Topical Antibiotic Update

• Brad Sutton, O.D., F.A.A.O.

• Indiana University School of Optometry

• Indianapolis Eye Care Center

• No financial disclosures

What do we have?

• We currently have many highly effective topical antibiotics in our arsenal

• Multiple categories including aminoglycosides, fluoroquinolones, and others

• Many are derived from successful oral drugs that were used first

What do we have?

• These various drugs as a whole are effective against a wide range of organisms and are well tolerated

• Many have very long track records of proven success

• Some have side effects that limit their usefulness and bacterial resistance is becoming an ever increasing problem

The ideal antibiotic would have the following characteristics…

• It would have no side effects• It would eradicate every infectious organism,

every time• It would work with a single, one-time dose• It would be free (or maybe the manufacturer

would pay the patient to use it!)• The bottle would dispense winning Powerball

tickets weekly

Since we’ll never have that we’ll have to accept……• A broad spectrum of antimicrobial activity• Excellent effectivity with minimal dosing• Affordability • A mechanism of action which severely

limits the potential for the development of resistant bugs

• An excellent side effect profile

Aminoglycosides

• Tobramycin• Gentamycin• Neomycin• All work by inhibiting bacterial protein synthesis.

Are bactericidal (actively kill bacteria, don’t just inhibit growth)

• Highly effective against gram-negative bacteria, especially Pseudomonas

• Effective against gram-positive bacteria but less so with ever increasing resistance

Aminoglycosides

• Side effects common to the entire class include PEK (epithelial toxicity), potential allergic reactions, and eyelid edema / erythema

• Cost effective due to generic availability (4$ plans)

Tobramycin .3%

• Available generically in drop and ointment form

• More effective and less toxic than Gentamycin

• Less allergic potential than Neomycin

• Tobradex (Tobramycin & Dexamethasone)

• Tobradex ST: lower concentration of dexamthasone (.05%)

• ZyLet (Tobramycin & Loteprednol)

Gentamycin .3 %

• Available generically in drop and ointment form

• Overall, slightly less effective and slightly more toxic than Tobramycin

• Less allergic potential than Neomycin• With the arrival of generic Tobramycin,

Gentamycin’s use dropped off considerably

Neomycin

• Not available as a stand alone drug• Ointment or drops in combination with other

medications. Highest potential for allergy• Neosporin drops (Neomycin, Polymyxin,

Gramacidin)• Neosporin Ointment (Neomycin,

Polymixin,Bacitracin)• Maxitrol / Dexacidin (Neomycin / Polymixin/

Dexamethasone)

Others

• Polytrim• Erythromycin• Bacitracin• Sulfacetamide 10%

Erythromycin

• .5% ointment only (Ilotycin)

• Bacteriostatic-inhibits protein synthesis

• Good gram-positive, marginal gram-negative

• Not good for active therapy, supportive only

• Prophylaxis for ophthalmia noenatorum

Bacitracin

• Ointment only• Degrades cell walls……works on gram

positive only• Great against Staph so good choice for

blepharitis treatment• Polysporin ointment (Bacitracin and

Polymixin). Good gram pos. and good gram negative from polymyxin

Polytrim

• Polymyxin-B and Trimethoprim)• Polymyxin great against gram negative,

destroys cell membranes• Trimethoprim inhibits folic acid synthesis

and creates bacteriostasis. Effective against gram-positive and gram-negative except Pseudomonas

Polytrim

• Excellent choice in pediatric infections• Very effective against Haemophilus (about

50% of pediatric conjunctivitis) and Streptococcus pneumonia which are the most common causes of childhood eye infections.

• Drop form only-generic available• Good against MRSA

Sulfacetamide 10%

• What’s old is new again….

• Many of today’s bacterial strains have never been exposed

• Resistance is currently actually low

• High allergy rate• Inactivated by pus-

like discharge

AzaSite

• 1% Azithromycin• Approved for bacterial conjunctivitis: Used for

MGD• Bacteriostatic, not bactericidal• Dosing is BID for two days, QD for five days so

nine drops total for treatment course• Very expensive, especially considering the fact

that only nine drops are used• May already be facing considerable resistance

due to long time systemic use

Fluoroquinolones

• First Generation (Chibroxin-not marketed in US)• Second Generation (Ocuflox, Ciloxan)• Third Generation (IQuix)• Fourth Generation (Zymaxid, Vigamox, Moxeza,

Besivance)• Minimal toxicity, minimal allergies

Fluoroquinolones (gen 1 & 2)

• Inhibit DNA gyrase (-) or topoisomerase 4 (+)• Uncoil DNA causing death-bactericidal• Very effective against gram-negative organisms• Highly effective against gram-positive bugs but

less so• Ocuflox and Ciloxan available generically

Ciloxan

• .3% Ciprofloxacin (Alcon), generic available• Second Generation• Good gram-negative coverage, adequate pos.• Weak against Strep, great against Pseudomonas • White precipitate often seen in bed of ulcer with treatment. Occurs

15% of the time, increases dramatically with age (ph based)• Has an available ointment

Ocuflox

• .3% Ofloxacin (Allergan) : generic• Second generation• Good gram-negative, better pos.• Less effective against Pseudomonas• Much better tissue penetration than

Ciloxan………present in therapeutic levels in the AC

• Very cost effective

Iquix

• 1.5% concentration of levofloxacin

• Only topical antibiotic ever to come to the market initially with FDA approval for treating bacterial keratitis (ulcers)

Fourth Generation

• Gatifloxacin .5% (Zymaxid)

• Zymar no longer made

• Moxifloxacin .5% (Vigamox)

• Moxeza, Besivance

Fourth generations

• Ciloxan and Ocuflox bind only to topoisomerase 4 or DNA gyrase, 4th

generations bind to both. Therefore not one but two genetic mutations are required for resistance!

Fourth generation

• A single genetic mutation can lead to resistance to the second generation fluoroquinolones and such a mutation occurs in one bacteria per ten million. The eyelids and large corneal ulcers can harbor around one million bacteria

• It takes two such mutations to confer resistance to fourth generation drugs and this can occur in one bacteria per ten trillion

Fourth generation

• A bacterial load of even two million is probably not possible in an ocular infection so resistance is statistically rare but certainly happens

• Remember………….resistant bugs already have one mutation so they only have to come up with the other one, not both

Gatifloxacin

• Zymaxid .5%• Excellent, broad

spectrum agent• TID for bacterial

conjunctivitis• Zymar has been

discontinued

Moxifloxacin

• Vigamox .5%• Excellent broad

spectrum agent• Preservative free• TID dosing for

conjunctivitis• Penetrates AC

better

• Moxeza .5%• Different vehicle

only• Longer contact

time, so BID conjunctivitis dosing

Besivance

• Besifloxacin .6%• Suspension, so

shake• No oral version, so

possibly less problems with resistance

Treatment tips

• Resistance develops when drugs are used at sub-lethal doses for extended periods of time (plasmids, mutations)

• Hit infections hard and stay the course for several days

• Biggest problem is sub-lethal dosing, not length of treatment alone

• Most resistance is from overuse of oral medications, not topicals. Oral Fluoroquinolonesare misused extensively leading to strains resistant to topicals and orals

Resistance

• It has been estimated that more bacteria are exposed to an oral antibiotic given for a severe gastrointestinal infection in a single patient than in prophylaxis for every cataract surgery done in the US for an entire year!

ARMOR study

• Studied 592 ocular isolates• 200 staph aureus, 144 coagulase negative

staph, 75 strep pneumoniae, 73 haemophilus, and 100 pseudomonus

• All susceptibility studies were performed at the same lab

ARMOR study

• 39% of staph aureus was MRSA• 80% of MRSA exhibited Fluoroquinolone

resistance• Besivance proved to show the least

resistance across isolates• Resistance was shown to be a significant

problem with multiple drugs and multiple bugs

Treatment

• Use the expected type of pathogen to guide treatment choice (gram positive lid disease for example)

• Culture rarely, but when needed

Cost comparisons (smallest bottle size, generic if app.)• Tobramycin and

Gentamycin: $4.00• Polytrim: $15.00

(brand $60.00)• Bacitracin ung:

$42.00• Azasite: $ 122.00

• Ocuflox: $10.00• Ciloxan: $20.00

(brand $102.00)• Ciloxan ung:

$137.00• Zymaxid: $134.00• Vigamox / Moxeza:

$120.00

Cost comparison

• Besivance: $140.00 • All cost comparisons of lowest available cost in pharmacies located in downtown Indianapolis

When good corneas go bad

• THE END