Infectious disease Flashcards
what is TB?
Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects the lungs.
**common exam question involves a patient coughing u sputum that grows acid-fast bacilli that stain red with Zeihl- neelsen staning - this is mycobacterium tuberculosis and the diagnosis of TB
what is the pathophysiology of TB?
Primary tuberculosis
A non-immune host who is exposed to M. tuberculosis may develop primary infection of the lungs. A small lung lesion known as a Ghon focus develops. The Ghon focus is composed of tubercle-laden macrophages. The combination of a Ghon focus and hilar lymph nodes is known as a Ghon complex
In immunocompotent people the intially lesion usually heals by fibrosis. Those who are immunocompromised may develop disseminated disease (miliary tuberculosis).
Latent - infected but no clinical or X ray signs of active TB, non-infectious, may persist for years.
Secondary (post-primary) tuberculosis
If the host becomes immunocompromised the initial infection may become reactivated. Reactivation generally occurs in the apex of the lungs and may spread locally or to more distant sites. Possible causes of immunocomprise include:
immunosuppressive drugs including steroids
HIV
malnutrition
The lungs remain the most common site for secondary tuberculosis. Extra-pulmonary infection may occur in the following areas:
central nervous system (tuberculous meningitis - the most serious complication)
vertebral bodies (Pott’s disease)
cervical lymph nodes (scrofuloderma)
renal
gastrointestinal tract
what are the risk factors for TB?
Known contact with active TB
Immigrants from areas of high TB prevalence
People with relatives or close contacts from countries with a high rate of TB
Immunosuppression due to conditions like HIV or immunosuppressant medications
Homeless people, drug users or alcoholics
what is the BCG vaccine?
The BCG vaccine involves an intradermal infection of live attenuated (weakened) TB. It offers protection against severe and complicated TB but is less effective at protecting against pulmonary TB.
Prior to the vaccine patients are tested with the Mantoux test and given the vaccine only if this test is negative. They are also assessed for the possibility of immunosuppression and HIV due to the risks related to a live vaccine.
who is the BCG vaccine offered to?
BCG vaccine is offered to patients that are at higher risk of contact with TB:
Neonates born in areas of the UK with high rates of TB
Neonates with relatives from countries with a high rate of TB
Neonates with a family history of TB
Unvaccinated older children and young adults (< 35) who have close contact with TB
Unvaccinated children or young adults that recently arrived from a country with a high rate of TB
Healthcare workers
what are the clinical features of pulmonary TB?
cough with or without haemoptysis lethargy fever or night sweats weight loss lymphadenopathy erythema nodosum
what are the symptoms of TB meningitis?
headache, drowsiness fever vomiting meningism worsening over 1-3 weeks CNS signs - papilloedema, CN palsies
how would TB present if spread to the lymph nodes?
cervical lymphadentis - scrofula
painless neck mass -no signs of infection (cold)
how would GU TB present?
frequency, dysuria, loin/back pain, haematuria sterile pyuria (puss in urine)
how would bone TB present?
vertebral collapse and potts vertebra
spinal pain
how would skin TB present?
lupus vulgaris (jelly-like nodules)
how would peritoneal TB present?
abdo pain
GI upset
ascites
how would adrenal TB present?
addisons disease
what are the investigations for TB?
- require specialst stains like the Ziehl-Neelsen stain
- there are two tests for an immune resonse to TB caused by previous, latent or active TB - the mantoux test an interferon-gamma release assay
- in patients where active disease is suspected a chest x-ray and cultures are used to suport the diagnosis
what is the mantoux test?
The Mantoux test is used to look for a previous immune response to TB. This indicates possible previous vaccination, latent or active TB.
This involves injecting tuberculin into the intradermal space on the forearm. Tuberculin is a collection of tuberculosis proteins that have been isolated from the bacteria. The infection does not contain any live bacteria.
Injecting the tuberculin creates a bleb under the skin. After 72 hours the test is “read”. This involves measuring the induration of the skin at the site of the injection. NICE suggest considering an induration of 5mm or more a positive result. After a positive result they should be assessed for active disease.
what is the interferon-gamma release assays?
This test involves taking a sample of blood and mixing it with antigens from the TB bacteria. In a person that has had previous contact with TB the white blood cells have become sensitised to those antigens and they will release interferon-gamma as part of an immune response. If interferon-gamma is released from the white blood cells then this is considered a positive result.
The IGRA test is used in patients that do not have features of active TB but do have a positive Mantoux test to confirm a diagnosis of latent TB.
what would xrays show at different stages of TB?
Primary TB may show patchy consolidation, pleural effusions and hilar lymphadenopathy
Reactivated TB may show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
Disseminated Miliary TB give a picture of “millet seeds” uniformly distributed throughout the lung fields
TIP: Disseminated miliary TB gives quite a characteristic appearance on a chest xray. This makes it a popular spot diagnosis in exams so it is worth looking at some pictures and remembering this.
should cultures be done for TB?
Performing a bacterial culture and collecting a sample of the bacteria is very useful prior to starting treatment. This allows testing the bacteria for resistance to antibiotics. Unfortunately cultures can take several months to grown an organism. Treatment is usually started whilst waiting for the culture results.
There are several ways to collect cultures:
Sputum. 3 samples should be collected and tested. If they are not producing sputum then hypertonic saline can be used to induce sputum that can be collected. They might require bronchoscopy with lavage to collect sputum samples.
Mycobacterium blood cultures. These require special blood culture bottle.
Lymph node aspiration or biopsy
how is active TB managed?
initial phase - first 2 months (RIPE)
- rifampicin
- isoniazid
- pyrazinamide
- ethambutol
Continuation phase - next 4 months
Rifampicin
Isoniazid
how do you manage TB meningitis?
Patients with meningeal tuberculosis are treated for a prolonged period (at least 12 months) with the addition of steroids (dexamethasone)
how do you manage latent TB?
The treatment for latent tuberculosis is 3 months of isoniazid (with pyridoxine) and rifampicin OR 6 months of isoniazid (with pyridoxine)
Base the choice of regimen on the person’s clinical circumstances. Offer:
3 months of isoniazid (with pyridoxine) and rifampicin to people younger than 35 years if hepatotoxicity is a concern after an assessment of both liver function (including transaminase levels) and risk factors
6 months of isoniazid (with pyridoxine) if interactions with rifamycins are a concern, for example, in people with HIV or who have had a transplant.
who may require directly obsrived therapy when on TB treatmet?
Directly observed therapy with a three times a week dosing regimen may be
indicated in certain groups, including:
homeless people with active tuberculosis
patients who are likely to have poor concordance
all prisoners with active or latent tuberculosis
what are the side effects of TB treatments?
Rifampicin can cause red/orange discolouration of secretions like urine and tears. It is a potent inducer of cytochrome P450 enzymes therefore reduces the effect of drugs metabolised by this system. This is important for medications such as the contraceptive pill.
Isoniazid can cause peripheral neuropathy. Pyridoxine (vitamin B6) is usually co-prescribed prophylactically to reduce the risk of peripheral neuropathy.
Pyrazinamide can cause hyperuricaemia (high uric acid levels) resulting in gout.
Ethambutol can cause colour blindness and reduced visual acuity.
Rifampicin, isoniazid and pyrazinamide are all associated with hepatotoxicity
TIP: A common exam question starts with “a patient has recently started treatment for tuberculosis. They noticed … Which medication is most likely to be implicated?” It is worth remembering the common side effects to help you answer these questions. They start feeling numbness or unusual sensations in their fingertips or feet: isoniazide (“I’m-so-numb-azid”). They noticed difficulty recognising colours: ethambutol (“eye-thambutol”). They noticed their urine or tears are orange or red: rifampicin (“red-an-orange-pissin’”).
how do you perform a gram stain?
A gram stain is used as a quick way to check a sample under the microscope to look for bacteria. It involves two main steps:
Add a crystal violet stain which binds to molecules in the thick peptidoglycan cell wall in gram positive bacteria turning them violet.
Then add a counterstain (such as safranin) which binds to the cell membrane in bacteria that don’t have a cell wall (gram negative bacteria) turning them red/pink.
whar are gram positive cocci?
stahylococcus
streptococcus
enterococcus
what are gram positive rods?
Use the mnemonic “corney Mike’s list of basic cars”:
Corney – Corneybacteria Mike’s – Mycobacteria List of – Listeria Basic – Bacillus Cars – Nocardia
what are gram positive anaerobes?
Use the mnemonic “CLAP”:
C – Clostridium
L – Lactobacillus
A – Actinomyces
P – Propionibacterium
what are gram negative bacteria?
Neisseria meningitis Neisseria gonorrhoea Haemophilia influenza E. coli Klebsiella Pseudomonas aeruginosa Moraxella catarrhalis
what are atypical bacteria ?
The definition of atypical bacteria is that they cannot be cultured in the normal way or detected using a gram stain. Atypical bacteria are most often implicated in pneumonia.
The atypical bacteria that cause atypical pneumonia can be remembered using the mnemonic “legions of psittaci MCQs”:
Legions – Legionella pneumophila Psittaci – Chlamydia psittaci M – Mycoplasma pneumoniae C – Chlamydydophila pneumoniae Qs – Q fever (coxiella burneti)
what is MRSA?
MRSA refers to staphylococcus aureus bacteria that have become resistant to beta-lactam antibiotics such as penicillins, cephalosporins and carbapenems
whar are ESBLs?
ESBLs are bacteria that have developed resistance to beta-lactam antibiotics. They produce beta lactamase enzymes that destroy the beta-lactam ring on the antibiotic. They can be resistant to a very broad range of antibiotics.
ESBLs tend to be e. coli or klebsiella and typically cause urinary tract infections but can also cause other infections such as pneumonia.
They are usually sensitive to carbapenems such as meropenem or imipenem.
what antibiotics inhibit cell wall synthesis?
Antibiotics with a beta-lactam ring
Penicillin
Carbapenems such as meropenem
Cephalosporins
Antibiotics without a beta-lactam ring
Vancomycin
Teicoplanin
what antibiotics inhibit folic acid metabolism?
Bacteria produce their own folic acid in a series of steps. This chain starts with para-aminobenzoic acid (PABA), which is directly absorbed in to the cell across the cell membrane. PABA is then converted to dihydrofolic acid (DHFA), then tetrahydrofolic acid (THFA) and finally folic acid.
Antibiotics can be used to disrupt steps along this chain:
Sulfamethoxazole blocks the conversion of PABA to DHFA
Trimethoprim blocks the conversion of DHFA to THFA
Co-trimoxazole is a combination of sulfamethoxazole and trimethoprim
what kind of bacteria does metronidazole work on?
The reduction of metronidazole into its active form only occurs in anaerobic cells. When partially reduced metronidazole inhibits nucleic acid synthesis. This is why metronidazole is effective against anaerobes and not aerobes.
what antibiotics inhibit protein synthesis by targeting the ribosome?
Macrolides such as erythromycin, clarithromycin and azithromycin Clindamycin Tetracyclines such as doxycycline Gentamicin Chloramphenicol
what is sepsis and septic shock?
sepsis is a condition where the body launches a large immune response to an infection that causes systemic inflammation and affects the functioning organs of the body
sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection
septic shock: a more severe form sepsis, technically defined as ‘in which circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone
what is the pathophysiology of sepsis?
The bacteria or other pathogens are recognised by macrophages, lymphocytes and mast cells. These cells release vast amounts of cytokines like interleukins and tumor necrosis factor to alert the immune system of an invader. These cytokines activate other parts of the immune system. This immune activation leads to further release of chemicals such as nitrous oxide that causes vasodilation. This full immune response causes inflammation throughout the body.
Many of these cytokines cause the endothelial lining of blood vessels to become more permeable. This causes fluid to leak out of the blood and in to the extracellular space leading to oedema and a reduction in intravascular volume. The oedema around blood vessels creates a space between the blood and the tissues reducing the amount of oxygen that reaches the tissues.
Activation of the coagulation system leads to deposition of fibrin throughout the circulation further compromising organ and tissue perfusion. It also leads to consumption of platelets and clotting factors as they are being used up to form the clots within the circulatory system. This leads to thrombocytopenia, haemorrhages and an inability to form clots and stop bleeding. This is called disseminated intravascular coagulopathy (DIC).
Blood lactate rises due to hypoperfusion of tissues that starves the tissues of oxygen causing them to switch to anaerobic respiration. A waste product of anaerobic respiration is lactate.
what are the risk factors for sepsis?
Any condition that impacts the immune system or makes the patient more frail or prone to infection is a risk factor for developing sepsis:
- Very young or old patients (under 1 or over 75 years)
- Chronic conditions such as COPD and diabetes
- Chemotherapy, immunosuppressants or steroids
- Surgery or recent trauma or burns
- Pregnancy or peripartum
- Indwelling medical devices such as catheters or central lines
what score is used to pick up the signs of sepsis?
The National Early Warning Score (NEWS) is used in the UK to pick up the signs of sepsis. This involves checking physical observations and their consciousness level:
Temperature Heart rate Respiratory rate Oxygen saturations Blood pressure Consciousness level
