Purpose. To assess the effect of minocycline on the ocular flora in patients with acne rosacea or blepharitis.
Methods. A total of ten patients were enrolled in this prospective study, with six patients diagnosed with acne rosacea with concomitant meibomianitis, two patients with acne rosacea without concomitant ocular involvement, and two patients with seborrheic blepharitis. The eyelids and conjunctiva of both eyes were cultured before the initiation of systemic minocycline therapy, after 3 months of active therapy, and 3 months after the discontinuation of therapy. Isolated bacteria were identified and quantified, and antibiotic susceptibility was determined.
Results. The colony-forming units (CFU) isolated from the eyelids significantly decreased after a 3-month treatment with minocycline (P = 0.0013). The CFU significantly increased to approach that of the baseline with the discontinuation of minocycline (P = 0.0275). The most common isolated bacteria, including coagulase-negative Staphylococcus (CNS), Staphylococcus aureus (S. aureus), and Propionibacterium acne (P. acne), except for corynebacterium, had a significant decrease in bacterial count with minocycline therapy compared with baseline (P < 0.05). There was a trend in the decrease of bacterial CFU isolated from the conjunctiva with minocycline therapy, although this was not statistically significant (P = 0.1955). Four of the ten patients carried tetracycline-resistant CNS strains, but none of the S. aureus or P. acne isolated at baseline was resistant to tetracycline. All six patients with acne rosacea and concomitant meibomianitis had marked clinical improvement.
Conclusion. Minocycline effectively decreased eyelid bacterial flora in patients with acne rosacea or blepharitis. One of the mechanisms of newer generation tetracycline analogues may be a decrease or elimination of bacterial flora from the eyelids.
Blepharitis is a chronic ocular condition commonly encountered by the ophthalmologist. The treatment of blepharitis can at times be frustrating for both the patient and the physician. We have previously described six clinically distinct groups of blepharitis, namely, staphylococcal blepharitis, seborrheic blepharitis, combined seborrheic and staphylococcal blepharitis, seborrheic blepharitis with meibomian seborrhea, seborrheic blepharitis with secondary meibomianitis, and meibomian keratoconjunctivitis. 1-3 Of these groups, meibomian keratoconjunctivitis generally has the most severe signs and symptoms. 3 Frequently, these patients will have an associated seborrheic dermatitis or acne rosacea. 1-3
The first report of the use of tetracycline to treat rosacea was published in 1966. 4 Since that time, several tetracycline analogues, including tetracycline, doxycycline, and minocycline, have been shown to be effective treatments for patients with acne rosacea. 5,6 However, the mechanism of action of tetracycline analogues on patients with meibomianitis is unclear. The most common bacteria isolated from patients with chronic blepharitis are Staphylococcal aureus (S. aureus), coagulase-negative staphylococci (CNS), Propionibacterium acnes, and corynebacteria. 7 These bacteria produce lypolytic exoenzymes, including fatty wax esterase, cholesteryl esterase, and triglyceride lipase, that may alter the composition of meibomian secretion, thereby contributing to the disease process. 8 The bacterial lipases hydrolyze wax and sterol ester to free fatty acids, which can be toxic to the ocular tissue and have an adverse effect on the tear film. 8,9 One mechanism of action of tetracycline analogues may be its ability to inhibit bacterial lipases and thereby reduce free fatty acid production. 10 A tetracycline analogue, minocycline, has also been shown to suppress the production of neutrophil chemotactic factors in P. acnes, P. granulosum, and CNS. 11-15 In addition, tetracycline analogues decrease the production of reactive oxygen species, such as O2-, H2O2, and OH•, by neutrophils. 11 In the past, the antimicrobial effects of the tetracyclines have not been considered to be significant in the treatment of blepharitis or meibomian gland inflammatory disease.
This study is designed to evaluate the effects of a tetracycline analogue, minocycline, on the bacterial eyelid and conjunctival flora of patients with acne rosacea or chronic blepharitis. We compared the change in bacterial eyelid flora during minocycline therapy and the corresponding clinical responses in patients with and without meibomianitis. Minocycline was chosen because it is used as first-line treatment in refractory cases of meibomianitis. Minocycline has minimal photosensitization and fewest side effects, particularly gastrointestinal side effects. Its dosing is more convenient at twice a day, rather than four times a day for tetracycline. Foods, especially dairy products, do not interfere with the absorption of minocycline as they do with tetracycline.