Case 12: Fever Flashcards
1
Q
Sensitivity testing
A
What antibiotic at what concentration prevents growth? Is it over the threshold value? E tests will show the MIC (minimum value of antibiotic which works)
2
Q
What do common organisms appear like on gram stain
A
- Gram positive cocci in clusters: Staph aureus (MSSA and MRSA)
- Gram positive cocci in pairs: Streptococcus pneumoniae
- Gram positive cocci in chains: Enterococci, Other streptococci (eg. Group A Strep)
- Gram positive rods: Clostridium perfringens, Listeria
- Gram negative cocci: Neisseria gonorrhoea, Neisseria meningitidis
- Gram negative rods: Pseudomonas aeruginosa, E.Coli, Klebsiella pneumoniae, Salmonella sp, Enterobacter sp.
3
Q
Culturing bacteria: Agar can have
A
- Additional growth factors to encourage fussy bacteria: eg. Chocolate agar contains lysed blood which releases NAD (factor V) and haemin (factor X) which Haemophilus influenza requires to grow
- Antibiotics to inhibit bacteria we are not interested in: eg. NYC agar for N.gonorrhoea contains both vancomycin and colistin to inhibit most gram positives and gram negatives but gonorrhoea is resistant to both of these and so can grow.
- Colour indicators to help identify bacteria: eg. CLED agar differentiates lactose-fermenting bacteria (eg. E.Coli) from non-lactose fermenting bacteria (eg. Proteus)
4
Q
Different causes of traveller related infections
A
- Short Incubation period <10 days: Influenza, Dengue, Yellow fever, Plague
- Indeterminate (10-21 days): Malaria, viral haemorrhagic fever, Typhoid fever, scrub typhus, African trypanosomiasis
- Long (>21 days): Malaria, Hepatitis ABCDE, Rabies, Schistosomiasis, Leishmaniasis, Amoebic liver abscess, Tuberculosis
- Most common: Dengue, Malaria, Mononucleosis, Enteric fever, Rickettsial
5
Q
Travel history
A
- Itinerary: Dates, times, routes, modes of transport
- Accommodation
- Activities: exposure to standing water
- Food
- Water: bottled, sterilised
- Sexual activity
- Vaccinations/prophylaxis: insect nets
- When was the last time you were outside the UK? and before that etc
6
Q
Investigations for fever in returning traveller
A
- Bloods: FBC, U&E, LFT, Coag, ABG, Blood culture.
- Throat/sputum/stool/Urine CSF as appropriate
- Malaria films
- Serology – e.g. Rickettsiae, Dengue, HIV, Viral hepatitis, Syphillis
- PCR – e.g. Dengue (blood), Herpes + enteroviruses for encephalitis (CSF), TB
- Special stains – ZN/auramine (TB), Grockott (fungi)
- Special cultures – mycobacterial, fungal
7
Q
Fever and rash in returning travelling
A
- Viral: Dengue, HIV seroconversion
- Bacterial: Meningococcal
- Rickettsial: Spotted fever
- Protozoal: Malaria
8
Q
Enteric fever
A
- Faecal oral: water and food. Conditions causing low gastric acidity allow for a lower dose to cause infection. Why PPI and H2 antagonists increase infection risk
- Enteric fever i.e. Typhoid and Paratyphoid
- Occurs more in Immunocompromised i.e. HIV
- Incidence is highest in India/South East Asia and other tropical areas
- Most common in children
- Is associated with dirty water and food
9
Q
Pathophysiology of enteric fever
A
- Salmonellae belong to the Enterobacteriacae family: gram negative enteric organisms
- Causative agent of typhoid: Salmenella Typhi
- Two subtypes are S.typhi and S.paratyphi (A,B,C)
- S.paratyphi (A,B): tend to spread in food where the organism has already multiplied- more predominant N+V
- S.paratyphi C: causes septicaemia without gut involvement
- PPI and H2 agonists increase risk of contacting enteric fever as lowers gastric acidity
10
Q
Structure of S.typhi
A
- Flagellar (H antigen): helps it move
- Somatic (O antigen)
- Capsule (V1 antigen): covers the O antigen and protects it from antibodies
11
Q
Pathophysiology of typhoid fever
A
- The organism attach and penetrate the mucosa of the small intestine.
- Transported by lymphatics to the mesenteric lymph glands.
- Then enter the blood stream via the Thoracic duct.
- And travel to the bone marrow, spleen, liver and gallbladder.
- The bacteria is then re-released into the blood stream causing secondary infection of the bowel. Macrophages accumulate causing necrosis and ulcers. After a week there can be perforation and bleeding
12
Q
Typhoid fever: where do nodules form
A
- Secondary bacteraemia causes symptom onset
- Typhoid nodules can form from Macrophage collections in the liver, spleen, bone marrow and lymph glands
- Later abscess formation in the bone, brain, liver and spleen
- Death is be perforation, haemodynamic shock (from bleeding) or Meningitis
13
Q
Typhoid fever signs and symptoms
A
- Incubation period:14 days
- Rash made of small pink spots on the trunk of the body
- Loss of appetite
- Constipation (more common) or diarrhoea
- Exhaustion
- Confusion
- Fever: gradual increases day by day, peaks in the evening , no rigors (39-40)
- Head and muscle aches
- Stomach pain
14
Q
Clinical features of typhoid fever by timeline
A
- 1st week: increasing fever, abdo pain, malaise, headache, constipation, bradycardia
- End of 1st week: rose spots appear on the upper abdomen, cough, splenomegaly, bronchitis, meningism abdo distension with tenderness, diarrhoea
- 2nd week: symptoms progress
- End of 2nd week: delirium, complications, gravely dehydrated, then coma and death (if untreated)
15
Q
Signs of Typhoid fever
A
- Rose spots: only seen if fair skinned, found from day >7. Pink macules on the trunk. Fade on pressure
- Relative Bradycardia: lower heart beat then expected for high fever (<100)
16
Q
Complications of typhoid fever
A
- Bowel: perforation (treat with surgery, antibiotics.. Occurs 3rd week onwards), haemorrhage
- Septicaemic: bone and joint infection, meningitis, Cholcystitis
- Toxic (resolves with antibiotics): Myocarditis, Nephritis
- Chronic: Persistent Gallbladder carriage (become chronic carriers, often occurs with gallstones)
17
Q
Typhoid/Enteric fever- Investigations
A
- 1st/2nd week; blood culture (first line- need a big sample)
- Bone marrow
- Not stool (can identify carriers but not acute infection)
- Aspirates: rose spots, CSF, Abscesses
- Widal test (measure antiboidies against Somatic O antigens and flagella H antigens)- wide test, cheap, widely available, low sensitivity, low specificity
18
Q
Treatment of typhoid fever
A
- Fluoroquinolones (Ciprofloxacin): 5 – 7 day course. Resistant strains in e.g. India, Vietnam. Nalidixic acid resistance as proxy marker for resistance
- Third-generation cephalosporins (Ceftriaxone): Effective against MDR strains (resistant strains), severe or complicated disease. Slower response, Expensive
- Azithromycin: Effective against MDR strains, Growing evidence in severe disease
- Rise of drug resistance
19
Q
Carrier state Typhoid/Enteric fever
A
- Common for several months post-infection- terminates on its own
- Gallbladder or urinary tract: chronic carriers (3% of cases). May have chronic gallstones or abnormalities in the urinary tract
- Variable/erratic excretion
- Ciprofloxacin 750mg BD for 28 days
- Cholecystectomy: if gallstones
- Typhoid fever is a notifiable disease
- Food handlers: may affect employment
20
Q
Concise complications of Typhoid fever
A
- osteomyelitis (especially in sickle cell disease whereSalmonellais one of the most common pathogens)
- GI bleed/perforation
- meningitis
- cholecystitis
- chronic carriage (1%, more likely if adult females)
21
Q
Encephalitis features
A
- fever, headache, psychiatric symptoms (personality), seizures, vomiting, reduced conscious level
- focal features e.g. aphasia
- peripheral lesions (e.g. cold sores) have no relation to the presence of HSV encephalitis
22
Q
Encephalitis pathophysiology and causes
A
- HSV-1 causes the majority of the cases then VZV
- Other causes: Japanese B encephalitis, TB, Acute disseminate encephalomyelitis (ADEM) triggered by infection or vaccination
- Often cause not identified
- Typically affects temporal and inferior frontal lobes
- Inflammation of the brain parenchyma
23
Q
Encephalitis investigations
A
- Lumbar puncture: elevated lymphocytes, elevated protein. PCR for HSV, VZV and enteroviruses
- CT: Medial temporal and inferior frontal changes (petechial haemorrhage), normal in 1/3rd of patients
- MRI: used before CT and shows brain parenchyma inflammation
- PCR for HSV
- EEG: lateralised periodic discharges at 2Hz, to rule out seizures
- HIV test
- Clinical features differentiate from viral meningitis
24
Q
When would you be concerned that its encephalitis- a patient with fever and headache with
A
- Seizures
- Focal neurological signs
- Neuropsychiatric features (confusion, personality change, agitation, hallucinations)
25
Q
Encephalitis management
A
- IV acyclovir in all cases of suspected encephalitis 10mg/kg TDS. 14-21 day course
- Supportive care
26
Q
When can you exclude HSV encephalitis
A
- LP may originally be negative so repeat in 24-48hrs
- HSV PCR in the CSF is negative on TWO occasions 24-48 hours apart, and MRI is normal
- HSV PCR in the CSF is negative ONCE >72 hours after neurological symptom onset, with unaltered consciousness, normal MRI (performed >72 hours after symptom onset), and normal WCC in CSF
27
Q
Complications of encephalitis
A
- Venous sinus thrombosis
- Status epilepticus
- Stroke
- Aspiration pneumonia
- Without treatment majority of patient die
- With treatment majority of patients are left with permanent neurological disability- neuro rehab
28
Q
Bacterial meningitis clinical features
A
- Present similar to viral so have high index of suspicion, often not common in babies
- Symptoms: headache, fever, Nausea/vomiting, photophobia, drowsiness/confusion, seizures
- Signs: neck stiffness, purpuric rash
- Non-blanching rash cause: N meningitides
29
Q
Causes of meningitis
A
- Viral, bacterial, TB
- Viral: enterovirus, HSV, VZV (more common then bacterial)
- Bacterial: strep pneumoniae (most common bacterial), nisseris meningitides. Haemophilia influenza b
- Group B streptococcus (GBS) and Listeria monocytogenes: particularly in neonates
- TB: with HIV and worldwide
- Inflammation of the meninges covering the brain
30
Q
Neisseria meningitidis
A
Gram negative diplococcus. Most common cause of bacterial meningitis. Causes a non-blanching rash
31
Q
Classic signs of meningitis
A
- Kernig’s sign: pain in back and legs when hip is flexed and the knee is extended
- Brudzinski’s sign: involuntary hip flexion when the head is flexed
- Poor sensitivity, good specificity (presence indicates meningitis)
- Non blanching purpuric rash suggests meningococcal sepsis
32
Q
What factors suggest poor prognosis in meningitis
A
- Rapidly progressive rash
- Poor peripheral perfusion, prolonged cap refill, oliguria and systolic BP <90
- RR <8 or >30
- Pulse rate <40 or >140
- Acidosis
- WBC <4
- Reduced consciousness
- Focal neurology
- Persistent seizures
- Bradycardia and hypertension
- Papilloedema
- Anything which suggest: DIC, septic shock, raised intracranial pressure
33
Q
Investigations for meningitis
A
- Bloods: FBC, U&E, LFT, CRP, coagulation screen, blood culture, whole-blood PCR
- blood glucose
- blood gas
- Lumbar puncture: gram stain, culture and PCR. Analysis can be affected due to delay or antibiotic treatment
- Tuberculosis meningitis: Ziehl-Neelson stain, PCR
34
Q
Meningitis- Brain imaging is not required prior to lumbar puncture unless:
A
- New onset or recent seizures
- Papilloedema
- Focal neurological deficit
- Reduced or deteriorating conscious level (GCS<12)
35
Q
Interpretation of Lumbar puncture: Meningitis
A
- Bacterial: cloudy appearance, low glucose, high protein, high neutrophils
- Viral: clear/cloudy appearance, normal glucose, normal protein, high WCC (lymphocytes)
- Tuberculosis: slightly cloudy, fibrin web, low glucose, high proteins
- Don’t do LP if signs of raised intracranial pressure
36
Q
Bacterial meningitis treatment by age
A
- < 3 months: Intravenous cefotaxime + amoxicillin
- 3 months - 50 years: Intravenous Cefotaxime/Ceftriaxone (Chloramphenicol if penicillin allergic) also give IV dexamethasone to reduce neurological sequelae
- > 50 years: Intravenous cefotaxime + amoxicillin
- ABCDE assessment, initiate Sepsis 6. Give antibiotics within 1 hour ideally post LP and blood cultures
37
Q
Meningitis- when should antibiotics be offered in primary care and dose
A
If suspected meningitis and a non blanching rash then IV or IM benzylpenicillin or Ceftriaxone
- <1 year- 300mg
- 1-9 years- 600mg
- > 10 years- 1200mg
38
Q
Meningitis treatment by cause
A
- Meningococcal meningitis: Intravenous benzylpenicillin or cefotaxime
- Pneuomococcal meningitis: Intravenous cefotaxime
- Meningitis caused by Haemophilus influenzae: Intravenous cefotaxime
- Meningitis caused by Listeria: Intravenous amoxicillin + gentamicin
39
Q
Pneumococcal meningitis (Strep pneumoniae)
A
Has the highest mortality and morbidity. IV dexamethasone reduces mortality and hearing loss.
40
Q
IV Dexamethasone
A
- ideally given before antibiotics (at least within 12hrs) and should be continues for 4 days if pneumococcal meningitis is confirmed.
- Reduces mortality and hearing loss
41
Q
Meningitis: Management of contacts
A
- Prophylaxis offered to household and close contacts and those exposed to respiratory secretions. If contact before 7 days of onset
- First line: Oral Ciprofloxacin (single dose) or Rifampicin (for two days), Single Ceftriaxone IM
- When serotype results are available offer vaccine or booster
- Only for Meningococcal meningitis
- Guided by local health protection team
42
Q
Complications of meningitis by cause
A
- Viral: fatigue, headache, slowed thinking, mood disturbance
- Bacterial: deafness, cognitive impairement, focal neurological deficits, epilepsy
- Pneumococcal has higher mortality then Pneumococcal
43
Q
Poor prognostic factors for meningitis
A
severe sepsis, DIC, raised ICP
44
Q
Vaccinations meningitis
A
- For UK infants
- Haemophilus influenzae b
- Meningitis ACWY
- Meningitis B
- Streptococcus pneumoniae
45
Q
Viral meningitis
A
- Most common cause of meningitis: Enteroviruses > Herpes Simplex Virus 1 &2 > Varicella zoster virus
- LP diagnostic: detect virus with PCR
- Self limiting managed supportively
- Can cause long term morbidity: fatigue, headaches, slowed thinking
46
Q
Describing a Lumbar puncture and Benefits
A
1.Explain the procedure: A ‘spinal tap’ that involves using a needle to obtain a sample of the fluid surrounding the brain and spinal cord from a space between vertebrae in the lower back. Aseptic technique
2.Describe the likely benefits: To aid diagnosis (therapeutic if raised intracranial pressure)
47
Q
Lumbar puncture- complications and important risks
A
–Common (>5%): back pain, shooting pain down legs at the time of procedure, localised bleeding
–Rare (<1%): persistent headache, infection, lower limb weakness
48
Q
Indications for Lumbar puncture
A
Diagnostic
- Infection: meningitis (bacterial/ viral/ fungal) or encephalitis
- Subarachnoid haemorrhage
- Other – multiple sclerosis, malignancy etc.
Indications for LP Therapeutic: Reduce intracranial pressure e.g. idiopathic intracranial hypertension
49
Q
Indications for LP: spinal epidural
A
- Pain relief (during labour)
- Anaesthesia (e.g. lower limb surgery)
50
Q
Contraindications for LP
A
- Deranged blood clotting or a low platelet count
- Taking anticoagulants (Warfarin if INR >1.4
- Signs of sepsis or rapidly evolving rash
- Infection at lumbar puncture site
- Raised ICP- concerned brainstem will protrude through the foramen magnum
