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Understaning the new antibiotics II: anti-inflammatory effects
Milton M. Hom, OD, FAAO.
[email protected]
Course description (1 hour): For some chronic ocular conditions, the immunomodulating
properties of antibiotics outperform steroids. Some believe sooner or later antibiotics will
become useless because of resistance. Are antibiotics the new anti-inflammatory agents?
We look at dermatologic conditions (lid disease, rosacea, and blepharitis), the resistance
question, and microbial keratitis strategies.
Learn about diagnosis and treatment of lid disease, rosacea and blepharitis
Learn about anti-inflammatory effects of antibiotics
Review ocular dermatological disorders
Definitions:
Antibiotic: chemical agent that has the capacity to inhibit growth or to kill microorganisms, especially bacteria, but which is also non-toxic to the host; used in the
treatment of infectious diseases.
Anti-inflammatory: an agent that acts to suppress inflammation; basically encompasses
two drug categories: corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs)
Antibiotics
Mechanism of action:
Inhibition of cell wall synthesis (e.g. penicillin, bacitracin)
Inhibition / destruction of cell membrane (e.g. polymyxin B)
Competitive inhibition of metabolism (e.g. sulfacetamide)
Inhibition of protein synthesis (e.g. tobramycin, tetracycline)
Inhibition of DNA / RNA synthesis (e.g. ciprofloxacin, rifampin)
Anti-inflammatory effects of antibiotics
Prescribed by dermatologists since early 1950s
Reduces inflammation by mechanisms:
Anticollagenolytic, Matrix metalloproteinases (MMPs) & Cytokine down-regulation
MMPs
Degrade extracellular proteins
Tetracyclines inhibit MMPs
Anti-inflammatory propreties
History of anti-inflammatory uses of antibiotics
Periodontitis: Low doses of doxyxycline
Rheumatoid arthritis: minocycline slows progression
Coronary artery disease: Macrolides help heart attack prevention
Respiratory treatment effects: Decreased length of stay and mortality
Cystic fibrosis: Azithromycin gives better lung function
Concerns
The resistance question
Resistance to erythromycin, clindamycin and tetracycline doubled 1991 to 2000
Macrolide resistance up to 43%
Example: Doxycycline for pneumonia
Decreased effectiveness against respiratory pathogens
Antibiotics prescribed for anti-inflammatory effects, resistance is secondary concern.
Antibiotic types
The tetracyclines:Achromycin (tetracycline) FDA approval 11/23/1955
Doxycycline, Periostat; Minocycline
Macrolides: Erythromycin, Ilotycin (erythromycin) FDA approval 06/29/1964;
Clindamycin; Azithromycin
Chronic conditions: Acne, Rosacea, Blepharitis
Minocycline decreases eyelid bacterial flora in patients with acne rosacea or blepharitis
Lid disease
International task force on dry eye guidelines (Cornea, 2006)
Lid sheet and regimen
Base Treatment: heat and massage
Add antibiotics for better results: Erythromycin ung hs, Oral antibiotics:
Minocycline, Doxycycline, Periostat for if stomach upset
Greater severity add topical combo meds
Zylet: Can use swab soaked in zylet for better cleaning in severe blepharitis
Tobradex ung: short term less than 3 weeks
Facial Dermis (Jerry Paugh)
Procedure:
1. General Facial Observation: Facial flush and nasal areas; look for signs of rosacea
(redness, telangiectasia, dermal pustules, rhinophyma).
2. Biomicroscope Examination: Margin inflammation, orifice squamous metaplasia,
margin irregularity, capping of individual orifices, hyperkeratinization (or a
callous like appearance) and the presence of foam. Madarosis (lash loss; found in
blepharitis), crusting (found in staphylococcal blepharitis) or oily residue (found
in seborrheic blepharitis).
Blepharitis diagnosis
1) history of dermatological conditions (e.g., rosacea), 2) redness on the facial flush and
lid margin dermis, and 3) relatively easily expressed meibomian oil.
Proper prescribing
Use in low doses
Microbial keratitis
Primary objective: Sterilize the ulcer as rapidly as possible with topical antibiotics
Combining topical with MMP inhibitors (oral doxycycline)
Speeds corneal healing (Brooks DE, Ollivier FJ. Matrix metalloproteinase inhibition in
corneal ulceration. Vet Clin North Am Small Anim Pract. 2004 May;34(3):611-22.)
Use for chenical injury
Protects cornea against proteolytic degradation
After moderate to severe ocular chemical injury
Used oral tetracyclines with topical tetracycline preparations and other therapeutic agents
Neovascularization
Topical doxycycline with either flurbiprofen or low molecular weight heparin
Effectively inhibit corneal neovascularization in animal studies.( Peyman, Gholam
A.et.al. The Effect of Combinations of Flurbiprofen, Low Molecular Weight Heparin,
and Doxycycline on the Inhibition of Corneal Neovascularization. Basic Investigations
Cornea. 25(5):582-585, June 2006)
2 young patients; Severe contact lens-associated Pseudomonas keratitis
Corneal melting: Treated with oral doxycycline and standard topical treatment
(McElvanney AM. Doxycycline in the management of pseudomonas corneal melting:
two case reports and a review of the literature. Eye Contact Lens. 2003 Oct;29(4):258-61)
Results : Corneal melting stabilized; Perforation avoided
“Doxycycline as an adjunctive therapy…may help to stabilize corneal breakdown and
prevent subsequent perforation.” AM. McElvanney
Tip: Start patient on oral doxycycline first day to enhance healing.
Breast cancer controversy
Two groups:
2266 females with breast cancer; 7953 female controls
More frequent use of antibiotics in breast cancer group. Conclusion: Use of antibiotics is
associated with increased risk of breast cancer.
Replicate with a similar study design in the United Kingdom.
Use of antibiotics was not associated with an increased risk of breast cancer. No direct
link between drug and breast cancer
Weakened immunity group
Increased risk of breast cancer
Likely to get more infections and take more antibiotics (Christine M. Velicer, et.al.
Antibiotic Use in Relation to the Risk of Breast Cancer JAMA. 2004;291:827-835.)