24. Topical Antibiotics & Clinical Use

Question 1

Why do topical eye drops almost always overflow?

Answer 1

Tear film contains 30μL of tears, whereas a drop in eye drops tend to have around 50μL, therefore it will overflow.

Question 2

Topical eye drops cannot maintain high bioavailability in a short amount of time due to quick drainage, what other methods can we use to increase contact time?

Answer 2

• Use ointments
• Slow down drainage by doing punctal occlusion

Question 3

What should be tapered and what should not be?

Answer 3

Steroids should be tapered, whereas antibiotics should not.

Question 4

Which condition is pulse dose commonly used on? How is it done?

Answer 4

Moderate anterior uveitis.
Start off intensively with one drop every 10 minutes for 4 hours then a drop every 2 hours.

Question 5

If there is no ..., the eye does not have ... infection. If there is, there will be ..., ... discharge. If there is ... conjunctival injection, the eye is ..., because ... will not cause just part of the eye to be red. Unless the patient gives ... or unless there is a true threat to the ..., the use of ... is of no clinical value.

Answer 5

If there is no discharge, the eye does not have bacterial infection. If there is, there will be greenish, mucopurulent discharge. If there is sectorial conjunctival injection, the eye is not infected by bacteria, because bacteria will not cause just part of the eye to be red. Unless the patient gives a history of mucopurulent discharge or unless there is a true threat to the cornea, the use of topical antibiotics is of no clinical value.

Question 6

What are the 3 common groups of topical antibacterials used in ocular diseases?

Answer 6

• *Chloramphenicol
• Fluoroquinolone (*ciprofloxacin, *ofloxacin)
• Aminoglycosides (gentamicin, *tobramycin, neomycin, framycetin)”

Question 7

What are the 3 common topical compounded antibacterials used in ocular diseases?

Answer 7

• Gramicidin
• Bacitracin
• Polymixin

Question 8

What are the 5 common oral antibacterials used in ocular diseases?

Answer 8

• Tetracyclines (doxycycline)
• Macrolides (azithromycin, erthromycin)
• Penicillins (flucloxacillin, amoxycillin)
• Cephalosporins (cefazolin, ceftriaxone)
• Glycopeptides (vancomycin)

Question 9

There are 4 different topical antibacterial formulations in Australia:
* Multi-use (...) eye drops: gentamicin, ..., framycetin, ..., ..., ...
* Single-use ... eye drops (...): gentamicin, ...
* Eye ...: tobramycin, framycetin, ...
* ... eye drops: gentamicin/ tobramycin 1.3% + ... %

Answer 9

There are 4 different topical antibacterial formulations in Australia:
* Multi-use (preserved) eye drops: gentamicin, tobramycin, framycetin, ciprofloxacin, ofloxacin, chloramphenicol
* Single-use non-preserved eye drops (Minims): gentamicin, chloramphenicol
* Eye ointments: tobramycin, framycetin, chloramphenicol
* Fortified eye drops: gentamicin/ tobramycin 1.3% + cephazolin 5%

Question 10

Compare the expense, sterility, application and properties of minims and bottle topical antibiotics.

Answer 10

Minims are more expensive, more sterile and non-preserved;

Bottle is generally less expensive, has questionable sterility since it is used over multiple patients and contains various preservatives.

Both are used the same way in terms of application.

Question 11

Chloramphenicol is a ... covering both ..., however it does not work against .... It has good ... and is .... It is ... rather than ..., meaning that it doesn’t kill the bacteria. It is usually the ..., unless the px’s issue correlates with ... use. This is commonly used for ..., ... after surgery, and .... There are associations between use of ... chloramphenicol and ..., however there are no associations with ... chloramphenicol.

Answer 11

Chloramphenicol is a broad spectrum antibacterial covering both G+ and G-, however it does not work against pseudomonas. It has good ocular penetration and is well tolerated. It is bacteriostatic rather than bactericidal, meaning that it doesn’t kill the bacteria. It is usually the first choice topical antibiotic, unless the px’s issue correlates with contact lens use. This is commonly used for conjunctival bacterial infection, prophylaxis after surgery, and superficial trauma. There are associations between use of oral chloramphenicol and aplastic anaemia, however there are no associations with topical chloramphenicol.

Question 12

There are two types of fluoroquinolones: ... and .... Both of these are ... and is excellent against ... bacteria, including ... associated with contact lens wear, and ... bacteria, including ` … and …. … has better corneal penetration but higher rates of … when used in high dosages. … commmonly … on … resulting in a transient …, however this does not interfere with healing. Fluoroquinolones are commonly used for …, … due to their …, …. Fluoroquinolones are used when there is …. Some surgeons use this off label for …`.

Answer 12

There are two types of fluoroquinolones: ofloxacin and ciprofloxacin. Both of these are bactericidal and is excellent against gram negative bacteria, including pseudomonas associated with contact lens wear, and gram positive bacteria, including staphylococcal and streptococcal.
Ofloxacin has better corneal penetration but higher rates of corneal perforation when used in high dosages.
Ciprofloxacin commmonly precipitates on microbial keratitis ulcers resulting in a ` transient white precipitate, however this does not interfere with healing. Fluoroquinolones are commonly used for microbial keratitis, CL related lesions due to their maximum gram negative coverage, severe conjunctivitis. Fluoroquinolones are used when there is poor responses to chloramphenicol. Some surgeons use this off label for post cataract surgery`.

Question 13

Aminoglycosides includes ..., ..., and .... These are mainly active against ... bacteria. They are commonly used for ..., ....hypersensitivity reaction, ` …. They maybe sometimes be used as … after surgery. Aminoglycosides are available in … and …` form.

Answer 13

Aminoglycosides includes framycetin, gentamicin, and tobramycin. These are mainly active against gram negative bacteria. They are commonly used for ocular irritation, type 4 delayed hypersensitivity reactions, contact blepharodermatitis. They maybe sometimes be used as prophylaxis after surgery. Aminoglycosides are available in topical eye drop and ointment form.

Question 14

Rank the causes of contact lens related microbial keratitis from most common to least common.

Answer 14

Pseudomonas aeruginosa> gram positive staphylococci > other gram negative > yeast & fungi / Acanthamoeba

Question 15

Uses of topical anti-bacterial in pregnancy and breastfeeding:
* ... - avoid use in ... or ...; but can be used in ...
* ... - caution use in ... but can be use in ... and in ..
* ... - safe to be used in ..., ... and in ...
* Topical antibiotics should be avoided in family history of ...

Answer 15

Uses of topical anti-bacterial in pregnancy and breastfeeding:
* Fluoroquinolones - avoid use in pregnancy or lactation; but can be used in kids
* Aminoglycosides - caution use in pregnancy but can be use in lactation and in kids
* Chloramphenicol - safe to be used in pregnancy, lactation and in kids
* Topical antibiotics should be avoided in family history of blood discrasia

Question 16

When do you decide to use oral or topical antibiotics?

Answer 16

Ocular surface infections are best treated using topical antibiotics. If infection is deeper, antibacterials with deeper penetrative properties through an intact epithelium should be used. Some ocular manifestations such that they are at the eyelids (blepharitis), chlamydia conjunctivitis, dacryocycstitis etc. may require oral medication.

Question 17

Compare and contrast the properties needed for a prophylactic and therapeutic antibiotic.

Answer 17

Prophylactic antibiotics should have a broad spectrum but also include the likely pathogen. The dosage should quickly allow protective levels to be reached, such as using loading dose. Prophylaxis should be prescribed until the risk of infection is over; Therapeutic antibiotics should target specific pathogens if it is known. The dosage shoud quickly allow therapeutic levels to be reached, such as using loading dose. Therapy should be continued until pathogen is eliminated. Minimum dosage is commonly QID = 4 times a day

Question 18

Acute bacterial conjunctivitis tend to present ..., then ... within days. There tends to be observation of irritation with .... After 24 hours, there will be ... and sometimes present with .... This condition is ... but treating with ... will help with .... The use also help ... and ....

Answer 18

Acute bacterial conjunctivitis tend to present unilateral, then bilateral within days. There tends to be observation of irritation with hyperaemia. After 24 hours, there will be mucopurlent/ purulent discharge and sometimes present with tarsal papillae. This condition is self limiting but treating with antibiotics will help with quicker resolution. The use also help prevent complications and limit the spread of infection to other people.

Question 19

What are the 6 surface compromising conditions where antibiotic prophylaxis has been proven to be of value?

Answer 19

• Post-surgical trauma
• Other trauma that is not sufficient for perforation
• RCE = recurrent corneal erosions
• Tonometry damage
• Disease-related compromise
• Steroid use → corneal compromise = steroid + antibiotics

Question 20

What are the common prescription for antibiotic prophylaxis?

Answer 20

• Chloramphenicol → most
• Fluoroquinolones → all CL wearers ∵ cover pseudomonas QID. 4 times a day after loading dose (q2h?)

Question 21

What is the common Rx for bacterial conjunctivitis in adult and children?

Answer 21

Chloramphenicol eye drops
OU
Loading dose = q2h for 1-2 days
QID for 5-7 days
May req use of ointment as adjunct at night or single agent QID in kids
A swab should be taken of the lesion, conjunctiva and lashes (3 separate swabs) → especially if cause is suspicious to be unusual → treat empirically until results come back

Question 22

What are the Rx that can be given for pain?

Answer 22

• In office cyclopentalate or isoptohomatropine 1 drop
• Pain med - tablet or liquid

Question 23

What are the common cause of bacterial conjunctivitis?

Answer 23

G+
• S. aureus (adults)
• S. pneumoniae (kids/ petechia haemorrhage)

G-
• H. Influenzae/ aegyptius (kids)
• N. gonorrheae (hyperacute)
• P.aeruginosa (CL wearers)
• Enterobacteriaceae
• M. lacunata (chronic)

Question 24

Acute bacterial conjunctivitis tend to present ..., then ... within .... There tends to be observation of .. with .... After 24 hours, there will be ... and sometimes present with .... This condition is ... but treating with ... will help with .... The use also help ... and limit the ... to other people.

Answer 24

Acute bacterial conjunctivitis tend to present unilateral, then bilateral within days. There tends to be observation of irritation with hyperaemia. After 24 hours, there will be mucopurlent/ purulent discharge and sometimes present with tarsal papillae. This condition is self limiting but treating with antibiotics will help with quicker resolution. The use also help prevent complications and limit the spread of infection to other people.

Question 25

How should corneal infiltrates/ ulcers/ break be managed?

Answer 25

Corneal breaks should be managed with both steroids and antibiotics. Steroids helps with inflammation and antibiotics acts as prophylaxis to prevent infections. Steroids should not be used alone.

Question 26

How can you differentiate between microbial keratitis ulcer and corneal infiltrate?

Answer 26

With NaFl staining, microbial ulcer will have a distinct border and clear green pooling due to loss of corneal epithelial and stromal tissues; Corneal infiltrate appears to have fluffy/ diffused edges due to disruption (hill-like) to corneal epithelium.

Question 27

Microbial keratitis tend to give px ... and the corneal lesion tends to be more ... and usually .... Px will have a more generalised .... The size of staining equals to .... It is also common to find cells in the ....

Corneal infiltrates is more ... and give px relatively .... Infiltrates arise from .... origins and tend to be more .... There can also be ... in one eye. Bulbar injection is more ... towards the lesion. Size of corneal staining will be ... the stromal lesion.

Answer 27

Microbial keratitis tend to give px significant pain and the corneal lesion tends to be more central and usually single. Px will have a more generalised bulbar injection. The size of staining equals to stromal lesion. It is also common to find cells in the anterior chamber.

Corneal infiltrates is more common and give px relatively less pain. Infiltrates arise from inflammatory origins and tend to be more peripheral. There can also be multiple infiltrates in one eye. Bulbar injection is more sectorial towards the lesion. Size of corneal staining will be less than the stromal lesion.

Question 28

Which is better for microbial keratitis ulcers? Fluoroquinolones or fortified antibiotics?

Answer 28

Fortified antibacterials (cephazoline+tobramycin) had 1% rate of corneal perforation compared to 14% with topical ofloxacin.

Question 29

Ciloxan are used for .... A ... is used, such that for a ..., start with 2 drops every ... mins for the first 6 hours, then 2 drops every ... mins for the remainder of the first day, then .... For bacterial conjunctivitis, ciloxan is prescribed ..., then ....

Answer 29

Ciloxan are used for corneal ulcers. A loading dose is used, such that for a corneal ulcer, start with 2 drops every 15 mins for the first 6 hours, then 2 drops every 30 mins for the remainder of the first day, then second day 2 drops every hour. For bacterial conjunctivitis, ciloxan is prescribed ` 1 drop every 2 hours for the first 2 days, then QID`.

Question 30

How should microbial keratitis be managed when using ciprofloxaxin monotherapy?

Answer 30

Ciprofloxacin monotherapy → 1 drop every 5 mins for the first hour, then once every hour until there is improvement.
Overnight therapy may be needed.
If clincal response is optimal, freqeucy of dosage may be decreased.
Atropine may be needed QID to relieve pain.

Question 31

Good practice for prescribing topical antibiotics:
1. Take a good ... →
* ... and ... health
* red flags
* pattern of ... or ...
* ... and ... considerations
2. Rule out underlying ... causes →
* most primary anterior eye presentations are ... in nature;
* ocular ... are uncommon;
* look for signs of ..., ..., ..., ..., ... etc.;
* May need to consider the use of ... for diagnosis with ` …` nature.

Answer 31

Good practice for prescribing topical antibiotics:
1. Take a good history →
* ocular and general health
* red flags
* pattern of injection or discharge
* pregnancy and kids considerations
2. Rule out underlying inflammatory causes →
* most primary anterior eye presentations are inflammatory in nature;
* ocular infections are uncommon;
* look for signs of ` microbial keratitis, lid infection, adenovirus, preseptal, Herpes simplex keratitis etc.; * May need to consider the use of steroids for diagnosis with inflammatory` nature.

Question 32

Good practice for prescribing topical antibiotics:
3. Use ... and ... to help select antibiotics
* Main selections: ..., ...., ..., ...
4. Antibiotics and contact lens wear
* Corneal lesions → differential between ... vs ...
* Consider ... vs ...
* CL-related microbial keratitis = 58% ... vs 24% ...
* Pseudomonas resistant to ... ∴ should use ... or ..
4. Fluoroquinolones vs Aminoglycosides
* Max ... coverage
* Fluoroquinolones has better ... and less .... Also suitable for kids over ...yo. Commonly used as monotherapy in suspected ...

Answer 32

Good practice for prescribing topical antibiotics:
3. Use pharmacology and clinical diagnosis to help select antibiotics
* Main selections: chloramphenicol, ciprofloxacin, ofloxacin, tobramycin
4. Antibiotics and contact lens wear
* Corneal lesions → differential between microbial keratitis vs infiltrative keratitis
* Consider prophylaxis vs treatment
* CL-related microbial keratitis = 58% pseudomonas vs 24% gram positive
* Pseudomonas resistant to chloramphenicol ∴ should use fluoroquinolones or aminoglycosides
4. Fluoroquinolones vs Aminoglycosides
* Max gram negative coverage
* Fluoroquinolones has better gram positive coverage and less sensitivity reactions. Also suitable for kids over 2 yo. Commonly used as monotherapy in suspected microbial keratitis.

Question 33

Good practice for prescribing topical antibiotics:
5. Optimise the dosage according to the ...
* Consider initial dosage greater than ... times a day
* Initial single drop of antibiotic can clear in ...
* Consider ... to reach ...
* Bacterial conjunctivitis → ... drops in first hour, then every ... hours until gain control
* Infiltrate keratitis → ... + ... loading dose first hour, then ...
* Microbial keratitis → ... dose e.g. 6 drops first hour, then dose every one to two hours
* Consider ..., ` need for … → … relief, … therapy for … treatment effect 6. When do you need culture and sensitivity exam? 7. * …; …; …; … * … detector testing * Microbial keratitis → deep/ …/ children/ Hx …/ post …/ …/ …. to therapy/ just returned from … * Suspect … related conjunctivitis`

Answer 33

Good practice for prescribing topical antibiotics:
5. Optimise the dosage according to the Australian Medicine Handbook
* Consider initial dosage greater than 4 times a day
* Initial single drop of antibiotic can clear in minutes
* Consider loading dose to reach therapeutic range
* Bacterial conjunctivitis → 6 drops in first hour, then every 1-2 hours until gain control
* Infiltrate keratitis → steroid + prophylaxis antibiotics loading dose first hour, then QID
* Microbial keratitis → loading dose e.g. 6 drops first hour, then dose every one to two hours
* Consider pathology, ` need for cycloplegia → pain relief, overnight therapy for maximal treatment effect 6. When do you need culture and sensitivity exam? 7. * Severe considitons; Chronic; Hyperacute; Unresponsive to therapy * Adenoviral detector testing * Microbial keratitis → deep/ elderly/ children/ Hx trauma/ post Sx/ immune compromised/ unresponsive to therapy/ just returned from overseas * Suspect COVID-19 related conjunctivitis`

Question 34

Good practice for prescribing topical antibiotics:
7. Consider oral antibiotics:
* Possible oral antibiotics = ..., cephalosporin, macrolides, ..., ...
* Dosing → refer to ...
* Lid infection → ... or ...
* Chlamydia → ...
*Inflammatory → ...

8. Which drugs are okay to use with kids?
   * Age = ... to ... yo
   * If <2yo → consider ... with GP or ...
   * Avoid agents with ... e.g. ... drugs, ...
   * Approved for kids >2 yo → ..., ..., ...
   * Same dosage as ...

Answer 34

Good practice for prescribing topical antibiotics:
7. Consider oral antibiotics:
* Possible oral antibiotics = penicillin, cephalosporin, macrolides, fluoroquinolones, tetracyclines
* Dosing → refer to Australian Medicine Handbook
* Lid infection → Augmentin or Keflex
* Chlamydia → Azithromycin
*Inflammatory → Doxycycline

8. Which drugs are okay to use with kids?
   * Age = 2 to 12 yo
   * If <2yo → consider co-management with GP or referral
   * Avoid agents with high sensitivity e.g. sulphur drugs, vasoconstrictors
   * Approved for kids >2 yo → chloramphenicol, ciprofloxacin, ofloxacin
   * Same dosage as adults