Choosing the right antibiotic in eye infections: which criteria to refer to.
Dr. Carlos Cólliga of the Clinica RementerÃa in Madrid is an ophthalmologist with a specific specialisation in microbiology and infectious diseases of the eye, as well as ocular surface diseases such as dry eye syndrome. We therefore asked him a few questions about proper antibiotic therapy.
When dealing with an eye infection, what are the criteria to follow when choosing the best antibiotic?
An appropriate antibiotic for the treatment of eye infections must fulfil several essential characteristics.
First of all, it must have a broad spectrum of antibiotic activity to cover all possible aetiological agents causing the infection.
Secondly, the antibiotic of choice should have a low antibiotic resistance rate in order to avoid both any complications that may arise from the infection and the need to change therapy, perform further tests, etc.
Thirdly, a good antibiotic for the treatment of eye infections, especially those affecting the ocular surface (which are the majority) must have a good tolerance profile, a good safety profile and low toxicity to the ocular surface, as antibiotic therapy sometimes has to be prolonged for several weeks or longer.
In this regard the netilmicin stands out as a broad-spectrum antibiotic for both Gram-positive and Gram-negative bacteria, and with a very low, almost non-existent rate of antibiotic resistance for the micro-organisms most frequently isolated in ocular infections. It is an aminoglycoside antibiotic with concentration-dependent bactericidal activity, with a good PK/PD (pharmacokinetic/pharmacodynamic ratio) pharmacotherapeutic profile and a maximum Cmax/MIC (MIC: Minimum Inhibitory Concentration) concentration higher than 10, which is essential for its efficacy and high post-antibiotic effect.
For which diseases is it important that the antibiotics used are not toxic to the ocular surface?
All those pathologies in which the integrity of the ocular surface is compromised, such as chronic conjunctivitis, chronic ocular allergies, dry eye syndrome, when wearing contact lenses, muco-cutaneous pathologies (pathologies affecting the skin and mucous membranes with ampullary vesicular lesions, usually bilateral and of autoimmune aetiology - such as pemphigoid), chronic use of topical hypotensive drugs, etc. In all these cases, antibiotic treatment that respects the integrity of the ocular surface is absolutely necessary.
In these cases, in particular, it is even more important to use an antibiotic with a low toxicity precisely because of the pre-existing damage that many of these patients present at the level of their ocular surface and the potential complications due to the use of drugs that increase epithelial toxicity, as well as to ensure adequate tolerance to the antibiotic and high adherence to therapy for the treatment of the infection.
Which antibiotic do you consider most toxic?
The toxicity of antibiotics depends very much on the time of use and the concentration, as well as the dosage.
Among the aminoglycosides, both gentamicin and tobramycin have been reported to be highly toxic to keratocytes and cells in other districts, such as the epithelium of the renal tubule, and are therefore nephrotoxic. In this respect, netilmycin is less toxic than tobramycin to the renal tubule epithelium, as has been demonstrated in both animal models and clinical studies.1,2
In studies on the retinal toxicity of intravitreal injections of aminoglycosides, the most retinotoxic antibiotic was gentamicin, above tobramycin and netilmycin.3
With regard to fluoroquinolones, antibiotics widely used in ophthalmology, ofloxacin proved to be significantly more toxic than netilmycin, with a 50% inhibition of cell proliferation and corneal epithelium viability, whereas netilmycin has no toxic effect on the same cells, according to the same study.4
In which population should special attention be paid to cytotoxicity?
In general, we should be particularly cautious about prescribing antibiotics to fragile populations, such as children and the elderly, some of whom have a damaged or immature enzyme metabolism.
In conclusion, for the treatment of infections one must use drugs that are safe at the minimum effective concentration, through the appropriate route of administration, for the necessary time without exceeding the minimum effective concentration, with the minimum rate of resistance5with a sufficiently wide therapeutic range, with no or minimal toxicity to the body and, in the specific case of eye infections, to the eye.
In these situations, topical netilmicin for the treatment of eye infections meets all these characteristics and is safe for administration in people of all ages.
1. Dahlager JI. The effect of netilmycin and other aminoglycosides on renal
function. A survey of the literature on the nephrotoxicity of netilmycin. Scand J
Infect Dis Suppl. 1980;Suppl 23:96-102. PMID: 7010549.
2. R.J. Szot, G. McCormick, M. Chung, B. Christie, E. Weinberg, E. Schwartz,
Comparative toxicity of netilmycin and tobramycin in dogs, Toxicology and
Applied Pharmacology, Volume 55, Issue 1, 1980.
3. D'Amico DJ, Caspers-Velu L, Libert J, Shanks E, Schrooyen M, Hanninen LA,
Kenyon KR. Comparative toxicity of intravitreal aminoglycoside antibiotics. Am J
Ophthalmol. 1985 Aug 15;100(2):264-75. doi: 10.1016/0002-9394(85)90792-5.
PMID: 4025468.
4. Papa V, Leonardi A, Getuli C, Pacelli V, Russo P, Milazzo G. Effect of ofloxacin
and netilmicin on human corneal and conjunctival cells in vitro. J Ocul
Pharmacol Ther. 2003 Dec;19(6):535-45. doi: 10.1089/108076803322660459.
PMID: 14733711.
5. Milazzo G, Papa V, Carstocea B, Chercota G, Rodica P, Gafencu O, Santocono
M. Topical netilmycin compared with tobramycin in the treatment of external
ocular infection. Int J Clin Pharmacol Ther. 1999 May;37(5):243-8. PMID:
10363623.
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