**1. Introduction**

Netilmicin is a third-generation aminoglycoside antibiotic considered a firstline therapy for the treatment of acute bacterial conjunctivitis. It is a semisynthetic 1-N-ethyl derivative of sisomycin, endowed with an excellent *in vitro* and *in vivo* activity against a wide range of ocular pathogens both Gram-positive and Gram-negative bacteria including *Staphylococcus aureus* (*S. aureus*), S*. epidermidis* (*S. epidermidis*) and others *Staphylococcus* Coagulase negative, *Acinetobacter* spp., *Pseudomonas* spp. and *Haemophilus influenzae* [1–3].

The most common causative agents for external ocular infections are *S. aureus* and *S. epidermidis* although the specific causal organisms are frequently unknown [2]. Of particular concern among ocular isolates is the increasing frequency of methicillinresistant *S. aureus* (*MRSA*) and methicillin-resistant *S. epidermidis* (*MRSE*) [4].

Various classes of topical antibacterial products have been used in the treatment of bacterial conjunctivitis. These include aminoglycosides (e.g. tobramycin, gentamycin and netilmicin), macrolides (e.g. azithromycin), chloramphenicol and, most recently, fluoroquinolones (e.g. ofloxacin and levofloxacin) [4].

Nonetheless, successful therapy for bacterial conjunctivitis continues to be limited by several factors. A primary concern is the development of bacterial resistance that may be impacted not only by widespread antibiotic use but also by antibacterial pharmacokinetics, such as maintenance of insufficient bactericidal concentrations at the site of infection [2, 4].

Importantly, netilmicin is active against strains and resistant to other aminoglycosides, such as tobramycin or gentamicin [2], including methicillin-resistant strains [1, 2, 5, 6]. Indeed, being an antibiotic almost totally dedicated to ophthalmology and not used for systemic route, netilmicin has maintained unchanged its susceptibility and resistance profile over the last 20 years towards the major strains responsible for eye infections [7, 8].

Netilmicin is available on the market in three different topical ophthalmic dosage forms: solution, gel and ointment. Those products are indicated for the treatment of bacterial ocular infections of the anterior segment of the eye and ocular adnexa [2]. Netilmicin ophthalmic formulation is able to cross the cornea of rabbits, reaching aqueous humor levels comparable with the minimal inhibitory concentration (MIC) for usual ocular pathogens [9]. Netilmicin has no toxic effect *in vitro* on human corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong-Kilbourne derivative of Chang conjunctiva) [10]. Bonfiglio *et al*. evaluated the *in vitro* activity of netilmicin of other antibiotics used in ophthalmology against gram-positive and gram-negative microorganisms isolated from ocular infections. The results of this study showed that the activity of netilmicin was superior to that of ofloxacin against both groups of bacteria, with more than 90% of the isolated strains being susceptible to netilmicin [3]. Additionally, in a study carried out on 1333 ocular clinical isolates, netilmicin was revealed to have the best susceptibility profile among aminoglycosides showing the lowest minimum inhibitory concentration (MIC) values against all isolates. Specifically, netilmicin superiority was pronounced against *S. aureus* and **c**oagulase-negative staphylococci (CoNS) [11]. These two Staphylococci strains represent the most diffused clusters of bacteria in ocular infections ranging from 65 to 76.2% of the total isolates under investigation [11, 12].

Moreover, Blanco *et al*. evidenced that netilmicin was effective as vancomycin against both methicillin-resistant *Staphylococcus aureus* (*MRSA*) and

*Potency of Netilmicin against Staphylococci Compared to Other Ophthalmic Antibiotics DOI: http://dx.doi.org/10.5772/intechopen.106441*

methicillin-resistant *Staphylococcus epidermidis* (*MRSE*) clinical-ocular isolates [13]. This result is worthy of note considering that an increasing incidence (55% from 2002 to 2008) of *MRSA* and *MRSE* strains was registered in ophthalmology with few antibiotics capable of being efficacious against these pathogens [14]. Considering this evidence, the aim of the present study was to, directly, compare, within the same experimental setting, anti-staphylococcal activity of netilmicin to those of the main ophthalmic antimicrobials on the market. To this end, two of the most important pharmacological indices for antibiotics, that is, the quotient of inhibition (QI), corresponding to the Cmax/MIC90 ratio [15], and the antibiotic kinetic of killing was investigated. Antibiotic QIs were calculated by mining respective maximum concentration (Cmax) and MIC90 data from peer-reviewed literature and from internal pharmacokinetic studies in rabbits carried out according to Good Laboratory Practice (GLP). The QIs of two netilmicin formulations, eye drops solution and gel, in single and multiple dose administrations (both in cornea and conjunctiva), were compared to those of tobramycin, ofloxacin, levofloxacin and azithromycin. The QI of chloramphenicol was not calculated since no data on Cmax in the target tissues (cornea and conjunctiva) were found in literature. Moreover, the same analysis was performed in human tears, comparing netilmicin eye drops solution with tobramycin ofloxacin and levofloxacin, all in single-dose administration. Concerning the killing kinetics against two ATCC Staphylococci strains and two Staphylococci methicillin-resistant ocular isolates, netilmicin activity was directly compared to those of the above-cited antibiotics and to chloramphenicol as well.
