1. Ocular Antibiotics and Anti-Infectives Regis P. Kowalski, MS, M(ASCP) Research Professor of Ophthalmology Executive Director of The Charles T Campbell Laboratory University of Pittsburgh, Pittsburgh, PA The Charles T. Campbell Ophthalmic Microbiology Laboratory

2. Areas of Infection

3. Normal Flora

5. Treatment Administration Topical – Most common (conjunctivitis, keratitis, blepharitis, prophylaxis) Topical – Most common (conjunctivitis, keratitis, blepharitis, prophylaxis) Intra-vitreal injection – endophthalmitis Intra-vitreal injection – endophthalmitis Systemic – not commonly used Systemic – not commonly used Subconjunctival – used to provide a constant flow of anti-infective to ocular surface. Subconjunctival – used to provide a constant flow of anti-infective to ocular surface.

6. Antibacterials Antibiotics – No Topical Standards for Interpreting Susceptibility Antibiotics – No Topical Standards for Interpreting Susceptibility Use Serum Systemic Susceptibility Standards - But we must assume that “The antibiotic concentrations reached in the ocular tissue by topical therapy is equal to or greater than the concentration of antibiotic in the blood serum”. Use Serum Systemic Susceptibility Standards - But we must assume that “The antibiotic concentrations reached in the ocular tissue by topical therapy is equal to or greater than the concentration of antibiotic in the blood serum”. Ocular antibiotics are developed from systemic antibiotics for conjunctivitis, keratitis Ocular antibiotics are developed from systemic antibiotics for conjunctivitis, keratitis

7. Antibiotics Parameters Concentration–dependent Concentration–dependent fluoroquinolones, aminoglycosides Time-dependent Time-dependent vancomycin, cefazolin Bactericidal – kill Bactericidal – kill FQs, vancomycin, Bacteristatic – inhibit Bacteristatic – inhibit erythromycin, azithromycin, sulfa Antiseptics – PI – kill immediately Antiseptics – PI – kill immediately

8. MIC MBC MPC Growth No growth but viable Death but possible mutations Death and NO mutations Susceptibility Parameters

9. Nature of Resistance of Bacteria A function of the anti-infective mechanism, A function of the anti-infective mechanism, Target bacteria, Target bacteria, The ocular tissue, and The ocular tissue, and The treatment regimen. The treatment regimen.

10. Problem with Resistance Organism acquires resistance to an antibiotic. Organism acquires resistance to an antibiotic. Resistance spreads to other patients Resistance spreads to other patients No antibiotic to cover resistance No antibiotic to cover resistance

11. ClassMode of ActionPrimary Indication besides conjunctivitis FluoroquinolonesDNA synthesiskeratitis, surgical prophylaxis (ciprofloxacin, ofloxacin,bactericidalBroad-spectrum coverage levofloxacin, gatifloxacin, moxifloxacin) besifloxacin Aminoglycosidesprotein synthesiskeratitis, endophthalmitis (gentamicin, tobramycin,cell wallsurgical prophylaxis amikacin)bactericidalBroad-spectrum coverage Cephalosporinscell wallkeratitis, endophthalmitis (cefazolin, ceftazidime)bactericidalGram-positive coverage Glycopeptidescell wallkeratitis, endophthalmitis (vancomycin)bactericidalMRSA prophylaxis Gram-positive coverage Macrolidesprotein synthesisblepharitis (erythromycin, azithro)bacteristaticGram-positive coverage Peptidescell wallblepharitis, keratitis (bacitracin, polymycin B)bactericidalBac – GMpos PB – GMneg Sulfa drugsenzyme inhibitorkeratitis, 2nd – line MRSA (sulfacetamide)bacteristaticBroad-spectrum coverage

12. Anti-Infective Test Batteries Keratitis EndophthalmitisConjunctivitis bacitracinvancomycinbacitracin vancomycingentamicinerythromycin ciprofloxacinciprofloxacingentamicin ofloxacinofloxacinciprofloxacin polymyxin Bcefazolinofloxacin cefazolinamikacintrimethoprim tobramycinceftazidimepolymyxin B sulfisoxazolecefoxitintobramycin cefoxitinampicillinsulfisoxazole gentamicinclindamycinazithromycin gatifloxacingatifloxacingatifloxacin moxifloxacinmoxifloxacinmoxifloxacin

13. Antifungal Drugs

15. Acanthamoeba Drugs Cationic Antiseptics (Chlorhexidine and PHMB) Cationic Antiseptics (Chlorhexidine and PHMB) Aromatic diamides (propamidine) Aromatic diamides (propamidine)

16. Thank You !!