3. Bacterial infections Flashcards
(14 cards)
How does the eye protect itself?
- Anatomical barriers - eyelids/lashes, immune cells in conjunctiva
- Blinking - removes irritant, ensures even spread of tears, lacrimal drainage.
- Tears - flushes out pathogens, antimicrobial components such as lyzozymes, IgA, lactoferrin, defensins
- Corneal epithelium - acts as a physical barrier
What is the general ocular response to infection?
When pathogen enters, the innate immune response is activated. We are born with innate immune response hence can fight infections during early stages with high efficiency. Cell mediated innate immunity is enabled by pronounced vasodilation to allow for more blood to emigrate white blood cells and other inflammatory factors.
If this is not enough to fight off the infection, bacteria proliferates leading to white blood cell accumulation and secretion of mucus with bactericidal proteins, like lactoferrin, from goblet cells.
Mucopurulent discharge is a sign of bacterial infection which is composed of mucus and white blood cells.
What are the sites of ocular inflammation and their names?
- Membrane of inner eyelid = conjunctivitis
- Eyelid = blepharitis
- Cornea = keratitis
- Iris = iritis
- Nasolacrimal sac = dacryocystitis
- Gland of Zeiss (eyelash) = hordeolum / stye
- intraocular cavity = endophthalmitis
- Retina and blood vessels = chorioretinitis
- optic nerve = neuroretinitis
(10. conjunctivitis in newborns= opthalmia neonatorum)
What are the types of bacteria that cause ocular infections?
Gram positive =
*Staphylococcus aureus
*Staphylococcus epidermidis
*Streptococcus pneumoniae
*Streptococcus viridans
Gram negative =
*Neisseria gonorrhoeae
*Haemophilis influenzae
*Pseudomonas aeruginosa
What is the difference between structure of gram positive and negative?
Gram negative has 2 cell membranes.
Gram positive has more peptidoglycan.
What are the ways of management of ocular infections?
- Topical antibiotics
- Oral antibiotics
- IV antibiotics
- Intravitreal antibiotics
- Culture and sensitivity testing
What are the different mechanisms of action for antibiotics?
- Cell wall structure or assembly
- Cell membrane permeability
- Protein synthesis
- DNA synthesis
Describe mechanism of action for antibiotics targeting bacterial cell wall.
Penicillin binds to penicillin binding protein which cross link the peptidoglycan strands. This inhibits activity for peptidoglycan formation. The binding is irreversible and permanently blocks peptidoglycan formation. The membrane becomes leaky leading to lysis and bacterial death. This is effective against both gram positive and negative bacteria, and is effective for overcoming bacterial resistance mechanisms.
Penicillins and cephalosporins have beta lactam ring which is responsible for their activity. Bacteria produce beta lactamase enzymes which break the ring structure, rendering the antibiotics ineffective.
Describe the availability of antibiotics targeting bacterial cell wall and their side effects.
Synthetic penicillins:
1. Flucloxacillin (is beta lactamase resistant)
2. Amoxicillin
3. Ampicillin
4. Pipericillin
Side effects:
*Nausea
*Diarrhoea
Cephalosporins:
1. Ceftazidime
2. Ceftriaxone
Side effects:
*Vitamin K deficiency - destroy bacteria that synthesise vit K
*Bleeding
*Nephrotoxicity
Adverse effects include allergic reactions Type 1 - Type 4 hypersensitivity reactions.
Vancomycin and Bacitracin also drugs which inhibit cell wall synthesis, effective against gram positive, but are no longer used.
Describe mechanism of action for antibiotics targeting bacterial cell membrane.
These are a mixture of antibiotics. They insert themselves into cell membrane and act as a detergent disrupting the cell membrane. The membrane becomes leaky and leads to secretion of enzymes that cause lysis resulting in bacterial cell death (Bactericidal)
Describe the availability of antibiotics targeting bacterial cell membrane and their side effects.
Topical use only.
Maxitrol:
1. Dexamethasone
2. Neomycin
3. Polymixin B - effective against gram negative
Sofradex:
1. Dexamethasone
2. Framecytin
3. Gramicidin - effective against both gram positive (except baccilli) and negative
These are used before infection occurs such as pre surgery.
Side effects:
*Polymixin B = neuro and nephrotoxic
*Gramicidin = causes haemolysis
Describe the availability and mechanism of action of antibiotics targeting DNA synthesis in bacteria.
Fluoroquinolone: prevents DNA unwinding so prevents DNA supercoiling and thus prevention of DNA synthesis.
1. Levofloxacin
2. Moxifloxacin
3. Ofloxacin
4. Ciprofloxacin
Dibromopropamidine: Inhibits uptake of DNA building blocks, thus prevention of DNA synthesis. It doesn’t kill bacteria only prevents growth. For blepharitis.
1. Brolene
How does protein synthesis occur in bacteria?
This is the process of translating RNA code copied from DNA into proteins. It is a multi step process occuring in the cytoplasm and is mediated by ribosomes with two subunits 30s and 50s.
During initiation mRNA binds to ribosome and ribosome finds start codon. tRNA brings first amino acid and starts. During elongation phase tRNA continues to bring amino acids to add to the polypeptide chain and ribosome moves along mRNA. At termination stage ribosome releases polypeptide chain when stop codon is reached.
Describe the availability and mechanism of action of antibiotics targeting protein synthesis in bacteria.
Aminoglycosides: This binds irreversibly to 30s subunit of ribosome causing inaccurate protein synthesis. Resistance to these antibiotics would come about due to mutations on the ribosomal binding site. Good against + and - bacteria
1. Gentamicin
2. Tobramycin
3. Neomycin
Adverse effects:
*allergic response, hypersensitivity.
Tetracyclines: This prevents binding to the 30s subunit of ribosome. Good against + and - bacteria
1. Doxycyline
Systemic side effects:
*Chelate calcium - affects teeth and bone growth.
Chloramphenicol: This binds to 50s subunit of ribosome. Good against + and - bacteria except P. aeurginosa.
Must not give 0.5% chloramphenicol to those under 2 as it contains boron which can impair fertility. Whereas, chloramphenicol 1% can be as it doesn’t have boron.
Systemic side effects:
*Aplastic anemia leading to agranulocytosis
Macrolides: This binds to 50s subunit of ribosome. Good against + and some - bacteria. Used for chlamydia infections.
1. Azitromycin
Side/adverse effects:
*Discomfort
*Allergy
Fusidic acid: This inhibits elongation factor G. Good against + and some - bacteria. 1st antibiotic to use when first qualified and it is easier to apply due to it’s viscosity. Would be an alternative to chloramphenicol if allergic.
1. Fucithalmic
Side effects:
*Dry eyes
*Mild irritation, blurring, burning, itching.
