Anti-infective agents are effective against a variety of infections (e.g., virus, rickettsiae, bacteria, fungi and protozoa) and cause competitive inhibition of a biochemical process of pathogens. Minimum inhibitory concentration (MICs) are often used for common anti-infective drugs. In the eye, route of drug administration is determined by the locus of infection. However, this ppt covers mostly topical and common antibacterial, antiviral and antifungal medicines.

1. Ocular Anti-Infective
Agents
Dr Gauri Sr Shrestha
IOM, TU

2. Background
• Are effective against a variety of infections (e.g., virus, rickettsiae,
bacteria, fungi and protozoa)
• Causes competitive inhibition of a biochemical process of pathogens
• Minimum inhibitory concentration (MICs) are often used for common
anti-infective drugs.
• In the eye, route of drug administration is determined by the locus of
infection.

3. Anti-
infective
Agents
(Commonly used
in an ophthalmic
clinic)
Antibiotics
Antivirals
Antifungals
Antiprotozoals (not included)

4. Interaction between Host – Bacteria – Drug
Drug
Bacteria
Infection
Host defence
Host
MR. H GEE MD, FRCOG Hon. Assoc. Clinical Professor, University of Warwick

5. Antibiotics
1. Inhibits cell wall synthesis - Penicillins, Cephalosporins,
Vancomycin, Bacitracin.
2. Causes leakage from cell membranes - Polymyxins,
Bacitracin, amphotericin B, Nystatin, colistin
3. Inhibit bacterial protein synthesis - Tetracyclines,
Chloramphenicol, Erythromycin, Clindamycin,
streptomycin
4. Cause misreading of m-RNA code and affect
permeability – Aminoglycoside, streptomycin, Gentamycin
5. Interfere DNA gyrase – Fluroquinolones, Ciprofloxacin
6. Interfere with metabolism - Sulphonamides,
Trimethoprim, Aminosalicylic acid

6. Common antibacterial eye medicines
Cephalosporins
• Action
• Inhibit cell wall
synthesis
• Contain β-
lactam ring for
antimicrobial
activity
• Active against
penicillinase-
producing
S.aureus
ß-Lactams
Penicillin
Narrow Spectrum
•Benzylpenicillin (Penicillin G)
•Phenoxymethylpenicillin (Pen V)
•Flucloxacillin
Broad Spectrum
•Amoxicillin/Co-amoxiclav
•Ampicillin
•Piperacillin with Tazobactam
(Tazocin)
Cephalosporin
•Cefalexin
•Cefuroxime
•Cefotaxime
•Ceftriaxone
Carbapenem
•Meropenem
•Imipenem
•Doripenem
•Ertapenem
MR. H GEE MD, FRCOG Hon. Assoc. Clinical Professor, University of Warwick

7. Common antibacterial eye medicines
Cephalosporins
• Side effects
• Hypersensitivity
reactions,
maculopapular
rash, urticaria,
fever,
bronchospasm,
anaphylaxis
• Can destroy
intestinal
microflora and vit
K,
• Renal impairment
• Contraindication
• haemophilia
maculopapular rash
urticaria

8. Common antibacterial eye medicines
Cephalosporins
1st generation 2nd generation 3rd generation 4th Generation
Cefazolin 50 mg/ml
(fortified), cephalexin
& cefradroxil
Cefamandole, cefaclor,
cefproxil, cefoxitin &
cefuroxime
Cetriaxone, cefixime,
cefoperazone, cefepime
Cefcidine, cefeprime,
cefluprenam, cefpirome,
cefoxopran, cefquiome
Effective
against Gm+ve
bacteria
Generally, more effective
against Gm–ve enteric
bacteria
Mostly Effective
against Gm–ve bacteria
Effective against Gm-ve
bacteria
Used in dacryocystitis
&
pneumococcal keratitis
dacryocystitis and preseptal
cellulitis in children
For gonococcal infections as conjunctivitis, ophthalmia
neonatorum, Pseudomonas keratitis (CL wearer)

9. Common antibacterial eye medicines
Chloramphenicol (0.5% solution, 1%
ointment)
• A broad-spectrum bacteriostatic antibiotic
with relatively less bacterial resistance than
aminoglycosides.
• Mechanism of Action: It inhibits bacterial
protein synthesis by inhibiting the activity
of peptidyl transferase
• Bacterial spectrum: Chlamydia spp,
mycoplasma spp, H influenzae, S
pneumoniae, S typhi, Neisseria meningitidis.
Neisseria gonorrhoeae, Brucella spp,
Bordetella pertussis

10. Chloramphenicol (0.5% solution, 1%
ointment)
• Pharmacokinetics: has well tissue
penetration, including aqueous humour,
blood-ocular barrier, 60% protein bound
(body-wide distribution), crosses the
placenta and is distributed into breast milk.
• Therapy: Bacterial conjunctivitis, blepharitis,
Gonococcal conjunctivitis and corneal ulcer,
dacryocystitis, dacryoadenitis
• Side effects: optic and peripheral neuritis on
long-term use, fever, macular and vesicular
rashes, angioedema, and urticaria.
Common antibacterial eye medicines

11. Common antibacterial eye medicines
Fluoroquinolones
• Mechanism of action: directly inhibit bacterial DNA synthesis by inhibiting
bacterial enzymes DNA gyrase and topoisomerase IV.
• Pharmacokinetics: penetrate well into the aqueous humour, moxifloxacin has
better corneal penetration than gatifloxacin.
• Side effects: delay epithelisation with ciprofloxacin, pain, discomfort, FB
sensation, itching, conjunctival hyperemia, crystalline precipitation, phototoxicity
(cipro>oflox>moxi)
• Precaution: arrhythmias, hypokalemia, hypomagnesemia, children, pregnant
women, breastfeeding mother

12. Common antibacterial eye medicines
Fluoroquinolones
1st generation 2nd generation 3rd generation 4th generation
Nalidixic acid,
cinoxacin, oxolinic acid,
pipernidic acid
Ciprofloxacin 0.3%,
ofloxacin 0.3%
Gatifloxacin 0.3%, levofloxacin
0.5%
Moxifloxacin 0.5%,
gemifloxacin, trovafloxacin
Highly bacterial
resistance
Mostly for Gram-
negatives, and some
Gram-positives
Both Gram –ve and +ve bacteria,
particularly penicillin-sensitive
and resistant S. penumoniae,
Mycoplasma pneunoniae and
Chlamydia pneumoniae
3rd generation + anaerobes,
mostly potents against
Pseudomonas spp
Historical purpose First-line as long as no
resistance
Mycobacteria, bacterial endophthalmitis
Acute bacterial conjunctivitis, gonococcal conjunctivitis, and keratitis, empirical mono-
therapy

13. Commonly available Fluoroquinolones eye
medicines

14. Common antibacterial eye medicines
Tetracyclines (1% ointment)
• Mechanism of action: Broad-spectrum antibiotics that inhibit bacterial protein
synthesis and are bacteriostatic.
• Pharmacokinetics: Penetrates into most body tissues and fluids and tetracycline
particularly penetrates well into the ocular tissue.
• Side effects: burning sensation of the stomach, diarrhea, sore mouth or tongue,
vestibular dysfunction (Minocycline), nausea, vomiting, anorexia (Azithromycin
and clarithromycin have a fewer gastrointestinal side-effects than erythromycin),
ventricular arrhythmias
• Precaution: Do not use in children below 7 years of age, during tooth
development

15. Common antibacterial eye medicines
Tetracyclines (1% ointment)
Naturally occurring Semi-synthetic
Tetracycline, Chlorotetracycline,
oxytetracycline BD to QID
Doxycycline (50 -100 mg OD to BD),
minocycline, methacycline
Gram+ve cocci (Staphylococcus spp., Streptococcus spp
Gram –ve cocci (Neisseria gonorrhoeae, Bacilus anthracis)
Gram –ve bacilli (Haemophilus influenzae, Helicobacter pylori)
Atypical bacteria (Chlamydia spp, Mycoplasa spp, Legionella spp, Ureaplsma)
Spirochetes (Treponema pallidum, Borrelia recurrentis, Borrelia burgdorferi)
Rickettsiae, Listeria, Vibrio cholera
Acute conjunctivitis, blepharitis, ophthalmia neonatorum, trachoma (the first
line of treatment), bacterial keratitis, Dacryocystitis, dacryoadenitis, bacterial
endophthalmitis

16. Common antibacterial eye medicines
Aminogycosides
• Mechanism of action: Bactericidal antibiotics which Inhibit
bacterial protein synthesis by irreversibly binding to 30S ribosomal
unit
• Pharmacokinetics: observed mostly through conjunctiva due to
their hydrophilic nature, distributed across the extracellular fluids,
do not penetrate well into the aqueous and vitreous fluids
• Side effects: nephrotoxicity (reversible), ototoxicity (irreversible,
dizziness, vertigo, ataxia, tinnitus, decreased hearing),
neuromuscular paralysis (myasthenia gravis)

17. Common antibacterial eye medicines
Aminogycosides
1st
generation
2nd generation
Streptomycin Tobramycin 1%, gentamycin 0.3%, neomycin 0.3 – 0.5%,
Amikacin (fortified)
M.
Tuberculosis
Tobramycin is more active against Pseudomonas spp. than
gentamycin. Gentamycin is more active against Serratia spp
(redominant species among CLW)
Pseudomonas conjunctivitis and keratitis, blepharitis,
blepharoconjunctivitis, Dacryocystitis and dacryoadenitis,
bacterial endophthalmitis
Gram –ve aerobes: E coli, Proteus spp, Enterobacter spp
Gram +ve aerobes: S. aureus and coagulase-negative
Staphylococci viridans, Streptococci, Enterococcus spp.
This formula came with FML (a
steroid) and in combination
with other steroids and
antibiotics

18. Common antibacterial eye medicines
Polymixin B (10000 IU/gm)
• Mechanism of action: narrow antibacterial spectrum,
causes leakage from cell membranes
• Gram +ve bacteria (Staphylococcus spp, Streptococcus
spp) are susceptible
• Side effects: serious nephrotoxicity and neurotoxicity
with systemic route, rashes, itching, eye swelling,
dizziness, temporary blurring of vision
• Precaution: pregnancy
Therapeutic application
Used in combination with other antibacterial agents such as bacitracin and neomycin to
treat conjunctivitis, blepharitis, Gram –ve associated blepharoconjunctivitis
This formula came with
chloramphenicol

19. Common antibacterial eye medicines
Glycopeptides (Vancomycin, fortified, 25 mg/ml)
• Mechanism of action: Inhibit peptidoglycan synthesis in the bacterial cell wall, prevents
cross-linkage of peptidoglycan chains
• Only active against Gm +ve bacteria, MRSA
• For serious or resistant bacterial infections in the eye
• Side effects: eyeball pain, visual disturbance, dilated pupil, blurred vision, swelling of
eyelids, skin rash, headache, weakness and dizziness, nephrotoxic (systemic use)
• Indication: bacterial conjunctivitis, bacterial keratitis, blepharoconjunctivitis
• Contraindications: pregnancy, breastfeeding (be cautious), myasthenia gravis, contact
lens wear
• Dose: 2 – 3 times a day for 3 to 5 days

20. Common antibacterial eye medicines
Summary
Cyclosporine (e.g., cefazoline)
• Bactericidal, Antibiotics of choice in many infections, Very safe in most cases
• Limitations: Allergy, Resistance due to beta-lactamase.
Fluoroquinolone (e.g., ciprofloxacin, ofloxacin, moxifloxacin)
• Wide range of activity against Gm +ve and -ve bacteria, very good tissue penetration, Excellent
bioavailability
Tetracycline
• Very good tissue penetration, Use usually limited to skin and soft tissue infections and Chlamydia
Aminoglycoside (tobramycin, gentamycin, neomycin)
• Restricted to aerobes, Best used in Gram-negative bloodstream infections
• Limitation: Toxic, needs level monitoring
Glycopeptide (e.g., vancomycin)
• Only active against Gm +ve bacteria

21. Common
antifungal eye
medicines
• Polyenes: Nystatin,
Amphotericin B, Natamycin,
Imidazoles
• Pyrimidines: Flucytosine
• Imidazoles: Miconazole,
Ketoconazole,
• Triazole azoles: Fluconazole,
Itraconazole
• Silver compounds:
Silversulphadiazine

22. Common antifungal eye medicines
Nystatin (3.5% ointment, 5% solution, 100,000
IU)
• Mechanism of action: Binds preferentially to
fungal ergosterol to alter membrane
permeability and disrupt the fungal cells.
• Mostly effective against Candida and Aspergillus
• Pharmacokinetics: a restricted use due to
insolubility and unstability.
• Therapeutic application: fungal blepharitis,
keratitis, and conjunctivitis
• Side effects: eye irritation and hypersensitivity
reactions

23. Common antifungal eye medicines
Amphotericin B (0.075 – 0.3% eye
drops hourly, fortified)
• Mechanism of action: Binds to
fungal ergosterol to alter
membrane permeability, which
leads to the formation of pores,
ion leakage and ultimately cell
death.
• Administration: topical,
subconjunctival, intravitreal
(potentially dangerous)

24. Common antifungal eye medicines
Amphotericin B (0.075 – 0.3% eye drops
hourly, fortified)
• Fungus: Candida, Histoplasma,
Aspergillus, Cryptococcus, Coccidioides,
Sporothrix, Blastomycosis, Histoplasma,
Mucormycosis
• Therapeutic application: filamentous
fungal keratitis, corneal ulcers,
keratocycoses
• Side effects: anaphylaxis, headache,
nausea, vomiting, fever, nephrotoxicity

25. Common antifungal eye medicines
Natamycin (5% suspension)
• A broad-spectrum antifungal
• Mechanism of action: binds to ergosterol in the plasm
membrane preventing ergosterol-dependent fusion of
vacuoles and membrane fusion and fission.
• Administration: topical, subconjunctival, intravitreal
(potentially dangerous)
• Fungus: Candida, Fusarium, Aspergillus,
Cephalosporium

26. Common antifungal eye medicines
Natamycin (5% suspension)
• Therapeutic application: drug of choice for
Fusarium solani keratitis, filamentary keratitis,
• Do not use subconjunctival injection
• Dose: 1 – 2 hours intervals for 24 – 48 hours,
decrease dose to 6 – 8 times, continue 14 – 21
days to prevent recurrence; 4 – 6 times a day
(Fungal blepharitis and conjunctivitis)
• Side effects: irritation, burning, allergic reactions

27. Common antifungal eye medicines
Fluconazole (0.3% solution every 4 hours)
• A water-soluble antifungal, that exhibits low protein binding
(12%)
• Mechanism of action: inhibit the conversion of lanosterol to
ergosterol via binding to fungal cytochrome P-450 and
subsequently disrupt fungal membranes.
• Therapeutic application: mostly effective against yeasts, few
dimorphic fungi, Candida albicans, Candida glabrata
(Many strains are intermediately susceptible), Candida
parapsilosis, Candida tropicalis, Cryptococcus
neoformans
• Systemic use in candida endophthalmitis in combination with
Amphotericin B
• Side effects: NA
• Precaution: Fluconazole is secreted in breastmilk at high
concentrations

28. Common antifungal eye medicines
Clotrimazole (1% solution, no much idea about its use in ophthalmology)
• Mechanism of action: inhibits the biosynthesis of ergosterol by inhibiting
lanosterol and damages the permeability barrier in the fungal cytoplasmic
membrane
• Dose:1% eye drop to be used in an hourly
• Therapeutic application: drug of choice for Aspergillus, also effective for
Fusarium solani, Candida, penicillium, Clasporium, and Actinomyces
• Side effects: irritation, punctate keratopathy, hepatotoxicity, diarrhoea

29. Common antifungal eye medicines
Miconazole (1% topical, 10 mg subconjunctival)
• Mechanism of action: inhibits the synthesis of ergosterol, interferes with
the barrier function of the membrane and with membrane bound
enzymes, Alter fungal cell wall, changes cellular permeability
• Therapeutic application: a broad-spectrum antifungal, Candida, Fusarium,
Aspergillus and more, Gm+ve bacteria
• A drug of choice for keratomycosis
• Doses: Administration: topical, subconjunctival, intravitreal (rare), 1%
topical instilled every hourly, Subconjunctiva: 5 – 10 mg every 48 hours for
2 – 3 days
• Side effects: conjunctival injection, pruritus, erythema, local irritation

30. Common antifungal drugs
Summary
• The mostly prescribed antifungal topical eye medicines are Natamycin and
Amphotericin B
• Natamycin (5%) solution is the first-line treatment in suspected mycotic
keratitis, has a broad spectrum of activities, is well-tolerated, stable, and
can be sterilized by heat.
• Amphotericin B (0.15 – 0.3%) topical eye drop has excellent activity against
Candida, Aspergillus, and Lasiodiplodia, penetrates deep corneal stroma
after topical application, bioavailability is sufficient for susceptible fungi.
• Nystatin (25,000 – 100,000 U/mL solution and 100,000 U/g ointment) is
clinically used to treat superficial keratitis, conjunctivitis, and superficial lid
lesions due to Candida, Cryptococcus and Dermatophytes.

31. Common antiviral eye medicines
• Antiherpes agents (for
herpes simplex virus)
• Acyclovir
• Valacyclovir
• Famiciclovir
• Idoxuridine
• Vidarabine
• trifluridine
• Antiretrovirals
• Zidovudine
• Didanosine
• Zacitabine
• Indinavir
• Others
• Interferons
• ribavirin
• For CMV retinitis
• Ganciclovir
• Foscarnet
• zidovudin
herpes simplex infection
of eyes
CMV retinitis

32. Common antiviral eye medicines
Acyclovir (3% ophthalmic ointment)
• Mechanism of action
• Monophosphorylation by either cellular or virus-encoded thymidine
kinase.
• Mimics thymidine triphosphate and incorporates into viral DNA and stop
lengthening of DNA strand (inhibits herpes virus DNA polymerase
competitively
• Pharmacokinetics
• 15% protein bound, 70% excreted unchanged in the urine through
glomerular filtration and tubular secretion, doses must be adjusted in
the presence of renal failure.
• Extremely safe and effective agent and the drug of choice for HSV and
HZV infections.

33. Common antiviral eye medicines
Acyclovir (3% ophthalmic ointment)
• Adverse effect
• Stinging and burning sensation
• Application
• 3% ophthalmic ointment has the best corneal penetration (intact
corneal epithelium) of any topical antiviral drugs (inhibitory for HSV-1
and HSV-2)
• Peak plasma level in 1.5 – 2 hours (oral)
• Doses
• Administer topically, intravenously and orally
• 5 times a day topically
• Oral use: prophylaxis after penetrating keratoplasty, dendritic ulcers
(400 mg 5 times a day), keratouveitis, adjust to immune-suppressive
(e.g., corticosteroids)
Herpetic keratouveitis

34. Common antiviral eye medicines
Ganciclovir (0.15%)
• Mechanism of action
• An acyclic nucleoside analog of deoxyguanosine.
• Ganciclovir Triphosphate - is incorporated into viral DNA with a consequent reduction
of DNA chain elongation and replication
• Host cellular polymerase is much less affected
• Pharmacokinetics:
• little to no metabolism, 90% of plasm ganciclovir is eliminated unchanged in the urine
(IV administration)
• Dose
• 5mg/kg twice daily for 2 weeks, 5mg/kg once daily for 7 days for maintenance (IV)
• Topical GCV 0.15% once every 6 hours for 2 weeks

35. Common antiviral eye medicines
Ganciclovir (0.15%)
• Adverse effect
• Neutropenia (40%) and thrombocytopenia (20%), often reversible
• Renal elimination correlated with creatinine clearance, non-nephrotoxic, adjust
the dose in case of renal dysfunction
• Rare events: fever, rash, phlebitis, nausea, hepatocellular dysfunction and
confusion
• Application
• Intravenous application
• A first drug to be approved by the FDA for the treatment of CMV retinitis (10 –
25X stronger than acyclovir)
• As active as acyclovir against HSV-1, HSV-2, VZV, EBV

36. Common antiviral eye medicines
Vidarabine (3% ophthalmic ointment)
• Action
• Phosphorylation intracellularly by host
enzymes to form Ara-ATP which inhibits viral
DNA polymerase
• Adverse effect
• Stinging. Burning, irritation, lacrimation,
conjunctival hyperemia, corneal edema,
delayed corneal wound healing, punctal
occlusion

37. Common antiviral eye medicines
Vidarabine (3% ophthalmic ointment)
• Application
• 3% ophthalmic ointment has the best corneal penetration (intact
corneal epithelium) of any topical antiviral drugs (inhibitory for
HSV-1 and HSV-2)
• Peak plasma level in 1.5 – 2 hours (oral)
• Dendritic or geographic epithelial keratitis by HSV
• Dose
• 5 times a day topically, continue 3 – 5 days after healing of the
infected wound

38. Common antiviral eye medicines
Trifluridine (Triflurothymidine, 1% ophthalmic
solution)
• Action
• Monophosphorylation by both cellular and viral-
encoded thymidine kinase, acts by inhibiting
DNA synthesis
• Acts against HSV-1, HSV-2 and adenovirus
• Pharmacokinetics
• topical trifluridine does not penetrate healthy
corneas
• significant amounts of unmetabolized drugs
reach the aqueous through diseased corneas

39. Common antiviral eye medicines
Trifluridine (Triflurothymidine, 1% ophthalmic solution)
• Adverse effect
• Well-tolerated, better than IDU (Idoxuridine), conjunctival cicatrization, anterior
segment ischemia, and corneal epithelial dysplasia.
• Application
• Used in primary keratoconjunctivitis and HSV-mediated recurrent epithelial keratitis
• Dose
• 1 drop every 2 hours until would healing is complete, followed by 1 drop every 4
hours for 7 days to prevent reactivation of disease. Discontinue after 21 days of
therapy.
• Discontinue if no improvement is seen by 7 days and re-epithelisation by 14 days

40. Thank you