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Netilmicin: new aminoglycoside effective against bacterial endophthalmitis
Abstract:
Bacterial endophthalmitis is difficult to treat because antibiotics administered systemically, subconjuctivally or topically cannot be delivered in bactericidal amounts to the infected tissues. Netilmicin, a new aminoglycoside, is active against Pseudomonas aeruginosa, Staphylococcus and most Enterobacteriaceae, including Escherichia coll, Klebsiella and Enterobacter, that have been resistant to other aminoglycosides. In rabbits an intravitreal injection of 250 mu g/0.1 ml rapidly provided a bactericidal concentration (greater than 10 mu g/ml) in the vitreous, and this level was maintained for 100 hours. This dose was not toxic to ocular tissues, unlike higher doses (1000 to 2000 mu g). Intravenous, subconjunctival and topical administration yielded only low concentrations of the drug in the vitreous, although subconjunctival injection yield significant concentrations in the aqueous for 4 hours. Experimentally induced Staphylococcus aureus endophthalmitis was quickly eradicated by a single intravitreal dose of netilmicin without detectable sequelae in 9 to 10 eyes studied. A solution of netilmicin infused during vitrectomy and lensectomy prevented infection.
Insights
Intravitreal netilmicin effectively treats bacterial endophthalmitis by reaching bactericidal levels in the eye. This new aminoglycoside eradicated Staphylococcus aureus infections in rabbits without toxicity.
Area of Science:
- Ophthalmology
- Microbiology
- Pharmacology
Background:
- Bacterial endophthalmitis treatment is challenging due to poor antibiotic penetration to ocular tissues.
- Systemic, topical, and subconjunctival antibiotics often fail to achieve bactericidal concentrations in the vitreous.
- Netilmicin demonstrates broad-spectrum activity, including against strains resistant to other aminoglycosides.
Purpose of the Study:
- To evaluate the efficacy and safety of netilmicin for bacterial endophthalmitis.
- To determine optimal administration routes and dosages for intravitreal netilmicin.
- To assess netilmicin's potential in preventing ocular infections during surgery.
Main Methods:
- Pharmacokinetic analysis of netilmicin concentrations in rabbit ocular tissues after various administration routes.
- Intravitreal injection of 250 µg/0.1 ml netilmicin in rabbits.
- Experimental induction of Staphylococcus aureus endophthalmitis in rabbits.
- Evaluation of netilmicin infusion during vitrectomy and lensectomy in rabbits.
Main Results:
- A single 250 µg intravitreal dose of netilmicin achieved rapid and sustained bactericidal concentrations in the vitreous for 100 hours.
- This dose was non-toxic to ocular tissues.
- Intravenous, subconjunctival, and topical routes resulted in low vitreous concentrations.
- Subconjunctival injection provided significant aqueous humor concentrations for 4 hours.
- A single intravitreal dose eradicated S. aureus endophthalmitis in 90% of rabbit eyes without sequelae.
- Intraoperative infusion of netilmicin prevented infection during vitrectomy and lensectomy.
Conclusions:
- Intravitreal netilmicin is a promising treatment for bacterial endophthalmitis, offering rapid and sustained bactericidal levels.
- Netilmicin's safety profile at therapeutic intravitreal doses supports its clinical use.
- Intravitreal administration is superior to other routes for achieving therapeutic concentrations in the vitreous.
- Netilmicin can be used prophylactically during intraocular surgeries to prevent infection.