalmol Vis Sci 1981;20:213221.

    • Search Google Scholar
    • Export Citation
  • 20

    Sweeney CR, Irby NL. Topical treatment of Pseudomonas sp–infected corneal ulcers in horses: 70 cases (1977–1994). J Am Vet Med Assoc 1996;209:954957.

    • Search Google Scholar
    • Export Citation
  • 21

    Kroll P, Busse H. A case of total keratomalacia due to soft contact lens wearing. Ann Ophthalmol 1980;12:13741376.

  • 22

    Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis 2006;43:S49S56.

    • Search Google Scholar
    • Export Citation
  • 23

    Lee EJ, Truong TN, Mendoza MN, et al. A comparison of invasive and cytotoxic Pseudomonas aeruginosa strain-induced corneal disease responses to therapeutics. Curr Eye Res 2003;27:289299.

    • Search Google Scholar
    • Export Citation
  • 24

    National Committee for Clinical Laboratory Standards. In:Performance standards for antimicrobial disk susceptibility tests; approved standard M2-A. 9th ed. Wayne, Pa: Clinical and Laboratory Standards Institute, 2006;135.

    • Search Google Scholar
    • Export Citation
  • 25

    Kowalski RP, Yates KA, Romanowski EG, et al. An ophthalmologist's guide to understanding antibiotic susceptibility and minimum inhibitory concentration data. Ophthalmology 2005;112:1987e11987e6.

    • Search Google Scholar
    • Export Citation
  • 26

    Romanowski EG, Mah FS, Yates KA, et al. The successful treatment of gatifloxacin-resistant Staphylococcus aureus keratitis with Zymar (gatifloxacin 0.3%) in a NZW rabbit model. Am J Ophthalmol 2005;139:867877.

    • Search Google Scholar
    • Export Citation
  • 27

    Wilhelmus KR, Abshire RL, Schlech BA. Influence of fluoroquinolone susceptibility on the therapeutic response of fluoroquinolone-treated bacterial keratitis. Arch Ophthalmol 2003;121:12291233.

    • Search Google Scholar
    • Export Citation
  • 28

    Riddle C, Lemons CL, Papich MG, et al. Evaluation of ciprofloxacin as a representative of veterinary fluoroquinolones in susceptibility testing. J Clin Microbiol 2000;38:16361637.

    • Search Google Scholar
    • Export Citation
  • 29

    Martin Barrasa JL, LupiolaGomez P, Gonzalez Lama Z, et al. Antibacterial susceptibility patterns of Pseudomonas strains isolated from chronic canine otitis externa. J Vet Med B Infect Dis Vet Public Health 2000;47:191197.

    • Search Google Scholar
    • Export Citation
  • 30

    Polk RE, Johnson CK, McClish D, et al. Predicting hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from fluoroquinolone use in US hospitals and their surrounding communities. Clin Infect Dis 2004;39:497503.

    • Search Google Scholar
    • Export Citation
  • 31

    Fridkin SK, Hill HA, Volkova NV, et al. Temporal changes in prevalence of antimicrobial resistance in 23 US hospitals. Emerg Infect Dis 2002;8:697701.

    • Search Google Scholar
    • Export Citation
  • 32

    Tejedor MT, Martin JL, Navia M, et al. Mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from canine infections. Vet Microbiol 2003;94:295301.

    • Search Google Scholar
    • Export Citation
  • 33

    Hooper DC. Emerging mechanisms of fluoroquinolone resistance. Emerg Infect Dis 2001;7:337341.

  • 34

    Kriengkauykiat J, Porter E, Lomovskaya O, et al. Use of an efflux pump inhibitor to determine the prevalence of efflux pump-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 2005;49:565570.

    • Search Google Scholar
    • Export Citation
  • 35

    Thomas LE, Couetdic G, Clermont O, et al. In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy. J Antimicrob Chemother 2001;48:553555.

    • Search Google Scholar
    • Export Citation
  • 36

    Alexandrakis G, Alfonso EC, Miller D. Shifting trends in bacterial keratitis in South Florida and emerging resistance to fluoroquinolones. Ophthalmology 2000;107:14971502.

    • Search Google Scholar
    • Export Citation
  • 37

    Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterial keratitis: a 5-year review. Ophthalmology 1999;106:13131318.

    • Search Google Scholar
    • Export Citation
  • 38

    Garg P, Sharma S, Rao GN. Ciprofloxacin-resistant Pseudomonas keratitis. Ophthalmology 1999;106:13191323.

  • 39

    Rhee MK, Kowalski RP, Romanowski EG, et al. A laboratory evaluation of antibiotic therapy for ciprofloxacin-resistant Pseudomonas aeruginosa. Am J Ophthalmol 2004;138:226230.

    • Search Google Scholar
    • Export Citation
  • 40

    Moshirfar J, Mirzaizn G, Feiz V, et al. Fourth-generation fluoroquinolone-resistant bacterial keratitis after refractive surgery. J Cataract Refract Surg 2006;32:515518.

    • Search Google Scholar
    • Export Citation
  • 41

    Chaudry NA, Flynn HW, Murray TG, et al. Emerging ciprofloxacin-resistant Pseudomonas aeruginosa. Am J Ophthalmol 1999;128:509510.

  • 42

    Epstein SP, Bottone EJ, Asbell PA. Susceptibility testing of clinical isolates of Pseudomonas aeruginosa to levofloxacin, moxifloxacin, and gatifloxacin as a guide to treating Pseudomonas ocular infection. Eye Contact Lens 2006;32:240244.

    • Search Google Scholar
    • Export Citation
  • 43

    Song A, McCulley TJ, Lam BL, et al. Pseudomonas aeruginosa in vitro corneal isolate sensitivity to ofloxacin, ciprofloxacin, and trovafloxacin: a comparative study. Am J Ophthalmol 2001;131:795796.

    • Search Google Scholar
    • Export Citation
  • 44

    Kunimoto DY, Sharma S, Garg P, et al. In vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin: emerging resistance. Ophthalmology 1999;106:8085.

    • Search Google Scholar
    • Export Citation
  • 45

    Lomholt JA, Kilian M. Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates from keratitis. Br J Ophthalmol 2003;87:12381240.

    • Search Google Scholar
    • Export Citation
  • 46

    Hsu DI, Okamoto MP, Murthy R, et al. Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition and impact on outcomes. J Antimicrob Chemother 2005;55:535541.

    • Search Google Scholar
    • Export Citation
  • 47

    Burgess DS. Use of pharmokinetics and pharmacodynamics to optimize antimicrobial treatment of Pseudomonas aeruginosa infections. Clin Infect Dis 2005;40:S99S104.

    • Search Google Scholar
    • Export Citation
  • 48

    Nakano M, Yasuda M, Yokoi S, et al. In vivo selection of Pseudomonas aeruginosa with decreased susceptibilities to fluoroquinolones during fluoroquinolone treatment of urinary tract infection. Urology 2001;58:125128.

    • Search Google Scholar
    • Export Citation

In vitro fluoroquinolone susceptibility of Pseudomonas aeruginosa isolates from dogs with ulcerative keratitis

View More View Less
  • 1 Departments of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
  • | 2 Cayuga Medical Center, Department of Microbiology, 101 Dates Dr, Ithaca, NY 14850
  • | 3 Departments of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
  • | 4 Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

Abstract

Objective—To determine the in vitro fluoroquinolone susceptibility profiles of Pseudomonas aeruginosa isolates from dogs with ulcerative keratitis.

Animals—27 dogs with P aeruginosa–associated ulcerative keratitis.

ProceduresP aeruginosa isolates from dogs with ulcerative keratitis were collected during a 3-year period. Isolates were tested by use of the disk diffusion method for their susceptibility to 7 fluoroquinolones that are available as commercial ophthalmic preparations. The antimicrobials included second- (ciprofloxacin, ofloxacin, norfloxacin, and lomefloxacin), third- (levofloxacin), and fourth-generation (gatifloxacin and moxifloxacin) fluoroquinolones. Isolates were designated as susceptible, intermediate, or resistant to the various antimicro-bials. The percentage of susceptible isolates was compared among individual fluoroquinolones and among fluoroquinolone generations.

Results—None of the dogs had received topical or systemic fluoroquinolone treatment prior to referral. Twenty-seven P aeruginosa isolates were collected during the study period. In vitro, bacterial resistance to the tested fluoroquinolones was infrequently identified (24/ 27 isolates were susceptible to all fluoroquinolones evaluated); susceptibility percentages ranged from 88.9% to 100% for individual antimicrobials. There were no significant differ-ences among isolate susceptibilities to the individual antimicrobials or among generations of fluoroquinolones.

Conclusions and Clinical Relevance—On the basis of these in vitro data, none of the 7 evaluated fluoroquinolones (individually or collectively by generation) appeared to offer a clinically important advantage in the treatment of P aeruginosa–associated ulcerative keratitis in dogs. Among the P aeruginosa isolates collected from dogs with ulcerative keratitis in this study, the likelihood of susceptibility to the fluoroquinolones evaluated was high.

Abstract

Objective—To determine the in vitro fluoroquinolone susceptibility profiles of Pseudomonas aeruginosa isolates from dogs with ulcerative keratitis.

Animals—27 dogs with P aeruginosa–associated ulcerative keratitis.

ProceduresP aeruginosa isolates from dogs with ulcerative keratitis were collected during a 3-year period. Isolates were tested by use of the disk diffusion method for their susceptibility to 7 fluoroquinolones that are available as commercial ophthalmic preparations. The antimicrobials included second- (ciprofloxacin, ofloxacin, norfloxacin, and lomefloxacin), third- (levofloxacin), and fourth-generation (gatifloxacin and moxifloxacin) fluoroquinolones. Isolates were designated as susceptible, intermediate, or resistant to the various antimicro-bials. The percentage of susceptible isolates was compared among individual fluoroquinolones and among fluoroquinolone generations.

Results—None of the dogs had received topical or systemic fluoroquinolone treatment prior to referral. Twenty-seven P aeruginosa isolates were collected during the study period. In vitro, bacterial resistance to the tested fluoroquinolones was infrequently identified (24/ 27 isolates were susceptible to all fluoroquinolones evaluated); susceptibility percentages ranged from 88.9% to 100% for individual antimicrobials. There were no significant differ-ences among isolate susceptibilities to the individual antimicrobials or among generations of fluoroquinolones.

Conclusions and Clinical Relevance—On the basis of these in vitro data, none of the 7 evaluated fluoroquinolones (individually or collectively by generation) appeared to offer a clinically important advantage in the treatment of P aeruginosa–associated ulcerative keratitis in dogs. Among the P aeruginosa isolates collected from dogs with ulcerative keratitis in this study, the likelihood of susceptibility to the fluoroquinolones evaluated was high.

Contributor Notes

Supported by a grant from the Cornell University Dean's Fund for Clinical Excellence.

Address correspondence to Dr. Ledbetter.