Pharmacological Management of Ocular Infection PDF

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Summary Notes for the Pharmacological Management of Ocular Infections....

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Week 10: Pharmacological Management of Ocular Infection Antimicrobial agents: An antimicrobial is an agent, either natural or synthetic, that kills or inhibits the growth of susceptible microorganisms. An antibiotic substance is produced by natural metabolic processes of some microorganisms that can inhibit or kill other microorganisms. Antimicrobials may be further classified as antibacterial, antiviral or antiprotozoal, depending on the type of organism against which they exert an effect.

Revision! – Bacteria •

Prokaryotic cells

Action of Antibacterial drugs: Site of action of antibacterial agents is commonly: • The cell membrane (or more selectively the cell wall) – allows uptake of nutrients by passive diffusion • The ribosomes – the site of protein synthesis • DNA gyrase – essential for bacterial replication

Common cause of ADR Entry Level Optometrists X

(Gentamicin / Tobramycin / Neomycin)

IP Optometrists √

Aminoglycosides Mechanism • Typically not used as first line treatment for bacterial conjunctivitis or bacterial keratitis as better for gram negative than gram positive bacteria • Gentamicin (and Tobramycin) used to treat P.Aeruginosa • Neomycin – broader spectrum but not effective against P. Aeruginosa, currently only available in combination drops with dexamethasone and polymyxin B (Maxitrol) • Neomycin used in combination with steroids to treat post-operative inflammation …. However becoming less commonly used for this purpose as now listed as “less suitable for prescribing in the BNF”

•

•

Gentamicin Cautions:

Interfere with ribosome function affecting protein synthesis (produce an abnormal codon) Bactericidal

• • •

Medicinal Forms: Available topical preparations • Gentamicin (0.3% Generic) (PoM) • (Tobramycin) • Neomycin in combination with steroid products (PoM)

Indications: Bacterial Eye infections

Interferes with Cell wall synthesis Bacteriocidal

Medicinal forms: Available for use as intracameral injection • Cefuroxime (Aprokam intracameral injection) (PoM)

Indications: • •

Prophylaxis of endophthalmitis after cataract surgery Advocated for this purpose by the Scottish Medicines Consortium

•

Dose:

Inhibits translocation during protein synthesis taking place at the ribosomes Bacteriostatic

Medicinal forms: •

•

Azithromycin (Azyter 1.5% SDU eye drops) (PoM) (Erythromycin)

Indications: • •

Chlamydia trachomatis treatment Bacterial conjunctivitis

Azyter – Azithromycin 15 mg per gram, 6 unit doses, bds for 3 days for both child and adults

Cautions: Patients should be informed that treatment should cease at the end of the last 3 day course even if residual symptoms remain

Interactions: Many varied interactions, consult the BNF, particularly problematic when prescribing systemic erythromycin.

Contraindications: Hypersensitivity to azithromycin, to any other macrolide or to the excipient Triglyceride

Undesirable Effects: •

•

Common - Eye discomfort - Blurred vision Uncommon - Eye allergy - Angioedema

Pregnancy and Breastfeeding: Listed as safe for use during pregnancy and breastfeeding

Undesirable effects:

Mechanism: •

Pregnancy and Breastfeeding:

• •

Cefuroxime Combined operations with cataract surgery Complicated cataract surgery Reduced endothelial cell count Severe risk of infection Severe thyroid eye disease

Interactions: More likely to cause nephrotoxicity if combined with other preparations such as aminoglycosides, methotrexate, acyclovir, ganciclovir, ketorolac

Pregnancy and Breastfeeding: Safe to use, present in breastmilk in low concentrations

1st line MGT Most commonly used in practice; Most cost effective

Interferes with DNA gyrase to inhibit protein metabolism Bacteriostatic Effective against Gram (+) & (-)

Medicinal forms: Available topical preparations • Ciprofloxacin (Ciloxan 0.3% eyedrops) (PoM) • Levofloxacin (Levofloxacin generic 5mg/ml eyedrops) (PoM) *Available as a Preservative Free option with Oftaquix sdus (single dose units) • Moxifloxacin (Moxivig 0.5% eyedrops) (PoM) • Ofloxacin (Exocin 0.3% eyedrops) (PoM)

Indications: •

• •

Ciprofloxacin is indicated for superficial bacterial eye infections, severe superficial eye infections, and corneal ulcers The other drugs in this class are indicated for eye infections. Ofloxacin is indicated for topical treatment of external ocular infections in adults and children caused by ofloxacinsensitive organisms.

Entry Level Optometrists X IP Optometrists √

Quinolones

Local sensitivity; blurred vision, eye irritation, burning sensation, stinging sensation, itching

Usage in pregnancy should only be considered in life-threatening situations where expected benefits outweigh possible risks. The amount of gentamicin ingested from the milk is unlikely to result in significant blood levels in breast-fed infants.

Ciprofloxacin Levofloxacin Moxifloxacin Ofloxacin

o o o o

In cases of a known allergy to aminoglycosides Due to neuromuscular blocking effects contraindicate in myasthenia gravis and related conditions

Cautions: • • • • •

•

• Quinolones

(Cefuroxime)

• •

• Other off label uses by ophthalmology: - Topical erythromycin and systemic penicillin to treat neonatal N. Gonorrheae conjunctivitis - Systemic erythromycin and topical azithromycin to treat neonatal chlamydial conjunctivitis

Concurrent use with other potentially nephrotoxic or ototoxic drugs should be avoided.

• Cephalosporins (2nd generation) Cephalosporins Mechanism:

against gram positive organisms and a few gram negative organisms (such as N. Gonorrheae) • Azithromycin commonly used for the treatment of blepharitis by ophthalmologists • Use in blepharitis is off label

Contraindications: • •

IP Optometrists √ Azithromycin

Nephrotoxicity Ototoxicity Neuromuscular blocking effects

Interactions: •

Entry Level Optometrists X

Macrolides Mechanism: • Erythromycin most useful

Erythromycin eyedrops available in the US only.

Antibacterials (Antibiotics) • Aminoglycosides

• Macrolides o Azithromycin

Ofloxacin Dose: Adults and children: 1-2 drops instilled into eye every 2-4 hours for the first 2 days and then 4 times daily. (Tx should not exceed 10 days).

Cautions: • Safety and effectiveness in infants below the age of one year have not been established. • Caution should be taken in patients with known risk factors for prolongation of the QT interval such as, for example: - Concomitant use of drugs that are shown to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) - cardiac disease (e.g. heart failure, myocardial infarction, bradycardia) - elderly patients and women may be more sensitive to QT-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including EXOCIN, in these populations.

Interactions: Certain antiarrhythmics and tricyclic antidepressants.

Contraindications: Contraindicated in those with a known allergy to the drug or the excipients in the formulation

Undesirable Effects: • Eye irritation and ocular discomfort • Ventricular arrhythmia (reported predominately in patients with risk factors for QT prolongation)

Pregnancy and Breastfeeding: Not suitable for use during pregnancy or breastfeeding.

• Other

Entry Level Optometrists √ IP Optometrists √

(Chloramphenicol / Fusidic Acid)

Chloramphenicol • Potent broad spectrum (effective against both gram positive and negative) • Ineffective against pseudomonas aeruginosa • Widely used due to: broad spectrum / good corneal penetration / little cross resistance • Used in management of bacterial conjunctivitis, hordeolum, staphylococcal and seborrheic blepharitis, nasolacrimal duct obstruction where there is evidence of infection, dacryocystitis, marginal keratitis ……… • Cost effective treatment • Can be use age 2 years + when supplied directly by an entry level optometrist, can write a written order as an exempted PoM for patients from age 1 month+ • Important to note that chloramphenicol is available as various branded eye drops and eye ointments, which are P meds, e.g. Optrex infected eyes, eye drops 0.5% chloramphenicol • These preparations are only suitable for treatment of acute bacterial conjunctivitis, and can only be used in patients over age 2 and can only be used for a maximum of 5 days

If using as P , only licensed for acute bacterial conjunctivitis only !!

Mechanism: • Inhibition of protein synthesis by interaction with bacterial ribosomes • Bacteriostatic Medicinal Forms: Available topical preparations • Chloramphenicol generic 0.5% eyedrops (5ml bottle and SDUs) (PoM) • Chloramphenicol generic 1% eye ointment (PoM) Indications: Superficial eye infections Dose: • 0.5% eyedrops Apply one drop into the infected eye every 2 hours for 48 hours. After this period, treatment should be every 4 hours during waking hours. Eye drops may be supplemented by ointment at night. The course of treatment should last 5 days (even if symptoms improve). • 1% eye ointment Put a small amount into the affected eye four times a day for two days, and then twice a day for five days. Cautions: Risk of aplastic anemia after topical chloramphenicol use is less than one per million treatment courses Interactions: • Safety for use during pregnancy and breastfeeding has not been established. • Avoid in patients taking drugs liable to depress bone marrow function. Contraindications: • Hypersensitivity to the drug or any of the excipients • Known personal or FH of blood dyscrasia, including aplastic anaemia Undesirable Effects: Transient irritation, burning, stinging, itching and dermatitis Pregnancy and Breastfeeding: Not recommended during pregnancy or breastfeeding

Fusidic Acid • Potent narrow spectrum antibiotic,

effective against gram positive bacteria, in particular staphylococcus aureus • Treatment of marginal keratitis,

blepharitis, conjunctivitis • Very expensive currently • Can be used on children of any age Fusidic acid is generally bacteriostatic in its overall action when used in the clinically recommended doses but at high doses, it can exert a slow bactericidal effect.

Mechanism: • Inhibition of protein synthesis by inhibiting DNA translocation • Bacteriostatic Medicinal Forms: Available topical preparations • Fusidic Acid 1% viscous eye drops (exempted PoM) Indications: Staphylococcal eye infections Dose: Apply twice daily, treatment should be continued for at least 48 hours after the eye returns to normal. Cautions: • Not to be worn with contact lenses • Contains BAK which can cause eye irritation and contact lens discolouration Interactions: Systemic interactions are unlikely since systemic exposure after application of Fusidic acid eye drops is negligible. Contraindications: Hypersensitivity to the drug or any of the excipients Undesirable Effects: • Common blurred vision, burning, redness and stinging on application • Uncommon hypersensitivity, eyelid oedema, lacrimation, skin rash, angioedema Pregnancy and Breastfeeding: Can be used during pregnancy and breastfeeding

Anti protozoal / Antibacterial •

Propamidine isethionate

Entry Level Optometrists √ IP Optometrists √

Mechanism: Aromatic diamidine disinfectant with antibacterial, antiprotozoal and antifungal actions

Medicinal Forms: Available topical preparations • Propamidine isethionate 0.1% eye drops (Brolene eye drops) (P) • Dibrompropamidine 0.15% eye ointment (GoldenEye Ointment) (P) • Propamidine isethionate 0.1% eye drops (GoldenEye drops) (P)

Indications: It may be used topically for the treatment of minor eye infections such as conjunctivitis and blepharitis.

Propamidine Isethionate • Propamidine isethionate is active against Gram-positive non-spore forming organisms, but less

active against Gram-negative bacteria and spore forming organisms. It also has antifungal properties. • It may be used off license in the treatment of acanthamoeba keratitis by specialists only • Works well even in the presence of copious purulent discharge [if it is a gram(+)]

Cautions: • If no significant improvement after 2 days discontinue and consult a physician • Unsuitable for use with contact lenses • If vision is disturbed or becomes worse during the treatment regime, discontinue and consult a physician

Interactions: None known

Contraindications: Hypersensitivity to the drug or any excipients

Undesirable Effects: Eye discomfort, blurred vision

Pregnancy and Breastfeeding: Not suitable during pregnancy or breastfeeding

Revision! – Viruses

Ganciclovir Take note:

• • •

• Can be used by IP

Simple noncellular structures Contain nucleic acid and a capsid (protein coat) Sometimes an envelope (an additional glycoprotein coat around the capsid) and a tail

Antivirals (Aciclovir / Ganciclovir)

• Antivirals (Aciclovir / Ganciclovir)

Action of Antiviral drugs: • Topical antiviral drugs are active against herpes simplex • Block the ability of the virus to replicate DNA • Topical antivirals (acyclovir and ganciclovir are prodrugs i.e. once biotransformed inside virus infected corneal and

conjunctival cells are active against the virus.

Entry Level Optometrists X

• The active drug blocks DNA transcription leading to DNA that is fragmented and no longer functional, as a result

IP Optometrists √

herpes simplex fails to replicate.

Topical Antiviral Mechanism: Block the actions of antiviral DNA/RNA polymerase enzymes Medicinal Forms: Available topical preparations • Acyclovir 3% ophthalmic ointment (Zoviraz) (PoM) • Ganciclovir 0.15% eye ointment (Virgan) (PoM) Indications: Herpes simplex keratitis

optometrists (and optometrists to treat uncomplicated superficial acute or recurrent herpes simplex keratitis) • Aciclovir may be used in children but use of ganciclovir in children is not recommended (not recommended under age of 18) • Not effective against other viral organisms which can cause conjunctivitis e.g. adenovirus

Cautions: • Stinging on instillation • Avoid wearing CL during treatment regime • Avoid if known hypersensitivity to acyclovir or valaciclovir Interactions: The concomitant administration of chloramphenicol with other drugs liable to depress bone marrow function should be avoided. Contraindications: • Hypersensitivity to the drug or any of the excipients • Myelosuppression during previous exposure to chloramphenicol • Known personal or family history of blood dyscrasias including aplastic anaemia Undesirable Effects: • Very common SPK (however, this did not necessitate an early termination of treatment and healed without sequaele). • Common – transient stinging on instillation, conjunctivitis • Rare – blepharitis • Very rare – Immediate hypersensitivity reactions including angioedema and urticaria Pregnancy and Breastfeeding: Manufacturer advises avoid unless no suitable alternative – limited information available....