Concentration and bioavailability of ciprofloxacin and teicoplanin in the cornea.
OBJECTIVE
To investigate the concentration and bioavailability of ciprofloxacin and teicoplanin in the cornea.


METHODS
A biological assay was developed with corneal tissue used as a carrier for the antimicrobial. Concentration and biological activity were determined with a chemical assay and zone of inhibition (ZOI) around corneal samples with epithelial and endothelial surfaces in contact with the indicator organism. Patients undergoing penetrating keratoplasty received ciprofloxacin 0.3% or teicoplanin 1%.


RESULTS
There were good correlations between antimicrobial concentration and ZOI, when either filter paper or corneal discs were used (R(2) > 92%). Of 33 patients, the mean (median) concentration of ciprofloxacin in the cornea was 1.37 mg/L (0.46 mg/L) and 1.89 mg/L (1.44 mg/L; bioassay) in the epithelial and endothelial orientations, respectively, and 14.87 mg/L (7.41) in the cornea and 0.51 mg/L (0.42) in the aqueous (chemical assay). For teicoplanin, the mean (median) concentration in the cornea was 9.58 mg/L (0 mg/L) in the epithelial and 4.78 mg/L (0 mg/L) in the endothelial orientations (bioassay). In the chemical assay, teicoplanin could not be detected in the cornea or aqueous at the lower limit of detection of 3.6 mg/L.


CONCLUSIONS
The ZOI produced by corneal tissue provides a potential bioassay of antimicrobial activity and concentration. Although in contrast to teicoplanin ciprofloxacin shows good corneal penetration, with high endothelial-to-epithelial levels, only approximately 10% of measured levels in a chemical assay are available, according to a bioassay. Teicoplanin shows relatively poor corneal penetration through intact epithelium. These methods may be useful in evaluating the biological activity across the cornea of antimicrobials introduced into ophthalmic practice to deal with changing bacterial resistance.
Kaye
Stephen B
SB
Department of Medical Microbiology, St Paul's Eye, Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom. s.b.kaye@liverpool.ac.uk
Neal
Timothy
T
Nicholson
Steven
S
Szkurlat
Jagoda
J
Bamber
Sharon
S
Baddon
Andrew C
AC
Anderson
Sarah
S
Seddon
Keeley
K
Dwyer
Nichola
N
Lovering
Andrew M
AM
Smith
Godfrey
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D003316:Corneal Diseases / Q000378:metabolism / Q000601:surgery; D004926:Escherichia coli / Q000187:drug effects; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D015948:Keratoplasty, Penetrating; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013552:Swine; D017334:Teicoplanin / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D017334:Teicoplanin