U13W2 CAP Flashcards
What is the mechanism of action of amlodipine?
Class: is a calcium ion channel blocker
Chem: small molecule, sihydropyridine
Pharm: Is a L-type voltage gated calcium channel gating inhibitor
Physiology: has a greater effect on smooth muscle than cardiac muscles, decreases Ca2+ mobilisation in sm. muscle, leads to vasodilation
Clinical: essential hypertension and angina.
What is the mechanism of action of clarithromycin?
Class: macrolide
Clinical: broad spectum against mainly gram positive bacteria.
Pharm: antagonist at 23s 50s subunit in bacterial ribosome
Physiology: inhibits protein synthesis by blocking the polypeptide exit tunel, which prevents peptide chain elongation.
Most peptides produces are short only 3-9 amino acids long.
Are bacteriostatic although can be bactericidal at high doses.
What is the mechanism of action of amoxicillin/flucloxacillin?
Class: penicillin
Clinical: A - wide spectrum beta lactam, gram positive and enterococci, Haemophilus and listeria
F - narrow spectrum, gram-positive particular skin and soft tissue but not MRSA
Pharm: Antagonist of transpeptidase enzymes (penicillin binding protein), located in the periplasmic space between peptidoglycan layer and the plasma membrane.
Forms a covalent bond between Beta lactam ring which mimics D-ala-D-ala on peptoglycan and serine residue in transpeptidase enzyeme
Physiology: Prevents crosslinking of peptoglycan, high internal osmotic pressure leads to cell lysis.
What are the main mechanism underpinning the risk factors for CAP?
Increased risk of exposure to pathogen
Impaired mucociliary clearance or decreases epithelial barrier integrity.
Impaire phagocytic function including alveolar macrophages and neutrophils
Impaired adaptive immunity.
What are some of the risk factors for pneumonia?
- Extreme age - babies, children, elderly - suffer from immunoscencenes or underdeveloped immune system - both share poor monocye/macrophage function, lack or diminished memory T cell function, poor tissue repair and diminished cytokine responses
- Smoking - impaired mucoscilliary escaltor, low grade inflammation in lungs damage integrity, inhibit macrophage response
- Co-morbidities - CF, asthma, heart conditions - weakened tolerance to illness, more vulnerable to atypical pathogens
- Compromised immune system - such as in flu, HIV/AIDs or post organ transplant.
What are the different types of causative pathogen for CAP?
Bacterial - norm streptococcus pneumoniae
Viral - influenza A
Fungal - pneumocystis, cryptococcis and aserpigillus
How can you differentiate between bacterial, viral and fungal pneumonia?
Viral v bacterial - v has slower symptom onset, also GIT symptoms, lower body temp, lack of purulent sputum
bacterial - sudden onset, purulent sputum, high-grade fever
Fungal - more variable symptoms may also experience weight loss and fatigue. Often have symptoms of underlying disease causing immunosuppression,
What are the different types of infections that staphylococcus aureus can cause?
Skin infections - impetigo, boils, scalded skin syndrome, cellulitis
Severe disease - endocarditis, pneumonia, sepsis, toxic shock syndrome
both community and hospital acquired pneumonia
How common are carriers of MRSA?
3% of the population are carriers of MRSA.
What features should be looked at when testing for staphylococcus aureus?
Gram-positive cocci in clusters
Catalase positive
Oxidase negative
Coagulase positive
Grows on CBA, MSA (red to yellow change), BPA and chromogenic agists
Inhibited on MacConkey agar (bile salts)
Name the organisms from the gram stain
Staphylococcus aureus.
What is the definition of Methicillin-Resistant Staphylococcus Aureus?
Strains with an MIC of 4µg/ml Oxacillin or more
What are the problems associated with MRSA?
Leading cause of hospital acquired infecrion.postop protheses
Causes a wide range of infections of the skin/soft tissue, bones and joints, pneumonia, endocarditis, bacteremia.
High mortality and morbidity
Significant length of stay and cost burden.
What is the test for catalase and what does it mean?
Tests for presence of catalse enzyme by the decomposition of hydrogen peroxide to release oxygen and water
Rapid formation of bubbles.
Bottle method - hydrogen peroxide in bottle, colony on side, flip bottle to cover colony with hydrogen peroxide observe for bubbles.
All staphyloccoci tend to be catalase positive
What is the test for oxidase and why is it important?
Used to test for presence of cytochrome C enzyme.
Can identify Neisseria gonorrhae and Pseudomonas, (pos) whilt staph and strep tend to be negative.
Oxidase bottle fill 3rd with distilled water to dissolve reagent.
Add drops of solution to filter paper in clean Petri dish
Use sterile method to move colony from agar plate to filter paper.
Purple colour within 5 to 10 seconds indicates oxidase positive.
TMPD is used as the oxidase reagent.
What is the test for coagulase?
What is its purpose?
Coagulases are enzymes that clot blood plasma.
Often follows a catalse test to differentiate between staph aureus (coag pos) and other staph species.
Saline drops on slide or test tube are emulsified with test organisms using a wire loop or wooden stick - observe for fibrin clot/string formation.
What are the different mechanism by which staphylococcus aureus can invade a host and cause infection?
- Enter bloodstream through open wound - may spread heamatogenously to distant site
- Weakened immune system - disrupts microbiome allows S.aureus to multiply unchecked, cause dysbiosis
- Seoncadry to viral infection which has damaged to mucosal linings of respiratory tract.
What are the virulence factors of staphylococcus aureus?
- alpha toxin - active metalloproteases, break adherens junction by cleaving E-cadherins, compromises actin skeleton and epithelial barrier integrity.
- Biofilm formation - such as on tampons in TSS - phenotype promotes antibiotic resistance.
- Phenol-soluble modulins - lysis of erythrocytes and leukocytes - compromise host immune defences.
- Abscess formation - difficult to treat with antibiotics.
How does S. aureus tend to colonise a person?
Asymptomatic colonnization becomes pathogenic
Or rarely, norm in hospital environments - transfer from formites ot infected individuals
Main site of colonisation = the nares, also skin and intestine.
What is the basic pathophysiology of community acquired pneumonia and lung remodelling?
Branching anatomy of the respiratory tract normally prevents inhlaed pathogens from reaching alveoli, this is aided by mucus, cough reflex, cilia, epithelial barrier, normal flora and immune surveillance, mucocilliary clearance (waft into pharnyx)
When alveolar macrophages are overwhelmed by a large inoculum of pathogens they release cyoktines and initiate and inflammatory cascade
Leukocytes invade the lung tissue, filling infected alveoli with purulent ecudates normally made from dead wbcs, tissue debris, and living or death pathogens (this impaired effective gase exchange).
What is ventilator associated pneumonia?
Pneumonia is contracted after 48 hours of mechanical ventilation.
How does antibiotic treatment guidelines vary based on HAP?
Patients who are recently hospitalisied but do not have additional risk factors for MDR pathogens or HAP can be treated with standard antibiotic therapy for CAP, rather than broad spectrum antibiotics used in HAP MDR suspicision.