Kresken 24/9/08 12:23 Page 14
Ocular Infection
Haemophilus influenzae: All isolates collected during Ocular TRUST 1 hours after the instillation of a single dose (one drop) of 0.5% levofloxacin
(n=32) were susceptible to levofloxacin, as were 355/356 (99.7%) of the ophthalmic solution was more than two-fold higher than the AUC
24h
after
archived isolates from TRUST, regardless of β-lactamase production.
18
The a single oral or intravenous administration of 750mg levofloxacin. In clinical
German surveillance study found that all 164 isolates examined showed practice the AUC should even be higher, as patients would receive multiple
susceptibility to levofloxacin.
19
doses per day. These data indicate that a 0.5% levofloxacin ophthalmic
solution is effective in the treatment of external ocular infections against
Other ocular pathogens: Data from the German resistance surveillance target pathogens.
study for ocular organisms indicated that none of the 46 E. coli isolates
and 6/45 (13.3%) of the P. aeruginosa isolates were resistant to Clinical Trials
levofloxacin,
19
five of which were isolated from hospitalised patients. A topical ophthalmic solution of 0.5% levofloxacin was effective in bacterial
conjunctivitis and keratitis.
35–39
In a study by Yactayo-Miranda et al., so far
Pharmacokinetic and Toxicological Properties published only as a poster, 0.5% levofloxacin eye drops were also effective
After a single drop of 0.5% levofloxacin ophthalmic solution applied to each in the treatment of chronic bacterial blepharoconjunctivits.
40
More recently,
eye of healthy volunteers, drug concentrations in the tear fluid remained there has been increasing interest in the use of levofloxacin as a prophylactic
above 2mg/l for at least six hours.
22
Following topical administration, the agent in intraocular surgery. Because of its broad spectrum of antibacterial
drug has also been demonstrated to effectively penetrate the cornea, and if activity and high corneal permeability, levofloxacin appears to be a suitable
the drug is frequently given over one hour, concentrations achieved in the agent for this purpose as it has been shown to reduce the bacterial
anterior chamber of the eye were above the MICs of most ocular bacterial conjunctival load, being the main source of bacteria causing post-operative
pathogens.
23–25
When combined with orally administered levofloxacin, infections, and to achieve drug levels inside the eye that are capable of
adequate drug levels were also achieved in the vitreous cavity of the eye.
26
preventing infection in cases of contamination.
23–25,41
Levofloxacin proved to
Topically applied fluoroquinolones have been considered to be more toxic be effective as prophylaxis in intraocular surgery and acted synergistically
to the corneal epithelium than other antibiotic agents.
27,28
However, in a when combined with the standard conjunctival povidone–iodine
recently published study levofloxacin did not negatively influence epithelial irrigation.
42,43
Recently, 0.5% levofloxacin eye drops were evaluated for the
wound healing.
29
Moreover, levofloxacin was shown to be less cytotoxic on prevention of post-cataract surgery intraocular infection. In this large-scale
human corneal keratocytes and epithelial cells than other fluoroquinolones, European multicentre trial, the difference in the rates of post-operative
including gatifloxacin, moxifloxacin, ciprofloxacin and ofloxacin.
30
infections between levofloxacin and placebo did not reach statistical
significance, although the dosing regimen was met with some criticism (low
Pharmacokinetic/Pharmacodynamic Relationships dose and late time-point of post-operative prophylactic treatment), and an
The ratio between the 24-hour area under the serum concentration curve unexpected high incidence of post-operative infections was observed in the
and MIC (AUC
24h
/MIC) and the peak concentration/MIC (C
max
/MIC) for placebo arm.
44
unbound drug are thought to be predictors of clinical and bacteriological
efficacy.
31
However, the magnitude of the pharmacokinetic/pharmaco- Conclusions
dynamic (PK/PD) index needed seems to vary according to the type of Despite the long-term extensive use of fluoroquinolones for the treatment
quinolone, bacterial species and immune status. A C
max
/MIC ratio of >10 of local and systemic infections, levofloxacin-resistant ocular isolates of
and an AUC
24h
/MIC ratio of 100–125 has been reported to provide S. pneumoniae and H. influenzae remain uncommon. Also, based on the
maximum bacterial eradication and to prevent resistance in critically ill data of the German surveillance study, the treatment of superficial ocular
patients with nosocomial lower respiratory tract infections caused by infections caused by E. coli and P. aeruginosa with levofloxacin still have a
Gram-negative bacteria such as P. aeruginosa.
32,33
However, in outpatients high likelihood of success. In contrast, levofloxacin, like other
with community-acquired respiratory tract infections such as acute fluoroquinolones, is not indicated if MRSA is suspected as a pathogen. Due
exacerbations of chronic bronchitis and community-acquired pneumonia to its high corneal penetration, levofloxacin represents one of the most
caused by S. pneumoniae, AUC
24h
/MIC ratios of about ≥25 are predictive valuable antibacterial agents for topical use in ophthalmology, especially for
for bacterial eradication.
10,34
Based on the tear concentrations measured in the treatment of fulminant bacterial keratitis. However, its role as a
the healthy volunteer study by Raizman et al.,
22
the calculated AUC over six prophylactic regimen in ocular surgery needs to be further elucidated. ■
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14 EUROPEAN OPHTHALMIC REVIEW
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