Chloramphenicol/hydrocortisone/polymyxin b ophthalmic Disease Interactions

Chloramphenicol may cause bone marrow depression and other hematologic toxicities, which can be irreversible or reversible. The former type is independent of dose and results in aplastic anemia with a high rate of mortality, generally from hemorrhage or infection. It has been reported following both systemic and topical administration of chloramphenicol and has an estimated incidence of 1 in 25,000 to 1 in 40,000 courses of therapy. Bone marrow aplasia or hypoplasia may occur after a single dose but more often develops weeks or months after the drug has been discontinued. A reversible myelosuppression occurs much more frequently and is characterized by anemia, vacuolation of red blood cells, decreased reticulocyte count, leukopenia, thrombocytopenia, increased serum iron concentrations, and increased serum iron-binding capacity. It is dose-dependent, occurring regularly at chloramphenicol dosages exceeding 4 g/day (in adults) or at plasma drug concentrations >= 25 mcg/mL, and usually responds to withdrawal of the drug. Therapy with chloramphenicol should be administered cautiously, if at all, in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts and differential reticulocyte counts should be performed in all patients prior to initiating therapy and approximately every 2 days during therapy. Marked depression of blood counts and/or development of other hematologic abnormalities may be indication for withdrawal of chloramphenicol therapy.

The use of ophthalmic corticosteroids is contraindicated in most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella; fungal diseases of ocular structures; mycobacterial infections, including tuberculosis, of the eye; and any acute, purulent, untreated ocular infections. Corticosteroids may decrease host resistance to infectious agents, thus prolonging the course and/or exacerbating the severity of the infection while encouraging the development of new or secondary infection. In addition, administration of ophthalmic corticosteroids in severe ocular disease, especially acute herpes simplex keratitis, may lead to excessive corneal and scleral thinning, increasing the risk for perforation. In less serious ocular infections, therapy with ophthalmic corticosteroids may be administered but only with caution and accompanied by appropriate antimicrobial agents. Besides compromising host immune response, corticosteroids may also mask the symptoms of infection, thus hindering the recognition of potential ineffectiveness of the antibiotic therapy. If infection does not improve or becomes worse during administration of an ophthalmic corticosteroid, the drug should be discontinued and other appropriate therapy initiated.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with ophthalmic corticosteroids should be administered cautiously in patients with a history of cataracts, glaucoma, or increased intraocular pressure. If these agents are used for more than 10 days, the manufacturers recommend that intraocular pressure be routinely monitored, including in children. The equatorial and posterior subcapsular portions of the lens should be examined for changes.