Micro Flashcards
Name three organisms that cause acute meningitis.
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae
How many serotypes of N. meningitidis are there?
3 – A, B and C
NOTE: the meningitis vaccine is for meningitis C (although there is one available for meningitis B)
List some other, rarer bacterial causes of acute meningitis.
Listeria monocytogenes
Group B Streptococcus
Escherichia coli
How long does N. meningitidis take to cause infection?
< 10 days
Outline the presentation of TB meningitis.
Similar presentation to acute meningitis but takes weeks to present
Tends to occur in immunocompromised patients
Involves the meninges and basal cisterns of the brain and spinal cord
hat is a typical MRI feature of TB meningitis?
Leptomeningeal enhancement
What is the most common infections of the CNS?
Aseptic meningitis
What are the most common causative organisms in aseptic meningitis?
Coxsackie group B viruses
Echoviruses
Which age group is susceptible to aseptic meningitis?
< 1 year
NOTE: normally self-resolving after 1-2 weeks
List some viruses that cause encephalitis
Mumps
Measles
Enteroviruses
Herpes viruses
What is becoming a leading cause of encephalitis worldwide?
West Nile virus
NOTE: this is transmitted by mosquitoes and birds
Which bacterium is associated with causing encephalitis?
Listeria monocytogenes
Name two types of amoeba that cause encephalitis.
Naegleria fowleri
Acanthamoeba species and Balamuthia mandrillaris
What is toxoplasmosis and how is it spread?
Obligate intracellular parasite
Spread via oral, transplacental or organ transplant route
Name a common spinal infection.
Pyogenic vertebral osteomyelitis
What are some long-term consequences of Pyogenic vertebral osteomyelitis?
Permanent neurologic defects
Significant spinal deformity
Death
Describe the typical CSF analysis results of Bacterial meningitis
Turbid
High polymorphs
High protein
Low glucose
Describe the typical CSF analysis results of Aseptic meningitis
Clear
High lymphocytes
High protein
Normal glucose
Describe the typical CSF analysis results of Tuberculous meningitis
Clear
High lymphocytes
High protein
Low glucose
Describe the Gram-stain and microscopic appearance of S. pneumoniae
Gram-positive alpha-haemolytic diplococci
Describe the Gram-stain and microscopic appearance of N. meningitidis
Gram-negative non-haemolytic diplococci
Describe the Gram-stain and microscopic appearance of L. monocytogenes
Gram-positive rods
Describe the Gram-stain and microscopic appearance of TB
Stains positively with Ziehl-Neelsen (red and blue)
Describe the Gram-stain and microscopic appearance of Cryptococcus
Stains positively with India ink (appears like an orbit – yeast in the middle with a capsule around the outside)
What is the generic therapy used in meningitis?
Ceftriaxone 2 g IV BD
If > 50 years or immunocompromised = amoxicillin 2 g IV 4 hourly
NOTE: this is because ceftriaxone does NOT cover Listeria
What is the generic therapy used in meningo-encephalitis?
Aciclovir 10 mg/kg IV TDS
Ceftriaxone 2 g IV BD
If > 50 years or immunocompromised = amoxicillin 2 g IV 4 hourly
Name the specific therapy for meningitis caused by S. pneumoniae
Pen G 18-24 mu/day
Name the specific therapy for meningitis caused by N. meningitidis
Ceftriaxone 4 g/day
Name the specific therapy for meningitis caused by H. influenzae
Cefotaxime 12 g/day
Name the specific therapy for meningitis caused by Group B Streptococcus
Pen G 18-24 mu/day
Name the specific therapy for meningitis caused by Listeria
Ampicillin 12 g/day
Name the specific therapy for meningitis caused by Gram-negative bacilli
Cefotaxime 12 g/day
Name the specific therapy for meningitis caused by Pseudomonas
Meropenem 6 g/day
List some reportable GI infections.
Campylobacter
Salmonella
Shigella
Escherichia coli O157
Listeria
What are the main characteristics of secretory diarrhoea?
Watery diarrhoea (no inflammatory cells in stool)
No fever
What are the main characteristics of inflammatory diarrhoea?
Fever
Diarrhoea (inflammatory cells present, may be bloody)
List some examples of severe GI infections that produce a fever with little stool changes.
Salmonella typhi
Enteropathogenic Yersinia
Brucella
What type of organism is Staphylococcus aureus?
Catalase and coagulase positive, Gram-positive coccus that appears in clusters
What type of toxin is produced by Staphylococcus aureus?
Enterotoxin – this is an exotoxin that can act as a superantigen in the GI tract triggering the release of IL1 and IL2
How is Staphylococcus aureus spread and what kind of GI symptoms can it cause?
Spread by skin lesions on food handlers
Causes prominent vomiting and watery, non-bloody diarrhoea
NOTE: it is self-limiting so does not require treatment
What type of organism is Bacillus cereus?
Gram-positive rods that are spore-forming
What type of GI symptoms does B. cereus cause?
Watery, non-bloody diarrhoea
NOTE: it can cause bacteraemia and cerebral abscesses in vulnerable populations
Clostridium botulinum
· From canned food
· Causes disease due to preformed toxin which blocks acetylcholine release at peripheral nerve synapses resulting in paralysis
· Treated with antitoxin
Clostridium perfringens
· From reheated food
· Generates a superantigen that mainly affects the colon
· Causes watery diarrhoea and cramps that last 24 hours
Which antibiotics are most commonly implicated in C. difficile colitis?
Cephalosporins
Clindamycin
Ciprofloxacin
How is C. difficile colitis treated?
Metronidazole
Vancomycin
What type of organism is Listeria monocytogenes?
Gram-positive, rod-shaped, facultative anaerobe
Beta-haemolytic, aesculin-positive with tumbling motility
What GI symptoms does Listeria tend to cause?
Watery diarrhoea, cramps, headache, fever and a little vomiting
NOTE: it comes from refrigerated food (e.g. unpasteurised dairy)
How is Listeria infection treated?
Ampicillin
What type of organisms are Enterobacteriaceae?
Facultative anaerobes
Lactose fermenters
Oxidase-negative
Name and describe the different types of E. coli infection
ETEC – toxigenic, main cause of travellers’ diarrhoea
EPEC – pathogenic, infantile diarrhoea
EIEC – invasive, dysentery
EHEC – haemorrhagic, caused by E. coli O157:H7
What causes haemolytic uraemic syndrome?
EHEC shiga-liked verocytotoxin
What type of bacteria are Salmonellae?
Non-lactose fermenting, Gram-negatives
Produce hydrogen sulphide (form black colonies)
Grows on TSI agar, XLD agar and selenite F broth
List three species of Salmonella.
Salmonella typhi (and paratyphi)
Salmonella enteritidis
Salmonella choleraesuis
Describe the presentation of Salmonella enteritidis.
Enterocolitis – loose stools
Transmitted by poultry, eggs and meat
Self-limiting diarrhoea that is non-bloody
No fever
Bacteraemia is rare
Describe the presentation of Salmonella typhi.
Transmitted only by humans
Multiplies in Peyer’s patches and spreads via the endoreticular system
Slow onset fever and constipation
May cause splenomegaly, rose spots, anaemia and leucopaenia
Blood cultures may be positive
Which subset of patients are at increased risk of Salmonella bacteraemia?
Sickle cell patients
How is Salmonella typhi treated?
Ceftriaxone
What are some key microbiological features of Shigella?
Non-lactose fermenter
Does NOT produce hydrogen sulphide
Non-motile
List some types of Shigella.
Shigella sonnei
Shigella dysenteriae
Shigella flexneri (MSM)
What is the most effective bacterial enteric pathogen and why?
Shigella – it has the lowest infective dose (50)
NOTE: Shigella has no animal reservoir and no carriers
How does Shigella infection manifest?
Dysentery – severe diarrhoea with blood and mucus in the faeces
NOTE: Shigella produces shiga toxin
NOTE: avoid antibiotics when treating Shigella
What are the microbiological features of Vibrio?
Comma-shaped
Late lactose-fermenters
Oxidase-positive
Gram-negative
What type of GI disturbance does Vibrio cholerae cause?
Produce watery diarrhoea without inflammatory cells
Treat the losses (water and electrolytes)
Vibrio parahaemolyticus
caused by ingestion of raw/undercooked seafood, causes self-limiting diarrhoea, grows on salty agar
Vibrio vulnificus
causes cellulitis in shellfish handlers, can cause fatal septicaemia with D&V in HIV patients, treated with doxycycline
What are the main microbiological features of Campylobacter?
Comma-shaped
Microaerobphilic
Oxidase-positive
Gram-negative
Motile
Describe the presentation of Campylobacter jejuni infection.
Watery, foul-smelling diarrhoea, bloody stools, fever and severe abdominal pain
NOTE: transmitted by food and water that has been contaminated by animal faeces
How is Campylobacter infection treated?
Only treated if immunocompromised
Erythromycin or ciprofloxacin
What are some complications of Campylobacter infection?
Guillain-Barre syndrome
Reactive arthritis
What are the key microbiological features of Entamoeba histolytica?
Motile trophozoite in diarrhoeal illness
Non-motile cyst in non-diarrhoeal illness
Killed by boiling
Contains four nuclei
No animal reservoir
Describe the presentation of GI infection by Entamoeba histolytica.
Dysentery, flatulence, tenesmus, liver abscess
How is Entamoeba histolytica infection diagnosed and treated?
Diagnosis: stool microscopy, serology of invasive disease
Treatment: metronidazole + paromomycin
What are the key microbiological features of Giardia lamblia?
Pear-shaped trophozoites
Two nuclei
Four flagellae and a suction disc
Outline the pathophysiologiy of GI disease caused by Giardia.
Transmitted by ingestion of cyst from faecally contaminated water
Excystation in the duodenum leads to trophozoite attachment
Results in malabsorption of protein and fat
Presentation: foul-smelling non-bloody diarrhoea, cramps, flatulence, NO fever
How is Giardia infection diagnosed and treated?
Stool microscopy
ELISA
String test
Treatment: metronidazole
What are the main features of Cryptosporidium parvum?
Causes severe diarrhoea in the immunocompromised
Oocysts can be seen in the stool using modified Kinyoung acid fast stain
Treated by boosting the immune system
What is rotavirus and what does it cause?
dsRNA virus
Replicates in the mucosa of the small intestine and causes secretory diarrhoea with no inflammation
NOTE: exposure to natural infection twice will confer lifelong immunity
Which causes of diarrhoeal illness have available vaccines?
Cholera (serogroup O1)
Campylobacter
ETEC
Salmonella typhi
Rotavirus (rotarix (live, monovalent), rotateq (pentavalent), rotashield (used if risk of intussusception))
What are some features of HIV encephalopathy?
Basal ganglia calcification
White matter changes
Atrophy
Vasculopathy/stroke
What is an effective barrier to HIV transmission from mother to baby?
Healthy placenta
NOTE: there are conditions that can damage the placenta (e.g. malaria, toxoplasmosis)
State a perinatal risk factor for HIV transmission.
Prolonged rupture of membranes
List some classes (with examples) of antiretroviral drugs.
NRTI (e.g. zidovudine)
NNRTI (e.g. efavirenz)
Integrase inhibitors (e.g. raltegravir)
Protease inhibitors (e.g. lopinavir)
Describe the typical clinical findings in Pneumocystis jirovecii pneumonia.
Widespread, bilateral ground-glass shadowing with reduced exercise tolerance and low saturations
How is PCP treated?
Co-trimoxazole
Which investigation can be used to confirm a diagnosis of PCP?
Bronchoalveolar lavage cytology
Which stain is used to identify PCP?
Silver stain (Grocott-Gomori stain)
What is Cryptococcus?
Yeast that causes fungal meningoencephalitis
What is Actinomyces and what does it cause?
Gram-positive rod that causes lung abscesses in immunocompromised patients (particularly alcoholics)
NOTE: it’s closely associated with Nocardia
Describe the histological features of Actinomyces.
Basophilic sulfur granules
Gram-positive rods that branch as they grow
List some indicators of severe disease in people with C. difficile infection.
High temperature
High heart rate
High WCC
Rising creatinine
Clinical or radiological signs of severe colitis
Failure to respond to therapy at 72 hours
What is the rapid plasma reagent test?
Test for active syphilis
What is a characteristic finding of CJD on a diffusion-weighted MRI?
Increased signal in the cortex of the right parietal lobe
What is a possible physiological role of the normal prion protein?
It may have some role in copper metabolism
Which gene mutation is associated with prion diseases?
PRNP
Give some examples of inherited prion diseases.
Fatal familial insomnia
Gerstmann-Straussler-Sheinker syndrome
Describe the clinical features of sporadic CJD.
Rapid dementia
Myoclonus
Cortical blindness
Akinetic mutism
LMN signs
NOTE: usually in older people (> 65)
Describe the EEG appearance in sporadic CJD.
Periodic, triphasic complexes
Describe the MRI appearance of sporadic CJD.
Increased signal in the basal ganglia
Increased intensity on DWI MRI of the cortex and basal ganglia
Which markers will be raised in the CSF of a patient with CJD?
14-3-3
S100
What is the only way of confirming a diagnosis of CJD?
Brain biopsy (usually at autopsy)
Describe the histological appearance of CJD.
Spongiform vacuolisation
NOTE: there are amyloid plaques but these are different from the plaques seen in Alzheimer’s disease
List the differential diagnosis for CJD.
Alzheimer’s disease
Vascular dementia
CNS neoplasms
Cerebral vasculitis
Paraneoplastic syndromes
Describe the clinical features of vCJD.
Younger age of onset (20s)
Psychiatric onset (dysphoria, anxiety, delusions, hallucinations)
Followed by neurological symptoms (peripheral sensory symptoms, ataxia, myoclonus, chorea, dementia)
What is a characteristic MRI feature of vCJD?
Pulvinar sign – high intensity in the putamen
How is the use of CSF markers different in vCJD?
14-3-3 and S100 are NOT useful in vCJD
Which investigation is most useful for vCJD?
Tonsillar biopsy – prions localise in lymphoid tissue
NOTE: this is not useful in CJD
What is the inheritance pattern of inherited prion diseases?
Autosomal dominant
What are some alternative diagnoses for someone presenting with features suggestive of prion disease?
Spinocerebellar ataxia
Huntington’s disease
Describe the clinical features of Gerstmann-Straussler-Sheinker syndrome.
Slowly progressive ataxia
Diminished reflexes
Dementia
NOTE: PRNP P102L mutation is most common
Describe the clinical features of fatal familial insomnia.
Untreatable insomnia
Dysautonomia (blood pressure and heart rate dysregulation)
Ataxia
Thalamic degeneration
NOTE: PRNP D178N mutation is most common
Outline the principles of treatment of CJD.
Symptomatic – clonazepam for clonus
Delaying prion conversion – quinacrine, pentosan, tetracycline
Anti-prion antibody – blocks progression in mice but cannot access CNS
Depletion of neuronal cellular prion protein – blocks neuronal cell loss and reverses early spongiosis in mice
In which groups of patients are UTIs considered ‘complicated’?
Men
Pregnant women
Children
Hospitalised patients
Which organism most commonly causes UTI?
E. coli
List some other organisms that cause UTI.
Proteus mirabilis
Klebsiella aerogenes
Enterococcus faecalis
Staphylococcus saprophyticus
Staphylococcus epidermidis (can cause infection in the presence of prosthesis (e.g. procedures, indwelling catheters))
List some symptoms of upper UTI.
Fever (and rigors)
Flank pain
Lower urinary tract symptoms
List some investigations for uncomplicated UTI.
Urine dipstick
MSU for urine MC&S
Bloods – FBC, CRP, U&E
List some further investigations that may be considered in complicated UTIs.
Renal ultrasound scan
IV urography
What are nitrites in the urine specific for?
They are produced by E. coli
List some patient groups in whom culture and sensitivities should be performed.
Pregnancy
Children
Pyelonephritis
Men
Catheterised
Failed antibiotic treatment
Abnormalities of the genitourinary tract
Renal impairment
What does the presence of squamous epithelial cells in the urine suggest?
Contamination
What is the microbiological definition of UTI?
Culture of single organisms > 105 colony forming units/mL with urinary symptoms
NOTE: this threshold may be reduced for organisms that are known to cause UTI (e.g. E. coli and S. saprophyticus)
In which patient groups should screening of the urine for white cells before MC&S NOT be performed?
Immunocompromised patients, pregnant women and children
List some causes of sterile pyuria.
STIs (e.g. chlamydia)
TB
Prior antibiotic treatment (MOST COMMON)
Calculi
Catheterisation
Bladder cancer
What type of agar is used for urine culture? What do the colours suggest?
Chromogenic agar
· Pink = E. coli
· Blue = other coliforms
· Light blue = Gram-positives
Outline the treatment options for Uncomplicated UTI in women
Cefalexin 500 mg BD PO for 3 days
OR
Nitrofurantoin 50 mg POQ QDS for 7 days (check renal function)
Outline the treatment options for UTI in pregnant or breastfeeding women
Cefalexin 500 mg BD PO for 7 days
2nd line: co-amoxiclav 625 mg TDS PO for 7 days
Outline the treatment options for UTI in men
Cefalexin 500 mg BD PO for 7 days
OR
Ciprofloxacin 500 mg BD PO for 14 days if suspicion of prostatitis
Chronic prostatitis: ciprofloxacin 500 mg BD PO for 4-6 weeks
Outline the treatment options for Pyelonephritis or systemically unwell with a UTI
Co-amoxiclav 1.2 g IV TDS
Consider adding IV amikacin or gentamicin
Penicillin allergy: ciprofloxacin 400 mg IV BD
Outline the treatment options for Catheter-associated UTI
Remove catheter (but give stat doses before removal of infected catheter)
Gentamicin 80 mg STAT IV/IM 30-60 mins before procedure
OR
Amikacin 140 mg STAT IV/IM 30-60 mins before procedure
In which patients do Candida UTIs tend to occur?
Patients with indwelling catheters
Which part of the kidney is more susceptible to infection?
Renal medulla
What is the main treatment option for pyelonephritis?
Co-amoxiclav with or without gentamicin
List some complications of pyelonephritis.
Perinephric abscess
Chronic pyelonephritis (scarring, renal impairment)
Septic shock
Acute papillary necrosis
How is hepatitis A spread?
Faecal-oral
Describe the natural history of hepatitis A infection.
2-6 weeks after the infection you will develop hepatitis (transaminitis)
This will be accompanied by a rise in IgM
A more gradual rise in IgG will follow
NOTE: hepatitis A infection is often subclinical
What is the diagnostic test for hepatitis A?
Anti-hepatitis A IgM
Which antibodies will be present if someone has received a hepatitis A vaccine?
High IgM and high IgG but NO transaminitis
How is hepatitis B transmitted?
Sexually transmitted
Blood products
Mother-to-baby
What is the risk of chronic hep b infection in adults and babies?
5-10% in adults
95% in babies
What serological features is suggestive of recent HBV infection?
Anti-HBV IgM antibodies
What serological feature is suggestive of chronic HBV infection?
Prolonged presence of HBsAg
What are some possible consequences of HBV infection?
Hepatocellular carcinoma
Cirrhosis
List the HBV disease stages.
Immune tolerant
Immune reactive
Inactive HBV carrier state
HBeAg negative chronic HBV
What is a strong indicator of risk of cirrhosis in people with hepatitis B infection?
HBV DNA level (copies/mL)
List some treatment options for chronic HBV.
Interferon alpha - not in liver transplant pts
Lamivudine
Tenofovir
Entecavir
Emtricitabine
What class of drugs are most antivirals used for hepatitis C?
Protease inhibitors
Inhibitors of non-structural components
Outline the serological changes that take place following HCV infection.
Anti-HCV antibodies develop after the acute infection has resolved (i.e. ALT has returned to normal)
How is HCV treated?
Early treatment with peginterferon alfa
What is the main difference in the treatment of genotype 1 and non-genotype 1 HCV?
Genotype 1 – high-dose long-lasting ribavirin is required for high cure rates
Non-genotype 1 – ribavirin does NOT increase cure rates
What is the difference between hepatitis D co-infection and superinfection?
Co-infection
· This happens when you are inoculated with HBV and HDV at the same time (e.g. sharing a needle with someone infected by both viruses)
· Anti-HDV IgM will rise after inoculation causing hepatitis
Superinfection
· This happens when someone with chronic hepatitis B infection is inoculated by HDV
· This is more severe than coinfection
· Patients can develop cirrhosis within 2-3 years
Which patient group has a high mortality if infected by hepatitis E?
Pregnant women
NOTE: mainly associated with genotype 1
List some rare complications of hepatitis E.
CNS disease (e.g. Bell’s palsy)
Chronic infection
Outline the treatment of hepatitis E.
Supportive
Ribavirin
Outline the serological changes that take place in hepatitis E infection.
Acute infection is accompanied by a rise in IgM anti-HEV antibody
Rarely you can get persistently high levels of HEV RNA
NOTE: it generally responds well to ribavirin
Name three major pathogens that cause surgical site infections.
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa
How is a surgical site infection caused by MRSA treated?
IV linezolid
Who should be offered nasal decontamination?
Patients who are found to be carrying S. aureus
List some organisms that can cause septic arthritis.
Staphylococcus aureus
Streptococci (pyogenes, pneumoniae, agalactiae)
Gram-negative organisms (E. coli, H. influenzae, N. gonorrhoeae and Salmonella)
Coagulase-negative staphylococci
RARE: Lyme disease, Brucellosis, Mycobacteria, Fungi
Describe the clinical features of septic arthritis.
1-2 week history of red, painful, swollen joint with restricted movement
NOTE: 90% monoarticular, 50% knee involvement
NOTE: patients with rheumatoid arthritis may have more subtle signs
List some investigations for septic arthritis.
Blood culture before antibiotics
Synovial fluid aspiration (send for MC&S, WCC > 50,000/mL is considered septic arthritis)
ESR and CRP
Ultrasound
CT (for bone erosion)
MRI (for joint effusion, articular cartilage destruction, abscess)
List some organisms that can cause vertebral osteomyelitis.
Staphylococcus aureus
Coagulase-negative staphylococcus
Gram-negative rods
Streptococcus
In which region of the vertebral column is vertebral osteomyelitis most common?
Lumbar
What are the symptoms of vertebral osteomyelitis?
Back pain
Fever
Neurological impairment
List some investigations for vertebral osteomyelitis.
MRI
Blood cultures
CT-guided/open biopsy
How is vertebral osteomyelitis treated?
Antibiotics (at least 6 weeks)
Outline the presentation of chronic osteomyelitis.
Pain
Brodie’s abscess
Sinus tract
How is chronic osteomyelitis diagnosed?
MRI
Bone biopsy for culture and histology
How is chronic osteomyelitis treated?
Radical debridement down to living bone
Remove sequestra (dead bone tissue) and infected bone tissue
Which organism most commonly causes prosthetic joint infection?
Coagulase-negative staphylococcus
Others: streptococci, enterococci, enterobacteriaciae, Pseudomonas aeruginosa, anaerobes
How is prosthetic joint infection diagnosed?
Radiology – shows loosening of the prosthesis
CRP > 13.5 for prosthetic knees
CRP > 5 for prosthetic hips
Joint aspiration (>1700/mL if knee; >4200/mL if hip)
List 5 HAIs in order of prevalence.
Pneumonia
Surgical site infection
UTI
Blood stream infection
Gastrointestinal infection
What type of bacterium is C. difficile?
Gram-positive spore-forming anaerobe
Define pyrexia of unknown origin.
A fever > 38.3 degrees lasting > 3 weeks with an uncertain diagnosis after 7 days in hospital
List some causes of PUO in HIV patients.
TB/NTM
PCP
Cryptococcal meningitis
Non-Hodgkin lymphoma
List some differentials for PUO.
Infection
· Infectious endocarditis
· HIV
· TB
Inflammation
· Polymyalgia rheumatica
· Still’s disease
· Sarcoidosis
· ANCA-associated vasculitis
· Rheumatoid arthritis
Malignancy
· Malignant lymphoma
· Castleman’s disease
List some routine diagnostic tests that should be requested in patients with PUO.
FBC
U&E
Total protein
LFTs
CRP
Blood cultures
Urine culture
HIV test – VERY IMPORTANT
List some infectious causes of PUO.
Bacteria
· TB/NTM
· Enteric fever (e.g. Salmonella typhi)
· Zoonoses
Viruses
· EBV/CMV
· HIV
· Hepatitis
Fungi
· Cryptococcosis
· Histoplasmosis
Parasites
· Malaria
· Amoebic liver abscess
· Schistosomiasis
· Toxoplasmosis
· Trypanosomiasis
Which organ will always light up in PET-CT?
Kidneys (FDG is excreted renally)
List two causes of very high ferritin.
Adult-onset Still’s disease
Macrophage activation syndrome
Why is a transthoracic echocardiogram an important investigation to perform in PUO?
To rule out infective endocarditis (important differential for PUO)
Outline the major and minor criteria for infective endocarditis.
Major
· Persistent bacteraemia (> 2 positive blood cultures)
· Vegetations on echocardiogram
· Positive serology for Bartonella, Coxiella or Brucella
Minor
· Predisposition (murmur, IVDU)
· Raised inflammatory markers
· Immune complexes (RBC in urine)
· Embolic phenomena (Janeway lesions)
· Atypical echo
· 1 positive blood culture
2 major + 1 minor OR 3 minor = infective endocarditis
List some key features of GCA.
Headache
Jaw claudication
Scalp tenderness
Changes in vision (50%)
How is GCA treated?
High dose prednisolone
Outline the key features of Adult-onset Still’s disease.
Salmon pink rash
Arthralgia
Sore throat
Lymphadenopathy
Fever
List some malignant causes of PUO.
Lymphoma (especially Non-Hodgkin)
Leukaemia
Renal cell carcinoma
Hepatocellular carcinoma and liver metastases
NOTE: lymphoma causes a high LDH
List some miscellaneous causes of PUO.
Subacute thyroiditis
Addison’s disease
PE
Dressler’s syndrome
Drugs – idiosyncratic or adverse drug reaction
NOTE: 25% of drug reactions will cause eosinophilia and a rash
Give examples of zoonoses in the UK that are transmitted by Farm/wild animals
Campylobacter
Salmonella
Give examples of zoonoses in the UK that are transmitted by Companion animals
Toxoplasmosis
Bartonella
Ringworm
Psittacosis
Give examples of zoonoses in tropical countries that are transmitted by Farm/wild animals
Brucella
Coxiella
Rabies
VHF
Give examples of zoonoses in tropical countries that are transmitted by Companion animals
Rabies
Tick-borne diseases
Spirilum minus
Which two diseases are caused by Bartonella henselae?
Cat scratch disease
Baciliary angiomatosis
Cat Scratch Disease presentation
Macule at site of inoculation
Becomes pustular
Regional adenopathy
Systemic symptoms (FLAWS)
Cat scratch disease management
Erythromycin
Doxycycline
Bacillary angiomatosis presentation
Skin papules
Disseminated
Leads to bursting of blood vessels in various organs and tissues
Can be FATAL
Bacillary angiomatosis management
Erythromycin
Doxycycline
Rifampicin
Toxoplasmosis presentation
Fever
Adenopathy
Stillbirth
Infants with progressive visual, hearing, motor and cognitive issues
Seizures
Neuropathy
Toxoplasmosis management
Spiramycin
Pyrimethamine + sulfadizine
Brucellosis presentation
Fever (and rest of FLAWS)
Back pain
Orchitis
Focal abscess (psoas or liver)
Brucellosis management
Doxycycline + gentamicin or rifampicin
Which organism causes Q fever?
Coxiella burnetii
Coxiella burnetii presentation
Fever
Flu-like illness
Pneumonia
Hepatitis
Endocarditis
Focal abscess (paravertebral, discitis)
Coxiella burnetii management
Doxycycline
Which infectious agent causes Rabies?
Lyssa virus
Rabies presentation
Seizures
Excessive salivation
Hydrophobia
Agitation
Confusion
Fever
Headache
NOTE: 100% mortality
Rabies management
Immunoglobulin
Vaccine
Which two infectious agents can cause rat bite fever?
Streptobacillus moniliformis
Spirilum minus
Rat bite fever presentation
Fevers
Polyarthralgia
Maculopapular progressing to purpuric rash
Can progress to endocarditis
Rat btie fever management
Penicillins
Hentavirus pulmonary syndrome presentation
Fever
Flu-like illness
Myalgia
Respiratory failure (USA)
Bleeding and renal failure (SE asia)
Viral haemorrhagic fever presentation
Fever
Myalgia
Flu-like illness
BLEEDING
What type of bacterium is Streptococcus pneumoniae?
Gram-positive cocci in chains
Alpha-haemolytic and optochin-sensitive
List the main organisms that cause CAP.
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Klebsiella pneumoniae
List the most prevalent pathogens causing CAP in 0-1 months
Escherichia coli
Group B Streptococcus
Listeria monocytogenes
List the most prevalent pathogens causing CAP in 1-6 months
Chlamydia trachomatis
Staphylococcus aureus
RSV
List the most prevalent pathogens causing CAP in 6 months – 5 years
Mycoplasma pneumoniae
Influenza
List the most prevalent pathogens causing CAP in 16-30 years
Mycoplasma pneumoniae
Streptococcus pneumoniae
Typical CAP causes
Streptococcus pneumoniae
Haemophilus influenzae
Atypical CAP causes
Legionella
Mycoplasma
Coxiella burnetii
Chlamydia psittaci
What is the CURB-65 score? How is it interpreted?
Confusion
Urea > 7 mmol/L
Respiratory rate > 30/min
BP < 90 systolic, < 60 diastolic
Score of 2 = consider hospital admission
Score of more than 2 = severe pneumonia that may need ITU admission
Outline the presentation of bronchitis.
Cough
Fever
Increased sputum production
Increased SOB
Which organisms cause bronchitis?
Viruses
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
List some bacterial causes of cavitating lung lesions.
Staphylococcus aureus
Klebsiella pneumoniae
TB
What type of bacterium is H. influenzae?
Gram-negative cocco-bacilli
What is a common feature of bacteria that cause atypical pneumonia?
They have NO cell wall
List four atypical organisms.
Mycoplasma
Legionella
Chlamydia
Coxiella
Which type of antibiotics do not work on atypical bacteria?
Penicillins
NOTE: this is because they act on cell walls
Which type of antibiotics do work on atypical bacteria?
Antibiotics that interfere with protein synthesis (macrolides, tetracyclines)
List some clinical features of Legionella pneumophila infection.
Confusion
Abdominal pain
Diarrhoea
Lymphopaenia
Hyponatraemia
Urinary antigens are associated with which causes of pneumonia?
Streptococcus pneumoniae
Legionella pneumophila
What is an empyema?
Collection of pus within the pleural cavity
What is the classical CXR feature of TB?
Upper lobe cavitation
Which types of staining are used when investigating TB?
Auramine staining
Ziehl-Neelsen stain
NOTE: they are red rods
List some organisms that cause HAP.
Enterobacteriaciae (MOST COMMON – e.g. E. coli, K. pneumoniae)
Staphylococcus aureus
Pseudomonas
Haemophilus influenzae
Acinetobacter baumanii
Fungi (e.g. Candida)
Describe the typical presentation of Pneumocystic jirovecii pneumonia.
Dry cough
Weight loss
SOB
Malaise
Walk test – desaturation on exertion
What is the treatment for PCP?
Co-trimoxazole (septrin)
What are the main features of allergic bronchopulmonary aspergillosis?
Chronic wheeze
Eosinophilia
Bronchiectasis
What is an aspergilloma?
Fungal ball often forming within a pre-existing cavity
May cause haemoptysis
How is invasive aspergillosis treated?
Amphotericin B
What is the treatment for mild-to-moderate CAP?
Amoxicillin
OR erythromycin/clarithromycin (if penicillin allergic)
What is the treatment for moderate-to-severe CAP?
Co-amoxiclav AND clarithromycin
What are the 1st and 2nd line treatment options for HAP?
1st = ciprofloxacin +/- vancomycin
2nd = tazocin AND vancomycin
Which antibiotics are used to treat HAP caused by MRSA
Vancomycin
Which antibiotics are used to treat HAP caused by Pseudomonas
Tazocin OR ciprofloxacin +/- gentamicin
List three types of mycobacterial complex.
Mycobacterium tuberculosis complex
· Mycobacterium tuberculosis
· Mycobacterium bovis
Mycobacterium avium complex
· Mycobacterium avium
· Mycobacterium intracellulare
Mycobacterium abscessus complex
· Mycobacterium abscessus
· Mycobacterium massiliense
· Mycobacterium bolletii
Describe the morphology of mycobacteria.
Non-motile rod-shaped bacteria
Relatively slow-growing
Cell wall composed of mycolic acids, complex waxes and glycoproteins
Acid-alcohol fast
What is used as a screening test for mycobacterial infections?
Auramine stain
How are non-tuberculous mycobacterial infections transmitted?
NOT person-to-person
From the environment
May be colonising rather than infecting
List three examples of slow-growing non-tuberculous mycobacteria and the diseases that they cause.
Mycobacterium avium intracellulare
· May invade bronchial tree or pre-existing bronchiectasis/cavities
· Disseminated infection in immunocompromised patients
Mycobacterium marinum
· Swimming pool granuloma
Mycobacterium ulcerans
· Skin lesions (e.g. Bairnsdale ulcer, Buruli ulcer)
· Chronic progressive painless ulcer
List three examples of rapid-growing non-tuberculous mycobacteria.
Mycobacterium abscessus
Mycobacterium chelonae
Mycobacterium fortuitum
How is Mycobacterium avium intracellulare treated?
Clarithromycin/azithromycin
Rifampicin
Ethambutol
+/- streptomycin/amikacin
What is the most common cause of death by infectious agent in the world?
1 = HIV
2 = TB
Describe the natural history of primary TB.
Usually asymptomatic
Ghon focus (granuloma in the lungs)
Controlled by cell-mediated immunity
Occasionally causes disseminated/military TB
What is post-primary TB?
Reactivation or exogenous re-infection
Happens > 5 years after primary infection
List some risk factors for reactivation of TB.
Immunosuppression
Chronic alcohol excess
Malnutrition
Ageing
List some types of extra-pulmonary TB.
Lymphadenitis (scrofula) – cervical lymph nodes most commonly
Gastrointestinal – due to swallowing of tubercle
Peritoneal – ascitic or adhesive
Genitourinary
Bone and joint – due to haematogenous spread (e.g. Pott’s disease)
Miliary TB
Tuberculous meningitis
Why is it important to take 3 sputum samples when investigating suspected TB?
Increases the sensitivity of the smear microscopy
What is the histological hallmark of TB?
Caseating granuloma
What are the disadvantages of the tuberculin skin test?
Cross-reacts with BCG
Cannot distinguish between active and latent TB
List some side-effects of Rifampicin
Raised transaminases
CYP450 induction
Orange secretions
List some side-effects of Isoniazid
Peripheral neuropathy (give with pyridoxine)
Hepatotoxicity
List some side-effects of Pyrazinamide
Hepatotoxicity
List some side-effects of Ethambutol
Visual disturbance
Describe the treatment regimen for TB.
RIPE for 2 months
Followed by rifampicin and isoniazid for 4 more months
What is multi-drug resistant TB?
Resistant to rifampicin and isoniazid
What are the diagnostic challenges of HIV and TB coinfection?
Clinical presentation is less likely to be classical
Symptoms may be absent if CD4+ count is low
More likely to have extra-pulmonary manifestations
Tuberculin skin test more likely to give false-negative
Low sensitivity for IGRAs
List three examples of neuraminidase inhibitors.
Oseltamivir (Tamiflu) – oral
Zanamivir (Relenza) – inhaled or IV
Peramivir – IV
List two examples of polymerase inhibitors.
Favipiravir
Baloxavir
What type of vaccine is the seasonal influenza vaccine used in high risk groups?
Purified fraction containing HA and NA of an inactivated virus
NOTE: often needs to be given with an adjuvant
What type of flu vaccine is given to school-aged children?
Live-attenuated vaccine
NOTE: this is a cold-adapted virus that is sprayed into the child’s nose
This provides broader and more cross-reactive immunity
What is a possible complication of shingles?
Post-herpetic neuralgia
What are two 2nd line treatment options for aciclovir-resistant VZV infection?
Foscarnet
Cidofovir
NOTE: they inhibit viral DNA synthesis
HSV encephalitis is a medical emergency. How should it be treated?
IMMEDIATE treatment with IV aciclovir 10 mg/kg TDS without waiting for test results
If confirmed, treat for 21 days
What is HSV meningitis and how should it be treated?
Usually self-limiting
Immunocompromised patients and those who are unwell enough to require hospital admission require treatment
IV aciclovir for 2-3 days followed by oral aciclovir for 10 days
In which cells does CMV lie dormant?
Monocytes and dendritic cells
List some consequences of CMV infection in immunocompromised patients.
Bone marrow suppression, retinitis, pneumonitis, hepatitis, colitis and encephalitis
What is a characteristic histological feature of CMV infection?
Owl’s eye inclusions
What is the 1st line treatment option for CMV infection?
Ganciclovir (IV)
What is a major side-effect of ganciclovir?
Bone marrow toxicity
NOTE: therefore, its use is limited in bone marrow transplant patients
What is a major side-effect of foscarnet?
Nephrotoxicity
What is a major side-effect of cidofovir?
Nephrotoxicity (requires hydration and probenecid)
What are three strategies for the treatment of CMV in transplant patients?
TREAT established disease
PROPHYLAXIS with ganciclovir or valganciclovir (mainly in solid organ transplant patients)
PRE-EMPTIVE THERAPY for bone marrow transplant patients (monitoring for the appearance of CMV in PCR of the blood and starting antiviral therapy when the viral load reaches a threshold)
In which cells does EBV cause continuous low-grade viral replication?
B cells
What is post-transplant lymphoproliferative disease?
Polyclonal expansion of B cells associated with immunosuppression used in organ transplants (due to breakdown of immunosurveillance keeping the B cells and EBV in check)
This predisposes to lymphoma
How is post-transplant lymphoproliferative disease treated?
Reduce immunosuppression
Rituximab (anti-CD20)
Name two examples of neuraminidase inhibitors.
Oseltamivir (Tamiflu) – oral
Zanamivir (Relenza) – dry powder
Outline the treatment of BK haemorrhagic cystitis.
Bladder washouts
Reduce immunosuppression
Cidofovir IV (may consider intravesical)
Outline the treatment of BK nephropathy.
Reduce immunosuppression
IVIG
NOTE: cidofovir cannot be used because it is nephrotoxic
In which subgroup of patients is adenovirus a major issue?
Paediatric transplant patients
Outline the treatment of adenovirus infection in transplant patients.
Cidofovir IV
IVIG
Brincidofovir (prodrug of cidofovir currently undergoing clinical trials)
What are the main treatment options for drug resistant HSV and CMV infection?
Foscarnet and cidofovir
What is the herd immunity threshold?
Threshold = 1 – 1/R0
What are the three main types of memory cell?
Memory B cells
Memory killer T cells
Memory T helper cells
List examples of inactivated vaccines
Influenza
Polio
Cholera
List examples of live attenuated vaccines
MMR
Yellow fever
List examples of toxoid vaccines
Diphtheria
Tetanus
List examples of subunit vaccines
Hepatitis B
HPV
List examples of conjugate vaccines
Haemophilus influenzae type B
List examples of heterotypic vaccines
BCG
List some contraindications for vaccines.
Previous anaphylactic reactions
Anaphylactic reaction to egg is contraindicated with the influenza vaccine
Immunocompromised and pregnant women should not receive live attenuated vaccines
If acutely unwell on the day of vaccination
DTP is contraindicated if evidence of neurological abnormality
List some examples of serious reactions associated with the following DTP vaccination
Encephalopathy
Shock
Anaphylaxis
List some examples of serious reactions associated with the following polio vaccination
Guillain-Barre syndrome
Polio
List some examples of serious reactions associated with the following measles vaccination
Anaphylaxis
Thrombocytopaenia
List some examples of serious reactions associated with the following rubella vaccination
Acute arthritis
List some examples of serious reactions associated with the following T/ DT/ Td vaccination
Guillain-Barre syndrome
Brachial neuritis
Anaphylaxis
List some examples of serious reactions associated with the following Hep B vaccination
Anaphylaxis
Which infections are screened for in pregnancy?
HIV
Hepatitis B
Syphilis
What are the possible outcomes for neonates with congenital toxoplasmosis?
Asymptomatic (60%) at birth but go on to develop long-term sequelae such as deafness, low IQ and microcephaly
Symptomatic (40%) at birth
· Choroidoretinitis
· Microcephaly/hydrocephalus
· Intracranial calcifications
· Seizures
· Hepatosplenomegaly/jaundice
What is the triad of features in congenital rubella syndrome?
Cataracts
Congenital heart disease (PDA is most common)
Deafness
Other features: microphthalmia, glaucoma, retinopathy, ASD/VSD, microcephaly, meningoencephalopathy, developmental delay
How is herpes simplex virus transmitted to the neonate?
Lesions in the genital tract can transmit HSV to the neonate
It causes a blistering rash and can cause disseminated infection with liver dysfunction and meningoencephalitis
How if Chlamydia trachomatis transmitted to the neonate and what disease does it cause in the neonate?
During delivery
Causes neonatal conjunctivitis or pneumonia
NOTE: it is treated with erythromycin
What type of bacterium is Group B Streptococcus?
Gram-positive coccus
Catalase negative
Beta haemolytic
What type of organism is E. coli and which diseases can it cause in the neonate?
Gram-negative rods
Can cause bacteraemia, meningitis and UTI
NOTE: the K1 antigen is particularly problematic
What type of organism is Listeria monocytogenes and what disease can it cause?
Gram-positive rods
Causes sepsis in the mother and the newborn
List some investigations that may be useful in early-onset sepsis.
FBC
CRP
Blood culture
Deep ear swab
LP
Surface swabs
CXR
Which antibiotic combination is often used in early-onset sepsis and why?
Benzylpenicillin and gentamicin
Benzylpenicillin covers Group B Streptococcus whilst gentamicin covers E. coli
What is late-onset sepsis?
Sepsis that occurs more than 48-72 hours after birth
What are the main causes of late-onset sepsis?
Coagulase negative staphylococci (e.g. S. epidermidis)
GBS
E. coli
Listeria monocytogenes
S. aureus
Enterococcus sp.
Gram-negatives (e.g. Klebsiella, Enterobacter, Pseudomonas)
List some clinical features of late-onset sepsis.
Bradycardia
Apnoea
Poor feeding
Irritability
Convulsions
Jaundice
Respiratory distress
Outline the treatment of late-onset sepsis.
Treat early with antibiotics
Guidelines differ
Example antibiotic regimen: 1st line = cefotaxime + vancomycin; 2nd line = meropenem
What are some common non-specific symptoms of infections in childhood?
Fever
Abdominal pain
List some investigations for meningitis in children.
Blood cultures
Throat swab
LP
Rapid antigen screen
EDTA for blood PCR
Clotted serum for serology
What is the main bacterial cause of meningitis at the moment?
Meningitis B
What type of organism is Streptococcus pneumoniae?
Gram-positive diplococcus
Alpha haemolytic
Which diseases can S. pneumoniae cause?
Meningitis
Pneumonia
Bacteraemia
What type of organism is Haemophilus influenzae?
Gram-negative cocco-bacilli
What are the typical causes of meningitis for under 3 months
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae
Group B Streptococcus
Escherichia coli
Listeria monocytogenes
What are the typical causes of meningitis for 3 months to 5 years
Neisseria meningitis
Streptococcus pneumoniae
Haemophilus influenzae
What are the typical causes of meningitis for over 6 years
Neisseria meningitidis
Streptococcus pneumoniae
What is the most important bacterial cause of respiratory tract infection in children?
Streptococcus pneumoniae
Which children are mainly affected by Mycoplasma pneumoniae?
Older children (> 4 years)
Which group of antibiotics are used to treat Mycoplasma pneumoniae?
Macrolides
Describe the classical presentation of Mycoplasma pneumoniae.
Fever
Headache
Myalgia
Pharyngitis
Dry cough
List some extra-pulmonary manifestations of Mycoplasma pneumoniae.
Haemolysis – IgM antibodies to I antigen on erythrocytes, cold agglutinins
Neurological – encephalitis, aseptic meningitis, peripheral neuropathy, transverse myelitis
Polyarthralgia
Cardiac
Otitis media
Bullous myringitis (vesicles on the tympanic membrane – pathognomonic of Mycoplasma)
If a respiratory tract infection fails to respond to conventional treatment, which diagnoses should be considered?
Whooping cough
TB
What are the main organisms responsible for UTI in children?
E. coli
Other coliforms (Proteus, Klebsiella, Enterococcus)
Coagulase-negative Staphylococcus (S. saprophyticus)
List three examples of Yeast
Candida
Cryptococcus
Histoplasma (dimorphic)
List three examples of Moulds
Aspergillus
Dermatophytes
Agents of mucormycosis
Which systemic infections can be caused by Candida?
Septicaemia, endocarditis, meningitis
List some agents that can cause candidiasis.
Candida albicans (MOST COMMON)
Candida glabrata
Candida krusei
Candida tropicalis
What does generalised candidiasis in babies usually occur secondary to?
Seborrhoeic dermatitis
Outline diagnostic tests used for candidiasis.
Swabs
Blood cultures
Beta-D glucan assay (serology)
Imaging
What type of agar is needed for culturing Candida?
Sabouraud agar – impregnated with antibiotics to prevent bacteria from outcompeting the fungi
Outline the management of candidiasis.
At least 2 weeks of antifungals after the last negative culture
Echo and fundoscopy to look for endocarditis/endophthalmitis
Echinocandins – empirical for non-albicans infections
Fluconazole – empirical for Candida albicans
Which group of antifungals is Cryptococcus inherently resistant to?
Echinocandins
What is the treatment of choice for Cryptococcus infection?
Ambisome (amphotericin B)
What is the main aetiological agent in cryptococcosis.
Cryptococcus neoformans
Why might a lumbar puncture be negative in cryptococcal meningitis?
Cryptococcal meningitis can cause hydrocephalus which prevents the circulation of CSF meaning that the sample taken at LP may not have been exposed to CSF within other parts of the ventricular system
Outline the treatment options for Cryptococcus infection.
3 weeks amphotericin B (ambisome) +/- flucytosine
Repeat LP for pressure measurement
Secondary suppression – fluconazole
List the diseases that can be caused by Aspergillus.
Mycotoxicosis
Allergic bronchopulmonary aspergillosis
Aspergilloma
Invasive/disseminated disease
What is the mainstay of diagnosis of Aspergillus infection?
Microscopy – looking at fungal spores
What is the mainstay of treatment for aspergillosis?
Amphotericin for at least 6 weeks
Other options: voriconazole, caspofungin, itraconazole
List some examples of dermatophyte infections.
Ringworm
Tinea
Nail infections
What is tinea pedis caused by?
Tricophyton rubrum
Tricophyton interdigitale
Epidermophyton floccosum
What is tinea cruris caused by?
Tricophyton rubrum
Epidermophyton floccosum
What is tinea corporis caused by?
Tricophyton rubrum
Tricophyton tonsurans
What is onychomycosis caused by?
Tricophyton spp.
Epidermophyton spp.
Microsporum spp.
How is onychomycosis treated?
Nail lacquers
If unsuccessful, systemic treatment with terbinafine
Itraconazole is also an option
How are dermatophyte infections diagnosed?
Skin scrapings and microscopy
What is pityriasis versicolor caused by?
Malassezia furfur
What is the characteristic clinical manifestation of mucormycosis?
Cellulitis of the orbit and face which progresses with discharge and black pus from the palate and nose
NOTE: black eschars may be seen as the fungus destroys tissues
What is the term used to describe invasion of the brain by mucormycosis?
Rhinocerebral mucormycosis
List three aetiological agents that can cause mucormycosis.
Rhizopum spp.
Rhizomucor spp.
Mucor spp.
How is mucormycosis managed?
SURGICAL EMERGENCY
Refer to ENT for debridement
May need high-dose amphotericin
List some examples of echinocandins.
Caspofungin
Micafungin
Anidulafungin
Which fungi are echinocandins active against?
Candida species
Aspergillus species (NOT other moulds)
IMPORTANT: it has NO coverage for Cryptococcus
List examples of azoles along with their usual indications:
Fluconazole – active against Candida and Cryptococcus
Voriconazole – similar to fluconazole but better activity against Aspergillus
Itraconazole – useful against dermatophytes
Posaconazole – activity against mucor
What is the main polyene antifungal?
Amphotericin B
Amphotericin B is active against most fungi except…
Aspergillus terreus
Scedosporium spp.
Which fungi are flucytosine active against?
Candidiasis
Cryptococcosis
What type of virus is rubella?
RNA virus
Togaviridae family
What is the role of pre-natal diagnosis of rubella?
All cases of symptomatic rubella infection in the 1st trimester should be considered for termination of pregnancy without prenatal diagnosis
What is the definition of congenital CMV infection?
Detection of CMV from bodily fluids (normally urine and saliva) or tissues within the first 3 weeks of life
NOTE: it is the MOST COMMON congenital viral infection
What is the main consequence of congenital CMV infection?
Sensorineural hearing loss
At what stage in pregnancy does CMV infection pose a risk to the foetus?
At any stage in pregnancy
What proportion of cases of congenital CMV infection are asymptomatic at birth?
90%
How is congenital CMV infection treated?
There is NO vaccine
Congenital CMV with significant organ disease
· Valganciclovir or ganciclovir for 6 months
· Audiology follow-up until age 6 years
· Ophthalmology review
In which scenario will the neonate be at highest risk of acquiring HSV from the mother?
Primary HSV infection in the 3rd trimester (particularly within 6 weeks of delivery)
C-section is recommended
Outline the manifestations of neonatal HSV disease.
Skin, eyes and mouth (SEM) disease
CNS disease with or without SEM
Disseminated infection involving multiple organs (high mortality)
Describe the clinical presentation of intrauterine HSV infection.
Neurological – microcephaly, encephalomalacia, intracranial calcification
Cutaneous – scarring, active lesions
Ophthlamologic – microophthalmia, optic atrophy, chorioretinitis
Outline the features of disseminated HSV infection.
DIC
Pneumonia
Hepatitis
CNS involvement
NOTE: has a 30% mortality
Outline the manifestations of HSV encephalitis.
Seizures
Lethargy
Poor feeding
Temperature instability
NOTE: this tends to present late – 10-28 days
Describe the treatment of neonatal HSV infection.
High-dose IV aciclovir (60 mg/kg/day) in three divided doses
For 21 days minimum in disseminated disease (repeat LP and CSF PCR until PCR-negative)
For 14 days minimum in SEM disease
Monitor neutrophil count
What type of virus is VZV?
DNA virus of the herpes family
What are the risks to the mother of VZV infection during pregnancy?
Pneumonia
Encephalitis
List the main features of congenital varicella syndrome.
LBW
Cutaneous scarring
Limb hypoplasia
Microcephaly
Chorioretinitis
Cataracts
At what stage in pregnancy is the risk of congenital varicella syndrome highest?
13-20 weeks
NOTE: shingles has no risk in pregnancy
List some complications of measles.
Opportunistic bacterial infection (otitis media, pneumonia, bronchitis)
Encephalitis
Subacute sclerosing panencephalitis
· Tends to occur 6-15 years after measles infection
· Present with delays motor skills and behavioural problems
What are the risks of measles in pregnancy?
Foetal loss (miscarriage, intrauterine death)
Preterm delivery
Increased maternal morbidity
IMPORTANT: NO congenital abnormalities to the foetus
How should pregnant women who have been in contact with suspected/confirmed measles be treated?
Measles immunoglobulin attenuates the illness if given within 6 days of exposure
What type of virus is parvovirus B19?
DNA virus
Parvoviridae family
Describe the clinical presentation of parvovirus B19 infection.
Erythema infectiosum (fifth disease, slapped cheek syndrome)
Transient aplastic crisis
Arthralgia
Non-immune hydrops fetalis
At what stage in pregnancy is parvovirus B19 infection most concerning?
< 20 weeks gestation
What are some consequences of Zika virus infection in pregnancy.
Miscarriage
Stillbirth
Congenital zika syndrome
· Severe microcephaly
· Decreased brain tissue
· Seizures
· Retinopathy/deafness
· Talipes
· Hypertonia
Name two groups of antibiotics that inhibit cell wall synthesis.
Beta-lactams
Glycopeptides
What are the three groups of beta-lactam antibiotics?
Penicillins
Cephalosporins
Carbapenems
Give two examples of glycopeptides.
Vancomycin
Tiecoplanin
Which type of bacteria are beta-lactams ineffective against?
Bacteria with no cell wall (e.g. Mycoplasma and Chlamydia)
List four types of penicillin.
Penicillin
Amoxicillin
Flucloxacillin
Piperacillin
For each of the following antibiotics, describe their coverage and mechanisms of resistance:
a. Penicillin
Active against Gram-positives (e.g. Streptococci, Clostridia)
Broken down by beta-lactamases (mainly produced by S. aureus)
NOTE: penicillin is the MOST ACTIVE beta-lactam antibiotic
b. Amoxicillin
Broad-spectrum penicillin
Extends coverage to Enterococci and Gram-negative organisms
Broken down by beta-lactamase produced by S. aureus and many Gram-negatives
c. Flucloxacillin
Similar to penicillin but less active
Does NOT get broken down by beta-lactamase produced by S. aureus
d. Piperacillin
Similar to amoxicillin
Extends coverage to Pseudomonas and other non-enteric Gram-negative organisms
Broken down by beta-lactamase produced by S. aureus and many Gram-negatives
Name two beta-lactamase inhibitors. What is the benefit of giving beta-lactamase inhibitors with beta-lactams?
Clavulanic acid
Tazobactam
Protect penicillins from breakdown by beta-lactamases thereby increasing the coverage to include S. aureus, Gram-negatives and anaerobes
List examples of 1st, 2nd and 3rd generation cephalosporins.
1st = cephalexin
2nd = cefuroxime
3rd = ceftriaxone, ceftazidime, cefotaxime
NOTE: as you go up the generations you get increasing activity against Gram-negatives and less activity against Gram-positives
What is ceftriaxone often used to treat?
Bacterial meningitis
What is a disadvantageous association of ceftriaxone?
Associated with C. difficile infection
What is a benefit of ceftazidime?
Good anti-Pseudomonas cover
What are extended spectrum beta-lactamases (ESBL)?
Type of beta-lactamase that also breaks down cephalosporins as well as penicillins
What is the main benefit of carbapenems?
They are stable to ESBL enzymes
List three examples of carbapenems.
Meropenem
Imipenem
Ertapenem
List examples of bacteria that have shown carbapenem resistance.
Acinetobacter
Klebsiella
Outline the key features of beta-lactam antibiotics.
Relatively non-toxic
Renally excreted (reduced dose in renal impairment)
Short half-life
Will not cross an intact blood-brain barrier (may cross inflamed meninges in meningitis)
Cross allergenic (penicillins have 5-10% cross-reactivity with cephalosporins and carbapenems)
Which type of bacteria are glycopeptides effective against and why?
Gram-positives
They are large molecules so they cannot cross the outer membrane of Gram-negative cell walls
What are glycopeptides often used to treat?
Serious MRSA infections
C. difficile infections (oral vancomycin)
What is a major side-effect of glycopeptides?
Nephrotoxic
Monitor blood levels to prevent accumulation
List some classes of antibiotics that work by inhibiting protein synthesis.
Aminoglycosides
Tetracyclines
Macrolides
Lincosamides (e.g. clindamycin)
Streptogramins (e.g. Synercid)
Chloramphenicol
Oxazolidinones (e.g. linezolid)
What are some major side-effects of aminoglycosides?
Ototoxic and nephrotoxic
Which aminoglycosides are particularly active against Pseudomonas aeruginosa?
Gentamicin
Tobramycin
Which class of antibiotics can aminoglycosides be used in combination with to produce a synergistic effect?
Beta-lactams (e.g. in endocarditis)
Which type of bacteria do aminoglycosides have no activity against?
Anaerobes
Which environmental feature will inhibit the activity of aminoglycosides?
Inhibited by low pH so are not very effective in abscesses
What are tetracyclines?
Broad-spectrum agents with activity against intracellular pathogens (e.g. Chlamydiae, Rickettsiae and Mycoplasmas) as well as most conventional bacteria
What is a major issue with tetracyclines?
Widespread resistance (most Gram-negatives)
Which groups of patients should not receive tetracyclines?
Children and pregnant women
Because it can deposit in bone and cause discoloration of growing teeth
What are macrolides mainly used for?
Mild staphylococcal and streptococcal infections in penicillin-allergic patients
Also active against Campylobacter, Legionella and Pneumophila
What are two major risks of taking chloramphenicol?
Aplastic anaemia
Grey baby syndrome – neonates have reduced ability to metabolise the drug
Which organisms are oxazolidinones active against?
Gram-positives (including MRSA and VRE)
Not active against Gram-negatives
List two groups of antibiotics that inhibit DNA synthesis.
Quinolones
Nitroimidazoles
List 3 examples of quinolones.
Ciprofloxacin
Moxifloxacin
Levofloxacin
List 2 examples of nitroimidazoles.
Metronidazole
Tinidazole
Describe the activity of quinolones.
Broad antibacterial activity, especially against Gram-negatives, including Pseudomonas aeruginosa
NOTE: newer agents increased activity against Gram-negatives and intracellular organisms
List some uses of quinolones.
UTIs
Pneumonia
Atypical pneumonia
Bacterial gastroenteritis
Describe the activity of rifampicin.
Mainly Mycobacteria and Chlamydiae
What should be monitored when on rifampicin?
LFTs (it is metabolised by the liver)
What is a common side-effect of rifampicin?
Orange secretions (urine, contact lenses)
Why should rifampicin never be used alone?
Resistance develops rapidly due to chromosomal mutation (single amino acid change in beta-subunit of RNA polymerase)
Name two cell membrane toxins.
Daptomycin
Colistin
Describe the activity of daptomycin.
Gram-positives
Likely to be used in treating MRSA and VRE
NOTE: it is a cyclic lipopeptide
Describe the activity of colistin.
Active against Gram-negatives including Pseudomonas aeruginosa, Acinetobacter baumanii and Klebsiella pneumoniae
NOTE: it is a polymyxin
Name two families of antibiotics that work by inhibiting folate metabolism.
Sulphonamides
Diaminopyrimidines
What is co-trimoxazole?
Sulphamethoxazole + trimethoprim
What is trimethoprim commonly used to treat?
Community-acquires UTIs
Which bacteria produce beta-lactamases?
S. aureus and Gram-negative bacilli (coliforms)
NOTE: this is not the mechanism of resistance in pneumococcus and MRSA
In which groups of bacteria is penicillin resistance not reported in?
Group A, B, C and G beta-haemolytic streptococci
What are extended spectrum beta-lactamases?
Able to breakdown cephalosporins as well as penicillins
Becoming more common in E. coli and Klebsiella
NOTE: if there is > 10% resistance then empirical therapy is not advised
What are AmpC beta-lactamases?
Breakdown penicillins and cephalosporins but are not inhibited by clavulanic acid
What type of antibiotics should be used in nosocomial infections and severe sepsis?
Broad-spectrum
Describe the type I pattern of antibiotic activity. Give an example of an antibiotic of this type.
Concentration-dependent killing
Peak above the MIC (Cmax) is the most important parameter
Example: aminoglycosides
These drugs tend to be given as one big dose
The benefits of achieving a higher Cmax must be balanced with the increased toxicity
Trough concentration should also be measured to ensure that the drug is being eliminated (this determines the frequency of drug administration)
Describe the type II pattern of antibiotic activity. Give an example of an antibiotic of this type.
Time-dependent killing
Time spent above the MIC is the most important factor
Example: penicillins
Therefore, penicillins need to be given frequently
Describe the type III pattern of antibiotic activity. Give an example of an antibiotic of this type.
Concentration and time-dependent
AUC above the MIC is the most important factor
Example: vancomycin
NOTE: infusions may be used to maintain an AUC above the MIC
Outline the typical length of treatment for N. meningitidis meningitis
7 days
Outline the typical length of treatment for Acute osteomyelitis
6 weeks
Outline the typical length of treatment for Bacterial endocarditis
4-6 weeks
Outline the typical length of treatment for Group A streptococcal pharyngitis
10 days
Outline the typical length of treatment for Simple cystitis
3 days
Name two common organisms that cause skin infections.
Streptococcus pyogenes
Staphylococcus aureus
How are simple skin infections treated?
Flucloxacillin
NOTE: unless penicillin allergic or MRSA
How should invasive group A streptococcal infection be treated?
Aggressive and early debridement
Early use of antibiotics (e.g. clindamycin)
Use of IVIG
List some common organisms that cause bacterial respiratory tract infections.
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Atypicals: Legionella, Mycoplasma, Chlamydia
What is used to treat Pharyngitis
Benzylpenicillin (10 days)
What is used to treat CAP (mild)
Amoxicillin
What is used to treat CAP (severe)
Co-amoxiclav and clarithromycin
List some treatment options for hospital-acquired pneumonia.
Cephalosporins
Ciprofloxacin
Tazocin
If MRSA, consider adding vancomycin
List the main pathogens that cause meningitis.
Neisseria meningitidis
Streptococcus pneumoniae
Listeria monocytogenes (in the very young, elderly and immunocompromised)
What is the mainstay of treatment for bacterial meningitis?
Ceftriaxone
NOTE: consider adding amoxicillin if Listeria is likely
How is meningitis in babies < 3 months treated?
Cefotaxime + amoxicillin
NOTE: ceftriaxone is NOT used in neonates because it displaces bilirubin from albumin and causes biliary sludging
What are the treatment options for N. meningitidis meningitis?
Benzylpenicillin
Ceftriaxone or cefotaxime
Outline the treatment of Simple cystitis
Trimethoprim (3 days)
Outline the treatment of Hospital-acquired UTI
Cephalexin or co-amoxiclav
Outline the treatment of Infected urinary catheter
Change catheter under gentamicin cover
How is C. difficile colitis treated?
Stop the offending antibiotic (usually a cephalosporin)
If severe, treat with metronidazole or vancomycin
List the major classes of immunosuppressive drugs.
Glucocorticoids
Calcineurin inhibitors (cyclosporin, tacrolimus)
Anti-proliferative agents (azathioprine, mycophenolate mofetil, sirolimus)
Antibodies (e.g. rituximab)
Co-stimulation blockers
List some iatrogenic causes of immunosuppression in order of increasing risk of opportunistic viral infection.
DMARDs and steroids (LOWEST RISK)
Cytotoxic chemotherapy
Monoclonal antibodies
Solid organ transplant
Advanced HIV
Allogeneic stem cell transplant (HIGHEST RISK)
What is a feature of chronic hepatitis B infection on serology?
Persistent HBsAg
What does parvovirus B19 cause in the immunocompromised?
Causes chronic anaemia
What are the three main types of worms? List some examples of each.
Cestodes (tape worms)
· Pork/beef/fish tapeworms
· Hydatid disease
Trematodes (flukes)
· Schistosomiasis
Nematodes (roundworms)
· Hookworms
· Ascarids
· Strongyloides
What are the two types of pork and beef tapeworms?
Taenia solium – pork (can invade human tissues causing cysticercosis)
Taenia saginata – beef
How are worms treated?
Praziquantel
What are the five main soil-transmitted helminths?
Ascaris lumbricoides
Strongyloides stercoralis
Trichuris trichiura
Enterobius vermicularis
Hookworm
NOTE: they are very well adapted to humans so cause little disease
How can soil-transmitted helminths cause disease?
Migration (Ascaris and Strongyloides)
Intestinal obstruction (large worm burden)
Malabsorption and blood loss
Psychological distress
How does Strongyloides caused damage?
Most are ASYMPTOMATIC
Hyperinfection
Larvae currens (itchy rash)
Malabsorption
How is Strongyloides treated?
Ivermectin
How are the nematode infections that cause filariasis spread?
Blackflies and mosquitoes
Outline the classification of filariasis.
Based on location
Lymphatic filariasis
· Wucheria
· Brugia
Subcutaneous filariasis
· Onchocerciasis
· Mansonella
· Loa Loa
Serous cavity filariasis
· Mansonella
· Dirofilaria
NOTE: adult worms are only found in humans
What is myiasis?
Parasitisation of human flesh by fly larvae
Name two types of myiasis.
Bot (South America)
Tumbu (Africa)
NOTE: damage is caused by maggots eating surrounding flesh
How is myiasis treated?
Removal of larvae by asphyxiation or surgery
List some causes of eosinophilia.
Atopy
Drug allergy
Some malignancy (mainly Hodgkin lymphoma)
Systemic autoimmune disease (e.g. SLE)
Some forms of vasculitis (e.g. Churg-Strauss syndrome)
Cholesterol embolism
Parasites
· Soil-transmitted helminths (especially Strongyloides)
· Schistosomiasis
· Filariasis
· Leaking hydatid cyst
Outline the components of a reasonable parasite screen.
Serology: Strongyloides, Schistosoma, filaria
Stool microscopy
What is the most common cause of adult-onset seizures worldwide?
Brain worms
Which organism causes cysticercosis?
Taenia solium
List some CNS manifestations of cysticercosis.
Epilepsy
Raised ICP
Headache
Altered mental state
Stroke
Blindness
How is the acquisition of pig tapeworm different from the acquisition of cysticercosis?
Ingesting cysts from undercooked pork will lead to the development of adult tapeworms in the human GI tract
Ingesting tapeworm eggs will lead to cysticercosis
Outline the management of cysticercosis.
Anticonvulsants
Advice not to drive
Ventriculo-peritoneal shunt if hydrocephalus
Cestocidal drugs (e.g. praziquantel, albendazole)
This MUST be given with steroids to reduce inflammation around dying cysts
List some risk factors for TB.
Malnutrition (most common)
HIV (very serious risk factor)
Poverty
Underweight
Past TB
What is the vector for malaria?
Anopheles mosquito (female)
What are the five species of Plasmodium.
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
Describe the clinical features of malaria.
Cyclical or continuous fevers with spikes
Malaria paroxysms – chills, high fever, sweats
List some clinical features of severe malaria.
High parasitaemia
Altered consciousness
ARDS
Circulatory collapse
Metabolic acidosis
Renal failure
Hepatic failure
Coagulopathy
Severe anaemia
Hypoglycaema
What is the main investigation for malaria?
Perform 3 thick and thin blood films
Thick – screening for parasites (sensitive)
Thin – identifying the species and quantifying the parasite (proportion of red cells that have been parasitised)
Which stains are used for malaria?
Giemsa
Field’s
Outline the treatment options for non-falciparum malaria.
Chloroquine – 3 days
Primaquine – 30 mg for 14 days
What must you do before giving someone primaquine?
Screen for G6PD deficiency as primaquine can cause extensive haemolysis
What counts as ‘mild’ falciparum malaria?
Not vomiting
Parasitaemia < 2%
Outline the treatment options for mild falciparum malaria.
Oral malarone (atovaquone and proguanil)
Artemisinin combination therapy (ACT)
Oral quinine (RARELY used)
Outline the treatment of severe falciparum malaria.
ABCDE approach
Correct hypoglycaemia
Cautious hydration
Organ support if necessary
IV artesunate
Daily parasitaemia monitoring
Follow on with oral antimalarials
What is the vector for dengue?
Aedes mosquito
Outline the clinical features of dengue.
Fever
Headache
Myalgia
Erythrodermic rash
Bleeding
Hepatitis
Severe: encephalitis, myocarditis
What are the complications of dengue? In which circumstances does this tend to occur?
Dengue haemorrhagic fever and dengue shock
This occurs in individuals who have previously been infected with a different dengue serotype
Which tropical virus is similar to dengue? What is a key difference?
Chikungunya
Arthralgia is more severe
How is dengue treated?
Identify those at risk of severe disease
Supportive
Outline the clinical course of dengue.
Fever reduces after about 4-5 days
What is the term used to describe a high temperature with a relatively normal heart rate? List some causes.
Sphygmothermic dissociation
Causes: typhoid, yellow fever, brucellosis, tularaemia
What is typhoid fever caused by?
Salmonella typhi and paratyphi
What type of organism is Salmonella typhi?
Gram-negative rod
Outline the clinical features of typhoid.
High prolonged fever
Headache
Rose spots
Constipation
Dry cough
What is the incubation period of typhoid?
7-18 days
List some complications of typhoid.
GI bleeding
Perforation
Encephalopathy
Outline the treatment of typhoid.
Ceftriaxone 2 g IV OD
Azithromycin PO 500 mg BD 7 days
What is a characteristic microscopic feature of mononucleosis?
Atypical lymphocytes
