Antibacterial Treatment of Ocular Disease

Question 1

Define Antibiotic and Antibacterial

Answer 1

Antibiotic - A naturally created compound produced by a microorganism that suppresses the growth/kills other microorganisms (Penicillin, tetraycycline)

Antibacterial - Any chemical, natural or synthetic that can suppress or kill other microorganisms

Question 2

What is the difference between Antibiotic and Antibacterial?

Answer 2

Antibiotic is just the natural selection while Antibacterial is both natural and synthetic, or rather antibiotics are kind of antibacterial

Question 3

Define Bacteriostatic and Bacteriocidal

Answer 3

Bacteriostatic - Inhibiting the organism’s growth and reproduction but not killing it; need something else to kill it

Bacteriocidal - Destroys the microorganism

Question 4

Define Spectrum of Activity and give some examples of a narrow vs a broad spectrum

Answer 4

Based on ability of antibiotic to inhibit/kill bacteria.
Gram (+) Narrow - Penicillin, Bacitracin (typically eye meds)
Gram (-) Narrow - Aminoglycosides, Polymyxin B
Broad (+ and -) - Tetracyclines, fluroquinolones

Question 5

Describe some of the general problems with antibacterials

Answer 5

No benefit for treating viral diseases

There are specific toxicities with each kind

Question 6

Describe the general problem of resistance with antibacterials

Answer 6

Bacteria becoming less sensitive to an AB.
This problem of resistance is the most frequent problem with AB
Overuse of ABs has led to resistance and more rational use of ABs for treatment can slow the development

Question 7

Describe the general problem of allergic sensitivity with antibacterials

Answer 7

A common problem with penicillin or neomycin as these are foreign to the body
May have to treat with a more toxic AB should one be allergic to another

Question 8

Describe the general problem with altering the normal flora with antibacterial use

Answer 8

You’re destroying the good microorganisms with the bad ones, can lead to ‘super-infection’ because you’re destroying a good bacteria keeping a bad one in check
Could lead to diarrhea and other GI issues if you’re killing GI flora for example

Question 9

Talk about the prophylactic use of ABs

Answer 9

Used as preventative treatment, but the most controversial form of AB treatment
May not be too effective and actually not reduce chance of infection

Question 10

List and briefly describe the ways a microorganism can develop resistance.

Answer 10

Synthesizing enzyme to destroy the AB
Altering cell membrane to prevent AB entry
Altering metabolic pathway to avoid a blockade due to AB
Altering receptors to decrease AB binding
All mechanisms have common cause of resistance

Question 11

Describe the difference between plasmid transfer and spontaneous mutation

Answer 11

Plasmid is a free floating piece of DNA that can be in the cell and incorporate or dissociate from genome, can also be transfered from bacteria to bacteria

Mutations cannot be transferred from one bacteria to another

Question 12

What is the problem with sub-optimal dosing with AB?

Answer 12

Need a certain amount to be used or else there won’t be enough of an effect

Question 13

List the factors that can encourage the development of resistance

Answer 13

Indiscriminate use of ABs or for the wrong indications
Delaying optimal treatment (bacteria growing exponentially)
Administration of sub-optimal dosing
Selection of the wrong AB
Inability of drug doesn’t get to site of action (topical drugs don’t make it into an intraocular infection)
Defective immune system.

Question 14

Give examples of antibacterials that work via inhibiting the synthesis of bacterial cell walls.

Answer 14

Penicillin
Bacitracin
Cephalosporins

Bacteriocidal

Question 15

Give examples of AB’s that work by causing the cell membrane to leak

Answer 15

Antibacterial -Polymyxin B (detergent like effect)

Antifungal - Natamycin and Amphotericin B

Question 16

Give examples of AB’s that work with reversible inhibition of protein synthesis

Answer 16

Chloramphenicol
Tetracycline
Erythromycin
Macrolides

Bacteriostatic

Question 17

Give examples of AB’s that work by inhibiting the 30S ribosome in bacterial protein synthesis

Answer 17

Aminoglycosides (These also alter membranes and transparent to allow for further AB to enter the cell more easily and are thus both bacteriostatic and bacteriocidal)

Question 18

Give examples of AB’s that act as antimetabolites

Answer 18

Sulfonamides (Competitively block folic acid synthesis and inhibit cell growth/replication)

Question 19

Give examples of ABs that block DNA gyrase and topoisomerases to ultimately disrupt DNA repair and synthesis

Answer 19

Fluroquinolones (Ciprofloxacin)

Question 20

Describe characteristics of the ideal antibacterial agent

Answer 20

Selective, effective and has high therapeutic index (good effect with low toxicity)
Bactericidal over bacteriostatic
Wont’ develop resistance
Pharmacokinetics that can reach a high serum level and maintained for a long time
Compatible with other AB’s
Abundantly available and cost effective

Question 21

How many AB’s meet the criteria of the ideal AB?

Answer 21

Well, none really. But the topical ocular drugs are very close
Good selectivity, good AB efficacy, minimal resistance developing but large concentration can be applied, limited distribution and low total dose used to limit systemic toxicity

Question 22

What is the MIC? (Minimum Inhibitory Concentration)

Answer 22

The minimum drug concentration that can cause a bacteriostatic effect

Question 23

What is the MBC? (Minimum Bacteriocidal Concentration)

Answer 23

Minimum drug concentration required to cause a bacteriocidal effect

Question 24

What is the problem with the use of penicillin?

Answer 24

Developing allergies to penicillin and its many derivatives

Question 25

What is the problem with chloramphenicol?

Answer 25

Developing aplastic anemia

Question 26

What is the problem with streptomycin (and other aminoglycosides)?

Answer 26

Ototoxicity (hearing loss)

Question 27

What is the problem with the use of tetracycline?

Answer 27

Permanent tooth discoloration and bone abnormalities in children and nursing mothers

Question 28

What is the problem seen with the use of some antifungals

Answer 28

Nephrotoxicity

Question 29

What selection factors should be considered for selecting an AB?

Answer 29

``` Cost of the drug Sensitivity of the patient to AB Sensitivity of bacteria to AB Seriousness of infection General health of the patient Establish a diagnosis! ```

Question 30

List the reasons for AB failure

Answer 30

``` Inaccurate diagnosis Resistant microorganism Inadequate drug dose Patient noncompliance Inadequate supplemental physical procedure Inadequate patient immune system ```

Question 31

How does a gram stain look for a + bacteria versus a - bacteria?

Answer 31

Gram (+) - Purple | Gram (-) - Pink

Question 32

In general what kinds of cocci (ball) bacteria infect the eye?

Answer 32

Gram (+) cocci bacteria (Streptococcus, staphylcoccus) Niceria is an exception as a cocci (-) bacteria more commonly seen if the patient has gonorrheal disease

Question 33

In general what kinds of bacilli (rod) bacteria infect the eye?

Answer 33

Pseudonomas and enteric bacteria

Question 34

What is the very best way to determine the cause of an ocular infection?

Answer 34

Taking a culture swab; but timely and can cause treatment delay Cost not always justified for a minor infection/self-limiting infection like blepharitis and conjunctivities

Question 35

In what cases will you ALWAYS send for a culture due to the chronicity/severity?

Answer 35

``` Any Red Eye Neonatal ophthalmia Chronic conjunctivitis Corneal ulcers (treat this one aggressively) Orbital cellulitis Endophthalmatis ```

Question 36

Without a culture result on hand how would you go about treatment?

Answer 36

Base treatment on gram stain and morphology Avoid systemics at first unless required Select appropriate drug

Question 37

If your patient had a gram (+) cocci infecting them, what would you treat with?

Answer 37

Penicillins Cephalosporins Fluroquinolones Bacitracin These are the more heavy duty drugs and are bacteriocidal

Question 38

Assuming you selected the proper drug for a gram (+) cocci infection but wanted an additional adjunct drug on top of it (bacteriostatic) what would you select?

Answer 38

Erythromycin Chloramphenicol Tetracyclines

Question 39

If your patient had a gram (-) bacilli infecting them, what would you treat with?

Answer 39

Aminoglycosides Fluroquinolones Extended spectrum penicillins (Ticarcillin and carbenicillin)

Question 40

Assuming you selected the proper drug for a gram (-) bacilli infection but wanted an additional adjunct drug on top of it (bacteriostatic) what would you select?

Answer 40

Chloramphenicol | Tetracyclines

Question 41

What ocular related conditions are best treated with topical ocular administration?

Answer 41

``` Common ocular infections Blepharitis Conjunctivitis Corneal ulcer External hordeolum ```

Question 42

What ocular related conditions are best treated with oral administration?

Answer 42

Internal hordeolum Preseptal cellulitis Severe conjunctivitis may require supplemental oral treatment

Question 43

What topical ABs have good ocular penetration?

Answer 43

Chloramphenicol - Use it if only indicated | Ampicillin and other cephalosporins penetrate into the eye after systemic administration

Question 44

What are some non-drug related treatments (physical procedures) that can be done for ocular disease?

Answer 44

Irrigate the site, especially with the site of an infection | Apply some heat to increase circulation and healing

Question 45

What are the guidelines for effective antimicrobial treatment?

Answer 45

Establish accurate clinical and laboratory diagnosis Select appropriate AB for the infective cause Select the least toxic AB Establish adequate drug levels at site of infection Select best route of administration Use appropriate drug regimen and for the appropriate length of time Augment the drug therapy with the physical procedures

Question 46

Describe the antibiotic activity in the healthy eye

Answer 46

Resident/transient bacteria present in the healthy eye Tear film flushing out bacteria and debris also with blinking Lysozymes in the tear layer Some immunoglobins in tears that may inactivate organisms WBCs that may migrate into the tears to phagocytise bacteria The intact cornea serving as a physical barrier