Anti-infective considered potent therapeutic with single-drop convenience

June 1, 2007

The fixed combination of loteprednol etabonate 0.5%/tobramycin 0.3% provides a safe and potent corticosteroid with an anti-infective agent that has broad-spectrum activity against important gram-negative and gram-positive organisms.

Key Points

"Many infectious ocular disorders have a significant inflammatory component. Likewise, many inflammatory conditions pose a risk for bacterial infection. The fixed combination of an anti-inflammatory drug and an anti-infective agent in this dual agent makes it a very useful option in a subspecialty practice that sees many patients with infections, injuries, and surface disease," said Dr. Sheppard, professor of ophthalmology, microbiology, and molecular cell biology, Eastern Virginia Medical School, Norfolk.

"It is also a valuable choice for use by primary care ophthalmologists who often see patients with conjunctivitis or atypical ocular surface inflammation [that] also can be best served by combination therapy," he added.

"The best agents to eradicate these organisms are not fluoroquinolones but rather aminoglycosides or a sulfa compound in our local sensitivity profile. The tobramycin in this combination drug is ideal for treating conditions that are created, exacerbated, or sustained by MRSA and methicillin-resistant Staphylococcus epidermidis [MRSE]," he said.

Dr. Sheppard said he also finds loteprednol etabonate 0.5%/tobramycin 0.3% useful in patients who have undergone ocular surface surgery, including pterygium surgery, stem cell grafting, or a glaucoma-filtering procedure. He said he prescribes it often for patients with traumatic injuries, including those with a metallic foreign body with a rust ring, conjunctival abrasion, or conjunctival chemical burn with loss of the surface epithelium.

Steroid benefit

Another important benefit of this combination drug is that its steroid component, loteprednol, is safer and more effective than dexamethasone, which is found in other tobramycin-corticosteroid combination products, he said.

"Dexamethasone is a good drug, but it has less potent anti-inflammatory activity than loteprednol. We see that difference clinically but have also studied both drugs in our lab and found loteprednol was superior," Dr. Sheppard said.

"Compared with dexamethasone, loteprednol was associated with significantly higher protection against protein leakage and inflammation in the cornea and aqueous," he continued. "At the molecular level, Western blot analysis studies showed loteprednol had 4.5-fold greater binding affinity to the surface glucocorticoid receptor. Furthermore, loteprednol was associated with greater nuclear internalization of the glucocorticoid receptor, which is requisite for initiating the molecular cascade leading to corticosteroid-induced anti-inflammatory activity."