W3 UTRI Flashcards
What is the main difference between the upper and lower respiratory tract?
The lower respiratory tract is sterile
Label the respiratory tract
Name some common bacteria associated with the URT (>50% of normal people)
- Viridans streptococci
- Anaerobic microorganisms (eg.Bacteroides sp)
- Haemophilus influenzae
- Candida albicans (mouth)
Name some occosional residents of the URT (<10% of normal people)
- Streptococcus pyogenes (Group A Streptococcus)
- Streptococcus pneumoniae
Organisms associated with colonisation of URT following antibiotic treatment (<1%)
- Coliforms (E.coli)
- Pseudomonas sp.
- Candida albicans (oral thrush)
What are professional invaders?
They successfully infect the healthy respiratory tract; possess mechanisms to attach and spread (They are true Pathogens)
What are the characteristics of true patholgens?
(a) Adhesion to normal mucosa (in spite of mucocilliary system) eg. surface proteins, capsid proteins
(b) Avoid host defence (eg. capsule)
(c) Damage local tissue: production of invasins and exotoxins eg. pneumolysin- potent exotoxin)
Give some examples of Professional / Secondary Invaders of the URT
- Rhinovirus- causes common cold
- Streptococcus pneumoniae
- Streptococcus pyogens
What are secondary invaders?
Give examples
They cause disease when host defences are impaired. This includes:
- Normal Flora eg. C. albicans
- Primary Invaders eg. S. pneumoniae
Symptoms worsen instead of getting better when you have a secondary infection
Risk factors for secondary invaders of URT: Post viral infection
Give an example
Rhinovirus
What can compromise the immune response?
AIDS, cancer chemotherapy, young / elderly, alcoholics
Risk factors for secondary invaders of URT: Foreign body
Give examples
Endotracheal tube (mechanical ventilation)
Give examples of some Secondary invaders of the URT
Give examples of upper respiratory tract infections
- Common cold
- Oral candidiasis
- Sinusitis
- Pharyngitis / tonsillitis
- Acute epiglottitis-
The epiglottis is a flap of tissue that sits beneath the tongue at the back of the throat.•Otitis (media, externa). _(I_nflammation and swelling of the epiglottis. It’s often caused by an infection, but can also sometimes happen as a result of a throat injury.)
- Otitis media- inflammation or infection located in the middle ear. Otitis media can occur as a result of a cold, sore throat, or respiratory infection.)
- Otitis externa inflammation of the external ear canal, which is the tube between the outer ear and eardrum. Otitis externa is often referred to as “swimmer’s ear” because repeated exposure to water can make the ear canal more vulnerable to inflammation
Describe the clinical manifestations of the Common Cold (coryza)
(i) Incubation period: 2-4 days
(ii) Nasal discharge; sneezing and sore throat; sometimes temperature and headache
(iii) May descend to cause infection of the larynx (laryngitis) and the trachea (tracheitis): pain on breathing in and out and hoarseness
(iv) Seasonal: Common during the winter and amongst all age groups but especially so amongst children aged 2-7. Symptoms disappear within a week
What are the causative organisms of the common cold?
•CAUSATIVE ORGANISMS: Viruses:
eg. Rhinovirus (>100 antigenic types, can keep getting the common cold), RSV (respiratory sycytial virus), Coronavirus (not COVID)
What are the treatmens for the common cold?
Can antibiotics be used?
- Supportive eg. paracetamol.
- Antibiotics are NOT indicated for common colds
What is Oral Candidiasis?
Thrush
Describe the clinical manifestations of Oral Candidiasis?
Changes in flora can upset the balance allowing for overgrowth of fungi. Raw inflamed mucous membranes, white fungal plaques
What are the predisposing factors to oral candidasis?
Broad spectrum antibiotics (eliminates batcerial flora); contraceptive pill; systemic steroids; chemotherapy; immunosuppression eg. HIV, extremes of age
What is the casusative microorganism of oral candidiasis?
Candida albicans
State some treatment options of oral candidasis?
- Nystatin (acts on fungal membranes) or clotrimazole pastilles 1 pastille 4 times daily (up to 7 days)
- Severe oral thrush in HIV patients may need treatment with a systemic (intravenal) antifungal drug eg. fluconazole (acts on yeast cell membrane) 100mg (14-30 days)
State the clinical maifestions of sinuitis
Facial pain localised tenderness and swelling
What is the causative organisms of sinusitis?
•Usually viral (usually adenovirus but sometimes influenza) but bacterial infection may occur due to secondary invaders Streptococcus pneumoniae and Haemophilus influenzae
Bacterial sinusitis can spread to brain
What are treatments for sinusitis?
Culture of sinus washout should support the clinical diagnosis
No treatment is indicated for viral infection
- Amoxicillin 125-250mg tds, 3-7 days
- Augmentin (amoxicillin+clavulanic acid which protects the beta lactam ring) for beta lactamase producing bacteria 250mg tds, 3-7 days
- Doxycycline (tetracycline) used if resistant to beta lactams 100mg daily, 3-7 days
- Erythromycin (macrolide) inhibits protein synthesis 250-500mg qds, 3-7 days
What are the clinical manifestations of Pharyngitis / tonsilliti?
•Common in children, fever, sore throat, cervical lymphadenopathy; purulent discharge
What are the casuative microorganisms of Pharyngitis / tonsillitis?
Viruses –main cause (70%) eg. adenovirus
If Bacterial: Most commonly group A strep such as Streptococcus pyogenes (common); Neisseria gonorrhoeae (rare)
What are some treatments of Pharyngitis / tonsillitis?
- Viral: No treatment
- Penicillin V: 500mg qds/10 days
- Cephalexin: 500mg qds/10 days
- Erythromycin: 500mg qds/10days
•Accurate diagnosis and adequate treatment is essential as post-streptococcal complications include:
- Peritonsillar abscess (PTA, quinsy)
- Rheumatic fever (autoimmune) Strep M proteins share structural similarities with parts of our human tissue (tropomyocin, myosin, laminin). We produce antibodies to step group A m proteins which can act on our heart and kideneys which causes rhematic fever.
Scarlett fever: result of erythrogenic, pyrogenic and superantigenic toxins
- Glomerulonephritis (autoimmune)
- Scarlet fever (toxin-associated)
Number of reported cases of scarlet fevel UK vs yearly antibiotic prescriptions per head
Cannot differentiate between viral and bacterial infection. GP’s think its viral so dont prescribe antibiotics so more people are getting ill with scarlett fever
Streptococcus pyogenes (Group A strep) Descibe the mechanisms of streptococcal pathogenicity
- Ability to colonise the host and invade tissues
- Ability to bypass host defences
- Ability to damage host through production of toxins
Which proteins promote adhesion in Streptococcus pyogenes ?
F-protein and M-protein
What does surface expressed F-protein recognise?
Host cell fibronectin eg. in pharynx
Where is M-protin found?
What is the issue with M proteins?
M-protein in anchored in the cytoplasmic membrane and protrudes as fimbriae / pili (aids attachment to the host). Expressed along with LTA
What is the function of M-protein?
Mediates adherence to epithelial cells / exocellular matrix
What are the properties of M-protein
- Highly antigenic
- >80 distinct immunological types (re-infection common)
Why do we get lots of strep infections?
Highly varialble M proteins
How does Streptococcus pyogenes evade host defences:
- Hyaluronic acid capsule:
- Immunoglobulin binding proteins
- C5a peptidase
What is the fuction of the hyaluronc acid capsule?
• Identical to human substance avoiding immune detection; binds to cellular hyaluron receptor CD44 mediating adherence and invasion
What is the function of Immunoglobulin binding proteins?
Binds to Fc region of IgG and IgA preventing opsonisation
What is the function of C5a peptidase?
Surface protein that inactivates C5a (a potent chemotactic peptide) thus limiting the recruitment of PMNs to the site of infection
Name some virulence factors secreted by Streptococcus pyogenes
- Streptolysin O
- DNAase
- Streptokinase
- Hyaluronidase
State the properties of streptolysin O
Protein; MW 60,000; haemolytic toxin; cardiotoxic; antigenic
State the function of DNAase
Hydrolyses nucleic acids, possible spreading factor (A,B,C,D)
State the function of streptokinase
Antigenic protein that combines 1:1 with plasminogen to make functional plasmin, a protease which can hydrolyze fibrin and other host proteins
State the functions of hyaluronidase
Dissolves cellular hyaluronic acid and promotes movement of bacteria through tissue
Name the Streptococcal pyrogenic exotoxins (SPEs)
What are superantigens?
A, B, C, F ‘erythrogenic toxins’; superantigens (promote an excessive cytokine response- bind non-specifically to MHC class II and/or to T cell receptors (TCRs) of both CD4+ and CD8+ T cells- they bypass the antigen specificity of the TCRs receptor); responsible for rash of scarlet fever
Diagnostic Clinical Microbiology: Case Study:
- 17 year old female presents to her GP with inflamed tonsils.
- On inspection, the GP observes intense erythema and pockets of yellow, creamy pus
- History: no predisposing /underlying illness; no sexual partner/ no travel abroad
What is the most likely bacterial infection?
What are the reasons for laboratory confirmation of infection?
Most likely bacterial pathogen: Streptococcus pyogenes (Group A Strep, GAS)
Reasons for laboratory confirmation of infection
- Prevent use of antibiotics if viral
- Ensure correct treatment if bacterial
- Avoid post streptococcal complications
Case study: Specimen collection and transport
- Remember the diagnostic template!
- Correctly labelled sample and request form
- Throat swab: good quality sample essential to avoid too much ‘mouth flora’ contamination
- Transport media (eg. Stuart’s semi-solid agar; contains charcoal to inactivate bacterial toxic bi-products)
- Transport <24h; refrigerate if needed
Describe the laboratory investigations (Non-culture techniques) for suspected streptococcal tonsillitis
Microscopy
- (provides little evidence; some indication of inflammation)
- H&S: S.pyogenes is a category 2 pathogen
Describe the laboratory investigations (culture techniques) for suspected streptococcal tonsillitis
(a) Blood agar (enriched) (CO2/24h/37oC)
(b) Neomycin selective agar (selective) witH added bacitracin disc (ANO2/24h/37oC)
Bacitracin acts on bacterial cell wall, strep group A are sensitive to bacitracin
Describe the basic identification of Streptococcus pyogenes
- Colonial appearance: 1-2mm grey colonies, entire edge, surrounded by a large zone of beta-haemolysis
- Bacitracin sensitive: large zone of inhibition provides presumptive identification of S. pyogenes (GAS)
Describe the full identification of Streptococcus pyogenes
•Lancefield Grouping: detection of group specific carbohydrate (CHO) cell wall antigen
Strep group A,B,D,E etc
Lancefield Grouping (Group A positive reaction)
How is it carried out?
What is group A carbohydrates made of?
Designed by microbiologist Rebecca Lancefieild
- Take a beta haemolyic colonies and mix it in nitrous acid
- That extracts the group carbohydrate into solution
- Take a sample of that solution and mix it with latex beats with antibodies against all the strep group carbohydrates
- Agglutination indicates which group carbohydrate is present
Extra info- Group A CHO antigen is repeating units of N-acetylglucosamine -rhamnose that surrounds the cell wall of sprep pyogenes
Name some common antibiotics for treating
upper respiratory tract infections
(URTI)
- Beta –lactams
- Tetracyclines
- Macrolides
Give examples of Beta-lactams
penicillin, amoxicillin, cephalosporins, augmentin
Act on penicillin binding proteins in the cell wall
Name the mechanism of action of Beta lactams
Beta lactams bind to membrane bound PBP resulting in cell lysis; bactericidal
What are the side effects of beta lactams?
(i) Hypersensitivity 1-10% individuals
(ii) Anaphylactic shock <0.05%
(iii) D&V
- Can reduce the effectiveness of the oral contaceptive pill
- Must complete the course of antibiotics!
Name some antibiotics in the class of tetracylines
tetracycline, doxycycline, oxytetracycline, minocycline
What is the mechanism of action of tetracyclines?
•Bacteriostatic; inhibits protein synthesis -prevents aminoacyl tRNA from binding to the 30S subunit of the ribosome
What are the side effects of tetracyclines?
(i) Deposits in growing teeth and bone (staining)- not recommended for children <12 years and pregnant women
(ii) D&V
Name sime interactions/patient advice associated with tetracyclines
(iii) Reduced oral contraceptive effect
(iv) Finish course of antibiotics
Name some macrolides
Erythromycin, azithromycin, clarythromycin, telithromycin
Describe the MOA of macrolides
- Bacteriostatic /cidal inhibits protein synthesis- binds to rRNA in the 50S subunit and blocks translocation preventing the release of tRNA
- Often used as an alternative to penicillin
What are the side effets of macrolides?
Nausea, D&V
What are the interactions/patient advice associated with macrolides?
(i) Reduced oral contraceptive effectiveness
(ii) Finish the course of antibiotics
What are the kry points of URTI’s
- The URT has a normal flora which may change (eg. immunosuppression, antibiotics)
- Professional invaders infect the healthy respiratory tract (common cold, Streptococcus pyogenes); secondary invaders cause disease when host defences are impaired (Staph.aureus, Haemphilus influenzae)
- Many URTI are viral: confirm microbiologically
- Confirmed bacterial URTI require prompt and effective treatment to avoid potentially serious complications.
- Streptococcus pyogenes may cause a severe URTI (tonsillitis) potentially associated with severe complications if inadequately treated.
