Block 9 Week 2 Flashcards
Gut microbiome
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Microbial protectors
How do commensal species cause infection ?
Clostridium difficile
When grows too much secretes a toxin which causes diarrohea
- Antibiotic associated diarrohea
- Spore former therefore can survive harsh treatments, normally cleaning procedures will not get rid
- Antibiotic causes other bacterium to die and allows clostridium difiicile to grow which causes diarrohea
How to reduce clostridium difficle overgrowth which causes chronic diarrohea
Dysbiosis
- Imbalance of the normal gut microbiota composition
- These changes- quantitative/qualitative; distribution;metabolism- results in harmful effects on the host
Prebiotics and Probiotics
Terminology
The main way we classify antibiotics is via their targets.
What are the targets antibiotics work against ?
Beta - lactams and Glycopeptides
Beta lactam eg. Penicillin and Cephalosporins
Glycopeptides eg. Vancomycin
Fosfomycin
Some antibiotics target protein synthesis
Some antibiotics target Nucleic acid synthesis
Some drugs interfere with metabolic pathways
Some drugs interfere with Cytoplasmic membrane
Examples of narrow spectrum and wide spectrum antibiotics
Antibiotic Resistance
Minimum Inhibitory Concentration
Ways we can reduce antibiotic resistance
What are the two ways you become antibiotic resistant ?
How is resistance acquired ?
- Horizontal gene transfer
How is resistance acquired ?
- Mutations
Multidrug resistance
MRSA resistance
Whats the future ?
Describe the factors (e.g. environment, lifestyle, level of immunity) which influence who gets infected, how and why ?
Examples of reservoirs
Reservoir: a organism who can have the bacteria without getting showing symptoms. The next organism who it gets passed onto may get the disease.
Human can act as reservoirs for which infection: staph aures, TB, HIV, Malaria
Summarise the importance of surveillance in communicable disease control
Describe the dangers of acquiring infections in a healthcare (hospital) setting and outline the steps taken to prevent and manage healthcare-acquired infections ?
Define an outbreak of infectious disease and explain how knowledge of routes of infections helps prevention, identification and management of outbreaks
Staphylococcus Aureus
- Gram positive bacteria
- Has penicillinase - enzyme to break down penicilin so penicilin antibiotics won’t work
- Has catalase - protects microbes from ROS
- Has coagulase - which converts fibrinogen to fibrin, leading to clot formation
- Facultative antibiotics - can grow in the presence and absence of antibiotics.
- Most commonly found on nares (nostrils), ears groin, axilla on human host
Meningitis
- Inflammation of the leptomeninges (arachnoid and pia mater). Between leptomeninges we have the subarachnoid space which houses the CSF
- Most common cause infection by Neisseria meningitidis bacteria or Herpes Simplex Virus
How do pathogens get to the menninges:
- Direct spread - Through skull or spinal column, penetrates meninges. Or up through nose.
- Hematogenous Spread - enters bloodstream then through the endothelial cells that make up the blood brain barrier.
- Bacteria multiply. Attract WBCs that release cytokines to attract more WBCs. Additional immune cells cause fluid to go to the meninges and cause local destruction as they try to control infection. Pressure in the meninges increases
Meningitis most common cause by age:
Pneumonic: EBHNS ( Explaining Big Hot Neck Stiffness)
Infants: E Coli, group B streptococus
Kids: Haemophilus influenzae
Young adults: Neisseria meningitidis
Elderly: Streptococcus pneumoniae
Meningitis
- Inflammation of the meninges surrounding the brain and spinal cord.
Signs and Symptoms:
- fever, headache, nuchal rigidity (neck stiffness) (classic triad 50% cases)
- Photophobia (discomfort with loud noises)
- Vomiting
- Kernig’s sign - resistance to knee extension when hip flexed 90 degrees
- Brudzinski’s sign - passive neck flexion - pain, involuntary flexion of hips and knees.
- Petechial rash - non- blanching rash when pressure applied to trunk and lower extremities
- headache worsens if patient asked to ‘jolt’ head from side to side.
Pneumonia
- Infection in lung tissue caused by microbes, the result is inflammation. Inflammation brings water into the lung tissue which makes it harder to breathe.
- Microbes colonise the bronchioles, multiply, move into lung tissue. Inflammatory response WBC, proteins, fluid and RBC.
- Bacteria, Viruses, Fungi and Myobacterium can all cause pneumoniae.
- Community acquired pneumonia: person gets ill outside of hospital or healthcare setting.
- Hospital acquired pneumonia (Nosocomial): Person already sick in hospital. More serious because sick people already have a weakened immune system. Also microbes in hospital are more resistant to antibiotics eg. MRSA
- Ventilator associated pneumonia: subset of hospital acquired pneumonia. Biofilm on ventilator.
- Aspiration pneumonia:
from food, drink and gastric contents (after vomiting)
Pneumonia categories depending on where the infection is
Bronchopneumonia - can be throughout the lungs. Around the bronchioles and alveoli
Atypical or Interstitial Pneumonia - infection outside alveoli in the interstitium.
- Lobar pneumonia - infection causes consolidation of a whole lobe of the lung, meaning the entire region is filled with fluid. Mainly caused by S.Pneumniae
Symptoms of Pneumonia
- Dyspnea - shortness of breath
- Chest pain
- Prodcutive cough - pus or bloody sputum
- Systemic symptoms - fatigue and fever
Diagnosis of Pneumonia
- Patient is working hard to breathe
- Patient is breathing quickly
- Chest x- ray help identify pneumonia.
- Dullness to percussion - suggests lung consolidation
- Tactile vocal Fremitus - more vibrations from persons back on repeating certain phrases. Sound travels better through fluid filled tissue than air filled healthy tissue.
- Late inspiratory crackles
- Bronchial breath sounds
- Bronchophony
- Egophony
Treatments of Pneumonia
- Depends on severity
- Antibiotics
- Cough suppressants
- Pain medications
Cholera
- When you have severe gastroenteritis and watery diarrhea.
- Caused by the pathogen Vibrio Cholerae. Gram negative curved bacteria. Positive for oxidase. Facultative anaerobe.
- Rapid dehydration can be fatal
Transmission of Cholera
- fecal to oral route: Inadequate access to clean water.
- Shellfish consumption in areas with sporadic cholera
- People with blood group O at higher for severe cholera.
Complications
- If left untreated dehydration and hypovolemic shock in 4-12 hours, death in 18 hrs to several days.
- Renal failure secondary to hypovolemia
- Electrolyte imbalances: hypokalemia, metabolic acidosis
- Pneumonia ( esp in children) due to aspiration of vomit.
Symptoms of Cholera
- watery diarrohea
- moderate to severe vomiting
- abdominal discomfort
- borborgymus ( gurgling noise made by the movement of fluid and gas in the intestines)
- Dehydration: thirst, dry mucous membranes, decreased skin turgor, sunken eyes, hypotension, tachycardia, tachypnea
- Altered mental state: somnolence ( desire to fall asleep, drowsy),
Tuberculosis
- Estimated 2 bilion people are infected with TB. 95% of people don’t even know they are infected this is because the immune system can contain it so that it isnt able to multiply. It usually remains Latent/dormant and can’t be spread to others.
- If the host immune system becomes debilitated like with AIDS or old age it can become ACTIVE and become very serious.
- Myobacterium Tuberculosis are Acid fast, aerobic bacteria.
- TB usually transmitted via inhalation.
TB
- Ghon complex is sometimes called a Ranke complex
- TB disseminates (spreads). In the lungs it can cause bronchopneumonia and can cause systemic miliary TB.
Systemic Miliary TB
Symptoms:
- Fever
- Night Sweats
- Weight loss
- Coughing up blood (hemoptysis)
Testing for TB:
- PPD (Purified Protein Derivative) Intradermal Skin Test ( Tuberculin test, Mantoux Test, TB Test).
- Interferon Gamma Release Assay (IGRA) - blood test
TB Treatment
How antibiotics work.
Types:
- Antimetabolites
- Antituberculosis medication
- Cephalosporins
- Penicilins
- Fluoroquinoloes
- Metrondiazole
- Miscellaneous cell wall inhibitors
- Miscellaneous protein synthesis inhibitors
- Aminoglycosides
- Tetracyclines
Cephalosporins: Cell wall synthesis inhibitors
- Belong to Beta - lactam antibiotic group. Target gram positive and negative.
- All beta lactams inhibit cell wall synthesis in bacteria.
- Bacterial cell walls are made up of murien ( aka peptidoglycan).
-NAG, NAM, TRanspeptide chain joined by enzymes DD - Transpeptidase/Penicilin binding proteins (PBPs)
- Beta lactams how they work: PBP bind to the Beta - Lactam antibiotic and is disabled. Which stops the crosslinking and wall becomes weak and unstable.
Which is the most common bacteria which is resistant to beta-lactam antibiotics ?
- Staphylococcus Aures because they contain the enzyme beta lactamase/ penicillinase
- To deal with this we created new drugs like Clavulanic acid and Methicillin. But then the S.Aures developed PBP mutations.
- The antibiotics wont fit into the PBP enzyme. That is how we developed MRSA ( Methicillin Resistant Staphylococcus Aures) .
- To treat MRSA we use reserve antibiotics such as Vancomycin and Teicoplanin
Tetracyclines: Protein synthesis Inhibitors
- Medications that prevent protein synthesis by binding to 30s subunit of ribosomes.
- Bind to the A -site on the 30S - inhibits binding of tRNA to mRNA ribosome complex. Shuts down protein synthesis before it starts.
Side effects
- Tetracyclines are broad spectrum. They target a wide variety of gram positive and negative bacteria.
- Often used to treat acne and community acquired pneumonia.
- Used to treat intracellular pathogens.
Side effects:
- Phototxicity (easily sunburn)
- Tinnitus
- Discoloiuration of teeth and bone
Contraindicated:
- Pregnant and breastfeeding women
- Children under 8 ( can accumulate in teeth and bone)
Penicillin: Cell wall synthesis inhibitors
- group beta-lactam antibiotics
- PBP enzymes bind to penicillin antibiotic and are destabalised (cannot function).
- Crosslining between peptidoglycan chains (NAM AND NAD) with transpeptide stops.
- Cell wall weak and unstable.
Aminoglycosides: Protein synthesis inhibitors
- inhibit bacterial ribosomes
- Only work on gram negative aerobic bacteria.
- irreversibly bind to 30S ribosomes - this decreases the amount of proteins synthesized.
- prevents translocation
Aminoglycoside side effects
- Ototoxic - damage hair and cochlea
- Inhibit the release of acetylcholine. can cause weakness and paralysis.
Contraindicated:
CANNOT USE FOR PREGNANT WOMEN
Sulfonamide: Antimetabolites
- Interefere with the synthesis of DNA, specifically folate.
- Folate/ Folic acid/ Vitamin B9 is neccesary for the synthesis of nucleic acids DNA and RNA.
- There are 3 stages to making folate. Sulfonamides block the first step.
- Bind to enzyme DHPS (DIhydropteroate Synthetase) and prevents the bacteria from making Dihydrioteroic acid.
Sulfonamides
- Broad spectrum can treat gram negative and gram positive
- Some people are allergic to sulfonamide - cause rash
- Some other med contain the sulfonamide functional group and can create sulfonamide when taken together such as Thiazide diuretics.
Trimethoprim
- Often used in combination with sulfamethoxazole. Combination called TMP/SMX. When used togther they are bacteriocidal.
- Inhibits the 3rd step of folate synthesis.
- Inhibits DHFR ( Dihydrofolate reductase) preventing the formation of Tetrahydrofolic acid.
- Broad spectrum antibiotic - gram negative and gram positive bacteria.
-
TMP/SMX
- Amongst other things effective against MRSA
Fluoroquinolones: DNA synthesis inhbitors
- floxacin
-Broad spectrum bactericidal antibiotics
- inhibit DNA topoisomerase
- Topoisomerase II (DNA gyrase) and Topoisomerase IV. Both cause double strand breaks in DNA.
- Topoisomerase allows the chromosomes to supercoil so that the DNA condenses. Without DNA can’t condense.
Macrolide antibiotics
- bind to the 50s subunit of ribosome and block translocation. The ribosome cant slide to the next codon on the mRNA
- Broad spectrum and bacteriostatic
- Used to treat Bartonella Pertussis, Typical Pneumonia, Atypical Pneumonia.
