Issues Abx request. Sneezing w/ post- nasal d/c & redness mucous membranes Throat. Chest px w/ coughing, difficulty breathing
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1 Week 5 Magic Bullets URTI + Pneumonia Presenting Sx Cough, sore throat & runny nose Aches & pains all over Shivers & fevers Respiratory Viruses Viruses causing flu Influenza A/B/C (orthomyxovirus) Respiratory Syncytial Virus (paramyxoviridae) Rhinoviruses (picornaviridae) Coronaviruses (coronaviridae) Adenoviruses (adenoviridae) Viral vs Bacterial Infections Issues Abx request Viral replication cycle Virus binds to surface proteins, endocytosed Viral constituents released into cytoplasm, migrate to nucleus Viral proteins replicate viral RNA + make messenger RNA RNA translated into viral protein New particles bud through cell membrane Sx Bacterial Viral Onset Faster 2-3 days Duration Persistent 7-10 days Temperature High fever + chills Low- grade fever Discharge/Sputum Thicker, purulent Watery clear Nasal More exudate than just redness Sneezing w/ post- nasal d/c & redness mucous membranes Throat More severe px, exudate on tonsil Minimal moderate discomfort Chest Chest px w/ coughing, difficulty breathing Mild, dry cough Overall Local, focal sx More generalised sx Community- Acquired Pneumonia Outpatient setting: Streptococcus pneumoniae (GPC) Haemophilus influenzae (GNR) Mycoplasma pneumoniae Chlamydophilia pneumoniae Respiratory viruses Inpatient setting: Streptococcus pneumoniae (GPC) Staphylococcus aureus (GPC) Legionella spp. (GNR) Klebsiella pneumoniae Haemophilus influenzae Relevant Hx for URTI; Viral Bacterial Damaged epithelium from virus allows secondary bacterial infection Hx asthma + bronchitis are pre- disposing factors
2 Antibiotics) Mechanism" Antibiotic"Group" Pharmacology" Primary"Effect" Inhibition"of"Cell"Wall"Synthesis" βmlactam)antibiotics% Inhibition"of"Protein"Synthesis" Inhibition"of"Nucleic"Acid"Synthesis Penicillins Cephalosporins Vancomycin Aminoglycosides(30S) Tetracyclines(30S) Macrolides(50S) Chloramphenicol(50S) Quinolones Fluoroquinolones Rifampin Norfloxacin Ciprofloxacin Bindtopenicillinbindingproteins (PBP)oncytoplasmicmembrane transpeptidaserequiredforcrossp linkingofpeptidoglycanchains 30S aminoacylptrna 50S ribosomeadvancement 50S peptidyltransferase topii Rifampin"=bacterialDNAP dependentrnapolymerase RNAsynthesis protein synthesis Bactericidal,esp.GPpos Bactericidal Bacteriostatic Bacteriostatic Bacteriostatic Bactericidal Rifampin:M.)tuberculosis%&M.)leprae Inhibition"of"Metabolism"(Folate" Sulphonamides topii Bacteriostatic Synthesis)" Trimethoprim Bacteriostatic Isonazid Bactericidal CellSmembrane"Disruption" PolymixinB Detergentdisruptingphopholipid BactericidalforGPneg membrane cellpermeability =death Consent Antibiotic)Resistance) Elements: Exceptions: Patient must have: 1. Freely & voluntarily Immediate emergency treatment Ability to take in + retain info 2. Informed for a specific Unconscious (emergency) Believe info treatment/procedure Authorised by Court order Otherwise: 3. Person must have legal capacity Authorised by statute Guardianship Act 1987 Guardianship Tribunal Failure to Obtain: Civil Liability Negligence Criminal liability Disciplinary action
3 Bacterial Resistance Intrinsic (natural) resistance Some bacteria are intrinsically resistant to a bacteria without any modification of the genome (eg. The outer membrane of gram negative bacteria creates a permeability barrier against some antibiotics, or in some bacteria there is a lack of specific target that prevents the antibiotic from working) Acquired resistance Development of resistance via several mechanism Vertical evolution Darwinian, driven by natural selection. Caused by: Spontaneous mutations in chromosomes selective environments that select out the mutant strain survival of resistant strain Horizontal evolution Acquisition of resistance genes from another strain or species, often following the development of resistance genes through the process of mutation and selection. Genetic exchange has 3 processes: Conjugation: bacterial cell transfers genetic material to another cell by cell- to- cell contact. Often via a plasmid or via pilli (bacterial sex woo) Transduction: genetic material moved from one cell to another using bacteriophage which takes up the DNA, and moves it into chromosomal material Transformation: genetic alteration of a cell resulting from the direct uptake, incorporation and expression of exogenous genetic material (exogenous DNA) from its surroundings and taken up through the cell membrane Evolution of multi- resistance Plasmid vectors often facilitate multiple gene clusters that contribute to multi resistance in bacteria. This can result in multi- resistance genes on a single plasmid. Examples of Resistant Bacteria Methicillin resistant Staph Aureus (MRSA) Vancomycin resistant enterococcus (VRE) Extended spectrum beta lactamases (ESBL) Bacterial mechanisms for resistance: 1. Modification of the outer membrane permeability (e.g. ciprofloxacin resistance in S. Aureus) 2. Active efflux (pumping antibiotic out of cell) - e.g. fluroquinolone resistance in some bacteria 3. Mutation in the antibiotic target (e.g. binding site) - for example, alteration of PBP the binding target site of penicillins in MRSA and other penicillin- resistant bacteria 4. Increased production of enzymes to break down antibiotics - for example, enzymatic deactivation of penicillin G in some penicillin- resistant bacteria through the production of β- lactamases 5. Alteration of metabolic pathway - for example, some sulfonamide- resistant bacteria that have multiple ways of synthesizing via the folate pathway
4 Disease Frequency & Association Incidence: no. of new cases occurring over a fixed period of time = frequency Incidence rate: No. of persons who develop the disease at a given time period / No. of person- time when people were at risk of developing the disease Prevalence: measure the amount of disease/condition in a population at a given point in time, expressed as a % No of people with a given disease at a given point in time / Total number of people in the population Rate ratio: Measure of disease in the exposed population Measure of disease in the unexposed pop RR > 1 exposure increase likelihood of outcome RR = 1 exposure has no effect on outcome RR < 1 exposure decreases likelihood of outcome Odds ratio: use as an estimate of the risk when the disease/condition is rare. Odds of exposure in cases /Odds of exposure in non- - - cases OR > 1 cases are more likely to have been exposed OR = 1 exposure has no association with outcome OR < 1 cases are less likely to have been exposed Incidence Prevalence Recovery Death Movement Rate differences: differences in incidence rates between groups Rate difference (attribute risk) = Risk (exposed) Risk (unexposed) = differences in incidence rates between groups. RD = 0 exposure has no effect on outcome RD > 0 exposure has an increased incidence RD < 0 exposure has a decreased incidence
5 Upper Respiratory Tract Infections Common Viruses Influenza A/B/C (orthomyxovirus) Respiratory Syncytial Virus (paramyxoviridae) Rhinoviruses (picornaviridae) Coronaviruses (coronaviridae) Adenoviruses Common Bacteria Group A streptococci; Streptococcus pyogenes (GPC, catalase -, beta hemolytic, bacitracin sensitive) Streptococcus pneumoniae (GPC (chains), catalase -, alpha hemolytic, optochin sensitive) Haemophilus influenzae type b, Hib (GNR, fastidious, requires factors X and V (CBA)) Bordetella pertussis (GNR) Community acquired URTI s Most common: Streptococcus pneumoniae (GPC) Common: Haemophilus influenzae, KlePbsaietlhlaoph Sp., Staphylococcus bacteria Atypical: Mycoplasma sp., Legionella sp. & Burkholderia pseudomallei Respiratory Viruses Viruses are catalogued on the: Nature of their nucleic acid (DNA or RNA) Symmetry of their protein shell (capsid) Presence or absence of a lipid membrane (envelope) Dimensions of the virion and capsid Influenza Virus Orthomyxoviridae - ssrna virus Enveloped Contains importance envolope proteins: Haemagluttinin (HA important in host cell adhesion to fascilitate entry into cell) + Neuraminidase (NA involved in active enxocytosis of newly formed virus units)
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