

## Penicillins
<ul>
  <li>Bactericidal</li>
  <li>Produced from fungi and molecular modification</li>
  <li>Interfere with bacterial cell wall production (disrupt) cross linking of glycan strands)</li>
  <li>Renally excreted</li>
  <li>Most effective:</li>
  <ul>
    <li>
      Staphylococci (although now commonly resistant, flucloxacillin prevents the action of
      beta-lactamases)
    </li>
    <li>Streptococci&nbsp;</li>
    <li>Clostridia (Gram positive bacilli)</li>
    <li>Gram negative bacilli such as E. coli and H. influenzae</li>
  </ul>
</ul>

## Cephalosporins
<ul>
  <li>Bactericidal</li>
  <li>Inhibit bacterial cell wall synthesis</li>
  <li>Broader spectrum than penicillins: effective against beta-lactamase producers</li>
  <li>
    Later generation agents have effectivity against more Gram negative organisms including
    pseudomonas and bacteroides
  </li>
</ul>

## Aminoglycosides: gentamicin
<ul>
  <li>Bactericidal</li>
  <li>
    Prevents the first ribosome from joining the mRNA by irreversibly binding to the 30S subunit
  </li>
  <li>Efficacy:&nbsp;</li>
  <ul>
    <li>Staphylococci</li>
    <li>Aerobic Gram negatives eg. pseudomonas, proteus</li>
  </ul>
  <li>Not effective against streptococci and anaerobes</li>
  <li>
    Parenteral administration associated with adverse effects: vestibular, cochlear, renal (rare)
  </li>
</ul>
<HotTopic>
  <p>
    Topical gentamicin can cause corneal epithelial toxicity and intravitreal can cause retinal
    toxicity
  </p>
</HotTopic>
<ul>
  <li>Amikacin is an aminoglycoside with good Gram negative activity</li>
  <ul>
    <li>Commonly given intravitreally</li>
    <li>Useful for patients with significant penicillin allergy</li>
    <li>Less retinotoxic than gentamicin</li>
  </ul>
</ul>
<HotTopic>
  <p>Amikacin has poor ocular penetration from the circulation:&nbsp;</p>
</HotTopic>
<ul>
  <li>Aminoglycosides do not cross the blood-brain barrier and so do not enter the vitreous</li>
  <li>Not given systemically in endophthalmitis</li>
</ul>

## Tetracyclines
<ul>
  <li>Bacteriostatic</li>
  <li>
    Interrupt amino acid attachment during protein synthesis, also by targeting the 30S subunit of
    the ribosome
  </li>
  <li>Broad spectrum</li>
  <li>Treatment of choice for chlamydial infections (eg. trachoma), brucellosis, Q fever</li>
</ul>
<HotTopic>
  <p>Tetracyclines are contraindicated in pregnancy and in patients under 10 years of age</p>
</HotTopic>
<ul>
  <li>Side effects</li>
  <ul>
    <li>GI upset</li>
    <li>Birth defects</li>
    <li>Permanent teeth staining in children</li>
    <li>Diarrhoea&nbsp;</li>
  </ul>
</ul>

## Chloramphenicol
<ul>
  <li>Bacteriostatic</li>
  <li>
    Prevents peptide chain transfer to other amino acids by targeting the 50S subunit of the
    ribosome: inhibiting protein synthesis (specifically inhibits peptidyltransferase)
  </li>
  <li>Potent against staphylococci (hence use for bacterial conjunctivitis)</li>
  <li>Systemic use limited to H. influenzae, meningitis, typhoid</li>
  <ul>
    <li>Can cause potentially fatal aplastic anaemia</li>
  </ul>
  <li>Contraindicated in pregnancy and breastfeeding: grey baby syndrome</li>
</ul>

## Metronidazole
<ul>
  <li>Disrupts DNA synthesis</li>
  <li>Crosses the blood-brain barrier</li>
  <li>Efficacy:&nbsp;</li>
  <ul>
    <li>Anaerobic organisms</li>
    <li>Protozoa including trichomonas and giardia</li>
  </ul>
</ul>

## Ofloxacin
<ul>
  <li>Fluoroquinolone</li>
  <li>Bactericidal&nbsp;</li>
  <li>Inhibits bacterial DNA gyrase: DNA synthesis inhibitor</li>
  <li>Broad spectrum:</li>
  <ul>
    <li>Pseudomonas</li>
    <li>Chlamydiae</li>
    <li>Mycoplasmas</li>
    <li>Rickettsia</li>
    <li>Enterobacteriaceae&nbsp;</li>
  </ul>
  <li>Less effective against Gram positives and anaerobes</li>
  <li>Good corneal penetration into the AC</li>
  <li>Systemic use: GI upset and photosensitivity</li>
</ul>
<HotTopic>
  <p>
    Long-term use of topical ciprofloxacin can cause corneal crystalline precipitates (probably
    representing precipitation of the drug which requires low pH for solubility).
  </p>
</HotTopic>

## Vancomycin
<ul>
  <li>Glycopeptide</li>
  <li>Bactericidal against Gram positives</li>
  <li>Inhibits peptidoglycan assembly and therefore cell wall synthesis</li>
  <li>Good Gram positive efficacy (ineffective against Gram negative)</li>
</ul>
<HotTopic>
  <p>
    Vancomycin has strong potency against staphylococci and does not cause retinal toxicity
    therefore widely used for intravitreal treatment of endophthalmitis.
  </p>
</HotTopic>
<ul>
  <li>Cannot penetrate the outer membrane of Gram negatives</li>
</ul>
<ul>
  <li>Poor GI absorption</li>
</ul>

## Amphotericin
<ul>
  <li>Macrolide polyene antifungal</li>
  <li>Broad spectrum including most fungi that infect humans</li>
  <li>
    Not absorbed enterally (must be given IV or intravitreally eg. for Candidal endophthalmitis)
  </li>
  <li>
    Binds to sterols in cell membranes and has a high affinity for ergosterol: the major sterol in
    fungal membranes
  </li>
  <ul>
    <li>Creates ion channels in the membrane leading to loss of membrane integrity</li>
  </ul>
  <li>Adverse effects:</li>
  <ul>
    <li>Anaemia</li>
    <li>Nephrotoxicity</li>
  </ul>
</ul>

## Fluconazole
<ul>
  <li>
    Azoles: alter fungal membranes by blocking synthesis of ergosterol leading to cell leakage
  </li>
  <li>Active against most Candida, Cryptococcus and Histoplasma</li>
  <li>Not effective against aspergillus or mucor</li>
  <li>Hepatotoxic</li>
  <li>Good CNS uptake</li>
  <li>Given intravenously or orally&nbsp;</li>
</ul>

## Flucytosine
<ul>
  <li>Disrupts fungal protein and DNA synthesis</li>
  <li>Effective against candida and cryptococcal infections</li>
  <li>Good tissue and CSF penetration</li>
  <li>Marrow aplasia (although not hepatotoxic)</li>
  <li>Fungal resistance is common</li>
</ul>

## Aciclovir
<ul>
  <li>Acyclic analogue of guanosine</li>
  <li>
    Activated via phosphorylation by viral thymidine kinase and thereafter inhibits DNA polymerase
  </li>
  <ul>
    <li>
      The viral form of thymidine kinase is more effective at this activation than the human form so
      infected cells are preferentially affected
    </li>
  </ul>
  <li>Highly specific for HSV and VZV (lesser activity against EBV and CMV).</li>
  <li>Side effects:</li>
  <ul>
    <li>Renal impairment (mild): with intravenous use</li>
    <li>GI upset</li>
    <li>Headache</li>
  </ul>
</ul>

## Ganciclovir
<ul>
  <li>Acyclic nucleotide analogue with a hydroxymethyl group (cp. with aciclovir)</li>
  <li>Virostatic&nbsp;</li>
  <li>Inhibits CMV DNA polymerase</li>
</ul>
<HotTopic>
  <p>
    Ganciclovir is many times more effective than aciclovir against CMV and similarly effective
    against HSV and VZV
  </p>
</HotTopic>
<ul>
  <li>Given intravenously or intravitreally (for CMV retinitis)</li>
  <li>
    Administered in inactive form which is phosphorylated after uptake by virally-infected cells
  </li>
  <li>UL97 mutation renders ganciclovir susceptible to resistance</li>
  <li>Side effects</li>
  <ul>
    <li>
      Haematological (bone marrow suppression: neutropenia (40% of patients), thrombocytopenia (20%)
    </li>
  </ul>
</ul>

## Foscarnet
<ul>
  <li>Antiviral: binds to DNA polymerase to prevent nucleotide binding</li>
  <li>Given intravenously or intravitreally</li>
  <li>Side effects: nephrotoxicity</li>
</ul>
<p>Summary Table: Bacteriostatic vs Bactericidal agents and mechanisms of action</p>
<div className="bg-blue-200 px-4 rounded-md shadow-lg dark:text-gray-700">
  <table>
    <tbody>
      <tr>
        <td>
          <span className="font-semibold">Bacteriostatic</span>
        </td>
      </tr>
      <tr>
        <td>Chloramphenicol</td>
        <td>Inhibits peptide chain transfer (protein synthesis)</td>
        <td>Potent against staphylococci but limited systemic use (aplastic anaemia)</td>
      </tr>
      <tr>
        <td>Tetracyclines</td>
        <td>Protein synthesis inhibitors</td>
        <td>Broad spectrum including chlamydia</td>
      </tr>
      <tr>
        <td>
          <span className="font-semibold">Bactericidal</span>
        </td>
      </tr>
      <tr>
        <td>Penicillins</td>
        <td>Cell wall synthesis inhibitors via glycan strand crosslinking</td>
        <td>Limited by beta-lactamase producers</td>
      </tr>
      <tr>
        <td>Cephalosporins&nbsp;</td>
        <td>Cell wall synthesis inhibitors</td>
        <td>Broader spectrum</td>
      </tr>
      <tr>
        <td>Fluoroquinolones (ofloxacin)</td>
        <td>DNA gyrase inhibitors</td>
        <td>Good gram negative cover and corneal penetration</td>
      </tr>
      <tr>
        <td>Vancomycin</td>
        <td>Glycopeptide: inhibits peptidoglycan assembly therefore cell wall synthesis</td>
        <td>Bactericidal against gram positives only. Poor GI absorption</td>
      </tr>
      <tr>
        <td>Aminoglycosides (gentamicin)</td>
        <td>Protein synthesis inhibitors</td>
        <td>Staphylococci and Gram negative cover. Retinal toxicity</td>
      </tr>
    </tbody>
  </table>
</div>

## anti-HIV agents
<ul>
  <li>Ritonavir: protease inhibitor&nbsp;</li>
  <ul>
    <li>Nausea and diarrhoea</li>
  </ul>
  <li>Zidovudine: reverse transcriptase inhibitor&nbsp;</li>
  <ul>
    <li>Cytopenia</li>
  </ul>
  <li>Didanosine: reverse transcriptase inhibitor</li>
  <ul>
    <li>Pancreatitis</li>
  </ul>
  <li>Zalcitabine: reverse transcriptase inhibitor</li>
  <ul>
    <li>Peripheral neuropathy</li>
  </ul>
</ul>

## Sulfadiazine
<ul>
  <li>Blocks the production of dihydrofolate from para-aminobenzoic acid</li>
  <li>Used in the treatment of Toxoplasma gondii</li>
</ul>

## Pyramethamine
<ul>
  <li>Dihydrofolate reductase inhibitor</li>
  <li>Used in the treatment of Toxoplasma gondii</li>
</ul>

## Antibiotic resistance
<ul>
  <li>Mutation</li>
  <li>Conjugation</li>
  <li>Plasmid transfer</li>
</ul>


Penicillins Bactericidal Produced from fungi and molecular modification Interfere with bacterial cell wall production (disrupt) cross linking of glycan…

Microbiology

Antimicrobials

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

Lacrimal Glands

Tear Film

Eyelids

Blinking

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Cornea

Corneal Structure And Development

Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

Lens

Posterior segment

Choroid

Vitreous

Retinal Macrostructure

Neurosensory Retina

Retinal Pigment Epithelium

Neuroanatomy

Venous Sinuses

Cerebral Ventricles

Cerebral Blood Supply

Supranuclear Gaze Pathways

Head And Neck Autonomic Nervous Supply

Head And Neck Glands

Osteology

Nerves

Muscles And Pharyngeal Arches

Extraocular Nerves

Sensory Nerves

Physiology

Physics Of Blood Flow

Neuronal Control Of Blood Vessels

Oxygen-Haemoglobin Dissociation Curve

Cytochrome p450

Pituitary Gland

Thyroid Hormone Production

Insulin

Glucagon

Parathyroid Hormone

Corticosteroids

Catecholamines

Cardiac Cycle

Renal Physiology

Fluid Balance

Acid-Base Balance

Muscle Physiology

Sensory Fibres

Cutaneous Receptors

Endocytosis

Glycosaminoglycans

Condensed Ocular Biochemistry

Eye Movements

Accomodation

Vision

Visual Cycle And Phototransuction

Visual Pathway

Visual Acuity

Colour Vision

Binocular Vision

Pathology

Collagen

Tissue Damage

Inflammation

Disease Entities

Wound Healing

Thrombosis / Atherosclerosis

Cell Growth

Neoplasia

Histopathology

Nystagmus

Free Radicals And Antioxidants

Immunology

Ocular Immunology

Viral Infections

Bacterial Infections

Fungal Infections

Protozoa

Nematodes

Genetics

Chromosomes

Mitosis

Meiosis

Genes

Polypeptide Synthesis

Histones

MicroRNA

Hardy-Weinberg Equilibrium

Mutations

Chromosome Defects

Autosomal Inheritance

X-Linked Inheritance

Mitochondrial Inheritance

Multifactorial Inheritance