Lecture 52 - Part 1 Clinical Infections - Vascular and CNS

Question 1

Bacteraemia

Answer 1

not a diagnosis - bacteria have been detected in the blood

Question 2

what indicates a blood stream infection

Answer 2

bacteraemia + symptoms/signs of infection

eg. intravascular catheter-related bloodstream infection

Question 3

Types of bacteraemia

Answer 3

Transient
Intermittent
Continuous

Question 4

Types of intermittent bacteraemia

Answer 4

pneumonia, pyelonephritis, abcess, meningitis, CRBSI

Question 5

Types of continuous bacteraemia

Answer 5

endocarditis, mycotic aneurysm, pacing lead infection, infected DVT

Question 6

Infective endocarditis

Answer 6

infection of the endocardium or devices within the heart

Question 7

Presentation of Infective endocarditis

Answer 7

• non-specific illness (lethargy, malaise, night sweats, anorexia, weight loss)
• Heart failure (SOB, orthopnea, PND)
• Results of extra-cardiac foci of infection (back pain from HVO, stroke, abdominal pain from splenic infarct

Particularly if known heart valve disease, pacemaker, prosthetic valve, congenital heart disease

Question 8

Clinical examination of infective endocarditis

Answer 8

fevers more than 38
splinter haemorrhages
oslers nodes
janeway lesions
roth spots
conjunctival haemorrhages
splenomegaly
new murmur

Question 9

Aetiology of infective endocarditis

Answer 9

Staphylococci and Streptococci, enterococci, pseudomonads, enterobacteriaceae

Question 10

Diagnosis of infective endocarditis

Answer 10

ECG (transthoracic and transoesophageal) and blood cultures ( 3 sets taken at different times) - 2 in severe sepsis

Question 11

Non-antimicrobial management of infective endocarditis

Answer 11

IE requires antimicrobial therapy - ideally directed towards pathogens identified by blood cultures

in addition, surgery may be required to:

Replace or repair damaged valves
Remove infection when antimicrobials don’t work
Remove infected devices e.g. pacemaker
Prevent complications like stroke
Drain purulent collections e.g. in spleen or spine

Question 12

Mycotic aneurysm

Answer 12

Definition: aneurysm resulting from, or secondarily infected by microorganisms

Question 13

Pathogenesis of mycotic aneurysm

Answer 13

Haematogenous seeding (e.g. secondary to IE)
trauma to arterial wall + direct contamination (e.g. IVDU)
extension from a contiguous infected focus
secondary to septic microemboli (e.g. secondary to IE)

Question 14

Presentation of mycotic aneurysm

Answer 14

usually systemic symptoms of infection and variable symptoms from aneurysm depending on location

• no localising symptoms
• painless swelling
• painful swelling
• symptoms caused by rupture (e.g. intracerebral haemorrhage, collapse.

Question 15

Aetiology of mycotic aneurysm

Answer 15

Salmonella spp., Staphylococcus aureus, Streptococcus spp., Pseudomonas aeruginosa, Escherichia coli.

Question 16

Diagnosis of mycotic aneurysm

Answer 16

Imaging (e.g. USS) and detection of bacteria within tissue.

Question 17

Management of myctoic aneurysm

Answer 17

surgical removal, stenting or coiling (depending on location) with antibiotics

Question 18

infected DVT

Answer 18

DVTs can be seeded with bacteria during bacteraemia or directly e.g. IVDU injecting into femoral vein, seeds femoral DVT

Question 19

presentation of INFECTED DVT

Answer 19

symptoms/signs of DVT and systemic infection and/or respiratory symptoms (when infected thrombus breaks from DVT travels via the venous system to the lungs – infected pulmonary emboli)

Question 20

Aetiology of infected DVT

Answer 20

Depends on mechanism but commonly S. aureus, streptococci and anaerobes in IVDU

Question 21

diagnosis of Infected dvt

Answer 21

Multiple (3) blood cultures, confirmation of DVT plus exclusion of other causes e.g. IE

Question 22

Management of infected DVT

Answer 22

Antibiotics plus anticoagulation

Question 23

What are the different types of primary infection of the central nervous system (CNS)

Answer 23

Meningitis
Encephalitis
Brain Abscess
Subdural Empyema

Question 24

How infectious agents can enter CNS

Answer 24

Haematogenous spread:

• most common
• usually via arterial route
• can be retrograde (veins)

Direct implantation

• most often is traumatic
• iatrogenic (rare)
• congenital (meningomyelocele)

Local extension (secondary to establish infections): most often from mastoid, frontal sinuses, infected tooth, etc.

Along peripheral nerves: usually viruses: Rabies, Herpes zoster

Question 25

What is meningitis

Answer 25

Meningitis refers to an inflammatory process of leptomeninges and CSF (Meningoencephalitis refers to inflammation to meninges and brain parenchyma)

Question 26

classification of meningitis

Answer 26

Acute pyogenic: usually bacterial meningitis Aseptic : usually viral meningitis Chronic: Mycobacterium tuberculosis (TBM), spirochetes (neurosyphilis), Cryptococcus

Question 27

Clinical features which suggest meningitis

Answer 27

``` Headache irritable neck stiffness photophobia fever vomiting varying levels of consciousness rash ``` groups below may have non-specific presentation - neonates - elderly - immunosuppressed

Question 28

Common bacterial pathogens in 0-4 wks

Answer 28

Streptococcus, agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella pneumoniae, Enterococcus spp, Salmonella spp

Question 29

Common bacterial pathogens in 4-12 wks

Answer 29

S, agalactiae, E coli, L. monocytogenes, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis

Question 30

Common bacterial pathogens in 3 months to 18 yrs

Answer 30

H influenzae, N meningitidis, S pneumoniae

Question 31

Common bacterial pathogens in 18-50 yrs

Answer 31

S pneumoniae, N. meningitidis

Question 32

Common bacterial pathogens in over 50 yrs

Answer 32

S pneumoniae, N meningitidis, L. monocytogenes, aerobic gram-negative bacilli

Question 33

Laboratory diagnosis for meningitis

Answer 33

Blood cultures Lumbar puncture: CSF for microscopy, Gram stain, culture & Biochemistry EDTA blood for PCR

Question 34

CSF Abnormalities in Meningitis

Answer 34

Normal - Clear colourless, 0-5 lymphocytes, Bacterial - Cloudy turbid, 100-2000 polymorphs, orgs, high protein, low glucose Viral (aseptic) - clear, slightly cloudy, 10-500 lymphocytes, protein normal, glucose normal TB (chronic) - Clear, slighlty cloudy, 10-500 lymphocytes protein high and glucose low cryptococcal -clear, 10-200 lymphocytes, protein slightly elevated, glucose slightly reduced

Question 35

Viral meningitis

Answer 35

primarily affects children and young adults milder signs and symptoms May start as respiratory or intestinal infection then viraemia CSF shows raised lymphocyte count (50-200/cu/mm); protein and sugar usually normal full recovery expected

Question 36

Causes of viral meningitis

Answer 36

Enteroviruses: Echo, coxsackie A,B, polio Paramyxovirus: mumps Herpes simples, VZV Adenoviruses Other: arboviruses, lymphocytic choriomeningitis, HIV

Question 37

Tuberculous meningitis

Answer 37

Higher incidence in immigrant populations who come from countries with high TB incidence Insidious onset High frequency of complications, cranial nerve palsies Delayed diagnosis makes complications more likely CSF shows predominantly lymphocytic response but polymorphs also present High protein, low/absent sugar -Remember increasing MDR TB

Question 38

Encephalitis

Answer 38

- Acute inflammatory process affecting the brain parenchyma - Viral infection is the most common and important cause, with over 100 viruses implicated worldwide Symptoms - fever - headache - behavioural changes - altered level of consciousness - focal ner

Question 39

Causes of viral encephalitis

Answer 39

Herpes virus - HSV-1, HSV-2, Varicella Zoster virus, cytomegalovirus, Epstein-barr virus, human herpes virus 6 -adenoviruses -influenza A - Enteroviruses, Poliovirus -Measles, mumps and rubella viruses -Rabies -Arboviruses: Japanese encephalitis; St. Louis encephalitis virus, West Nile encephalitis virus

Question 40

Herpes encephalitis

Answer 40

Most common cause of sporadic encephalitis in previously healthy May be evidence of herpes infection of skin, mucosae Causes severe haemorrhagic encephalitis affecting temporal lobe Focal signs and epilepsy features 2-4 cases/million people/year Acute infection or more commonly reactivation of latent infection (trigeminal nerve ganglion) 30% mortality with treatment 70% mortality without treatment High mortality so treatment urgently needed with Aciclovir

Question 41

treatment for herpes encephalitis

Answer 41

Aciclovir

Question 42

Recurrent meningitis symptoms

Answer 42

>2 episodes meningitis Symptom-free intervals Normal CSF between episodes Must be differentiated from chronic meningitis

Question 43

Rabies

Answer 43

Acute, progressive viral encephalitis Highest case fatality of any infectious disease One of the most ancient diseases described Model zoonosis

Question 44

Pathogenesis of rabies

Answer 44

Virus enters through bite, grows at trauma site for a week and multiplies, then enters nerve endings and advances toward the ganglia, spinal cord and brain. Infection cycle completed when virus replicates in the salivary glands

Question 45

Clinical phases of rabies

Answer 45

Prodromal phase – fever, nausea, vomiting, headache, fatigue; some experience pain, burning, tingling sensations at site of wound Furious phase – agitation, disorientation, seizures, twitching, hydrophobia Dumb phase – paralyzed, disoriented, stuporous Progress to coma phase, resulting in death

Question 46

Brain abscess

Answer 46

A brain abscess is a focal suppurative process within the brain parenchyma (pus in the substance of the brain)

Question 47

how do brain abscesses occur

Answer 47

Direct spread from “contiguous” suppurative focus (e.g. from ear 40%, sinuses, teeth) Haematogenous spread from a distant focus e.g. endocarditis, bronchiectasis (often multiple abscesses) Trauma (e.g., open cranial fracture, post-neurosurgery) Cryptogenic (no focus is recognised ~15-20 per cent of cases).

Question 48

Causes of brain abscesses

Answer 48

bacteria depend on the pathogenic mechanism involved Brain abscesses are often mixed (polymicrobial) Streptococci (60-70 %) e.g. Streptococcus “milleri” Staphylococcus aureus (10-15 percent) most common pathogen in abscesses after trauma/surgery Anaerobes e.g. Bacteroides spp. Gram negative enteric bacteria (E.coli, Pseudomonas spp.) Others e.g. fungi, Mycobacterium tuberculosis, Toxoplasma gondii

Question 49

Clinical presentation of brain abscesses

Answer 49

``` Headache Focal neurological deficit (30-50%) fever (<50%) Nausea, vomiting seizures neck stiffness papilloedema ```

Question 50

Management of brain abscesses

Answer 50

Drainage is treatment of choice (N.B small abscesses can be treated with antibiotics alone) to urgently reduce intracranial pressure to confirm diagnosis to obtain pus for microbiological investigation to enhance efficacy of antibiotics to avoid spread of infection into the ventricles

Question 51

Principles in antibiotic treatment of CNS infections

Answer 51

Physiological properties of blood-brain barrier and blood CSF-barrier are distinct Penetration of drugs into CSF and brain tissue differ Ampicillin, Penicillin, Cefotaxime, Ceftazidime, and Metronidazole achieve therapeutic concentrations in intracranial pus

Question 52

Steroids used for CNS infections

Answer 52

Dexamethasone 10mg IV 15 minutes prior to antibiotics Shown to decrease morbidity & mortality in S. pneumoniae but NOT N. meningitidis

Question 53

What is neurosyphilis

Answer 53

Central nervous system invasion occurs early in infection in 30-40% of patients Asymptomatic neurosyphilis can occur at any stage of syphilis Early symptomatic forms (months to a few years) Acute meningitis Meningovascular (stuttering stroke) Late symptomatic forms (> 2 years) General paresis Tabes dorsalis Diagnosis by blood & CSF serology