Acute respiratory infection Flashcards
Learning outcomes
- Describe the fundamental differences between bacterial and viral infection
- Describe the presentation, diagnosis, management and prevention of viral upper respiratory tract infections including influenza
- Understand why self-limiting bacterial or viral infections are unlikely to benefit from antimicrobials
- Identify and suggest suitable treatment for upper respiratory tract infection and otitis media
- Describe key features of pneumonia, typical and atypical forms, and the best narrow spectrum antibiotics to prescribe and length of antibiotic course
Bacterial infection
Interactions with most bacteria is commensal or mutualistic, however they can cause illnesses through infection(e.g chronic disease processes/ cancers)
Infection is invasion of host cells, then multiplication causing tissue damage- immune/inflamm. response to bacteria/toxins
Viral infection
Obligate intracellular pathogens- must live inside a host cell to replicate
- Through specific receptors on host cells and specific tissue tropism
•Direct damage by viral infection, and damage due to immune response
•Like bacteria, a variety of outcomes after viral infection:
Cell lysis-the cells are killed after the virus has replicated itself-e.ginfluenza;
Persistence-the cell stays alive and the virus goes on replicating at low levels-e.ghepatitis B;
Latency-the virus remains quiet, not replicating but remains in the host cell cytoplasm-e.g. Herpes viruses;
Incorporation into the host genome-the genetic material of the virus is incorporated into the host cell genome, so all future daughter cells are infected-e.g. retroviruses such as Human Immunodeficiency Virus (HIV).Malignant transformation-viruses that are oncogenic-cancer causing, examples include Human Papilloma virus associated with cervical cancer and Epstein-Barr virus associated with nasopharyngeal cancer. Certain viruses can remain latent in various cells life long, and then cause secondary infections when re-activated, possibly in response to stress or immunocompromise.
Comparing bacteria and viruses
Bacteria: Cells Adherence to host tissues: pili/ fimbriae Invasiveness hyaluronase;streptokinase Evasionof host defences phagocytosis; antigenic variation or disguise Toxins endotoxins,exotoxins
Viruses: Obligate intracellular parasites Receptors at site of entry to the body Respiratory Gastrointestinal Genitourinary Dissemination Local-apical surfaces Distant-basement membranes-viraemia Multiplication in target organs Shedding
Respiratory tract infections
- Sinusitis•Otitis media•Pharyngitis•Epiglotitis(URTI)
- Laryngitis
- Tracheitis•Bronchiolitis•Pneumonia (LRTI)
- Cytokines/ leukins/ interleukins- may give primary symptoms around body, e.g tiredness general pain, nausea, myopathy
- Specific to inflamed area
Rubor, Calor, Tumor, Dolor and Functiolaesa-Redness, Heat, Swelling, Pain (or hardness), Loss of function. If you image the respiratory epithelium getting red, hot, swollen, painful and losing its normal functions then you can predict the symptoms a patient will have and the examination signs you will witness. The paranasal sinuses and middle ear are essentially boneyboxes lined by respiratory epithelium. ‘Tumor’: swelling of the epithelium in these settings can quickly lead to intense pain.One of the standard responses to infection (and indeed other forms of inflammation) in the respiratory tract is increased mucous production. This can present as rhinorrhoea (runny nose) or pain localising to the sinuses due to accumulation of 7
mucous that cannot drain quickly enough. This excess mucous often represents a soup of excess secretions, cell debris, inflammatory fluid including white blood cells and infectious agents. Influenza, typically leads to both systemic and tissue specific symptoms, but its systemic symptoms often pre-dominate
Describe the diagnosis of viral RTI
Sample the site of the infection
•or where you expect the organisms to be
•Once in the lab
•We can visualise the organism (microscope)
•We can find an antibody response to the organism* or nucleic acid amplification tests
•We can detect a little bit of the organism*
•We can grow the organism
•This is Culture, and if we can culture an organism, we do
Describe management of viral RTI
Symptomatic relief
•?reduce fever
•Reduce/ move excess mucous
- Specific agents for influenza
- Osteltamivir(Per Oral-PO)
- Zanamivir (nebulised)
•Covid19 •Dexamethasone •Remdesivir •Tocilizumab Management is mainly sypmtom relief- self limiting infections, use pyretics (e.g paracetamol) to reduce fever
Describe the prevention of viral upper respiratory tract infections including influenza
- Infection prevention
- Wash your hands
- Bin your tissues
- ‘respiratory etiquette’
- Wear a mask, avoid crowds
- Passive immunisation
- Palivizumab for Respiratory syncytial virus
- Vaccination
- Seasonal influenza vaccine
Understand why self-limiting bacterial or viral infections are unlikely to benefit from antimicrobials
•Self limiting infections- Innate immune system acts fast against invaders
Barriers
Mucosal antibody (IgA)
Clearance mechanisms such as muco-ciliary escalator
Phagocytes such as macrophages and neutrophils
Fever
•Benefit and risk balance
Antibiotics are good drugs, but overuse limits their usefulness (antibiotic resistance)
Antibiotic benefit is for the individual but risk of resistance is to the population
Increasingly aware of risks to individual taking antibiotics also
C. diff in elderly
Microbiome dysfunction in young
Overgrowth with fungi-candidiasis
Longer and higher doses of antibiotics are more toxic
•Antimicrobials
Antimicrobials
Antibacterial tree in slide 14
Cell wall deficiency in bacteria
1.They don’t stain well with the Gram stain-because the Gram stain is taken up by the peptidoglycan cell wall;2.When we want to give antibiotics to kill cell wall deficient bacteria we have to give agents that DO NOT act on the bacterial cell wall-so one of the classes of drugs on the right hand stem of the antibacterial tree.To cover the bacteria that cause typical pneumonia we prefer a beta-lactam.
Beta lactam drugs and the peptidoglycan cell wall
Beta lactams are the commonest prescribed antibiotics
Penicillin-type agents are the commonest beta-lactams Eukaryotes have no cell wall-so a good antibiotic target
Cell wall made of Peptidoglycan
Beta-lactams inhibit cross linking of Peptidoglycan chains
- Monomers of n-acetyl muramic acid (NAMA) and n-acetyl glucosamine (NAG) form a complex polymer called Peptidoglycan
- These monomers are formed into chains
- The chains are ‘cross-linked’ by the action of the transpeptidase enzyme. This enzyme catalyses binding between amino acids on NAMA monomers on adjacent chains. The effect is a net structure. These nets stack on top of one another to form a multi-layered cell wall.
- The transpeptidase enzyme is also known as the penicillin binding protein: This enzyme is inhibited by allbeta lactam drugs
- The penicillin structure has the 4-membered beta-lactam ring at its centre. All beta-lactam antibiotics have this ring at their core.
- Beta-lactam drugs therefore stop bacterial cells from making cell walls
Identify and suggest suitable treatment for upper respiratory tract infection and otitis media: Which bacteria may be involved?
- Streptococcus pneumoniae
- Commonest cause of bacterial pneumonia
- Haemophilus influenzae
- Along with Strep Pneumo cause a wide variety of respiratory tract infections
- Streptococcus pyogenes
- ‘Strep throat’: pharyngitis/ tonsillitis
- Other similar streptococci (known as the beta-haemolytic streptococci) can cause similar infections
Key features of typical pneumonia
Pleuritic/sharp Chest pain, productive cough and sputum
•‘pleuritic’ chest pain
•Purulent ?Blood stained sputum
•Protein and cell rich exudate in the small airways
•‘consolidation’ seen radiologically
•Strep. Pneumoniae*, Haemophilus influenzae
•Others-staphylococcus aureus, klebsiella pneumoniae et cetra
Key features of atypical pneumonia
- Atypical bacterial pathogens
- Legionella pneumophila
- Chlamydophila pneumoniae
- Mycoplasma pneumoniae
- Coxiella burnetii
- Atypical clinical syndromes
- Systemic diseases
- Specific epidemiological features
- Atypical x-ray findings
- Atypical Cell wall deficient bacteria need different classes of antibiotics
Key features of atypical pneumonia
Systematic infection with lung component
•Atypical bacterial pathogens- no meaningful peptidoglycan cell wall, not antibiotics that act on cw
•Legionella pneumophila
•Chlamydophila pneumoniae
•Mycoplasma pneumoniae
•Coxiella burnetii
•Atypical clinical syndromes
•Systemic diseases
•Specific epidemiological features
•Atypical x-ray findings
•Atypical Cell wall deficient bacteria need different classes of antibiotics
