Fortified Vancomycin

Vancomycin 50 mg/ml · compounded ophthalmic solution

Antibiotic

Approved uses

Serious methicillin-resistant staphylococcal infections (intravenous, non-ocular)

Adults with normal renal function: 2 g IV daily, as 500 mg every 6 hours or 1 g every 12 hours, each infused over at least 60 minutes

OFF-LABELNot in the FDA label for this product

Gram-positive bacterial keratitis, including MRSA

Fortified 25 to 50 mg/mL topically; for central or severe ulcers a loading dose every 5 to 15 minutes, then applications about every hour

Guideline · case series · n=52

Dosing is guideline-based, not trial-based: the AAO Bacterial Keratitis Preferred Practice Pattern lists topical vancomycin 25 to 50 mg/mL for gram-positive cocci and recommends the loading-then-hourly schedule for central or severe keratitis. The best clinical comparison is a retrospective series of 52 culture-proven MRSA keratitis eyes in which fortified vancomycin gave no difference in final visual acuity, treatment duration, or need for surgery versus fourth-generation fluoroquinolones; the authors note the vancomycin-treated ulcers tended to be more severe at presentation, so this is a null result under confounding, not a demonstration of equivalence.

American Academy of Ophthalmology Preferred Practice Pattern Cornea/External Disease Panel. Bacterial Keratitis Preferred Practice Pattern. Ophthalmology. 2024;131(4):P87-P133 (practice guideline). Durrani AF, Atta S, Bhat AK, et al. Am J Ophthalmol. 2020;214:119-126 (retrospective case series, 52 eyes).

Severe bacterial keratitis, empirically paired with a gram-negative agent

Fortified 5% (50 mg/mL) with fortified gentamicin 1.4%, both given as a loading dose every 5 to 15 minutes then applications about every hour

Prospective cohort · n=49

Prospective cohort of 49 bacterial keratitis patients treated empirically: ulcers healed in 85.7% on gentamicin plus vancomycin, 44.4% on ceftazidime plus vancomycin, and 64.5% on moxifloxacin, a difference that was not statistically significant (p = 0.259). Median time to epithelialization was 21 days with gentamicin plus vancomycin versus 30 days for each of the other two arms (log-rank p = 0.020). Gram-positive isolates in that cohort were 93.3% susceptible to vancomycin, and coagulase-negative staphylococci were 100% susceptible. The authors recommend fortified gentamicin plus vancomycin in severe bacterial keratitis; the frequency of application comes from the AAO practice pattern, not from this cohort.

Nayel AA, Hamdy NA, Massoud TH, Mohamed NM. Graefes Arch Clin Exp Ophthalmol. 2024;262(6):1865-1882 (prospective cohort). Frequency from American Academy of Ophthalmology Bacterial Keratitis Preferred Practice Pattern. Ophthalmology. 2024;131(4):P87-P133.

Contraindications

Known hypersensitivity to vancomycin.

Available Forms

Compounded, no fixed ophthalmic package size, source single-dose vials 500 mg and 1 g, 500 mg vial yields 10 mL at 50 mg/mL

Mechanism of Action

Glycopeptide; bactericidal primarily by inhibiting bacterial cell wall biosynthesis, with added effects on cell membrane permeability and RNA synthesis. No in vitro activity against gram-negative bacilli, mycobacteria, or fungi, so empiric keratitis coverage needs a gram-negative partner drug.

Warnings & Precautions

Off-label ocular route: No FDA-approved ophthalmic vancomycin exists; the linked label covers intravenous use only, so every ocular application on this card is off-label.
Hemorrhagic occlusive retinal vasculitis: Occurred, including permanent vision loss, after intracameral or intravitreal injection during or after cataract surgery; the drug is not indicated for endophthalmitis prophylaxis and safety by those routes is unestablished.
Gram-negative coverage gap: No in vitro activity against gram-negative bacilli, mycobacteria, or fungi, so empiric keratitis regimens pair it with an aminoglycoside or ceftazidime.
Room-temperature potency loss: Fortified drops degrade off the cold chain; a 25 mg/mL preparation lost 38% of potency by day 14 at 24 C and 48% by day 7 and 78% by day 14 at 35 C, while staying constant at 4 C. Reconstituted 50 mg/mL solution may be refrigerated 14 days without significant loss of potency, and the 500 mg vial is reconstituted with 10 mL sterile water for injection.
Systemic toxicity profile: Nephrotoxicity, ototoxicity, severe cutaneous reactions (TEN, SJS, DRESS, AGEP, linear IgA bullous dermatosis), and C. difficile colitis are labeled for systemic exposure and are not established for topical drops.

Common Side Effects

Ocular surface: No human incidence data on this label or in the retrieved literature; in a rabbit MRSA keratitis model, 50 mg/mL produced significantly worse corneal epithelial erosion than topical linezolid at 1 or 2 mg/mL or saline.
Systemic exposure: Infusion reactions (hypotension, upper-body flushing, wheezing, dyspnea, urticaria, pruritus), acute kidney injury, ototoxicity, drug fever, chills, nausea, and eosinophilia; the label gives no percentages and all of it reflects intravenous dosing rather than drops.
Hematologic: Reversible neutropenia, usually beginning a week or more into therapy or after more than 25 g total, reported in several dozen patients on intravenous therapy.

Pregnancy & Lactation

Pregnancy: No animal reproduction studies conducted. In a controlled study of pregnant women given intravenous therapy in the second and third trimesters, drug was found in cord blood and no sensorineural hearing loss or nephrotoxicity was attributed to it; the study was small, so whether it causes fetal harm remains unknown.

Lactation: Excreted in human milk; weigh continuing nursing against continuing the drug, taking its importance to the mother into account.

Pediatric Use

No ophthalmic data.