TOBRADEX Eye drops, suspension Ref.[4793] Active ingredients: Dexamethasone Tobramycin

Pharmacotherapeutic group: Anti-inflammatory agents and anti-infectives in combination, corticosteroids and anti-infectives in combination
ATC code: S01CA01

Dexamethasone

The efficacy of corticosteroids for the treatment of inflammatory conditions of the eye is well established. Corticosteroids achieve their anti-inflammatory effects through suppression of vascular endothelial cell adhesion molecules, cyclooxygenase I or II, and cytokine expression. This action culminates in a reduced expression of pro-inflammatory mediators and the suppression of adhesion of circulating leukocytes to the vascular endothelium, thereby preventing their migration into inflamed ocular tissue. Dexamethasone has marked anti-inflammatory activity with reduced mineralocorticoid activity compared with some other steroids, and is one of the most potent anti-inflammatory agents.

Tobramycin

Tobramycin is a potent, broad-spectrum, rapidly bactericidal aminoglycoside antibiotic. It exerts its primary effect on bacterial cells by inhibiting polypeptide assembly and synthesis on the ribosome. Tobramycin in this combination provides antibacterial protection against susceptible bacteria.

The following MIC breakpoints, separating susceptible from intermediate susceptible organisms, and intermediate susceptible from resistant organisms, are suggested: S (<4 μg/ml), R (>8 μg/ml). The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. The following information gives only an approximate guidance on probabilities whether bacteria will be susceptible to tobramycin in TOBRADEX.

The breakpoint definitions classifying isolates as susceptible or resistant are useful in predicting clinical efficacy of antibiotics that are administered systemically. However, when the antibiotic is administered in very high concentrations topically directly on the site of infection, these breakpoint definitions may not be applicable. Most isolates that would be classified as resistant by systemic breakpoints are indeed successfully treated topically.

In vitro studies have shown tobramycin to be active against most strains of common ocular pathogens and common skin flora bacteria as listed in the Table below:

Categories / Frequency of Acquired Resistance in Europe

SENSITIVE SPECIES

Aerobic Gram-Positive Microorganisms::

Corynebacterium species / 0-3%
Staphylococcus aureus Methicillin -S^a / 0-3%
Staphylococcus epidermidis Methicillin -S^a / 0-28%
Other Coagulase-negative Staphylococci / 0-40%

Aerobic Gram-Negative Microorganisms:

Acinetobacter species / 0%
Citrobacter species / 0%

Escherichia coli / 0%
Enterobacter species / 0%
Haemophilus influenzae / 0%

Klebsiella species / 0%
Moraxella species / 0%
Proteus species / 0%
Pseudomonas aeruginosa / 0%

MODERATELY SUSCEPTIBLE SPECIES (in vitro, intermediate susceptibility)

Aerobic Gram-Negative Microorganisms:

Serratia marcescens

INHERENTLY RESISTANT SPECIES

Aerobic Gram-Positive Microorganisms:

Enterococcus species
Staphylococcus aureus Methicillin –R^a / 50–70%
Staphylococcus epidermidis Methicillin –R^a / 30–40%
Streptococcus pneumoniae
Streptococcus species

Aerobic Gram-negative microorganisms:

Burkholderia cepacia
Stenotrophomonas maltophilia

Anaerobic microorganisms:

Strict anaerobic bacteria

Others:

Chlamydia species
Mycoplasma species
Rickettsia species

^a Methicillin-susceptible (S), Methicillin-resistant (R). The beta-lactam (i.e., methicillin; penicillin) resistance phenotype is unrelated to the aminoglycoside resistance phenotype and both are unrelated to the virulence phenotypes. Some methicillin-resistant (R) S. aureus strains (MRSA) are susceptible to tobramycin (MIC: S <4); conversely some strains of methicillin–susceptible (S) S. aureus (MSSA) are resistant to tobramycin (MIC: S ≥8)

The frequency of methicillin resistance (R) may be up to 50% of all staphylococci in some European countries

Paediatric Population

The safety and efficacy of TOBRADEX in children have been established by broad clinical experience, but only limited data are available. In a clinical study of TOBRADEX suspension for the treatment of bacterial conjunctivitis, 29 paediatric patients, ranging in age from 1 to 17 years, were treated with 1 or 2 drops of TOBRADEX every 4 or 6 hours for 5 or 7 days. In this study, differences in the safety profile between adult and paediatric patients were not observed.

Other information

Cross-resistance between aminoglycosides (e.g., gentamicin and tobramycin) is due to the specificity of the enzyme modifications, Adenyltransferase (ANT) and Acetyltransferase (ACC). However, cross-resistance varies between the aminoglycoside antibiotics due to the differing specificity of the various modifying enzymes. The most common mechanism of acquired resistance to aminoglycosides is antibiotic inactivation by plasmid and transposon-encoded modifying enzymes.