Review of third-and fourth-generation fluoroquinolones in ophthalmology: in-vitro and in-vivo efficacy.
BACKGROUND
Beginning with second-generation ciprofloxacin 0.3% and ofloxacin 0.3%, fluoroquinolones have been widely used in the treatment and prophylaxis of ocular infections. However, their in-vitro potencies have been decreasing steadily since their introduction. Third-generation levofloxacin 0.5% produces higher ocular tissue penetration, thereby reducing the risk of selecting for decreased fluoroquinolone potency. Fourth-generation gatifloxacin 0.3% and moxifloxacin 0.5% have structural modifications that both reduce risk of resistance and improve potency against Gram-positive bacteria. A new third-generation formulation, levofloxacin 1.5%, was recently introduced, demonstrating increased ocular penetration compared with gatifloxacin 0.3% but clinical equivalence to its second-generation parent, ofloxacin 0.3%, in two randomized trials.


METHODS
We investigated the therapeutic potential of levofloxacin 1.5% and compared it to that of existing fourth-generation fluoroquinolones. A MEDLINE search was conducted using the following search terms: moxifloxacin or gatifloxacin; levofloxacin; minimum inhibitory concentration or prevention or prophylaxis; keratitis or endophthalmitis.


RESULTS
Nine eligible studies published between 2002 and 2008 were identified, eight of which are presented. The five in-vitro studies demonstrated that moxifloxacin and gatifloxacin are statistically more potent than levofloxacin against Gram-positive organisms and similar in potency in most cases of Gram-negative bacteria. In-vivo animal models testing moxifloxacin or gatifloxacin against levofloxacin 0.5% (no clinical trials testing the efficacy of levofloxacin 1.5% have yet been published) demonstrated that fourth-generation agents were superior to third-generation levofloxacin 0.5% for prophylaxis of Gram-positive bacteria-induced infections and were equal to, or better than, levofloxacin 0.5% for the treatment of Gram-negative infections.


CONCLUSIONS
Fourth-generation agents have increased potency against Gram-positive bacteria compared with levofloxacin, while maintaining similar potency against Gram-negative bacteria. Although levofloxacin 1.5% has demonstrated superior ocular penetration relative to gatifloxacin, the limited available data do not suggest this translates into superior clinical activity compared with moxifloxacin, which has significantly greater ocular penetration and better Gram-positive potency than gatifloxacin.
Scoper
Stephen V
SV
Virginia Eye Consultants, Norfolk, Virginia 23502, USA. sscoper@vec2020.com
D000287:Administration, Topical; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use*; D009877:Endophthalmitis / Q000188:drug therapy; D024841:Fluoroquinolones / Q000627:therapeutic use*; D000077734:Gatifloxacin; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007634:Keratitis / Q000188:drug therapy; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000627:therapeutic use; D009885:Ophthalmology; D011804:Quinolines / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin