Topical Antibiotic Update. Brad Sutton, O.D., F.A.A.O. Indiana University School of Optometry Indianapolis Eye Care Center No financial disclosures
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1 Topical Antibiotic Update Brad Sutton, O.D., F.A.A.O. Indiana University School of Optometry Indianapolis Eye Care Center No financial disclosures
2 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
3 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
4 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
5 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
6 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
7 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)
8 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)
9 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
10 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)
11 Others Polytrim Erythromycin Bacitracin Sulfacetamide 10%
12 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
13 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
14 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
15 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
16 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 puslike discharge
17 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
18 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
19 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
20 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
21 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
22 Iquix 1.5% concentration of levofloxacin Only topical antibiotic ever to come to the market initially with FDA approval for treating bacterial keratitis (ulcers)
23 Fourth Generation Gatifloxacin.5% (Zymaxid) Zymar no longer made Moxifloxacin.5% (Vigamox) Moxeza, Besivance
24 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!
25 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
26 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
27 Gatifloxacin Zymaxid.5% Excellent, broad spectrum agent TID for bacterial conjunctivitis Zymar has been discontinued
28 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
29 Besivance Besifloxacin.6% Suspension, so shake No oral version, so possibly less problems with resistance
30 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 Fluoroquinolones are misused extensively leading to strains resistant to topicals and orals
31 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!
32 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
33 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
34 Treatment Use the expected type of pathogen to guide treatment choice (gram positive lid disease for example) Culture rarely, but when needed
35 Cost comparisons (smallest bottle size, generic if app.) Tobramycin and Ocuflox: $10.00 Gentamycin: $4.00 Ciloxan: $20.00 Polytrim: $15.00 (brand $60.00) Bacitracin ung: $42.00 Azasite: $ (brand $102.00) Ciloxan ung: $ Zymaxid: $ Vigamox / Moxeza: $120.00
36 Cost comparison Besivance: $ All cost comparisons of lowest available cost in pharmacies located in downtown Indianapolis
37 When good corneas go bad THE END
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