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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 Areas of Infection Normal Flora Streptococcus Coagulase-negative staphylococcus Diphtheroids Staphylococcus aureus Gram negatives No growth 60 Percent Incidence 50 40 30 20 10 0 Newborns Children Adults Distribution of Bacteria Isolated from Endophthalmitis (1993-2010) (N=518) Gram-positives = 92.5% Gram-negatives = 7.5% Coagulase Negative Staphylococcus 57.7% (299) Streptococcus species - 19.5% (101) Other Gram Negatives - 7.5% (39) Other Gram Positives - 4.8% (25) Staphylococcus aureus - 10.5% (54) Treatment Administration Topical – Most common (conjunctivitis, keratitis, blepharitis, prophylaxis) Intra-vitreal injection – endophthalmitis Systemic – not commonly used Subconjunctival – used to provide a constant flow of anti-infective to ocular surface. Antibacterials 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”. Ocular antibiotics are developed from systemic antibiotics for conjunctivitis, keratitis Antibiotics Parameters Concentration–dependent fluoroquinolones, aminoglycosides Time-dependent vancomycin, cefazolin Bactericidal – kill FQs, vancomycin, Bacteristatic – inhibit erythromycin, azithromycin, sulfa Antiseptics – PI – kill immediately Susceptibility Parameters Death and NO mutations MPC Death but possible mutations MBC No growth but viable MIC Growth Nature of Resistance of Bacteria A function of the anti-infective mechanism, Target bacteria, The ocular tissue, and The treatment regimen. Problem with Resistance Organism acquires resistance to an antibiotic. Resistance spreads to other patients No antibiotic to cover resistance Class Mode of Action Fluoroquinolones DNA synthesis (ciprofloxacin, ofloxacin, bactericidal levofloxacin, gatifloxacin, moxifloxacin) besifloxacin Primary Indication besides conjunctivitis keratitis, surgical prophylaxis Broad-spectrum coverage Aminoglycosides (gentamicin, tobramycin, amikacin) protein synthesis keratitis, endophthalmitis cell wall surgical prophylaxis bactericidal Broad-spectrum coverage Cephalosporins (cefazolin, ceftazidime) cell wall bactericidal keratitis, endophthalmitis Gram-positive coverage Glycopeptides (vancomycin) cell wall bactericidal keratitis, endophthalmitis MRSA prophylaxis Gram-positive coverage Macrolides (erythromycin, azithro) protein synthesis blepharitis bacteristatic Gram-positive coverage Peptides (bacitracin, polymycin B) cell wall bactericidal Sulfa drugs (sulfacetamide) enzyme inhibitor keratitis, 2nd – line MRSA bacteristatic Broad-spectrum coverage blepharitis, keratitis Bac – GMpos PB – GMneg Anti-Infective Test Batteries Keratitis bacitracin vancomycin ciprofloxacin ofloxacin polymyxin B cefazolin tobramycin sulfisoxazole cefoxitin gentamicin gatifloxacin moxifloxacin Endophthalmitis vancomycin gentamicin ciprofloxacin ofloxacin cefazolin amikacin ceftazidime cefoxitin ampicillin clindamycin gatifloxacin moxifloxacin Conjunctivitis bacitracin erythromycin gentamicin ciprofloxacin ofloxacin trimethoprim polymyxin B tobramycin sulfisoxazole azithromycin gatifloxacin moxifloxacin Antifungal Drugs Acanthamoeba Drugs Cationic Antiseptics (Chlorhexidine and PHMB) Aromatic diamides (propamidine) Thank You !!