Microbiology

Question 1

What are the four processes that occur in septicaemia?

Answer 1

Capillary leak – albumin and other plasma proteins lead to hypovolaemia
Coagulopathy – leads to bleeding and thrombosis, endothelial injury results in platelet release reactions, the protein C pathway and plasma anticoagulants are affected
Metabolic derangement – particularly acidosis
Myocardial failure – and multi-organ failure

Question 2

What is a typical MRI feature of TB meningitis?

Answer 2

Leptomeningeal enhancement

Question 3

Name two types of amoeba that cause encephalitis.

Answer 3

Naegleria fowleri

Acanthamoeba species and Balamuthia mandrillaris

Question 4

What is toxoplasmosis and how is it spread?

Answer 4

Obligate intracellular parasite
Spread via oral, transplacental or organ transplant route
From raw/undercooked meats (particularly in France) and contact with cat faeces

Question 5

List some organisms that can cause brain abscesses.

Answer 5

Staphylococci
Streptococci
Gram-negative organisms (mainly in neonates)
TB 
Actinomyces and Nocardia species

Question 6

Describe the Gram-stain and microscopic appearance of:

a. S. pneumoniae
b. N. meningitidis
c. L. monocytogenes
d. TB
e. Cryptococcus

Answer 6

a. S. pneumoniae
Gram-positive alpha-haemolytic diplococci
b. N. meningitidis
Gram-negative non-haemolytic diplococci
c. L. monocytogenes
Gram-positive rods
d. TB
Stains positively with Ziehl-Neelsen (red and blue)
e. Cryptococcus
Stains positively with India ink (appears like an orbit – yeast in the middle with a capsule around the outside)

Question 7

What is another key clinical feature of Cryptococcal meningitis?

Answer 7

High opening pressure

Question 8

What is the generic therapy used in meningitis?

Answer 8

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

Question 9

What is the generic therapy used in meningo-encephalitis?

Answer 9

Aciclovir 10 mg/kg IV TDS
Ceftriaxone 2 g IV BD
If > 50 years or immunocompromised = amoxicillin 2 g IV 4 hourly

Question 10

Name the specific therapy for meningitis caused by:

a. S. pneumoniae
b. N. meningitidis
c. H. influenzae
d. Group B Streptococcus
e. Listeria
f. Gram-negative bacilli
g. Pseudomonas

Answer 10

a.	S. pneumoniae
Pen G 18-24 mu/day
b.	N. meningitidis
Ceftriaxone 4 g/day
c.	H. influenzae
Cefotaxime 12 g/day
d.	Group B Streptococcus
Pen G 18-24 mu/day
e.	Listeria
Ampicillin 12 g/day
f.	Gram-negative bacilli
Cefotaxime 12 g/day
g.	Pseudomonas
Meropenem 6 g/day

Question 11

What type of toxin is produced by Staphylococcus aureus?

Answer 11

Enterotoxin – this is an exotoxin that can act as a superantigen in the GI tract triggering the release of IL1 and IL2

Question 12

What type of organism is Bacillus cereus?

Answer 12

Gram-positive rods that are spore-forming

Question 13

Name three types of Clostridium infection and describe the diseases that they cause.

Answer 13

Clostridium botulinum – causes botulism
• From canned food
• Causes disease due to preformed toxin which blocks acetylcholine release at peripheral nerve synapses
- Causes descending paralysis
• Treated with antitoxin
Clostridium perfringens – food poisoning
• From reheated food
• Generates a superantigen that mainly affects the colon
• Causes watery diarrhoea and cramps that last 24 hours
Clostridium difficile – pseudomembranous colitis
• Hospital-acquired infection related to antibiotic use

Question 14

Which antibiotics are most commonly implicated in C. difficile colitis?

Answer 14

Cephalosporins
Clindamycin
Ciprofloxacin

Question 15

What type of organism is Listeria monocytogenes?

Answer 15

Gram-positive, rod-shaped, facultative anaerobe

Beta-haemolytic, aesculin-positive with tumbling motility

Question 16

What type of organisms are Enterobacteriaceae?

Answer 16

Facultative anaerobes
Lactose fermenters
Oxidase-negative

Question 17

What type of bacteria are Salmonella enteritidis?

Answer 17

Gram-negatives
Oxidase negative
Urease negative
Non-lactose fermenting
Produce hydrogen sulphide (form black colonies)
Grows on TSI agar, XLD agar and selenite F broth

Question 18

Which antigens are found on Salmonellae?

Answer 18

Cell wall O (groups A-I)
Flagellar H
Capsular Vi (virulence, antiphagocytic)
NOTE: differences in these antigens help identify types of Salmonellae

Question 19

Describe the presentation of Salmonella typhi.

Answer 19

Slow onset fever and constipation
May cause splenomegaly, rose spots, bradycardia, anaemia and leucopaenia
Blood cultures may be positive
Transmitted only by humans
Ingested by monocytes and multiplies in Peyer’s patches and spreads via the endoreticular system

Question 20

How is Salmonella typhi treated?

Answer 20

Ceftriaxone

Question 21

List some types of Shigella.

Answer 21

Shigella sonnei
Shigella dysenteriae
Shigella flexneri (MSM)

NOTE: avoid antibiotic treatment (use ciprofloxacin if necessary)

Question 22

What are the microbiological features of Vibrio?

Answer 22

Comma-shaped
Late lactose-fermenters
Oxidase-positive
Gram-negative

Question 23

Name and describe the key features of other types of Vibrio.

Answer 23

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

Question 24

What are the main microbiological features of Campylobacter?

Answer 24

Comma-shaped 
Microaerophilic 
Oxidase-positive 
Gram-negative 
Motile

Question 25

What are the key microbiological features of Entamoeba histolytica?

Answer 25

Motile trophozoite in diarrhoeal illness Non-motile cyst in non-diarrhoeal illness Killed by boiling Contains four nuclei No animal reservoir

Question 26

Describe the pathophysiology of diarrhoeal illness caused by Entamoeba histolytica?

Answer 26

Ingestion of cysts  trophozoites move into the ileum  colonise the colon  causes flask-shaped ulcers

Question 27

How is Entamoeba histolytica infection diagnosed and treated?

Answer 27

Diagnosis: stool microscopy, serology of invasive disease Treatment: metronidazole + paromomycin

Question 28

What are the key microbiological features of Giardia lamblia?

Answer 28

Pear-shaped trophozoites Two nuclei Four flagellae and a suction disc

Question 29

Outline the pathophysiologiy of GI disease caused by Giardia.

Answer 29

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

Question 30

What are the main features of Cryptosporidium parvum?

Answer 30

Causes severe diarrhoea in the immunocompromised Oocysts can be seen in the stool using modified Kinyoun acid fast stain Rx: paromomycin

Question 31

Which stain is used to identify PCP?

Answer 31

Silver stain (Grocott-Gomori stain)

Question 32

Which organisms do the following defects make you susceptible to? a. T cell defect b. B cell defect c. Neutrophil defect d. Complement defect

Answer 32

``` a. T cell defect Sepsis CMV, EBV, VZV Candida, PCP Usually aggressive opportunistic infections b. B cell defect Streptococcus, Staphylococcus, Haemophilus Giardia Usually recurrent sinopulmonary infections c. Neutrophil defect Staphylococcus, Pseudomonas Candida, nocardia, aspergillus d. Complement defect Neisseria ```

Question 33

What is Actinomyces and what does it cause?

Answer 33

Gram-positive rod that causes lung abscesses in immunocompromised patients (particularly alcoholics) NOTE: it’s closely associated with Nocardia

Question 34

Describe the histological features of Actinomyces.

Answer 34

Basophilic sulfur granules | Gram-positive rods that branch as they grow

Question 35

How is non-severe C. difficile disease treated?

Answer 35

Metronidazole 400 mg TDS for 10-14 days | If intolerant or not responding at 72 hours, change to vancomycin 125 mg QDS for 10-14 days

Question 36

Describe the MRI appearance of sporadic CJD.

Answer 36

Increased signal in the basal ganglia | Increased intensity on DWI MRI of the cortex and basal ganglia

Question 37

On which chromosome is the normal prion gene found?

Answer 37

20

Question 38

On which codon are the three polymorphisms of prion proteins found? What are the three polymorphisms?

Answer 38

``` Codon 129 MM (predisposes to prion diseases) MV VV NOTE: M = methionine, V = valine ```

Question 39

Which gene mutation is associated with prion diseases?

Answer 39

PRNP

Question 40

Which investigation is most useful for vCJD?

Answer 40

Tonsillar biopsy – prions localise in lymphoid tissue | NOTE: this is not useful in CJD

Question 41

Outline the clinical features of iatrogenic CJD.

Answer 41

Starts with progressive ataxia | Dementia and myoclonus occur at a later stage

Question 42

Describe the clinical features of Gerstmann-Straussler-Sheinker syndrome.

Answer 42

Slowly progressive ataxia Diminished reflexes Dementia NOTE: PRNP P102L mutation is most common

Question 43

Describe the clinical features of fatal familial insomnia.

Answer 43

``` Untreatable insomnia Dysautonomia (blood pressure and heart rate dysregulation) Ataxia Thalamic degeneration NOTE: PRNP D178N mutation is most common ```

Question 44

What number of white cells in the urine represents inflammation?

Answer 44

More than 10^4/mL

Question 45

In which patient groups should screening of the urine for white cells before MC&S NOT be performed?

Answer 45

Immunocompromised patients, pregnant women and children

Question 46

List some causes of sterile pyuria.

Answer 46

``` STIs (e.g. chlamydia) TB Prior antibiotic treatment (MOST COMMON) Calculi Catheterisation Bladder cancer ```

Question 47

What type of agar is used for urine culture? What do the colours suggest?

Answer 47

Chromogenic agar • Pink = E. coli • Blue = other coliforms • Light blue = Gram-positives

Question 48

In which groups of patients is a short course of antibiotics not appropriate?

Answer 48

Women with a history of UTI caused by antibiotic resistant organisms More than 7 days of symptoms Men

Question 49

Which part of the kidney is more susceptible to infection?

Answer 49

Renal medulla NOTE: the kidney is a frequent site for abscesses in patients with S. aureus endocarditis

Question 50

What is the main treatment option for pyelonephritis?

Answer 50

Co-amoxiclav with or without gentamicin

Question 51

What is the incubation period for hepatitis A?

Answer 51

2-6 weeks

Question 52

Describe the molecular organisation of hepatitis B virus.

Answer 52

DNA virus with four overlapping reading frames (core, X, polymerase and surface antigen) NOTE: as they overlap, a mutation in one reading frame could affect others

Question 53

What is a strong indicator of risk of cirrhosis in people with hepatitis B infection?

Answer 53

HBV DNA level (copies/mL)

Question 54

What components constitute the viral RNA genome of hepatitis C?

Answer 54

Core Envelope Non-structural components NOTE: most drugs used for hep C are protease inhibitors

Question 55

What is the incubation period of HCV?

Answer 55

6-8 weeks

Question 56

List some treatment options for chronic HBV.

Answer 56

``` Interferon alpha Lamivudine Tenofovir Entecavir Emtricitabine ```

Question 57

How is HCV treated?

Answer 57

Early treatment with peginterferon alfa

Question 58

How is the response to treatment with peginterferon-alfa assessed in HCV infection?

Answer 58

Sustained viral response (SVR12) – no HCV RNA 12 weeks after stopping treatment NOTE: SVR 24 can also be done

Question 59

What is the main difference in the treatment of genotype 1 and non-genotype 1 HCV?

Answer 59

Genotype 1 and 4 – less responsive to ribavirin and protease-based therapy, requires longer treatment Genotype 2 and 3 - more responsive to protease-based therapy NOTE: ribavirin can also be used to treat RSV

Question 60

Outline the treatment of hepatitis E.

Answer 60

Supportive | Ribavirin

Question 61

Name three major pathogens that cause surgical site infections.

Answer 61

Staphylococcus aureus Escherichia coli Pseudomonas aeruginosa

Question 62

What are the three levels of surgical site infections?

Answer 62

Superficial incisional – skin and subcutaneous tissues Deep incisional – fascial and muscle layers Organ/space infection – any part of the anatomy that is not the incision

Question 63

List some bacterial factors that enable bacteria to cause septic arthritis.

Answer 63

Staphylococcus aureus has receptors such as fibronectin-binding protein Kingella kingae have bacterial pili which adhere to the synovium Some strains of S. aureus produce Panton-Valentine Leukocidin which is associated with fulminant infections

Question 64

List some host factors that increase the risk of septic arthritis.

Answer 64

Leukocyte-derived proteases and cytokines Raised intra-articular pressure Deletion of macrophage-derived cytokines Absence of IL-10

Question 65

Outline the presentation of chronic osteomyelitis.

Answer 65

Pain Brodie’s abscess Sinus tract

Question 66

Name two techniques for treating chronic osteomyelitis.

Answer 66

Laubenbach technique – debridement all the way to healthy bleeding bone and removal of all prosthetic material. Double lumen irrigation used to instil antibiotics into the central lumen Papineau technique – complete excision of infected tissue and necrotic bone followed by open cancellous bone grafting and split skin grafting to the close the wound

Question 67

Which organism most commonly causes prosthetic joint infection?

Answer 67

Coagulase-negative staphylococcus | Others: streptococci, enterococci, enterobacteriaciae, Pseudomonas aeruginosa, anaerobes

Question 68

How is prosthetic joint infection diagnosed?

Answer 68

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)

Question 69

How should specimens be taken intraoperatively?

Answer 69

Specimens should be taken from at least 5 sites around the implant and sent for histology NOTE: if 3 or more specimens yield identical organisms, this is suggestive of prosthetic joint infection

Question 70

List 5 HAIs in order of prevalence.

Answer 70

``` Pneumonia Surgical site infection UTI Blood stream infection Gastrointestinal infection ```

Question 71

Define pyrexia of unknown origin.

Answer 71

A fever > 38.3 degrees lasting > 3 weeks with an uncertain diagnosis after 7 days in hospital

Question 72

List some differentials for PUO.

Answer 72

``` Infection • Infectious endocarditis • HIV • TB Inflammation • Polymyalgia rheumatica • Still’s disease • Sarcoidosis • ANCA-associated vasculitis • Rheumatoid arthritis Malignancy • Malignant lymphoma • Castleman’s disease ```

Question 73

List some infectious causes of PUO.

Answer 73

``` 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 ```

Question 74

What are the different components of EBV serology?

Answer 74

Viral capsid antigen (VCA) IgM – rises early in acute infection VCA IgG – rises later in infection EBNA-1 IgG – rises later in infection EBNA DNA – rapidly cleared if immunocompetent so will be negative in most, may be positive if immunocompromised NOTE: the heterophile antibody test is not recommended because of poor sensitivity and specificity

Question 75

List two causes of very high ferritin.

Answer 75

Adult-onset Still’s disease | Macrophage activation syndrome

Question 76

Outline the major and minor criteria for infective endocarditis.

Answer 76

``` 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 ``` IMPORTANT: 3 blood cultures should be taken in suspected infective endocarditis

Question 77

Outline the key features of Adult-onset Still’s disease.

Answer 77

``` Salmon pink rash Arthralgia Sore throat Lymphadenopathy Fever ```

Question 78

List some miscellaneous causes of PUO.

Answer 78

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

Question 79

Give examples of zoonoses in the UK that are transmitted by: a. Farm/wild animals b. Companion animals

Answer 79

``` a. Farm/wild animals Campylobacter Salmonella b. Companion animals Toxoplasmosis Bartonella Ringworm Psittacosis ```

Question 80

For Campylobacter, describe the following: a. Reservoir b. Transmission c. Clinical presentation d. Investigations e. Management

Answer 80

``` a. Reservoir Poultry Cattle b. Transmission Contaminated food c. Clinical presentation Bloating Diarrhoea Cramps d. Investigations Stool culture e. Management Supportive ```

Question 81

For Salmonella, describe the following: a. Reservoir b. Transmission c. Clinical presentation d. Investigations e. Management

Answer 81

``` a. Reservoir Poultry Reptiles/amphibians b. Transmission Contaminated food Poor hygiene c. Clinical presentation Diarrhoea Vomiting Fever d. Investigations Stool culture e. Management Supportive Ciprofloxacin Azithromycin ```

Question 82

For Cat Scratch Disease, describe the following: a. Presentation b. Investigations c. Management

Answer 82

``` a. Presentation Macule at site of inoculation Becomes pustular Regional adenopathy Systemic symptoms (FLAWS) b. Investigations Serology c. Management Erythromycin Doxycycline ```

Question 83

For baciliary angiomatosis, describe the following: a. Presentation b. Investigations c. Management

Answer 83

``` a. Presentation Skin papules Disseminated multi-organ and vasculature involvement Leads to bursting of blood vessels in various organs and tissues Can be FATAL b. Investigations Histopathology Serology c. Management Erythromycin Doxycycline Rifampicin ```

Question 84

For Toxoplasmosis, describe the following: a. Reservoir b. Transmission c. Clinical presentation d. Investigations e. Management

Answer 84

``` a. Reservoir Cats Sheep b. Transmission Infected meat Faecal contamination c. Clinical presentation Fever Adenopathy Stillbirth Infants with progressive visual, hearing, motor and cognitive issues Seizures Neuropathy d. Investigations Serology e. Management Spiramycin Pyrimethamine + sulfadizine ```

Question 85

For Brucellosis, describe the following: a. Reservoir b. Transmission c. Clinical presentation d. Investigations e. Management

Answer 85

``` a. Reservoir Cattle Goats b. Transmission Unpasteurised milk Undercooked meat Aerosolisation c. Clinical presentation Fever (and rest of FLAWS) Back pain/bone pain Orchitis Focal abscess (psoas or liver) Hepatosplenomegaly d. Investigations Blood/pus culture Serology NOTE: the lab should be warned that you are sending suspected Brucella (they are Gram-negative cocco-bacilli) e. Management Doxycycline + gentamicin or rifampicin ```

Question 86

Which two infectious agents can cause rat bite fever?

Answer 86

Streptobacillus moniliformis | Spirilum minus

Question 87

For rat bite fever, describe the following: a. Reservoir b. Transmission c. Clinical presentation d. Investigations e. Management

Answer 87

``` a. Reservoir Rats b. Transmission Bites Contact with infected urine or droppings c. Clinical presentation Fevers Polyarthralgia Maculopapular progressing to purpuric rash Can progress to endocarditis d. Investigations Joint fluid MC&S Blood culture e. Management Penicillins ```

Question 88

List the most prevalent pathogens causing CAP in the following age groups: a. 0-1 months b. 1-6 months c. 6 months – 5 years d. 16-30 years

Answer 88

``` a. 0-1 months Escherichia coli Group B Streptococcus Listeria monocytogenes b. 1-6 months Chlamydia trachomatis Staphylococcus aureus RSV c. 6 months – 5 years Mycoplasma pneumoniae Influenza d. 16-30 years Mycoplasma pneumoniae Streptococcus pneumoniae ```

Question 89

What medium is Legionella grown on?

Answer 89

Buffered charcoal yeast extract

Question 90

How is PCP investigated?

Answer 90

Bronchoalveolar lavage

Question 91

How is invasive aspergillosis treated?

Answer 91

Amphotericin B

Question 92

Which organisms cause pneumonia in the following subgroups of patients: a. HIV b. Neutropaenia c. Bone marrow transplant d. Splenectomy

Answer 92

``` a. HIV PCP TB Atypical mycobacteria b. Neutropaenia Fungal (e.g. Aspergillus) c. Bone marrow transplant CMV d. Splenectomy Encapsulated organisms (e.g. Streptococcus pneumoniae, Haemophilus influenzae) ```

Question 93

Which respiratory organism is investigated using immunofluorescence?

Answer 93

PCP | NOTE: PCP can also be detected using silver stain

Question 94

What are the 1st and 2nd line treatment options for HAP?

Answer 94

``` 1st = ciprofloxacin +/- vancomycin 2nd = tazocin AND vancomycin ```

Question 95

Which antibiotics are used to treat HAP caused by: a. MRSA b. Pseudomonas

Answer 95

a. MRSA Vancomycin b. Pseudomonas Tazocin OR ciprofloxacin +/- gentamicin

Question 96

What is the difference between yeasts and moulds?

Answer 96

``` Yeast = unicellular Moulds = multicellular and has filaments (hyphae) ```

Question 97

List three types of mycobacterial complex.

Answer 97

``` Mycobacterium tuberculosis complex • Mycobacterium tuberculosis • Mycobacterium bovis Mycobacterium avium complex • Mycobacterium avium • Mycobacterium intracellulare Mycobacterium abscessus complex • Mycobacterium abscessus • Mycobacterium massiliense • Mycobacterium bolletii ```

Question 98

Describe the morphology of mycobacteria.

Answer 98

Non-motile rod-shaped bacteria Relatively slow-growing Cell wall composed of mycolic acids, complex waxes and glycoproteins Acid-alcohol fast

Question 99

List three examples of slow-growing non-tuberculous mycobacteria and the diseases that they cause.

Answer 99

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

Question 100

List three examples of rapid-growing non-tuberculous mycobacteria.

Answer 100

Mycobacterium abscessus Mycobacterium chelonae Mycobacterium fortuitum

Question 101

What are the two types of Mycobacterium leprae infection?

Answer 101

Paucibacillary tuberculoid – few skin lesions, robust T cell response Multibacillary lepromatous – multiple skin lesions, poor T cell response NOTE: tends to present with paraesthesia and hairless skin plaques

Question 102

List some types of extra-pulmonary TB.

Answer 102

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

Question 103

What is NAAT and why is it useful for TB?

Answer 103

Nucleic acid amplification test Allows speciation and the detection of drug resistance mutations Rapid

Question 104

List some side-effects of: a. Rifampicin b. Isoniazid c. Pyrazinamide d. Ethambutol

Answer 104

``` a. Rifampicin Raised transaminases CYP450 induction Orange secretions b. Isoniazid Peripheral neuropathy (give with pyridoxine) Hepatotoxicity c. Pyrazinamide Hepatotoxicity Hyperuricaemia d. Ethambutol Visual disturbance ```

Question 105

What is multi-drug resistant TB?

Answer 105

Resistant to rifampicin and isoniazid

Question 106

What is extremely drug resistant TB?

Answer 106

Resistant to rifampicin, isoniazid, fluoroquinolones and at least 1 injectable (e.g. amikacin, capreomycin)

Question 107

Which valvular defect is most common in rheumatic fever?

Answer 107

Mitral stenosis

Question 108

What is the most common cause of hospital-acquired pneumonia?

Answer 108

Pseudomonas aeruginosa

Question 109

Which congenital infection is associated with periventricular calcification?

Answer 109

CMV

Question 110

Why does influenza cause respiratory disease in humans?

Answer 110

The virus has a haemagglutinin (HA) protein which must be cleaved for the virus to be able to fuse with the endosome membrane and release its genome into the host Human airway tryptase found in the lining of the lung is capable of cleaving HA NOTE: there are some mutated forms of influenza that do not require cleavage of HA to be able to enter host cells (these are particularly virulent)

Question 111

Describe the influenza life cycle.

Answer 111

The virus attaches to cells via the sialic acid receptor They enter through endosomes The acidity of the endosome triggers a fusion event by which the virus releases its genome into the host cell The genome travels to the nucleus and takes over host factors to drive transcription and translation New viral products are produced, which assemble at the surface of the cell and bud off producing hundreds of copies of the virus

Question 112

Which specific mutation is associated with enabling influenza to cross into humans from birds?

Answer 112

PB2 627K (polymerase protein)

Question 113

What is the mechanism of action of amantadine?

Answer 113

Targets the M2 ion channel | A single amino acid mutation (S31N) renders the virus resistant

Question 114

List three examples of neuraminidase inhibitors.

Answer 114

Oseltamivir (Tamiflu) – oral Zanamivir (Relenza) – inhaled or IV Peramivir – IV NOTE: effective if given < 48 hours after infection

Question 115

List two examples of polymerase inhibitors used to treat influenza.

Answer 115

Favipiravir | Baloxavir

Question 116

Outline the mechanism of action of aciclovir.

Answer 116

Guanosine (nucleoside) analogue that is incorporated into growing viral DNA and blocks further elongation Requires activation by viral thymidine kinase (which is only present in host cells that are infected by the virus) Aciclovir has a higher affinity for viral DNA polymerase than host DNA polymerase

Question 117

What are two 2nd line treatment options for aciclovir-resistant VZV infection?

Answer 117

Foscarnet Cidofovir NOTE: they inhibit viral DNA synthesis

Question 118

HSV encephalitis is a medical emergency. How should it be treated?

Answer 118

IMMEDIATE treatment with IV aciclovir 10 mg/kg TDS without waiting for test results If confirmed, treat for 21 days

Question 119

What is HSV meningitis and how should it be treated?

Answer 119

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

Question 120

List some indications for treatment of VZV.

Answer 120

Chickenpox in adults (high risk of pneumonitis) Shingles in adults > 50 years (risk of post-herpetic neuralgia) Infection in immunocompromised patients Neonatal chickenpox If increased risk of complications (e.g. underlying lung disease)

Question 121

In which cells does CMV lie dormant?

Answer 121

Monocytes and dendritic cells

Question 122

What is a characteristic histological feature of CMV infection?

Answer 122

Owl’s eye inclusions

Question 123

What is the 1st line treatment option for CMV infection?

Answer 123

Ganciclovir (IV)

Question 124

How is ganciclovir activated?

Answer 124

Requires activation by viral UL97 kinase enzyme | NOTE: ganciclovir is used in conjunction with IVIG in patients with CMV pneumonitis

Question 125

What is a major side-effect of ganciclovir?

Answer 125

Bone marrow toxicity | NOTE: therefore, its use is limited in bone marrow transplant patients

Question 126

What is the mechanism of action of foscarnet?

Answer 126

Non-competitive inhibitors of viral DNA polymerase NOTE: foscarnet does NOT require activation Tends to be used in CMV infections if ganciclovir is contraindicated

Question 127

What is the mechanism of action of cidofovir?

Answer 127

Competitive inhibitors of viral DNA synthesis (nucleotide analogue) NOTE: does not require activation

Question 128

What is a major side-effect of foscarnet and cidofovir?

Answer 128

Nephrotoxicity | Cidofovir requires hydration and probenecid

Question 129

What is the mechanism of action of maribavir?

Answer 129

Inhibits viral kinase | Effective in vitro, currently undergoing clinical trials

Question 130

What is the mechanism of action of letermovir?

Answer 130

CMV DNA terminase inhibitor | Approved in the USA for CMV prophylaxis in bone marrow transplant patients

Question 131

What are the roles of haemagglutinin and neuraminidase in the influenza virus?

Answer 131

Haemagglutinin – mediates viral binding and entry into target cell Neuraminidase – allows release of progeny virus particles from the host cell

Question 132

What are the 3 indications for use of neuraminidase inhibitors in the community according to NICE?

Answer 132

National surveillance indicates that influenza is circulating Patient is in a risk group Within 48 hours of onset of symptoms

Question 133

What disease states does BK virus cause?

Answer 133

Bone marrow transplant  haemorrhagic cystitis | Renal transplants  BK nephritis and ureteric stenosis

Question 134

Outline the treatment of BK haemorrhagic cystitis.

Answer 134

Bladder washouts Reduce immunosuppression Cidofovir IV (may consider intravesical)

Question 135

Outline the treatment of BK nephropathy.

Answer 135

Reduce immunosuppression IVIG NOTE: cidofovir cannot be used because it is nephrotoxic

Question 136

Outline the treatment of adenovirus infection in transplant patients.

Answer 136

``` Cidofovir IV IVIG Brincidofovir (prodrug of cidofovir currently undergoing clinical trials) ```

Question 137

What are most cases of HSV drug resistance caused by?

Answer 137

Mutations in viral thymidine kinase

Question 138

What are most cases of CMV drug resistance caused by?

Answer 138

Mutations in protein kinase gene UL97

Question 139

What are the main treatment options for drug resistant HSV and CMV infection?

Answer 139

Foscarnet and cidofovir

Question 140

What is the herd immunity threshold?

Answer 140

Threshold = 1 – 1/R0

Question 141

Describe the following types of vaccines: a. Inactivated b. Live attenuated c. Toxoid d. Subunit e. Conjugate f. Heterotypic

Answer 141

a. Inactivated Whole microorganism is destroyed (using heat, radiation or antibiotics) NO risk of causing infection in the host Immune response may not be particularly strong or long-lasting b. Live attenuated Live organisms are modified to be less virulent Risk of acquiring virulence Should be avoided in pregnant women and immunocompromised patients c. Toxoid Inactivated toxin components d. Subunit Protein components of the microorganism or synthetic virus-like particles Lack genetic material and are unable to replicate e. Conjugate Poorly immunogenic antigens are paired with a protein that is highly immunogenic (adjuvant) f. Heterotypic Using pathogens that infect other animals but do NOT cause disease in humans

Question 142

List examples of the following types of vaccine: a. Inactivated b. Live attenuated c. Toxoid d. Subunit e. Conjugate f. Heterotypic

Answer 142

``` a. Inactivated Influenza Polio Cholera b. Live attenuated MMR Yellow fever c. Toxoid Diphtheria Tetanus d. Subunit Hepatitis B HPV e. Conjugate Haemophilus influenzae type B f. Heterotypic BCG ```

Question 143

List some contraindications for vaccines.

Answer 143

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

Question 144

List some examples of serious reactions associated with the following vaccines: a. DTP b. Poliovirus c. Measles d. Rubella e. T/DT/Td f. Hepatitis B

Answer 144

``` a. DTP Encephalopathy Shock Anaphylaxis b. Poliovirus Guillain-Barre syndrome Polio c. Measles Anaphylaxis Thrombocytopaenia d. Rubella Acute arthritis e. T/DT/Td Guillain-Barre syndrome Brachial neuritis Anaphylaxis f. Hepatitis B Anaphylaxis ```

Question 145

Which type of genome do all herpes viruses have?

Answer 145

DNA

Question 146

What is the most common cause of UTI in young, sexually active women?

Answer 146

Staphylococcus saprophyticus

Question 147

List some antibiotics that have anti-Pseudomonas activity.

Answer 147

Gentamicin Ciprofloxacin Tazocin

Question 148

What is the most common viral cause of rapidly progressive glomerulonephritis?

Answer 148

Hepatitis B

Question 149

Which organisms most commonly cause non-bloody diarrhoea and vomiting soon after eating contaminated food?

Answer 149

Bacillus cereus | Staphylococcus aureus

Question 150

What are the two types of paralysis caused by clostridia?

Answer 150

Botulinum --> flaccid paralysis | Tetani --> spastic paralysis

Question 151

What are the possible outcomes for neonates with congenital toxoplasmosis?

Answer 151

``` 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 ```

Question 152

What is the triad of features in congenital rubella syndrome?

Answer 152

Cataracts Congenital heart disease (PDA is most common) Deafness Other features: microphthalmia, glaucoma, retinopathy, ASD/VSD, microcephaly, meningoencephalopathy, developmental delay

Question 153

How if Chlamydia trachomatis transmitted to the neonate and what disease does it cause in the neonate?

Answer 153

During delivery Causes neonatal conjunctivitis (ophthalmia neonatorum) or pneumonia NOTE: it is treated with erythromycin

Question 154

Which mycoplasma species can cause neonatal infection?

Answer 154

Mycoplasma hominis | Ureaplasma urealyticum

Question 155

What are the three main organisms that cause early-onset infection?

Answer 155

Group B Streptococcus E. coli Listeria monocytogenes

Question 156

What type of bacterium is Group B Streptococcus?

Answer 156

Gram-positive coccus Catalase negative Beta haemolytic

Question 157

What type of organism is Listeria monocytogenes and what disease can it cause?

Answer 157

Gram-positive rods | Causes sepsis in the mother and the newborn

Question 158

Which antibiotics are commonly used to treat early-onset sepsis?

Answer 158

Benzylpenicillin + gentamicin

Question 159

What are the main causes of late-onset sepsis?

Answer 159

Coagulase negative staphylococci (e.g. S. epidermidis) GBS E. coli Listeria monocytogenes S. aureus Enterococcus sp. Gram-negatives (e.g. Klebsiella, Enterobacter, Pseudomonas)

Question 160

Outline the treatment of late-onset sepsis.

Answer 160

Treat early with antibiotics Guidelines differ Example antibiotic regimen: 1st line = cefotaxime + vancomycin; 2nd line = meropenem

Question 161

What is the main bacterial cause of meningitis at the moment?

Answer 161

Meningitis B

Question 162

What type of organism is Streptococcus pneumoniae?

Answer 162

Gram-positive diplococcus | Alpha haemolytic

Question 163

What type of organism is Haemophilus influenzae?

Answer 163

Gram-negative cocco-bacilli

Question 164

What is the most common cause of death in: a. Postnatal children (1-59 months) b. Neonates

Answer 164

``` a. Postnatal children (1-59 months) Pneumonia Followed by congenital anomalies b. Neonates Prematurity Followed by intra-partum complications ```

Question 165

Which children are mainly affected by Mycoplasma pneumoniae?

Answer 165

Older children (> 4 years)

Question 166

List some extra-pulmonary manifestations of Mycoplasma pneumoniae.

Answer 166

Haemolysis – IgM antibodies to I antigen on erythrocytes, cold agglutinins Neurological – encephalitis, aseptic meningitis, peripheral neuropathy, transverse myelitis Polyarthralgia Otitis media Bullous myringitis (vesicles on the tympanic membrane – pathognomonic of Mycoplasma) Erythema multiforme

Question 167

List three examples of: a. Yeast b. Moulds

Answer 167

``` a. Yeast Candida Cryptococcus Histoplasma (dimorphic) b. Moulds Aspergillus Dermatophytes Agents of mucormycosis ```

Question 168

List some patient groups that are at risk of invasive Candida infection.

Answer 168

VLBW infants Immunocompromised Patients on ITU (especially if they have lines in) Patients receiving TPN Immunocompetent patients who have had antibiotic treatment

Question 169

List some agents that can cause candidiasis.

Answer 169

Candida albicans (MOST COMMON) Candida glabrata Candida krusei Candida tropicalis

Question 170

Describe a screening test for candidiasis.

Answer 170

Candida albicans forms a germ tube | Can be identified by microscopy

Question 171

What does generalised candidiasis in babies usually occur secondary to?

Answer 171

Seborrhoeic dermatitis

Question 172

What type of agar is needed for culturing Candida?

Answer 172

Sabouraud agar – impregnated with antibiotics to prevent bacteria from outcompeting the fungi

Question 173

Outline the management of candidiasis.

Answer 173

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

Question 174

What is the treatment of choice for Cryptococcus infection?

Answer 174

Ambisome (amphotericin B) NOTE: it is inherently resistant to echinocandins

Question 175

Describe the appearance of Cryptococcus under the microscope.

Answer 175

Distinct capsule around the yeast India ink can be used to stain NOTE: the capsule is not always present

Question 176

Why might a lumbar puncture be negative in cryptococcal meningitis?

Answer 176

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

Question 177

Outline the treatment options for Cryptococcus infection.

Answer 177

3 weeks amphotericin B (ambisome) +/- flucytosine Repeat LP for pressure measurement Secondary suppression – fluconazole

Question 178

List the aetiological agents that can cause Aspergillus infection.

Answer 178

``` Aspergillus fumigatus Aspergillus flavus Aspergillus niger Aspergillus niduland Aspergillus terreus ```

Question 179

List some investigations used in the diagnosis of Aspergillus infection.

Answer 179

``` Blood test Serology (check IgE for allergic response (e.g. ABPA)) • Antigen detection (galactomannan) • Also detected in BAL PCR Histology Culture ```

Question 180

What is the mainstay of treatment for aspergillosis?

Answer 180

Amphotericin for at least 6 weeks | Other options: voriconazole, caspofungin, itraconazole

Question 181

What is tinea pedis caused by?

Answer 181

``` Tricophyton rubrum (MOST COMMON) Tricophyton interdigitale Epidermophyton floccosum (can also cause tinea cruris) ```

Question 182

What is pityriasis versicolor caused by?

Answer 182

Malassezia furfur NOTE: it has a spaghetti and meatballs appearance on microscopy

Question 183

Which groups of patients are affected by mucormycosis?

Answer 183

Immunocompromised patients | Patients with poorly controlled diabetes

Question 184

What is the characteristic clinical manifestation of mucormycosis?

Answer 184

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

Question 185

What is the term used to describe invasion of the brain by mucormycosis?

Answer 185

Rhinocerebral mucormycosis

Question 186

List three aetiological agents that can cause mucormycosis.

Answer 186

Rhizopum spp. Rhizomucor spp. Mucor spp.

Question 187

List antifungals that target: a. Cell membrane b. DNA/RNA synthesis c. Cell wall

Answer 187

``` a. Cell membrane Polyene – amphotericin B, nystatin Azole – ketoconazole, itraconazole, fluconazole, clotrimazole b. DNA/RNA synthesis Flucytosine (pyrimidine analogue) c. Cell wall Echinocandins – caspofungin acetate ```

Question 188

What is the mechanism of action of azoles?

Answer 188

Inhibit ergosterol production by inhibiting CYP450 enzyme lanosterol 14-demethylase This inhibition leads to the accumulation of toxic steroids in the cell membrane which cause cell death

Question 189

List examples of the following types of azoles along with their usual indications: a. Water-soluble triazoles b. Lipophilic triazoles

Answer 189

a. Water-soluble triazoles Fluconazole – active against Candida and Cryptococcus Voriconazole – similar to fluconazole but better activity against Aspergillus b. Lipophilic triazoles Itraconazole – useful against dermatophytes Posaconazole – activity against mucor

Question 190

List some examples of echinocandins.

Answer 190

Caspofungin Micafungin Anidulafungin

Question 191

What is the mechanism of action of echinocandins?

Answer 191

Cyclic lipopeptide antibiotic that inhibits beta-(1,3) D-glucan synthase This enzyme is responsible for the production of beta D-glucan which is a component of the fungal cell wall This inhibition results in osmotic fragility of the cell

Question 192

Which fungi are echinocandins active against?

Answer 192

Candida species Aspergillus species (NOT other moulds) IMPORTANT: it has NO coverage for Cryptococcus

Question 193

How is amphotericin B produced?

Answer 193

Fermentation product of Streptomyces nodusus

Question 194

Describe the mechanism of action of amphotericin B.

Answer 194

Binds to ergosterol in the fungal cell membrane and creates transmembrane channels leading to electrolyte leakage This leads to fungal cell death

Question 195

Amphotericin B is active against most fungi except…

Answer 195

Aspergillus terreus | Scedosporium spp.

Question 196

What is the main side-effect of amphotericin B? Describe the mechanism of this toxicity.

Answer 196

Nephrotoxicity Renovascular – decrease in renal blood flow leads to reduced GFR (azotaemia) Tubular – distal tubular ischaemia, wasting of sodium, potassium and magnesium

Question 197

Describe the mechanism of action of flucytosine.

Answer 197

Inhibits DNA synthesis (pyrimidine analogue)

Question 198

What are some mechanisms of resistance to flucytosine?

Answer 198

``` Decreased uptake (permease activity) Altered 5-FC metabolism ```

Question 199

Which fungi are flucytosine active against?

Answer 199

Candidiasis | Cryptococcosis

Question 200

Which fungi are flucytosine active against?

Answer 200

Candidiasis | Cryptococcosis

Question 201

Describe the mechanisms of teratogenicity of rubella.

Answer 201

Decrease in rate of cell division (leading to structural malformation) Decrease in overall number of cells (small babies) Interference with the development of key organs Tissue necrosis due to viral replication

Question 202

Describe some tests that are used in the diagnosis of rubella.

Answer 202

Rubella IgG • Seroconversion – if woman initially has negative IgG but then has a positive IgG result after possible exposure, it suggests that they have been exposed to rubella • Avidity – high avidity means that exposure occurred > 3 months ago • This is part of routine antenatal screening Rubella IgM Detection of virus (PCR) – blood, urine, tissues

Question 203

What is the role of pre-natal diagnosis of rubella?

Answer 203

All cases of symptomatic rubella infection in the 1st trimester should be considered for termination of pregnancy without prenatal diagnosis

Question 204

What is the definition of congenital CMV infection?

Answer 204

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

Question 205

What is the term used to describe congenital changes that occur as a result of CMV infection? List some features.

Answer 205

Cytomegalic inclusion disease • CNS: microcephaly, mental retardation, epilepsy • Eye: chorioretinitis • Ear: sensorineural deafness • Liver: hepatosplenomegaly, jaundice • Lung: pneumonitis • Hear: myocarditis • Thrombocytopaenic purpura • Haemolytic anaemia NOTE: late sequelae include hearing defects and reduced intelligence RCHEP: retinitis, colitis, hepatitis, encephalitis, pneumonitis

Question 206

Outline some tests used in the diagnosis of CMV infection.

Answer 206

Virus detection – cell culture, detection of early antigen fluorescent foci (DEAFF), CMV DNA (PCR) Serology – IgG seroconversion, IgG avidity, IgM

Question 207

How is congenital CMV infection treated?

Answer 207

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

Question 208

Outline the manifestations of neonatal HSV disease.

Answer 208

Skin, eyes and mouth (SEM) disease CNS disease with or without SEM Disseminated infection involving multiple organs (high mortality)

Question 209

Describe the clinical presentation of intrauterine HSV infection.

Answer 209

Neurological – microcephaly, encephalomalacia, intracranial calcification Cutaneous – scarring, active lesions Ophthlamologic – microophthalmia, optic atrophy, chorioretinitis

Question 210

Describe the treatment of neonatal HSV infection.

Answer 210

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

Question 211

List the main features of congenital varicella syndrome.

Answer 211

``` LBW Cutaneous scarring Limb hypoplasia Microcephaly Chorioretinitis Cataracts NOTE: risk is highest at 13-20 weeks ```

Question 212

Describe the manifestations of neonatal varicella infection.

Answer 212

Mild course Disseminated skin lesions Visceral infection Pneumonia

Question 213

List some complications of measles.

Answer 213

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

Question 214

What are the risks of measles in pregnancy?

Answer 214

Foetal loss (miscarriage, intrauterine death) Preterm delivery Increased maternal morbidity IMPORTANT: NO congenital abnormalities to the foetus

Question 215

How should pregnant women who have been in contact with suspected/confirmed measles be treated?

Answer 215

Measles immunoglobulin attenuates the illness if given within 6 days of exposure

Question 216

What type of virus is parvovirus B19?

Answer 216

DNA virus Parvoviridae family NOTE: MMR are all RNA viruses

Question 217

What does the virus require in order to infect red cell precursors?

Answer 217

P blood antigen receptor (globoside)

Question 218

Describe the pathophysiology of congenital parvovirus B19 infection.

Answer 218

Virus crosses the placenta and destroys foetal red blood cell precursors causing foetal anaemia  high-output congestive cardiac failure  hydrops fetalis Virus can also directly damage myocardial cells

Question 219

Describe how maternal parvovirus B19 infection can be diagnosed.

Answer 219

PCR – DNA amplification Serology – parvovirus IgG seroconversion and IgM Foetal infection – same tests

Question 220

What are some consequences of Zika virus infection in pregnancy.

Answer 220

``` Miscarriage Stillbirth Congenital zika syndrome • Severe microcephaly • Decreased brain tissue • Seizures • Retinopathy/deafness • Talipes • Hypertonia ```

Question 221

Give two examples of glycopeptides.

Answer 221

Vancomycin | Tiecoplanin

Question 222

Outline the mechanism of action of beta-lactam antibiotics.

Answer 222

Inactivate enzymes that are involved in the terminal stages of cell wall synthesis Inhibits transpeptidases (aka penicillin-binding protein) This means that there are no peptide crosslinks between peptidoglycan chains so the cell wall is weak Beta-lactam is a structural analogue of the enzyme substrate NOTE: they are ineffective against bacteria with no cell wall (e.g. mycoplasma, chlamydia)

Question 223

For each of the following antibiotics, describe their coverage and mechanisms of resistance: a. Penicillin b. Amoxicillin c. Flucloxacillin d. Piperacillin

Answer 223

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

Question 224

What is a disadvantageous association of ceftriaxone?

Answer 224

Associated with C. difficile infection

Question 225

What is a benefit of ceftazidime?

Answer 225

Good anti-Pseudomonas cover

Question 226

List examples of bacteria that have shown carbapenem resistance.

Answer 226

Acinetobacter | Klebsiella

Question 227

Outline the key features of beta-lactam antibiotics.

Answer 227

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)

Question 228

What are glycopeptides often used to treat?

Answer 228

Serious MRSA infections | C. difficile infections (oral vancomycin)

Question 229

What is a major side-effect of glycopeptides?

Answer 229

Nephrotoxic | Monitor blood levels to prevent accumulation

Question 230

Outline the mechanism of action of glycopeptides.

Answer 230

Glycopeptides bind to amino acid chains at the end of peptidoglycan precursors and prevent glycosidic bonds being formed (via transglycosidase) and prevent peptide crosslinks being formed (via transpeptidase) NOTE: they are similar to beta-lactams but instead of binding to the enzymes, they bind to substrates (cell wall component precursors)

Question 231

List some classes of antibiotics that work by inhibiting protein synthesis.

Answer 231

``` Aminoglycosides Tetracyclines Macrolides Lincosamides (e.g. clindamycin) Streptogramins (e.g. Synercid) Chloramphenicol Oxazolidinones (e.g. linezolid) ```

Question 232

Outline the mechanism of action of aminoglycosides.

Answer 232

Binds to amino-acyl site of the 30S ribosomal subunit and prevents elongation of the polypeptide chain It also causes misreading of the codons along the mRNA

Question 233

What are some major side-effects of aminoglycosides?

Answer 233

Ototoxic and nephrotoxic

Question 234

Which aminoglycosides are particularly active against Pseudomonas aeruginosa?

Answer 234

Gentamicin | Tobramycin

Question 235

Which type of bacteria do aminoglycosides have no activity against?

Answer 235

Anaerobes

Question 236

List some examples of aminoglycosides.

Answer 236

``` Gentamicin Tobramycin Amikacin Neomycin Paromomycin ```

Question 237

Which environmental feature will inhibit the activity of aminoglycosides?

Answer 237

Inhibited by low pH so are not very effective in abscesses

Question 238

Which class of antibiotics are particularly effective against intracellular bacteria (e.g. chlamydia, rickettsia, mycoplasma)?

Answer 238

Tetracyclines Newer quinolones are also effective

Question 239

List some examples of tetracyclines.

Answer 239

Tetracycline Doxycycline Oxytetracycline

Question 240

Which new tetracycline has extended the spectrum of tetracyclines?

Answer 240

Tigacycline Before this, there was widespread resistance amongst Gram-negatives

Question 241

Which groups of patients should not receive tetracyclines?

Answer 241

Children and pregnant women Because it can deposit in bone and cause discoloration of growing teeth NOTE: a well known side-effect is a light-sensitive rash

Question 242

Outline the mechanism of action of tetracyclines.

Answer 242

Binds to the ribosomal 30S subunit and prevents the binding of aminoacyl-tRNA to the ribosomal acceptor site, thereby inhibiting protein synthesis

Question 243

What are macrolides mainly used for?

Answer 243

Mild staphylococcal and streptococcal infections in penicillin-allergic patients Also active against Campylobacter, Legionella and Pneumophila

Question 244

Outline the mechanism of action of macrolides.

Answer 244

Binds to the 50S ribosomal subunit and interferes with translation Also stimulates the dissociation of peptidyl-tRNA

Question 245

What are two major risks of taking chloramphenicol?

Answer 245

Aplastic anaemia | Grey baby syndrome – neonates have reduced ability to metabolise the drug

Question 246

Outline the mechanism of action of chloramphenicol.

Answer 246

Binds to the peptidyl transferase of the 50S ribosomal subunit and inhibits the formation of peptide bonds during translation

Question 247

Outline the mechanism of action of oxazolidinones.

Answer 247

Binds to the 23S components of the 50S subunit to prevent the formation of a functional 70S initiation complex (needed for translation)

Question 248

Which organisms are oxazolidinones active against?

Answer 248

Gram-positives (including MRSA and VRE) | Not active against Gram-negatives

Question 249

What are some disadvantages of oxazolidinones?

Answer 249

Expensive | May cause thrombocytopaenia and optic neuritis

Question 250

List two groups of antibiotics that inhibit DNA synthesis.

Answer 250

Quinolones | Nitroimidazoles

Question 251

List 3 examples of quinolones.

Answer 251

Ciprofloxacin Moxifloxacin Levofloxacin

Question 252

List 2 examples of nitroimidazoles.

Answer 252

Metronidazole | Tinidazole

Question 253

Outline the mechanism of action of quinolones.

Answer 253

Acts on the alpha-subunit of DNA gyrase predominantly with other actions

Question 254

Describe the activity of quinolones.

Answer 254

Broad antibacterial activity, especially against Gram-negatives, including Pseudomonas aeruginosa NOTE: newer agents increased activity against Gram-negatives and intracellular organisms

Question 255

Outline the mechanism of action of nitroimidazoles.

Answer 255

Under anaerobic conditions, an active intermediate is formed, which causes DNA strand breakage

Question 256

Describe the activity of nitroimidazoles.

Answer 256

Active against anaerobic bacteria and protozoa (e.g. Giardia)

Question 257

Outline the mechanism of action of rifampicin.

Answer 257

Inhibits RNA synthesis by binding to DNA-dependent RNA polymerase thereby inhibiting initiation

Question 258

Describe the activity of rifampicin.

Answer 258

Mainly Mycobacteria and Chlamydiae

Question 259

Why should rifampicin never be used alone?

Answer 259

Resistance develops rapidly due to chromosomal mutation (single amino acid change in beta-subunit of RNA polymerase)

Question 260

Name two cell membrane toxins.

Answer 260

Daptomycin | Colistin

Question 261

Describe the activity of daptomycin.

Answer 261

Gram-positives Likely to be used in treating MRSA and VRE NOTE: it is a cyclic lipopeptide

Question 262

Describe the activity of colistin.

Answer 262

Active against Gram-negatives including Pseudomonas aeruginosa, Acinetobacter baumanii and Klebsiella pneumoniae NOTE: it is a polymyxin

Question 263

Name two families of antibiotics that work by inhibiting folate metabolism.

Answer 263

Sulphonamides (sulfamethoxazole) | Diaminopyrimidines (trimethoprim)

Question 264

List some mechanisms of antibiotic resistance.

Answer 264

Chemical modification or inactivation of the drug Modification or replacement of the target Reduced antibiotic accumulation (impaired uptake or enhanced efflux) Bypass antibiotic-sensitive step in cell division

Question 265

Which bacteria produce beta-lactamases?

Answer 265

S. aureus and Gram-negative bacilli (coliforms) | NOTE: this is not the mechanism of resistance in pneumococcus and MRSA

Question 266

Describe how MRSA uses ‘altered targets’ as a mechanism of resistance.

Answer 266

MRSA has a mecA gene which encodes novel PBP2a | This has a low affinity for binding beta-lactams therefore is not inactivated by beta-lactams

Question 267

Describe the mechanism of resistance in Streptococcus pyogenes.

Answer 267

Results from acquisition of a series of stepwise mutations in PBP genes Lower level resistance can be overcome by increasing the dose

Question 268

What are AmpC beta-lactamases?

Answer 268

Breakdown penicillins and cephalosporins but are not inhibited by clavulanic acid

Question 269

Describe the mechanism of resistance to macrolides.

Answer 269

Adenine-N6 methyltransferase modifies the 23S RNA This reduces the binding of macrolides thereby resulting in resistance Encoded by erm (erythromycin ribosome methylation) genes NOTE: caution when using clindamycin in Staphylococcus and Streptococcus which is resistant to macrolides because lincosamides can induce this mechanism of resistance

Question 270

Name two methods of rapid antigen detection.

Answer 270

PCR | Immunofluorescence

Question 271

Describe the type I pattern of antibiotic activity. Give an example of an antibiotic of this type.

Answer 271

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)

Question 272

Describe the type II pattern of antibiotic activity. Give an example of an antibiotic of this type.

Answer 272

Time-dependent killing Time spent above the MIC is the most important factor Example: penicillins Therefore, penicillins need to be given frequently

Question 273

Describe the type III pattern of antibiotic activity. Give an example of an antibiotic of this type.

Answer 273

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

Question 274

How should invasive group A streptococcal infection be treated?

Answer 274

Aggressive and early debridement Early use of antibiotics (e.g. clindamycin) Use of IVIG

Question 275

How is meningitis in babies < 3 months treated?

Answer 275

Cefotaxime + amoxicillin | NOTE: ceftriaxone is NOT used in neonates because it displaces bilirubin from albumin and causes biliary sludging

Question 276

List some primary causes of immune compromise.

Answer 276

UNC93B deficiency and TLR deficiency (associated with predisposition to herpes simplex encephalitis) Epidermodysplasia verruciformis SCID Haemophagocytic lymphohistiocytosis in perforin deficiency HHV8 is associated with STIM1 mutation NOTE: perforin deficiency is also associated with increased incidence of EBV

Question 277

List some iatrogenic causes of immunosuppression in order of increasing risk of opportunistic viral infection.

Answer 277

``` DMARDs and steroids (LOWEST RISK) Cytotoxic chemotherapy Monoclonal antibodies Solid organ transplant Advanced HIV Allogeneic stem cell transplant (HIGHEST RISK) ```

Question 278

List some diseases that it is important to monitor for in post-transplant patients.

Answer 278

CMV monitoring and prophylaxis EBV monitoring Adenovirus monitoring (in paediatric BMT) HSV prophylaxis if indicated

Question 279

List the sites of latent infection of: a. VZV b. CMV c. EBV

Answer 279

``` a. VZV Dorsal root ganglion b. CMV Monocytes c. EBV B cells ```

Question 280

In bone marrow transplant patients, describe the timescale in which the herpes infections tend to occur.

Answer 280

HSV, HHV6 and HHV7 tend to occur < 1 month after transplant | CMV, VZV and EBV tend to reactivate later

Question 281

List some manifestations of VZV infection.

Answer 281

``` Skin lesions Pneumonitis Encephalitis Hepatitis Purpura fulminans (neonates) Acute retinal necrosis VZV-associated vasculopathy ```

Question 282

What is the pathological hallmark of CMV infection?

Answer 282

Owl’s eye appearance of lung pneumocytes due to the presence of inclusion bodies

Question 283

How is the risk of reactivation of CMV different in solid organ transplantation compared to bone marrow transplantation?

Answer 283

Solid organ: greatest risk is if the donor has had past CMV but the recipient is naïve Bone marrow transplant: greatest risk is if the donor is naïve and the recipient has had past CMV infection NOTE: CMV is a destructive virus that directly threatens the graft and damaged endothelial cells

Question 284

Which other diseases is HHV8 associated with?

Answer 284

Primary effusion lymphoma | Multicentric Castleman’s disease

Question 285

What deadly condition is JC virus associated with?

Answer 285

Progressive multifocal leukoencephalopathy (PML) This is a dementing process characterised by loss of higher functions (personality change, motor deficits, focal neurological signs) Characterised by demyelination of white matter NOTE: diagnosed by MRI or PCR of CSF

Question 286

Which specific medication is associated with an increased risk of PML?

Answer 286

Natalizumab – monoclonal antibody used in the treatment of multiple sclerosis

Question 287

What can BK virus cause?

Answer 287

``` BK cystitis (post-stem cell transplant) BK nephropathy (post-renal transplant) NOTE: can be treated by reducing immunosuppression ```

Question 288

List some manifestations of adenovirus infection in bone marrow transplant patients.

Answer 288

Fever Encephalitis Pneumonitis Colitis

Question 289

How is parvovirus B19 infection in the immunocompromised treated?

Answer 289

IVIG | Blood transfusion may be required to correct the anaemia

Question 290

Which treatments particularly increase the risk of hepatitis B infection?

Answer 290

B-cell depleting therapies (e.g. rituximab) This can be prevented by using nucleoside analogue (e.g. tenofovir) prophylaxis

Question 291

What are the three main types of worms? List some examples of each.

Answer 291

``` Cestodes (tape worms) • Pork/beef/fish tapeworms • Hydatid disease Trematodes (flukes) • Schistosomiasis Nematodes (roundworms) • Hookworms • Ascarids • Strongyloides ```

Question 292

What are the two types of pork and beef tapeworms?

Answer 292

Taenia solium – pork (can invade human tissues causing cysticercosis) Taenia saginata – beef

Question 293

Outline the lifecycle of schistosomiasis.

Answer 293

Cercariae invade human skin when in contact with contaminated water Worms develop in the venous plexus Eggs are excreted into the urine and faeces They hatch into miracidia, which parasitise snails Snails release cercariae

Question 294

How is schistosomiasis diagnosed?

Answer 294

``` Microscopy • Urine: S. haematobium • Stools: S. mansoni, S. japonicum Serology Biopsy Response to treatment ```

Question 295

What are the five main soil-transmitted helminths?

Answer 295

``` Ascaris lumbricoides Strongyloides stercoralis Trichuris trichiura Enterobius vermicularis Hookworm NOTE: they are very well adapted to humans so cause little disease ```

Question 296

Outline the lifecycle of Strongyloides.

Answer 296

Larvae invade skin Mature into adult pinworms in the small bowel Eggs are produced which hatch to release rhabtidiform larvae They mature into filariform larvae (infectious) These can autoinfect via perianal skin NOTE: in the stool microscopy of someone with Strongyloides, you will see motile larvae rather than eggs

Question 297

How is Strongyloides treated?

Answer 297

Ivermectin

Question 298

How are the nematode infections that cause filariasis spread?

Answer 298

Blackflies and mosquitoes

Question 299

Outline the classification of filariasis.

Answer 299

``` 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 ```

Question 300

What causes damage in filariasis?

Answer 300

Adults: lymphatic filariasis (scrotal swellings, elephantiasis) and oncho nodules Microfilariae: onchocerciasis (depigmentation, river blindness)

Question 301

What is myiasis?

Answer 301

Parasitisation of human flesh by fly larvae

Question 302

Outline the components of a reasonable parasite screen.

Answer 302

Serology: Strongyloides, Schistosoma, filaria | Stool microscopy

Question 303

How is the acquisition of pig tapeworm different from the acquisition of cysticercosis?

Answer 303

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 NOTE: humans and pigs are immunologically very similar

Question 304

Outline the management of cysticercosis.

Answer 304

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

Question 305

How long does TB take to divide?

Answer 305

18-24 hours

Question 306

List some risk factors for TB.

Answer 306

``` Malnutrition (most common) HIV (very serious risk factor) Poverty Underweight Past TB ```

Question 307

List some clinical features of severe malaria.

Answer 307

``` High parasitaemia Altered consciousness ARDS Circulatory collapse Metabolic acidosis Renal failure Hepatic failure Coagulopathy Severe anaemia Hypoglycaema ```

Question 308

Which stains are used for malaria?

Answer 308

Giemsa | Field’s

Question 309

Outline the treatment options for non-falciparum malaria.

Answer 309

Chloroquine – 3 days | Primaquine – 30 mg for 14 days

Question 310

What must you do before giving someone primaquine?

Answer 310

Screen for G6PD deficiency as primaquine can cause extensive haemolysis

Question 311

Outline the treatment options for mild falciparum malaria.

Answer 311

``` Oral malarone (atovaquone and proguanil) Artemisinin combination therapy (ACT) Oral quinine (RARELY used) ```

Question 312

Outline the treatment of severe falciparum malaria.

Answer 312

``` ABCDE approach Correct hypoglycaemia Cautious hydration Organ support if necessary IV artesunate Daily parasitaemia monitoring Follow on with oral antimalarials ```

Question 313

Why is quinine not used in this situation?

Answer 313

Extensive side effects: • Cinchonism: tinnitus, dizziness, nausea and vomiting • Arrhythmias • Hyperinsulinaemia

Question 314

Outline the clinical features of dengue.

Answer 314

``` Fever Headache (retro-orbital pain) Myalgia Erythrodermic rash Bleeding Hepatitis Severe: encephalitis, myocarditis ```

Question 315

Which tropical virus is similar to dengue? What is a key difference?

Answer 315

Chikungunya | Arthralgia is more severe

Question 316

What is the term used to describe a high temperature with a relatively normal heart rate? List some causes.

Answer 316

Sphygmothermic dissociation | Causes: typhoid, yellow fever, brucellosis, tularaemia

Question 317

What type of organism is Salmonella typhi?

Answer 317

Gram-negative rod

Question 318

Outline the clinical features of typhoid.

Answer 318

``` High prolonged fever Headache Rose spots Constipation Dry cough Hepatosplenomegaly ```

Question 319

What is the incubation period of typhoid?

Answer 319

7-18 days

Question 320

Outline the treatment of typhoid.

Answer 320

1st line: ciprofloxacin Ceftriaxone 2 g IV OD Azithromycin PO 500 mg BD 7 days

Question 321

List some investigations for mononucleosis.

Answer 321

Monospot IgM EBV/CMV NOTE: always consider HIV

Question 322

Which antibiotic should be given as prophylaxis in close contacts of a patient with meningococcal meningitis?

Answer 322

Ciprofloxacin (or rifampicin)

Question 323

Which organism can cause bacterial endocarditis after a colonoscopy?

Answer 323

Streptococcus bovis

Question 324

How is latent TB treated?

Answer 324

Isoniazid for 6 months NOTE: TB meningitis and spinal TB chas the same treatment as pulmonary TB but R + I are taken for 8-10 months

Question 325

What type of bacterium is Moraxella catarrhalis?

Answer 325

Gram-negative coccus Associated with smoking

Question 326

What type of bacterium is Klebsiella pneumoniae?

Answer 326

Gram-negative rod (enterobacter) NOTE: more common in alcoholics and the elderly

Question 327

Which bacteria tend to cause respiratory infection in cystic fibrosis patients?

Answer 327

Pseudomonas aeruginosa | Burkholderia cepacia

Question 328

List some causes of painful genital ulcers.

Answer 328

Herpes | Chancroid

Question 329

List some causes of painless genital ulcers.

Answer 329

Syphilis (also causes snail track ulcer in the mouth) Lymphogranuloma venereum (LGV) Granuloma inguinale

Question 330

How is gonorrhoea treated?

Answer 330

IM Ceftriaxone 250 mg single dose NOTE: if resistant - IM spectinomycin 2 g single dose

Question 331

Which serovars of chlamydia cause genital chlamydia?

Answer 331

D-K NOTE: A, B and C cause trachoma (infection of the eyes that can lead to blindness)

Question 332

How is chlamydia diagnosed?

Answer 332

NAAT NOTE: chlamydia cannot be grown on agar, it needs to be grown on cell culture (as it is an obligate intracellular bacterium)

Question 333

How is chlamydia treated?

Answer 333

Azithromycin 1 g stat | Doxycycline 100 mg BD for 7 days

Question 334

What causes lymphogranuloma venereum?

Answer 334

Chlamydia trachomatis serovars L1, L2 and L3 NOTE: starts with a painless genital ulcer and progresses to cause systemic upset, inguinal buboes and rectal symptoms (affects the lymphatics)

Question 335

Which investigations are used for syphilis?

Answer 335

Dark ground microscopy Non-Treponemal Tests (VDRL, RPR) - detects non-specific antigens and used as a screening test Treponemal Tests (EIA, TPHA, TPPA) - detects antibodies against specific antigens for T. pallidum. More specific

Question 336

Outline the stages of syphilis.

Answer 336

Primary - painless genital ulcer (may persist for weeks) Secondary - systemic bacteraemia, low grade fever, non-pruritic, maculopapular rash, condylomata lata Tertiary - neurosyphilis, cardiovascular complications, gumma NOTE: tabes dorsalis is a demyelinating condition caused by advanced syphilis

Question 337

How is syphilis treated?

Answer 337

IM benzathine penicillin (doxycycline if allergic)

Question 338

What causes chancroid?

Answer 338

``` Haemophilus ducreyi (Gram-negative coccobacillus) Grows on chocolate agar ```

Question 339

What causes granuloma inguinale?

Answer 339

Donovanosis - Klebsiella granulomatis (Gram-negative bacillus) Causes large expanding ulcers with a beefy red appearance

Question 340

What might be seen on microscopy of bacterial vaginosis?

Answer 340

Clue cells

Question 341

What is herpangina?

Answer 341

Painful mouth ulcers caused by Coxsackie A virus

Question 342

What feature may be seen on blood film analysis of P. vivax and P. ovale?

Answer 342

Shuffner's dots NOTE: these types of malaria tend to predominate in the hypnozoite (liver) stage NOTE: in falciparum malaria you would see Maurer's clefts on blood film

Question 343

What is Mollaret's meningitis?

Answer 343

Benign recurrent aseptic meningitis usually due to HSV-2 NOTE: unlike most herpes simplex encephalitis which is caused by HSV-1

Question 344

What is Herpes gladiatorum?

Answer 344

Scrum pox - painful blisters, inguinal lymphadenopathy, rugby players

Question 345

Which cell type can be seen in cytological analysis of scrapings from herpes viruses?

Answer 345

Tzanck cells - acanthocytic cells found in HSV, VZV and CMV

Question 346

What are the different types of GI disease that can be caused by E. coli?

Answer 346

ETEC - toxigenic, travellers' diarrhoea, heat labile toxin stimulated adenyl cyclase and cAMP, heat stable toxin stimulates guanylate cyclase EIEC - invasive dysentery EHEC - haemorrhagic, caused by verotoxin HUS - anaemia, thrombocytopaenia, renal failure (O157:H7 toxin) EPEC - infantile diarrhoea

Question 347

What does Yersinia enterocolitis cause?

Answer 347

Enterocolitis, mesenteric adenitis with necrotising granulomas associated with reactive arthritis and erythema nodosum

Question 348

What is leptospirosis?

Answer 348

Disease caused by Leptospira interrogans This is excreted in dog/cat urine, penetrates broken skin from contaminated water Causes high spiking temperature, headache, jaundice, meningism, carditis, renal failure and haemolytic anaemia Ix: microscopic agglutination test

Question 349

How does anthrax manifest?

Answer 349

Caused by Bacillus anthracis Cutaneous - painless round black lesions with a rim of oedema Pulmonary (Woolsorters disease) - massive lymphadenopathy, mediastinal haemorrhage, pleural effusion

Question 350

What is Q fever?

Answer 350

Caused by Coxiella burnetii From cattle/sheep Fever, dry cough, fatigue, diarrhoea (like atypical pneumonia)

Question 351

What are the different types of Leishmania?

Answer 351

Cutaneous - transmitted through bite of sandly, causes skin ulcer at bite site, local lymphadenopathy Diffuse cutaneous - in patients with immunodeficiency, nodular skin lesions Mucocutaneous - dermal ulcer, affects mucous membranes, disfiguring facial features Visceral (Kala-Azar) - caued by L. donovani, young malnourished children, abdominal discomfort and distension, hepatosplenomegaly, dermal disease

Question 352

What is the preferred first line treatment choice for Hepatitis B?

Answer 352

Entecavir + peginterferon alpha 2a + tenofovir NOTE: treatment usually initiated if HBV DNA > 2000 iU/mL, moderate-severe histology or raised aminotransferases

Question 353

What are the risks of influenza in pregnancy?

Answer 353

``` Stillbirth Preterm delivery Severe influenza NO congenital abnormalities Pregnant women should receive the vaccine ```

Question 354

What are the most common causative organisms in aseptic meningitis?

Answer 354

Coxsackie group B viruses Echoviruses NOTE: babies < 1 year are susceptible for aseptic meningitis

Question 355

Which bacterium is particularly associated with causing encephalitis?

Answer 355

Listeria monocytogenes

Question 356

List some reportable GI infections.

Answer 356

``` Campylobacter Salmonella Shigella Escherichia coli O157 Listeria ```

Question 357

Describe the mechanism by which Vibrio cholerae causes secretory diarrhoea.

Answer 357

The cholera toxin has subunits A and B which stimulate adenylate cyclase This leads to the production of cAMP which opens chloride channels on the membranes of enterocytes Chloride efflux into the lumen is accompanied by water and electrolyte loss

Question 358

What type of toxins does B. cereus produce?

Answer 358

Heat stable emetic toxin | Heat labile diarrhoeal toxin

Question 359

List three species of Salmonella.

Answer 359

Salmonella typhi (and paratyphi) Salmonella enteritidis Salmonella choleraesuis

Question 360

Which subset of patients are at increased risk of Salmonella bacteraemia?

Answer 360

Sickle cell patients

Question 361

How does Shigella infection manifest?

Answer 361

Dysentery – severe diarrhoea with blood and mucus in the faeces NOTE: Shigella produces shiga toxin NOTE: avoid antibiotics when treating Shigella

Question 362

How is Campylobacter infection treated?

Answer 362

Only treated if immunocompromised | Erythromycin/clarithromycin or ciprofloxacin

Question 363

What are some complications of Campylobacter infection?

Answer 363

Guillain-Barre syndrome | Reactive arthritis

Question 364

How is Giardia infection diagnosed and treated?

Answer 364

Stool microscopy ELISA String test Treatment: metronidazole

Question 365

Which bacteria are all stool samples tested for?

Answer 365

Salmonella Shigella E. coli O157 If > 65 years, C. difficile is also checked

Question 366

Which C. difficile ribotype caused a severe outbreak in June 2005?

Answer 366

Ribotype 027

Question 367

What are the actions of the two toxins produced by C. difficile?

Answer 367

One damages the epithelial cells (cytotoxin) resulting in neutrophilic infiltration of the tissues The other disrupts tight junctions leading to loss of fluid into the bowel NOTE: high WCC and low CRP is a common feature in C. difficile colitis

Question 368

Describe the clinical features of sporadic CJD.

Answer 368

``` Rapid dementia Myoclonus Cortical blindness Akinetic mutism LMN signs NOTE: usually in older people (> 65) ```

Question 369

Describe the clinical features of vCJD.

Answer 369

Younger age of onset (20s) Psychiatric onset (dysphoria, anxiety, delusions, hallucinations) Followed by neurological symptoms (peripheral sensory symptoms, ataxia, myoclonus, chorea, dementia) NOTE: characteristic MRI feature is pulvinar sign (high intensity in the putamen)

Question 370

What are some alternative diagnoses for someone presenting with features suggestive of prion disease?

Answer 370

Spinocerebellar ataxia | Huntington’s disease

Question 371

Which virulence factor allows S. saprophyticus to stick to the urinary tract epithelium?

Answer 371

P-fimbriae | NOTE: S. saprophyticus causes infection in young women

Question 372

In which patients do Candida UTIs tend to occur?

Answer 372

Patients with indwelling catheters Treated by removal of catheter only (unless renal transplant)

Question 373

Which bacterium is associated with causing infection on prosthetic heart valves?

Answer 373

Staphylococcus epidermidis

Question 374

Which antiviral can be used to prevent RSV infection in at risk infants?

Answer 374

Ribavirin NOTE: ribavirin is a guanosine nucleoside analogue

Question 375

What is the mechanism of action of zidovudine?

Answer 375

Nucleoside reverse transcriptase inhibitor (NRTI)

Question 376

Which virus is associated with causing acute necrotising encephalitis?

Answer 376

HSV1 This is the MOST COMMON cause of encephalitis

Question 377

What are the three classes of herpes viruses?

Answer 377

Alpha: neurotropic Beta: epitheliotropic Gamma: lymphotropic

Question 378

What causes oral hairy leukoplakia and which patient subgroup is associated with this condition?

Answer 378

EBV | Immunocompromised (e.g. HIV or IVDU)

Question 379

Which naturally occurring cytokine can inhibit HIV fusion with CD4 cells?

Answer 379

MIP-1-alpha

Question 380

Describe the main clinical features of giardiasis.

Answer 380

Severe flatulence Bloating Explosive diarrhoea

Question 381

Where does cryptococcus neoformans come from?

Answer 381

Pigeon droppings and pigeon nests NOTE: histoplasmosis also comes from bird droppings

Question 382

What are the typical symptoms of rubella?

Answer 382

Macular rash beginning behind the ears Lymphadenopathy Joint pain Fever

Question 383

List some causes of ring-enhancing brain lesions.

Answer 383

Abscess Tuberculoma Toxoplasmosis CNS lymphoma

Question 384

What is the most common cause of UTI in catheterised men?

Answer 384

E. coli

Question 385

Describe the typical presentation of bacterial prostatitis.

Answer 385

Fever and rigors Lower back pain Dysuria

Question 386

Describe the microbiological appearance of Enterococcus.

Answer 386

Gram-positive cocci in chains (or pairs)

Question 387

Describe the microbiological appearance of Pseudomonas.

Answer 387

Gram-negative bacilli Produce green pigment Oxidase positive

Question 388

List some examples of Gram-positive bacilli.

Answer 388

``` Bacillus cereus, bacillus anthracis Clostridia Corynebacterium diphtheriae Listeria Actinomyces ```

Question 389

List some examples of Gram-negative bacilli.

Answer 389

``` E. coli Klebsiella Proteus Salmonella Shigella Yersinia Pseudomonas Bordatella pertussis Haemophilus influenzae Legionella ```

Question 390

List some examples of Gram-negative comma-shaped or curved bacteria.

Answer 390

Vibrio Campylobacter Helicobacter

Question 391

List some examples of spiral-shaped bacteria (spirochete).

Answer 391

Treponema pallidum Borrelia burgdorferi Leptospira interrogans

Question 392

What CXR feature might be seen in invasive aspergillosis?

Answer 392

Halo sign

Question 393

How is a surgical site infection caused by MRSA treated?

Answer 393

IV linezolid

Question 394

Which investigation should be requested if the initial tests for PUO fail to establish a diagnosis?

Answer 394

PET-CT

Question 395

List some organisms that cause HAP.

Answer 395

``` Enterobacteriaciae (MOST COMMON – e.g. E. coli, K. pneumoniae) Staphylococcus aureus Pseudomonas Haemophilus influenzae Acinetobacter baumanii Fungi (e.g. Candida) ```

Question 396

What counts as a positive result on the Mantoux Test?

Answer 396

> 15 mm: if no risk factors for TB > 10 mm: from high-prevalence country, employees in high-risk settings, comorbidities that increase risk (e.g. DM) > 5 mm: HIV positive, recent contact with TB patient, immunosuppressed, CXR changes

Question 397

How is post-transplant lymphoproliferative disease treated?

Answer 397

Reduce immunosuppression | Rituximab (anti-CD20)

Question 398

Which score is used to determine if a patient has sepsis?

Answer 398

Q-SOFA Altered Mental Status (GCS < 15) Tachypnoea (22 or more) Hypotension (< 100 mm Hg) Score of 2 or more is high risk

Question 399

What are Amsel's criteria for diagnosing BV?

Answer 399

Thin, white homogenous discharge Clue cells on microscopy: stippled vaginal epithelial cells Vaginal pH > 4.5 Positive whiff test (addition of potassium hydroxide results in fishy odour) Needs 3 out of 4

Question 400

Which antibiotic should be given in a case of human or animal bite?

Answer 400

Co-amoxiclav

Question 401

Which antibiotics are used to treat the following GI infections: Campylobacter Salmonella Shigella

Answer 401

Campylobacter = clarithromycin or erythromycin | Salmonella or Shigella = ciprofloxacin

Question 402

``` Give one example of each of the following types of HIV drugs: NRTI NNRTI Protease Inhibitor Integrase Inhibitor ```

Answer 402

NRTI: zidovudine NNRTI: nevirapine Protease Inhibitor: saquinavir Integrase Inhibitor: raltegravir

Question 403

State the antibiotic regimens used to treat subacute and acute bacterial endocarditis.

Answer 403

Subacute: Benzylpenicillin + gentamicin; or vancomycin for 4 weeks Acute: Flucloxacillin for MSSA, rifampicin + vancomycin + gentamicin for MRSA.

Question 404

Name three types of brucella.

Answer 404

``` Brucella abortus (cows) Brucella melitensis (goats) Brucella suis (pigs) ```

Question 405

Which respiratory pathogen commonly causes pneumonia in smokers with COPD?

Answer 405

Haemophilus influenzae NOTE: Moraxella catarrhalis is also associated with smoking

Question 406

When does pneumonia caused by S. aureus tend to occur?

Answer 406

After a recent viral infection (influenza)

Question 407

Outline the management of an infective exacerbation of COPD.

Answer 407

Mild: doxycycline/amoxicillin/clarithromycin + inhalers + prednisolone Mod/Severe: IV antibiotics + nebulisers + hydrocortisone

Question 408

``` List diarrhoeal diseases that have the following incubation periods: < 6 hours 12-48 hours 48-72 hours > 1 week ```

Answer 408

< 6 hours: Bacillus cereus, Staphylococcus aureus 12-48 hours: Salmonella enteritidis, E. coli 48-72 hours: Shigella, Campylobacter, V. cholerae > 1 week: Listeria, typhoid, Giardia, amoebiasis

Question 409

Which emerging fungal infection causes invasive hospital-acquired infections?

Answer 409

Candida auris | Particularly in immunocompromised patients with indwelling catheters

Question 410

How can Aspergillus flavus cause hepatocellular cancer?

Answer 410

Aflatoxin A1

Question 411

What is a fungal cell wall made up of?

Answer 411

Glucan | Chitin

Question 412

List some investigations used for PUO.

Answer 412

``` Urine (dipstick, antigen, microscopy) Bloods (FBC, eosinophils, ESR, 3 x blood culture, thick and thin blood films) HIV test Autoantibody screen CXR CT-TAP ```

Question 413

How is infective endocarditis treated?

Answer 413

S. viridans: benzylpenicillin + gentamicin S. aureus: flucloxacillin MRSA: vancomycin + gentamicin May require removal of the valve

Question 414

What is the most common cause of fever in the returning traveller?

Answer 414

Malaria

Question 415

Describe the clinical presentation of lyme disease.

Answer 415

Localised: flu-like illness, erythema migrans Early disseminated: heart block, pericarditis, aseptic meningitis, bilateral facial palsy Late: chronic arthritis, short-term memory loss and confusion Treatment: doxycycline

Question 416

Which medications are used to treat hepatitis C?

Answer 416

Protease inhibitor (e.g. sofosbuvir + daclatasvir) with or without ribavirin is the mainstay NOTE: interferon-based treatments are no longer used

Question 417

What is the technical term for dog tapeworm?

Answer 417

Echinococcus granulosus

Question 418

List the bacteria that fall under alpha, beta and gamma haemolytic streptococci.

Answer 418

Alpha: S. pneumoniae, S. viridans Beta: S. pyogenes, S. epidermidis Gamma: Enterococcus (faecalis, faecum) NOTE: beta haemolytic streptococci are further divided into Lancefield groups

Question 419

Which bacteria is optochin sensitivity useful to differentiate between?

Answer 419

Optochin Sensitive: S. pneumoniae | Optochin Resistant: S. viridans (and other alpha haemolytic streptococci)

Question 420

List the organisms that are oxidase-positive.

Answer 420

``` Pseudomonas Neisseria Campylobacter Helicobacter Moraxella Vibrio Legionella ``` Mnemonic: PuNCH Me Very Lightly

Question 421

Which organisms cause the following types of leishmaniasis: Visceral Cutaneous Mucocutaneous

Answer 421

Visceral: L. donovani, L. infantu, L. chagasi Cutaneous (most common): L. major, L. tropica Mucocutaneous: L. braziliensis

Question 422

What are the main clinical features of trypanosomiasis and what are the two main forms?

Answer 422

Subcutaneous chancre at the site of Tsetse fly bite Fevers, weakness, arthralgia and headache Later: disturbance of sleep cycle, ataxia T. brucei gambiense (95%) - chronic course, West and Central Africa T. brucei rhodesiense (5%) - rapid infection (over weeks/months), Southern Africa T. cruzi - Chagas disease

Question 423

Briefly describe the lifecycle of plasmodium.

Answer 423

Injected into the blood as sporozoites from the female Anopheles mosquito Moves to liver Become merozoites which escape the liver and infect blood cells (erythrocytic phase) Multiply in erythrocytes and are released at intervals Some merozoites become gametocytes NOTE: in the liver, sporozoites can sometimes lie latent as hypnozoites

Question 424

What is the best diagnostic test for hepatitis C?

Answer 424

HCV RNA NOTE: chronic infection is defined as the persistence of HCV RNA after 6 months

Question 425

How long is the HIV incubation period?

Answer 425

3-12 weeks Therefore, an HIV test should only be performed 3 months after exposure

Question 426

What are the first and second line treatment options for PCP?

Answer 426

1st line: co-trimoxazole | 2nd line: clindamycin and primaquine

Question 427

Which viral and fungal/parasite infections are T and B cell deficiencies associated with?

Answer 427

``` T cells - Viruses: CMV, EBV, VZV - Fungi/Parasites: Candida, PCP B cells - Viruses: enteroviral encephalitis - Fungi/Parasites: Giardia ```

Question 428

What is a 'complicated' UTI?

Answer 428

``` Infection in a UTI with structural or functional abnormalities (including indwelling catheters and calculi) Includes any UTI in: - Men - Pregnant Women - Children - Hospitalised patients ```

Question 429

How would you manage a patient with leucocyte positive, nitrite negative urine?

Answer 429

Treat if severe symptoms and send urine culture

Question 430

When should patients with a UTI have urine sent for microscopy, culture and sensitivities?

Answer 430

Pregnancy, children or men Suspected pyelonephritis Catheterised patients Failed antibiotic treatment (resistance) Abnormalities of the genitourinary tract Renal impairment

Question 431

What is the antibiotic regimen of choice for an uncomplicated UTI in a woman?

Answer 431

Nitrofurantoin or Cephalexin

Question 432

What is the antibiotic regimen of choice for a UTI in a pregnant woman?

Answer 432

1st line: nitrofurantoin (avoid at term) | 2nd line: cefalexin or co-amoxiclav

Question 433

What is the antibiotic regimen of choice for a UTI in a man?

Answer 433

Cefalexin or ciprofloxacin | Chronic prostatitis: ciprofloxacin 500 mg BD PO for 4-6 weeks

Question 434

What is the antibiotic regimen of choice for pyelonephritis or urosepsis?

Answer 434

IV co-amoxiclav Consider adding IV amikacin or gentamicin Penicillin allergy: ciprofloxacin 400 mg IV BD If frail, elderly and high-risk of C. difficile: IV gentamicin or IV amikacin

Question 435

How is catheter-associated UTI treated?

Answer 435

``` Remove catheter (but give stat doses before removal of infected catheter) Gentamicin or Amikacin (stat 30-60 mins before the procedure) ```

Question 436

What eye condition can be caused by candida?

Answer 436

Endophthalmitis

Question 437

How is cryptococcus diagnosed?

Answer 437

EIA looking for antigen components

Question 438

Which organisms cause tinea capitis and onychomycosis?

Answer 438

Tinea capitis: Tricophyton rubrum, Trichophyton tonsurans | Onychomycosis: Tricophyton spp., Epidermophyton spp. and Microsporum spp.

Question 439

List the classes of beta-lactam containing antimicrobials.

Answer 439

Penicillins Cephalosporins Carbapenems Monobactams

Question 440

Outline the different generations of cephalosporins.

Answer 440

1st: Cephalexin 2nd: Cefuroxime 3rd: Ceftriaxone, Cefotaxime, Ceftazidime

Question 441

Which classes of antibiotic have bacteriostatic action?

Answer 441

Tetracyclines Macrolides Chloramphenicol

Question 442

Which classes of antibiotic have bactericidal action?

Answer 442

``` Beta lactams Glycopeptides Aminoglycosides Quinolones Rifampicin Nitroimidazoles ```

Question 443

For each of the three types of antibiotic pharmacokinetics, list the classes of antibiotics that fall into that category.

Answer 443

``` Type 1 (concentration-dependent): aminoglycosides, daptomycin, quinolones Type 2 (time-dependent): all beta-lactams, erythromycin, linezolid Type 3 (mixed): tetracyclines, oxazolidinones, vancomycin, clindamycin, azithromycin ```

Question 444

How are mild and severe community-acquired pneumonias treated?

Answer 444

Mild: amoxicillin Severe: co-amoxiclav + clarithromycin

Question 445

How are hospital-acquired UTIs treated?

Answer 445

Cephalexin or co-amoxiclav

Question 446

How is aspiration pneumonia treated?

Answer 446

Cefuroxime + metronidazole

Question 447

Name an antibiotic that has good cover against pseudomonas but poor anaerobe cover.

Answer 447

Ciprofloxacin

Question 448

Name two Gram-negative lactose-fermenting rods.

Answer 448

E. coli Klebsiella NOTE: lactose fermentation status is based on growth on MacConkey agar

Question 449

Which drug is red man syndrome associated with?

Answer 449

Vancomycin Characterised by pain and thrombophlebitis

Question 450

Describe the mechanism of HIV entry into CD4 cells.

Answer 450

1. Initial interaction between gp120 and CD4. 2. Conformational change in gp120 allows for secondary interaction with CCR5. 3. The distal tips of gp41 are inserted into the cellular membrane. 4. gp41 undergoes significant conformational change; folding in half and forming coiled-coils. This process pulls the viral and cellular membranes together, fusing them.

Question 451

Describe the appearance of erysipelas and state which organism is most commonly implicated.

Answer 451

Red, well demarcated, oedematous rash on the face | Usually caused by S. pyogenes

Question 452

What is the most common cause of acute viral haemorrhagic cystitis in children?

Answer 452

Adenovirus

Question 453

Which organism causes gas gangrene? Describe its presentation.

Answer 453

Clostridium perfringens Oedema and discoloration with necrotic bullae Soil-transmitted through breaks in the skin

Question 454

For which conditions is post-exposure prophylaxis available?

Answer 454

Rabies HIV Tetanus

Question 455

List some examples of anaerobic bacteria.

Answer 455

``` Actinomyces Bacteroides Clostridium Porphyromonas Propionibacterium ```

Question 456

Which types of bacteria are chocolate agar used to grow?

Answer 456

Fastidious bacteria Haemophilus influenza Neisseria meningitidis (usually requires a variant of chocolate agar which contains antibiotics called Thayer-Martin agar) NOTE: Mueller-Hinton agar is an alternative

Question 457

What is sporotrichosis?

Answer 457

Rose gardener's disease (caused by Sporothrix schenckii) Fungus found in plants and soil Prick by thorn leads to nodular lesions to appear on the skin They are initially small and painless but will become ulcerated Infection can spread to joints, bone and muscle

Question 458

What are the HACEK organisms?

Answer 458

``` Fastidious Gram-negative bacteria that are an unusual cause of infective endocarditis Haemophilus Aggregatibacter Cardiobacterium Eikenella Kingella ```

Question 459

What is the mechanism of action of tenofovir?

Answer 459

NucleoTide reverse transcriptase inhibitor (NtRTI)

Question 460

What is the mechanism of action of lamivudine and entecavir?

Answer 460

Nucleoside reverse transcriptase inhibitor (NRTI)

Question 461

List some examples of obligate intracellular bacteria and protozoa.

Answer 461

Bacteria: Chlamydia, Rickettsia, Coxiella, Mycobacteria Protozoa: toxoplasma, cryptosporidium, leishmania

Question 462

Which organisms can be identified with wet slide microscopy?

Answer 462

BV TV Candida

Question 463

``` For each of each of the following types of GI infection, state a likely source: B. cereus C. botulinum Campylobacter C. perfringens E. coli Hep A Listeria Salmonella Shigella Staphylococcua Vibrio ```

Answer 463

B. cereus - rice C. botulinum - canned food Campylobacter - milk, chicken, shellfish C. perfringens - beef, poultry (reheated) E. coli - leafy greens, beef, milk Hep A - shellfish, water Listeria - dairy, pate Salmonella - vegetables, chicken, pork, eggs Staphylococcus - sliced meat, pastry, sandwiches Vibrio - shellfish