8. Neu HC, Chi NX. In vitro activity of the new fluoroquinolone CP-
99,219. Antimicrob Agents Chemother. 1994;38:2615–2622.
9. Hynduik RA, Eiferman RA, Caldwell DR, et al. Comparison of
ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-
cefazolin in treating bacterial corneal ulcers. Ophthalmology.
1996;103:1854–1863.
10. Leibowitz HM. Clinical evaluation of ciprofloxacin 0.3% oph-
thalmic solution for treatment of bacterial keratitis. Am J Oph-
thalmol. 1991;112:34S–47S.
11. Weisbecker CA, Fraunfelder FT, Gold AA, Naidoff M, Tippermann
R. Physicians’ Desk Reference for Ophthalmology. Montvale, NJ:
Medical Economics; 1996:216–289.
12. Reidy JJ, Hobden JA, Hill JM, Forman K, O’Callaghan RJ. The
efficacy of topical ciprofloxacin and norfloxacin in the treatment
of experimental Pseudomonas keratitis. Cornea. 1991;10:25–28.
13. Brown SI, Bloomfield SE, Wai-fong IT. The cornea-destroying
enzyme of Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci.
1974;11:174–180.
14. Fisher E, Allen JH. Mechanism of corneal destruction by
Pseudomonas proteases. Am J Ophthalmol. 1958;46:249.
15. O’Brien TP, Maguire MG, Fink NE, Afonso E, McDonnell P, and
the Bacterial Keratitis Study Research Group. Efficacy of
ofloxacin vs cefazolin and tobramycin in the therapy for bacterial
keratitis. Arch Ophthalmol. 1995;113:1257–1265.
16. Parks DJ, Abrams DA, Sarfarazi FA, Katz HR. Comparison of top-
ical ciprofloxacin to conventional antibiotic therapy in the treat-
ment of ulcerative keratitis. Am J Ophthalmol. 1993;115:471–477.
17. Lauffenburger MD, Cohen KL. Topical ciprofloxacin versus topi-
cal fortified antibiotics in rabbit models of Staphylococcus and
Pseudomonas keratitis. Cornea. 1993;12:517–521.
18. Gritz DC, McDonnell PJ, Lee TY, Tang-Lui D, Hubbard BB, Gwon
A. Topical ofloxacin in the treatment of Pseudomonas keratitis in
a rabbit model. Cornea. 1992;11:143–147.
19. Madaras-Kelly KJ, Larsson AJ, Rotschafer JC. A pharmacody-
namic evaluation of ciprofloxacin and ofloxacin against two
strains of Pseudomonas aeruginosa. J Antimicrobial Chem. 1996;
37:703–710.
20. Diamond JP, White L, Leeming JP, Hoh HB, Easty DL. Topical
0.3% ciprofloxacin, norfloxacin, and ofloxacin in the treatment in
bacterial keratitis: a new method for comparative evaluation of
ocular drug penetration. Br J Ophthalmol. 1995;79:606–609.
21. Brooks GF, Butel JS, Ornston LN. Medical Microbiology. Norwalk,
Conn: Appleton & Lange; 1995:603.
22. Behrens-Baumann W. Absorption of topically administered
ciprofloxacin, ofloxacin and gentamicin in the inflamed rabbit
eye. Ophthamologica. 1996;210:119–122.
23. Ellner PD, Neu HC. The inhibitory quotient: a method for inter-
preting minimum inhibitory concentration data. JAMA. 1981;246:
1575–1578.
24. Price FW, Whitson WE, Collins KS, Gonzales JS. Corneal tissue
levels of topically applied ciprofloxacin. Cornea. 1995;14:152–156.
25. Donnenfeld ED, Perry HD, Snyder RW, Moadel K, Elsky M, Jones
H. Intracorneal aqueous humor, and vitreous humor penetration
of topical and oral ofloxacin. Arch Ophthalmol. 1997;115:173–176.
26. Roussel TJ, Osato MS, Robinson NM. Resistant Pseudomonas
keratitis. J Ocular Ther Surg. 1984;3:136.
27. Gelender H, Rettich C. Gentamicin-resistant Pseudomonas aerug-
inosa corneal ulcers. Cornea. 1984;3:21–26.
28. Epley DE, Katz HR, Herling I, Lasky JB. Platinum spatula versus
mini-tip culturette in culturing bacterial keratitis. Cornea. 1998;
17:74–78.
29. Tunkel AR, Scheld WM. Applications of therapy in animal models
to bacterial infection in human disease. Infect Dis Clin North Am.
1989;3:441–459.
shown in animal studies and in clinical trials to be
effective against P aeruginosa keratitis.17,18
Data on antibiotic potency, as measured by mini-
mum inhibitory concentration, indicate that P aerugi-
nosa is more sensitive to ciprofloxacin than to
ofloxacin. However, most studies show that the
corneal concentration of ofloxacin is somewhat higher
than ciprofloxacin with equivalent dosing.23 The
inhibitory quotient, which integrates antibiotic poten-
cy and antibiotic tissue concentration, favors
ciprofloxacin over ofloxacin in the treatment of P
aeruginosa keratitis.20 In addition, pharmacodynamic
data using kill curves indicate that ciprofloxacin
reduces the colony-forming units of P aeruginosa
more rapidly than does ofloxacin.19
Our study used a previously described model of P
aeruginosa keratitis in rabbits28 to determine whether
the in vitro difference in the fluoroquinolones
described above is also observed in an in vivo model.29
In pilot studies, we found that both antibiotics, given
enough time, were able to sterilize the infected
corneas. However, early in the course of treatment the
reduction of colony-forming units was statistically
greater with 0.3% ciprofloxacin than with 0.3%
ofloxacin. This early reduction of colony-forming
units may decrease corneal tissue destruction result-
ing from release of bacterial proteases.13
Our in vivo study shows that 0.3% ciprofloxacin is
more effective than 0.3% ofloxacin in reducing colony-
forming units in the early treatment of P aeruginosa
keratitis in rabbits. Thus, both in vitro and in vivo
data suggest that 0.3% ciprofloxacin may be more
effective than 0.3% ofloxacin in the treatment of P
aeruginosa keratitis.
References
1. Baum JL. Initial therapy of suspected microbial corneal ulcers. I:
broad antibiotic therapy based on prevalence of organisms. II:
specific antibiotic therapy based on corneal smears. Surv Oph-
thalmol. 1979;24:97–105.
2. Levey SB, Katz HR, Abrams DA, Hirschbein MJ, Marsh MJ. The
role of cultures in the management of ulcerative keratitis. Cornea.
1997;16:383–386.
3. Liesegang TJ. Bacterial keratitis. Infect Dis Clin North Am. 1992;
6:815–829.
4. Neu HC. Microbiology aspects of fluoroquinolones. Am J Oph-
thalmol. 1991;112:15S–24S.
5. Rolando M, Brezzo V, Campagna P, et al. Toxic effects of antimi-
crobials on the ocular surface of healthy volunteers. Chibret Int J
Ophthalmol. 1991;8:46.
6. Wolfson JS, Hooper DC. The fluoroquinolones: structures, mecha-
nisms of action and reistance, and spectra of activity in vitro.
Antimicrob Agents Chemother. 1985;28:581–586.
7. Campoli-Richards DM, Monk JP, Price A, Benfield P, Todd PA,
Ward A. Ciprofloxacin: a review of its antibacterial activity, phar-
macokinetic properties and therapeutic use. Drugs. 1988;35:373–
447.
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