Ocular Antibiotics Ocular Antibiotics and Anti-Infectivesand 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 The Charles T. Campbell Ophthalmic Microbiology Ophthalmic Microbiology LaboratoryLaboratory

Areas of Infection

Per

cent

Inc

iden

ce

0

10

20

30

40

50

60

Newborns Children Adults

No growth

StreptococcusCoagulase-negative staphylococcusDiphtheroidsStaphylococcus aureusGram negatives

Normal Flora

Distribution of Bacteria Isolated from Endophthalmitis (1993-2010) (N=518)

Staphylococcus aureus - 10.5% (54)

Other GramPositives - 4.8% (25)

Streptococcusspecies - 19.5% (101)

Coagulase NegativeStaphylococcus 57.7% (299)

Other GramNegatives - 7.5% (39)

Gram-positives = 92.5%Gram-negatives = 7.5%

Treatment AdministrationTreatment Administration

Topical Topical – Most common (conjunctivitis, – Most common (conjunctivitis, keratitis, blepharitis, prophylaxis)keratitis, blepharitis, prophylaxis)

Intra-vitreal injectionIntra-vitreal injection – endophthalmitis – endophthalmitis

SystemicSystemic – not commonly used – not commonly used

SubconjunctivalSubconjunctival – used to provide a – used to provide a constant flow of anti-infective to ocular constant flow of anti-infective to ocular surface.surface.

AntibacterialsAntibacterials

Antibiotics – No Topical Standards for Interpreting Antibiotics – No Topical Standards for Interpreting SusceptibilitySusceptibility

Use Serum Systemic Susceptibility Standards - Use Serum Systemic Susceptibility Standards - But we must assume that But we must assume that “The antibiotic “The antibiotic concentrations reached in the ocular tissue by concentrations reached in the ocular tissue by topical therapy is equal to or greater than the topical therapy is equal to or greater than the concentration of antibiotic in the blood serum”.concentration of antibiotic in the blood serum”.

Ocular antibiotics are developed from systemic Ocular antibiotics are developed from systemic antibiotics for conjunctivitis, keratitisantibiotics for conjunctivitis, keratitis

Antibiotics ParametersAntibiotics Parameters

Concentration–dependentConcentration–dependent

fluoroquinolones, aminoglycosidesfluoroquinolones, aminoglycosides Time-dependentTime-dependent

vancomycin, cefazolinvancomycin, cefazolin Bactericidal – killBactericidal – kill

FQs, vancomycin,FQs, vancomycin, BacteristaticBacteristatic – inhibit – inhibit

erythromycin, azithromycin, sulfaerythromycin, azithromycin, sulfa AntisepticsAntiseptics – PI – kill immediately – PI – kill immediately

MIC

MBC

MPC

Growth

No growth but viable

Death but possible mutations

Death and NO mutations

Susceptibility Parameters

Nature of Resistance of BacteriaNature of Resistance of Bacteria

A function of the anti-infective A function of the anti-infective mechanism,mechanism,

Target bacteria,Target bacteria, The ocular tissue, and The ocular tissue, and The treatment regimen.The treatment regimen.

Problem with ResistanceProblem with Resistance

Organism acquires resistance to an Organism acquires resistance to an antibiotic.antibiotic.

Resistance spreads to other patientsResistance spreads to other patients No antibiotic to cover resistanceNo antibiotic to cover resistance

Class Mode of Action Primary Indicationbesides conjunctivitis

Fluoroquinolones DNA synthesis keratitis, surgical prophylaxis(ciprofloxacin, ofloxacin, bactericidal Broad-spectrum coveragelevofloxacin, gatifloxacin,moxifloxacin) besifloxacin

Aminoglycosides protein synthesis keratitis, endophthalmitis(gentamicin, tobramycin, cell wall surgical prophylaxisamikacin) bactericidal Broad-spectrum coverage

Cephalosporins cell wall keratitis, endophthalmitis(cefazolin, ceftazidime) bactericidal Gram-positive coverage

Glycopeptides cell wall keratitis, endophthalmitis(vancomycin) bactericidal MRSA prophylaxis

Gram-positive coverage

Macrolides protein synthesis blepharitis(erythromycin, azithro) bacteristatic Gram-positive coverage

Peptides cell wall blepharitis, keratitis(bacitracin, polymycin B) bactericidal Bac – GMpos PB – GMneg

Sulfa drugs enzyme inhibitor keratitis, 2nd – line MRSA(sulfacetamide) bacteristatic Broad-spectrum coverage

Anti-Infective Test BatteriesAnti-Infective Test Batteries

KeratitisKeratitis EndophthalmitisEndophthalmitis ConjunctivitisConjunctivitisbacitracinbacitracin vancomycinvancomycin bacitracinbacitracinvancomycinvancomycin gentamicingentamicin erythromycinerythromycinciprofloxacinciprofloxacin ciprofloxacinciprofloxacin gentamicingentamicinofloxacinofloxacin ofloxacinofloxacin ciprofloxacinciprofloxacinpolymyxin Bpolymyxin B cefazolincefazolin ofloxacinofloxacincefazolincefazolin amikacinamikacin trimethoprimtrimethoprimtobramycintobramycin ceftazidimeceftazidime polymyxin Bpolymyxin Bsulfisoxazolesulfisoxazole cefoxitincefoxitin tobramycintobramycincefoxitincefoxitin ampicillinampicillin sulfisoxazolesulfisoxazolegentamicingentamicin clindamycinclindamycin azithromycinazithromycingatifloxacingatifloxacin gatifloxacingatifloxacin gatifloxacingatifloxacinmoxifloxacinmoxifloxacin moxifloxacinmoxifloxacin moxifloxacinmoxifloxacin

Antifungal DrugsAntifungal Drugs

Acanthamoeba DrugsAcanthamoeba Drugs Cationic Antiseptics (Chlorhexidine Cationic Antiseptics (Chlorhexidine

and PHMB)and PHMB) Aromatic diamides (propamidine)Aromatic diamides (propamidine)

Thank You !!