Pharmacological Management of Ocular Infection Flashcards
What are the common antibacterials and types?
- Aminoglycosides:
o Gentamicin
o Tobramycin
o Neomycin - Cephalosporins, 2nd gen
o Cefruroxime - Macrolides
o Azithryomycin - Quinolones
o Ciprofloxacin
o Levofloxacin
o Moxifloxacin
o Ofloxacin - Other
o Chloramphenicol
o Fusidic acid
What are antimicrobial agents?
- An agent, either natural or synthetic, that kills or inhibits growth of susceptible microorganisms – could be bacteria, viral or fungal
- Antibiotic substance is produced by natural metabolic processes of some microorganisms that can inhibit or kill other microorganisms
o Always derived from natural process - Antimicrobials may be further classified as antibacterial, antiviral or antiprotozoal, depending on type of organism against which they exert an effect
What are the main microorganisms associated with ocular infections?
Bacteria:
Staph aureus, streptococcus pneumoniae, neisseria gonorrhaea, pseudomonas aeruginosa*
Viruses:
Adenovirus, enterovirus, herpes simplex virus
Fungi:
Candida species
Protozoa:
Acanthamoeba species, naegleria species
* = particularly associated with CL use
What is bacteria?
- Prokaryotic cells – does not have nucleus or membrane-bound organelles
- Classification:
o Many methodologies
o Gram staining particularly important for classification of bacteria for purposes of using effective tx regimes
What is the action of antibactrial drugs?
- Site of action of antibacterial agents is commonly:
o The cell membrane (or more selectively the cell wall) - allows uptake of nutrients by passive diffusion – if disrupt function of cell wall then it cannot replicate
o The ribosomes - the site of protein synthesis
o DNA gyrase – replication of genetic material of bacterial cells essential for bacterial replication – so if disrupt activities of DNA gyrase then that will hinder replication of bacterial cells
What is the mechanism, medicinal forms, indications and important points to note about aminoglycosides?
- Mechanism
o Interfere w/ ribosome function affecting protein synthesis
By combining mRNA to produce an abnormal codon
o Bacteriocidal – kills bacteria
o Broad spectrum antibiotics, affecting protein synthesis taking place at ribosomes
Mechanism is slightly different to chloramphenicol or fusidic acid. The aminoglycosides inhibit protein synthesis by disruption of the function of the 30S ribosomes causes a misreading of the peptidyl tRNA identities - This results in incorrect peptides & proteins being produced
They have bacteriostatic effects as well as a slow bactericidal effect (esp. in gram negative bacteria) as it works on the bacterial cell membrane and may exert weak inhibitory effects on bacterial DNA replication
o Generic is listed in BNF as non-proprietary - Medicinal Forms: available topical presentations
o Gentamicin (0.3% Generic) (PoM)
o (Tobramycin) – not currently available
o Neomycin in combo w/ steroid product (PoM) - Indications:
o Bacterial eye infections - TO NOTE:
o Typically, not used as 1st line tx for bacterial conjunctivitis or bacterial keratitis as better for gram negative than gram positive bacteria
o Gentamicin (and Tobramycin) used to treat P. Aeruginosa
May be used in 2ndary care for pxs w/ CL associated keratitis
Gentamicin 0.3% 3mg per 1ml 10ml
o Neomycin – broader spectrum but not effective against P. Aeruginosa, currently only available in combination drops with dexamethasome and polymixicin B (Maxitrol)
o Neomycin used in combo with steroids to treat post operative inflammation
BUT becoming less commonly used for this purpose as now listed as “less suitable for prescribing” in BNF
o Aminoglycosides can be toxic to OCULAR surface, typically response occurs after 1-2 weeks of use & is not serious typical undesirable effects as a result of ocular toxicity are punctate keratitis, injection of inferior cul de sac, and a weepy erythema with oedema of eyelid tissues
What are the cautions, interactions, contraindications, undesirable effects, info on pregnancy/breastfeeding for gentamicin (aminoglycoside)?
IP OPTOMS
* Cautions:
o Nephrotoxicity – kidneys
o Ototoxicity – damage to inner ear
No evidence of above 2 when gentamicin used topically
o Neuromuscular blocking effects – can block neuromuscular transmission at the neuromuscular junction which can cause paralysis of effected the skeletal muscles – unlikely to happen in topical use
* Interactions:
o Concurrent use with other potentially nephrotoxic or ototoxic drugs should be avoided (unless considered essential)
Potent diuretics such as ethacrynic acid & frusemide are believed to enhance any risk of ototoxicity whilst amphotericin B, cisplatin & cyclosporin & cephalosporins are potential enhancers of nephrotoxicity.
* Contraindications:
o In cases of known allergy to aminoglycosides
o Due to neuromuscular blocking effects contraindicated in myasthenia gravis & related conditions
* Undesirable effects:
o Local sensitivity; blurred vision, eye irritation, burning sensation, stinging sensation, itching
* Pregnancy & Breastfeeding:
o Usage in pregnancy should only be considered in life-threatening situations where expected benefits outweigh possible risks
o Amount of gentamicin ingested from milk is unlikely to result in significant blood levels in breast-fed infants – so is relatively safe to use gentamicin in mothers who are breast-feeding
Describe mechanism, medicinal forms, indications, cautions, interactions and pregnancy/breastfeeding info for cephalosporins?
None available topically but one available for use as intracameral injection
* Mechanism:
o Interferes with cell wall synthesis
o Bateriocidal
* Medicinal forms:
o Available for use as intracameral injection
o Cefuroxime (Aprokam intracameral injection) (PoM)
Cefuroxime brand name APROKAM 1mg injected into the anterior vitreous at the end of cataract surgery
* Indications:
o Prophylaxis of endophthalmitis after cataract surgery
Advocated for this purpose by the Scottish Medicines Consortium
* Cautions:
o Combined operations with cataract surgery – e.g. combined trabeculectomy with cataract surgery – use it with caution due to increased risks associated with that surgery
o Complicated cataract surgery – may wish not to use cefuroxime
o Reduced endothelial cell count
o Severe risk of infection
o Severe thyroid eye disease
* Interactions:
o More likely to cause nephrotoxicity if combined w/ other preparations such as aminoglycosides, methotrexate, acyclovir, ganciclovir, ketorolac
More likely if these drugs are administered systemically
* Pregnancy & Breastfeeding:
o Safe to use in pregnancy, present in breastmilk in low concs (but still safe for use) – but unlikely for female who is of fertile age to be having cataract surgery
What is the mechanism, medicinal forms, indications, off label uses by opthalmology and resistance of macrolides?
IP OPTOMS
* Mechanism:
o Inhibits translocation during protein synthesis taking place at ribosomes
o Bacteriostatic effect by disrupting protein synthesis which involves binding to ribosomes – same site of action as chloramphenicol so if both agents are used simultaneously some competition at drug site may occur
o Reasonably broad spectrum
* Medicinal Forms:
o Available topic preparations
Azithromycin (Azyter 1.5% SDU eye drops) (PoM) – 15mg per gram unit dose, bds for 3 days for both children & adults
(Erythromycin) – only available in US
* Indications:
o Chlamydia trachomatis tx
Macrolide antibiotic drugs block protein synthesis in bacteria, including Chlamydia (mechanism is slightly different from chloramphenicol, aminoglycosides, tetracyclines or fusidic acid) and they reduce the replication rate of bacteria.
o Bacterial conjunctivitis
o Also used off licensed in stubborn blepharitis
* Erythromycin most useful against gram +ve organisms & a few gram -ve organisms (such as N. Gonorrheae)
* Azithromycin commonly used for the treatment of blepharitis by ophthalmologists
o Use in blepharitis is off label
Azyter has demonstrated notable additional anti-inflammatory activities when compared to standard eyelid care ie. Lid hygiene and hot compresses
Some evidence that topical azithromycin gives a superior result to systemic azithromycin for blepharitis
* Other off label uses by ophthalmology:
o Topical erythromycin and systemic penicillin to treat neonatal N. Gonorrheae conjunctivitis
o Systemic erythromycin and topical azithromycin to treat neonatal chlamydial conjunctivitis
* Resistance to macrolides (not as much of a consideration when using topically, more so when systemically) is brought by modification of ribosomes & can occur when used widely as a prophylactic
o Has been shown to be case in group of children where erythromicin resistant staphylocci were found when these children had been administered erythromycin to prevent ophthalmia neonatorum
o That’s why it is never used prophylactically – only used in active infections
What are the cautions, interactions, contraindications, undesirable effects and info on pregnancy/breastfeeding for azithromycin (type of macrolide)?
IP OPTOMS
* Cautions:
o Pxs should be informed that tx should cease at end of 3 day course even if residual sxs remain
* Interactions:
o Many varied interactions – consult BNF – particularly problematic when prescribing systemic erythromycin
* Contraindications:
o Hypersensitivity to azithromycin, to any other macrolide (e.g. erythromycin) or to excipient Triglyceride – would not use Azyter if allergic to either of these
* Undesirable effects:
o Common:
Eye discomfort
Blurred vision
o Uncommon:
Eye allergy
Angioedema –area of swelling of lower layer of skin & tissue just under skin or mucous membranes.
* Swelling may occur in face, tongue, larynx, abdomen, or arms and legs. Often associated with hives, which are swelling within upper skin – can occur to periorbital skin when using topical agent
* Pregnancy & Breastfeeding:
o Listed as safe for use during pregnancy & breastfeeding
Need to discuss the frequency of undesirable effects with pxs when prescribing
Describe mechanism, medicinal forms, and indications of quinolones?
IP OPTOMS
* Extremely effective topical antibacterials
* Mechanism:
o Interferes with the production of DNA by inhibiting the enzyme (DNA gyrase) responsible for producing the coils of nucleic acid in the bacterial cells – inhibits protein metabolism
o Bacteriostatic
o Effective against gram +ve and gram -ve – broad spectrum
* Medicinal Forms:
o Available topical preparations
Ciprofloxacin (Ciloxan 0.3% eyedrops) (PoM) – next cheapest drug in this class £4.70 per 5ml bottle
Levofloxacin (Levofloxacin generic 5mg/ml eyedrops)(PoM) – there is a preservative free version of this available
Moxifloxacin (Moxivig 0.5% eyedrops) (PoM)
Ofloxacin (Exocin 0.3% eyedrops) (PoM) – v commonly used in practice – most cost-effective drug in this class £2.15 per 5ml bottle
* Indications:
o Ciprofloxacin indicated for superficial bacterial eye infections, severe superficial eye infections, and corneal ulcers
o The other drugs in this class are indicated for eye infections
What are the cautions, interactions, contraindications, undesirable effects, info on pregnancy/breastfeeding for ofloxacin (type of quinolone)?
IP OPTOMS
* Cautions:
o Safety & effectiveness in infants below age of 1 year have not been established – so should be used with EXTREME caution in this age group
o Caution should be taken in patients w/ known risk factors for prolongation of QT interval such as, for example:
Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides (systemic), antipsychotics)
Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
Elderly patients & women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including EXOCIN® (topical quinolone), in these populations
Use with caution in pxs with uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
The above 4 points apply more to systemic application rather than topical application (except point 3)
* Interactions:
o As per above
* Contraindications:
o In those with known allergy to drug or excipients in formulation
* Undesirable effects:
o Eye irritation & ocular discomfort
o Ventricular arrhythmia – reported predominantly in pxs w/ risk factors for QT prolongation
* Pregnancy & Breastfeeding:
o Not suitable for use during pregnancy & breastfeeding
Use in pregnancy: There have been no adequate & well-controlled studies performed in pregnant women. Since systemic quinolones have been shown to cause arthropathy in immature animals, it is recommended that EXOCIN® not be used in pregnant women.
Use during lactation: Because ofloxacin and other quinolones taken systemically are excreted in breast milk, and there is potential for harm to nursing infants, a decision should be made whether to temporarily discontinue nursing or not to administer the drug, taking into account the importance of the drug to the mother
What is the mechanism, medicinal forms, indications, dose, cautions, interactions, contraindications, undesirable effect and pregnancy/breastfeeding info for chloramphenicol?
Exempted PoM
* Mechanism:
o Inhibition of protein synthesis by interaction with bacterial ribosomes
Protein synthesis requires amino acids to be brought to ribosome sites, arranged in correct sequence & linked to the one next to it
Chloramphenicol blocks this linking of the amino acids resulting in a reduction and eventual halt in the overall rate of cell division.
However, resistance to chloramphenicol can occur as a result of alterations (mutations) in the ribosome binding sites
* Little evidence of this resistance occurring in topical chloramphenicol
o Bacteriostatic
* Medicinal Forms:
o Available topical preparations
Chloramphenicol generic 0.5% eyedrops (5ml bottle and SDUs) (PoM)
Chloramphenicol generic 1% eye ointment (PoM)
* Both available as exempted PoMs for optoms
* Indications:
o Superficial eye infections – when used as PoM
o When used as P med – only indicated for bacterial conjunctivitis
* Dose:
o 0.5% eyedrops: apply one drop into the infected eye every 2 hrs for 48 hours
After this period, treatment should be every four hours during waking hours. Eye drops may be supplemented by ointment at night.
The course of treatment should last five days (even if symptoms improve within this time).
o 1% eye ointment: put a small amount into affected eye 4 times a day for 2 days, and then twice a day for 5 days.
* Cautions:
o Risk of aplastic anaemia after topical chloramphenicol use is less than 1 per million tx courses
* Interactions:
o Safety for use during pregnancy & breastfeeding has not been established
o Avoid in pxs taking drugs liable to depress bone marrow function
* Contraindications:
o Hypersensitivity to drug or any of excipients
o Immune system deficits: Hypersensitivity reactions including angioedema, anaphylaxis, urticaria, fever, vesicular and maculopapular dermatitis
o Blood & Lymphatic system disorders: Bone marrow depression and rarely aplastic anaemia has been reported following topical use of chloramphenicol. Whilst the hazard is a rare one, it should be borne in mind when assessing the benefits expected from the use of this compound
Above 2 points are only theoretical risks when applying chloramphenicol topically
o Known personal or FH of blood dyscarsias, including aplastic anaemia
* Undesirable effect:
o Transient irritation, burning, stinging, itching & dermatitis on skin around eye
* Pregnancy & Breastfeeding:
o Not recommended in either
What is other info to know about chloramphenicol?
- Potent broad spectrum (effective against both gram positive and negative)
- Ineffective against pseudomonas aeruginosa (gram -ve bacteria) – so if px CL wearer and has eye infection, chloramphenicol SHOULD NOT BE USED AS 1ST LINE AGENT
- Widely used due to:
o Broad spectrum
o Good corneal penetration
o Little cross resistance – when used topically - PoM: 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 used 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 +
o Chloramphenicol has a dual classification. When classified a POM it can be used from 1 month. When as a P medicine for 2 years and over - 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
- P med: 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
- For details of the latest drug preparations see the BNF, however this may not list all P meds
More and more toddlers coming to optoms with bacterial conjunctivitis – knowing your rights & knowing way you can use the legislation means can treat 6mth old baby if feel within your competence & so long as used via a signed order.
If supplying directly to px (without signed order) – can only use it in bacterial conjunctivitis (cannot use it for e.g. hordeolum) & can only use it in children >2yrs.
What is the mechanism, medicinal forms, indications, dose, caution, interactions, contraindications, undesirable effects and info on pregnancy/breastfeeding for fusidic acid?
- Mechanism:
o Inhibition of protein synthesis taking place at ribosomes by inhibiting DNA translocation but does not bind to ribosomes
o Chemically related to the cephalosporin antibiotics, but is a protein synthesis inhibitor
o Mechanism of action of fusidic acid is similar to that of chloramphenicol, tetracyclines and te macrolides
o Fusidic acid is a translocase inhibitor, indirectly interfering with translocase enzyme (by binding to a protein associated with the enzyme). If the translocase is blocked, the incoming peptidyl tRNA molecules cannot bind and protein synthesis is stopped
o Bacteriostatic – when used in clinically recommended doses
But at high doses can exert a slow bactericidal effect - Medicinal Forms:
o Available topical preparations
Fusidic acid 1% viscous eye drops – exempted PoM - Indications:
o Staphylococcal eye infections – particularly good for gram +ve bacteria - Dose:
o Apply twice daily, tx should be continued for at least 48hrs after the eye returns to normal - Cautions:
o Not to be worn w/ CLs – microcrystalline fusidic acid may cause scratches in the contact lens or cornea. Contact lenses are kept out until all symptoms of the infection have gone.
o Contains BAK which can cause eye irritation & CL discolouration - Interactions:
o Systemic interactions are unlikely since systemic exposure after application of Fusidic acid eye drops is negligible - Contraindications:
o Hypersensitivity to drug or any excipients – including BAK - Undesirable Effects:
o Common: blurred vision (thick preparation), burning, redness & stinging on application
o Uncommon: hypersensitivity, eyelid oedema, lacrimation, skin rash, angioedema - Pregnancy & Breastfeeding:
o Can be used during pregnancy & breastfeeding